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  1. Effect of Diet and Age on Arterial Stiffening Due to Atherosclerosis in ApoE(-/-) Mice.

    PubMed

    Cilla, M; Pérez, M M; Peña, E; Martínez, M A

    2016-07-01

    This work analyzes the progressive stiffening of the aorta due to atherosclerosis development of both ApoE(-/-) and C57BL/6J mice fed on a Western (n = 5) and a normal (n = 5) chow diet for the ApoE(-/-) group and on a normal chow diet (n = 5) for the C57BL/6J group. Sets of 5 animals from the three groups were killed after 10, 20, 30 and 40 weeks on their respective diets (corresponding to 17, 27, 37 and 47 weeks of age). Mechanical properties (inflation test and axial residual stress measurements) and histological properties were compared for both strains, ApoE(-/-) on the hyper-lipidic diet and both ApoE(-/-) and C57BL/6J on the normal diet, after the same period and after different periods of diet. The results indicated that the aorta stiffness in the ApoE(-/-) and C57BL/6J mice under normal diet remained approximately constant irrespective of their age. However, the arterial stiffness in the ApoE(-/-) on the hyper-lipidic diet increased over time. Statistical differences were found between the group after 10 weeks and the groups after 30 and 40 weeks of a hyper-lipidic diet. Comparing the hyper-lipidic and normal diet mice, statistical differences were also found between both diets in all cases after 40 weeks of diet, frequently after 30 weeks, and in some cases after 20 weeks. The early stages of lesion corresponded to the first 2 weeks of diet. Advanced lesions were found at 30 weeks and, finally, the aorta was completely damaged after 40 weeks of diet. In conclusion, we found substantial changes in the mechanical properties of the aorta walls of the ApoE(-/-) mice fed with the hyper-lipidic diet compared to the normal chow diet groups for both the ApoE(-/-) and C57BL/6J groups. These findings could serve as a reference for the study of changes in the arterial wall properties in cases of atherosclerosis.

  2. ApoE gene polymorphism and its relationship with coronary artery disease in ethnic Kashmiri population.

    PubMed

    Afroze, Dil; Yousuf, Adfar; Tramboo, Nisar A; Shah, Zaffar A; Ahmad, Asrar

    2016-11-01

    Apolipoprotein E is a fundamental component of various lipoproteins and plays substantial role in cholesterol/lipid transport among cells of various tissues. The ApoE gene is polymorphic with three alleles ε2, ε3, and ε4, coding for isoforms E2, E3, and E4 having different binding inclination for corresponding receptors. This work aimed to investigate the association between ApoE gene polymorphism and coronary artery disease (CAD) in Kashmiri population. APOE genotyping was done by polymerase chain reaction-restriction fragment length polymorphism. Our study indicated ApoE ε3/ε3 to be the most common genotype in both CAD and control group. The frequency of ε2, ε3, and ε4 alleles of ApoE gene in cases was observed to be 0.06, 0.72, and 0.20, while in control subjects it was 0.075, 0.82, and 0.11, respectively. A significant difference was found between cases and controls with respect to TC, LDL, and HDL levels. Our data showed that frequency of ε4/ε4, ε4/ε3 genotype and ε4 allele was significantly higher in cases than in controls (p = 0.02, p = 0.004, p < 0.001 respectively). Moreover, the CAD patients carrying ε4 allele had significantly higher TC and LDL levels (p value <0.01). Thus our data showed a significant association of ApoE ε4 allele with the risk of CAD. The data revealed that ApoE ε4 allele is associated with increased risk of CAD and increased levels LDL and TC in Kashmiri population.

  3. Porphyromonas gingivalis accelerates inflammatory atherosclerosis in the innominate artery of ApoE deficient mice.

    PubMed

    Hayashi, Chie; Viereck, Jason; Hua, Ning; Phinikaridou, Alkystis; Madrigal, Andrés G; Gibson, Frank C; Hamilton, James A; Genco, Caroline A

    2011-03-01

    Studies in humans support a role for the oral pathogen Porphyromonas gingivalis in the development of inflammatory atherosclerosis. The goal of this study was to determine if P. gingivalis infection accelerates inflammation and atherosclerosis in the innominate artery of mice, an artery which has been reported to exhibit many features of human atherosclerotic disease, including plaque rupture. Apolipoprotein E-deficient (ApoE-/-) mice were orally infected with P. gingivalis, and magnetic resonance imaging (MRI) was used to monitor the progression of atherosclerosis in live mice. P. gingivalis infected mice exhibited a statistically significant increase in atherosclerotic plaque in the innominate artery as compared to uninfected mice. Polarized light microscopy and immunohistochemistry revealed that the innominate arteries of infected mice had increased lipids, macrophages and T cells as compared to uninfected mice. Increases in plaque, total cholesterol esters and cholesterol monohydrate crystals, macrophages, and T cells were prevented by immunization with heat-killed P. gingivalis prior to pathogen exposure. These are the first studies to demonstrate progression of inflammatory plaque accumulation in the innominate arteries by in vivo MRI analysis following pathogen exposure, and to document protection from plaque progression in the innominate artery via immunization. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  4. Porphyromonas gingivalis Accelerates Inflammatory Atherosclerosis in the Innominate Artery of ApoE Deficient Mice

    PubMed Central

    Hayashi, Chie; Viereck, Jason; Hua, Ning; Phinikaridou, Alkystis; Madrigal, Andres G.; Gibson, Frank C.; Hamilton, James A.; Genco, Caroline A.

    2011-01-01

    Objective Studies in humans support a role for the oral pathogen Porphyromonas gingivalis in the development of inflammatory atherosclerosis. The goal of this study was to determine if P. gingivalis infection accelerates inflammation and atherosclerosis in the innominate artery of mice, an artery which has been reported to exhibit many features of human atherosclerotic disease, including plaque rupture. Methods and Results Apolipoprotein E-deficient (ApoE−/−) mice were orally infected with P. gingivalis, and Magnetic Resonance Imaging (MRI) was used to monitor the progression of atherosclerosis in live mice. P. gingivalis infected mice exhibited a statistically significant increase in atherosclerotic plaque in the innominate artery as compared to uninfected mice. Polarized light microscopy and immunohistochemistry revealed that the innominate arteries of infected mice had increased lipids, macrophages and T cells as compared to uninfected mice. Increases in plaque, total cholesterol esters and cholesterol monohydrate crystals, macrophages, and T cells were prevented by immunization with heat-killed P. gingivalis prior to pathogen exposure. Conclusions These are the first studies to demonstrate progression of inflammatory plaque accumulation in the innominate arteries by in-vivo MRI analysis following pathogen exposure, and to document protection from plaque progression in the innominate artery via immunization. PMID:21251656

  5. Contralateral artery enlargement predicts carotid plaque progression based on machine learning algorithm models in apoE(-/-) mice.

    PubMed

    Li, Bing; Jiao, Yun; Fu, Cong; Xie, Bo; Ma, Genshan; Teng, Gaojun; Yao, Yuyu

    2016-12-28

    This study specifically focused on anatomical MRI characterization of the low shear stress-induced atherosclerotic plaque in mice. We used machine learning algorithms to analyze multiple correlation factors of plaque to generate predictive models and to find the predictive factor for vulnerable plaque. Branches of the left carotid artery in apoE(-/-) and C57BL/6J mice were ligated to produce the partial left carotid artery model. Before surgery, and 7, 14, and 28 days after surgery, in vivo serial MRI measurements of carotid artery diameter were obtained. Meanwhile, proximal blood flow was evaluated. After image acquisition and animal sacrifice, carotid arteries were harvested for histological analysis. Support vector machine (SVM) and decision tree (DT) were used to select features and generate predictive models of vulnerable plaque progression. Seven days after surgery, neointima formation was visualized on micro-MRI in both apoE(-/-) and C57BL/6J mice. Ultrasonography showed that blood flow had significantly decreased compared to that in the contralateral artery. Partial ligation of the carotid artery for 4 weeks in apoE(-/-) mice induced vulnerable plaque; however, in C57BL/6J mice this same technique performed for 4 weeks induced arterial stenosis. Contralateral carotid artery diameter at 7 days after surgery was the most reliable predictive factor in plaque progression. We achieved over 87.5% accuracy, 80% sensitivity, and 95% specificity with SVM. The accuracy, sensitivity, and specificity for the DT classifier were 90, 90, and 90%, respectively. This study is the first to demonstrate that SVM and DT methods could be suitable models for identifying vulnerable plaque progression in mice. And contralateral artery enlargement can predict the vulnerable plaque in carotid artery at the very early stage. It may be a valuable tool which helps to optimize the clinical work flow process by providing more decision in selecting patients for treatment.

  6. Phospholipid chlorohydrin induces leukocyte adhesion to ApoE-/- mouse arteries via upregulation of P-selectin.

    PubMed

    Dever, Gary J; Benson, Robert; Wainwright, Cherry L; Kennedy, Simon; Spickett, Corinne M

    2008-02-01

    HOCl-modified low-density lipoprotein (LDL) has proinflammatory effects, including induction of inflammatory cytokine production, leukocyte adhesion, and ROS generation, but the components responsible for these effects are not completely understood. HOCl and the myeloperoxidase-H(2)O(2)-halide system can modify both protein and lipid moieties of LDL and react with unsaturated phospholipids to form chlorohydrins. We investigated the proinflammatory effects of 1-stearoyl-2-oleoyl-sn-3-glycerophosphocholine (SOPC) chlorohydrin on artery segments and spleen-derived leukocytes from ApoE(-/-) and C57 Bl/6 mice. Treatment of ApoE(-/-) artery segments with SOPC chlorohydrin, but not unmodified SOPC, caused increased leukocyte-arterial adhesion in a time- and concentration-dependent manner. This could be prevented by pretreatment of the artery with P-selectin or ICAM-1-blocking antibodies, but not anti-VCAM-1 antibody, and immunohistochemistry showed that P-selectin expression was upregulated. However, chlorohydrin treatment of leukocytes did not increase expression of adhesion molecules LFA-1 or PSGL-1, but caused increased release of ROS from PMA-stimulated leukocytes by a CD36-dependent mechanism. The SOPC chlorohydrin-induced adhesion and ROS generation could be abrogated by pretreatment of the ApoE(-/-) mice with pravastatin or a nitrated derivative, NCX 6550. These findings suggest that phospholipid chlorohydrins formed in HOCl-treated LDL could contribute to the proinflammatory effects observed for this modified lipoprotein in vitro.

  7. LDLR, ApoB and ApoE genes polymorphisms and classical risk factors in premature coronary artery disease.

    PubMed

    Abd El-Aziz, Tarek A; Mohamed, Randa H

    2016-09-30

    Lipoproteins play a central role in the development of atherosclerotic disease. So, with their ability to affect lipid levels, the LDLR, ApoB and ApoE polymorphisms could be one of the factors influencing development of atherosclerosis. This hypothesis has been tested in different populations with conflicting results. The purpose of the present study was to investigate the association between the LDLR, ApoB and ApoE genes polymorphisms with premature CAD (PCAD) in Egyptians. One hundred thirty-five patients of PCAD and one hundred thirty-two ages and sex matched control subjects were included in the study. LDLR and ApoB genes polymorphisms were analyzed by polymerase chain reaction (PCR). The ApoE genotypes were identified by multiplex amplification refractory mutation system (multi-AMRS). We found that LDLR A(+)A(+) genotype, ApoB X(+) allele and ApoE E4 allele increased the risk of PCAD by 1.8, 2.1 and 12.1 respectively. The present study proved that smoking, metabolic syndrome, ApoB X(+)X(+) genotype and ApoE E4 allele were independent risk factors for the development of PCAD. This is the first study investigate the association between low density lipoprotein receptor, apolipoprotein B and apolipoprotein E genes polymorphisms with PCAD and lipid levels in Egyptians and we concluded that the LDLR A(+)A(+) genotype, ApoB X(+) allele and ApoE E4 allele may be associated with an increased risk for development of PCAD by elevated levels of total cholesterol (TC) and low density lipoprotein (LDLc). The coexistence of CAD risk factors with LDLR A(+)A(+) genotype, ApoB X(+) allele and ApoE E4 allele may increase the risk of the development of PCAD in Egyptian patients. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Serum Apo A-1 and Its Role as a Biomarker of Coronary Artery Disease

    PubMed Central

    Rahim, Salma; Ali, Yousaf; Khan, Uzma I; Ullah, Waqas; Shahzad, Muhammad A; Waleed, Muhammad

    2016-01-01

    Objectives To evaluate the role of apolipoprotein(Apo A-1) as a biomarker of coronary artery disease (CAD) and its comparison with the traditional marker high-density lipoprotein (HDL). Methodology One hundred patients proven to have coronary artery disease by angiography were recruited and their serum biomarkers were compared with 100 normal individuals adjusted for age and sex. Result The mean +/-standard deviation (SD) value of plasma Apo A-1 levels in the normal individuals were observed to be 207.42 +/- 41.35 (mg/dL) against 90.69 +/- 20.77 (mg/dL) in the cardiac patients. On the other hand the serum HDL levels were 52.93 +/-33.58 (mg/dL) in the normal individuals and 37.86 +/- 23.19 (mg/dL) in the cardiac patients. Both of these differences were statistically significant (p < 0.001). For Apo A-1, a large proportion of patients (85%) were found to be in the abnormal range when compared to the control group in which only 7% had an abnormal value. For HDL, a majority (70%) of the cardiac patients had abnormal values while 40% of the normal individuals also had abnormal values. The sensitivity of Apo A-1 for detecting CAD was 85%, while for HDL, it was only 69%. Similarly, the specificity of Apo A-1 for detecting CAD was 93%, while for HDL, it was 60%. When plotted on a receiver operating characteristic (ROC) curve, Apo A-1 had a much larger area under the curve when compared to HDL. Conclusion This study suggests that Apo A-1 may, in fact, be more sensitive than HDL as a predictor of CAD. However, to completely elucidate its role as a biomarker, to set target serum levels and to increase its clinical use, further studies are required. PMID:28123922

  9. Liver X receptor activation attenuates plaque formation and improves vasomotor function of the aortic artery in atherosclerotic ApoE(-/-) mice.

    PubMed

    Chen, Jianghong; Zhao, Li; Sun, Dongdong; Narsinh, Kazim; Li, Chunhong; Zhang, Zheng; Qi, Shun; Wei, Guangquan; Li, Weijie; Guo, Wenyi; Cao, Feng

    2012-12-01

    The severity of atherosclerosis is primarily determined by overall lipid metabolism and the degree of inflammation present within the vessel wall. We evaluated the effects of T-0901317, a liver X receptor agonist, on the atherosclerosis process, and especially on the endothelial function in ApoE(-/-) mice. ApoE(-/-) mice were treated with LXR agonist T-0901317 (1 μmol/L) for 6 weeks. ApoE(-/-) mice receiving T-0901317 were found to have markedly improved overall serum lipid profiles, albeit increased serum triglycerides. MRI imaging demonstrated that T-0901317 attenuated the atherosclerotic plaque burden in the aorta of ApoE(-/-) mice. Transmission electron microscopy and immunohistochemistry revealed attenuated ultrastructural changes as well as enhanced expression of the ATP-binding cassette transporter ABCA1. In addition, treatment with the LXR agonist improved the vasomotor function of atherosclerotic arteries, as assessed by KCl/norepinephrine-induced vasoconstrictive and acetylcholine-induced vasorelaxation functional assays. In vitro studies showed increased ABCG1, phospho-Akt and phospho-eNOS expression in ApoE(-/-) mice aorta endothelial cells (ECs) after T0901317 treatment. The present study suggest that LXR agonists protect the endothelium against atherosclerotic insults by increasing ABCA1 and ABCG1 expression, and improve the endothelial-dependent vasomotor function probably by promoting Akt and eNOS phosphorylation.

  10. The relation between apolipoprotein E (APOE) genotype and peripheral artery disease in patients at high risk for cardiovascular disease.

    PubMed

    Koopal, Charlotte; Geerlings, Mirjam I; Muller, Majon; de Borst, G J; Algra, Ale; van der Graaf, Yolanda; Visseren, Frank L J

    2016-03-01

    The apolipoprotein E gene (APOE) is associated with coronary heart disease and stroke, but the relation with peripheral artery disease (PAD) is unknown. We investigated the relation of APOE genotype with PAD and other types of vascular disease. The cross-sectional association between APOE genotype and ankle-brachial index (ABI) and vascular disease prevalence; and the prospective relation with incident PAD and other types of vascular disease (coronary artery disease, stroke and vascular mortality) were evaluated in 7418 patients from the Secondary Manifestations of ARTerial disease (SMART) study. This is a prospective cohort study in patients with cardiovascular disease or a cardiovascular risk factor. Analyses were adjusted for age and sex. Mean age was 56.7 ± 12.4 years and 68% of the patients was male. APOE genotype frequencies were ε2ε2 1.3%; ε2ε3 9.9%; ε2ε4 2.4%; ε3ε3 56.9%; ε3ε4 26.7% and ε4ε4 2.8%. Median follow-up time was 8.1 years (IQR 5.4-11.4) in which 452 new PAD events occurred. The ε2ε2 genotype was significantly associated with a lower ABI (regression coefficient -0.04, 95%CI -0.07 to -0.01), increased PAD prevalence (prevalence ratio 1.54, 95%CI 1.01-2.17) and a higher risk of incident PAD (HR 2.31, 95%CI 1.29-4.12) compared with ε3ε3. No relations between APOE genotypes and other vascular disease were observed. Of the six APOE genotypes, the ε2ε2 variant is associated with an increased risk for PAD in patients at high risk for cardiovascular disease. No association was observed between APOE genotype and coronary artery disease, stroke or vascular mortality in this population. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. [Serum levels of Apo-AI and B as markers of synthetic graft stenosis after bypass for peripheral artery disease].

    PubMed

    Guzmán-Lepe, Sergio; Anaya-Prado, Roberto

    2008-01-01

    Hyperlipidemias are the main risk factors for atherosclerosis and cardiovascular disease. Nevertheless, the protein fractions of these lipids such as apolipoprotein B (Apo-B) can lead to arterial obstruction. In this study we investigated levels of apolipoproteins AI and B in patients with chronic occlusive peripheral arterial disease (PAD) of the lower extremities and their association with either patency or stenosis of synthetic grafts. This cohort study included 24 patients with chronic occlusive PAD who underwent infrainguinal revascularization with polytetrafluoroethylene (PTFE) synthetic graft. Patients were divided into two groups according to whether or not they were exposed to Apo-B, thus integrating two cohorts: the unexposed group (group 1, normal levels of Apo-B) and the exposed group (group 2, high levels of Apo-B). Variables investigated at 3, 6 and 12 months included arm/ankle index (AAI) and its association with levels of Apo-AI and Apo-B, and levels of cholesterol, triglycerides, and fibrinogen. The study was comprised of 67% men and 33% women. Average age was 65.2 +/- 8.4 years. There was a correlation between AAI and high levels of Apo-B (p <0.001). Apo-AI levels were not significantly different between groups. Fibrinogen remained elevated in both groups with no statistical difference. Triglycerides demonstrated a significant difference between groups in basal measurements (p <0.05). Cholesterol remained normal in both groups without statistical difference. This study demonstrates that patients exposed to high levels of Apo-B had synthetic graft failure (obstruction), as demonstrated by AAI <1.

  12. Artery Tertiary Lymphoid Organs Control Multilayered Territorialized Atherosclerosis B-Cell Responses in Aged ApoE−/− Mice

    PubMed Central

    Srikakulapu, Prasad; Hu, Desheng; Yin, Changjun; Mohanta, Sarajo K.; Bontha, Sai Vineela; Peng, Li; Beer, Michael; Weber, Christian; McNamara, Coleen A.; Grassia, Gianluca; Maffia, Pasquale; Manz, Rudolf A.

    2016-01-01

    Objective— Explore aorta B-cell immunity in aged apolipoprotein E-deficient (ApoE−/−) mice. Approach and Results— Transcript maps, fluorescence-activated cell sorting, immunofluorescence analyses, cell transfers, and Ig-ELISPOT (enzyme-linked immunospot) assays showed multilayered atherosclerosis B-cell responses in artery tertiary lymphoid organs (ATLOs). Aging-associated aorta B-cell–related transcriptomes were identified, and transcript atlases revealed highly territorialized B-cell responses in ATLOs versus atherosclerotic lesions: ATLOs showed upregulation of bona fide B-cell genes, including Cd19, Ms4a1 (Cd20), Cd79a/b, and Ighm although intima plaques preferentially expressed molecules involved in non–B effector responses toward B-cell–derived mediators, that is, Fcgr3 (Cd16), Fcer1g (Cd23), and the C1q family. ATLOs promoted B-cell recruitment. ATLO B-2 B cells included naive, transitional, follicular, germinal center, switched IgG1+, IgA+, and IgE+ memory cells, plasmablasts, and long-lived plasma cells. ATLOs recruited large numbers of B-1 cells whose subtypes were skewed toward interleukin-10+ B-1b cells versus interleukin-10− B-1a cells. ATLO B-1 cells and plasma cells constitutively produced IgM and IgG and a fraction of plasma cells expressed interleukin-10. Moreover, ApoE−/− mice showed increased germinal center B cells in renal lymph nodes, IgM-producing plasma cells in the bone marrow, and higher IgM and anti–MDA-LDL (malondialdehyde-modified low-density lipoprotein) IgG serum titers. Conclusions— ATLOs orchestrate dichotomic, territorialized, and multilayered B-cell responses in the diseased aorta; germinal center reactions indicate generation of autoimmune B cells within the diseased arterial wall during aging. PMID:27102965

  13. Genetic variants of ApoE and ApoER2 differentially modulate endothelial function.

    PubMed

    Ulrich, Victoria; Konaniah, Eddy S; Herz, Joachim; Gerard, Robert D; Jung, Eunjeong; Yuhanna, Ivan S; Ahmed, Mohamed; Hui, David Y; Mineo, Chieko; Shaul, Philip W

    2014-09-16

    It is poorly understood why there is greater cardiovascular disease risk associated with the apolipoprotein E4 (apoE) allele vs. apoE3, and also greater risk with the LRP8/apolipoprotein E receptor 2 (ApoER2) variant ApoER2-R952Q. Little is known about the function of the apoE-ApoER2 tandem outside of the central nervous system. We now report that in endothelial cells apoE3 binding to ApoER2 stimulates endothelial NO synthase (eNOS) and endothelial cell migration, and it also attenuates monocyte-endothelial cell adhesion. However, apoE4 does not stimulate eNOS or endothelial cell migration or dampen cell adhesion, and alternatively it selectively antagonizes apoE3/ApoER2 actions. The contrasting endothelial actions of apoE4 vs. apoE3 require the N-terminal to C-terminal interaction in apoE4 that distinguishes it structurally from apoE3. Reconstitution experiments further reveal that ApoER2-R952Q is a loss-of-function variant of the receptor in endothelium. Carotid artery reendothelialization is decreased in ApoER2(-/-) mice, and whereas adenoviral-driven apoE3 expression in wild-type mice has no effect, apoE4 impairs reendothelialization. Moreover, in a model of neointima formation invoked by carotid artery endothelial denudation, ApoER2(-/-) mice display exaggerated neointima development. Thus, the apoE3/ApoER2 tandem promotes endothelial NO production, endothelial repair, and endothelial anti-inflammatory properties, and it prevents neointima formation. In contrast, apoE4 and ApoER2-R952Q display dominant-negative action and loss of function, respectively. Thus, genetic variants of apoE and ApoER2 impact cardiovascular health by differentially modulating endothelial function.

  14. Effect of open-label infusion of an apoA-I-containing particle (CER-001) on RCT and artery wall thickness in patients with FHA.

    PubMed

    Kootte, Ruud S; Smits, Loek P; van der Valk, Fleur M; Dasseux, Jean-Louis; Keyserling, Constance H; Barbaras, Ronald; Paolini, John F; Santos, Raul D; van Dijk, Theo H; Dallinga-van Thie, Geesje M; Nederveen, Aart J; Mulder, Willem J M; Hovingh, G Kees; Kastelein, John J P; Groen, Albert K; Stroes, Erik S

    2015-03-01

    Reverse cholesterol transport (RCT) contributes to the anti-atherogenic effects of HDL. Patients with the orphan disease, familial hypoalphalipoproteinemia (FHA), are characterized by decreased tissue cholesterol removal and an increased atherogenic burden. We performed an open-label uncontrolled proof-of-concept study to evaluate the effect of infusions with a human apoA-I-containing HDL-mimetic particle (CER-001) on RCT and the arterial vessel wall in FHA. Subjects received 20 infusions of CER-001 (8 mg/kg) during 6 months. Efficacy was assessed by measuring (apo)lipoproteins, plasma-mediated cellular cholesterol efflux, fecal sterol excretion (FSE), and carotid artery wall dimension by MRI and artery wall inflammation by (18)F-fluorodeoxyglucose-positron emission tomography/computed tomography scans. We included seven FHA patients: HDL-cholesterol (HDL-c), 13.8 [1.8-29.1] mg/dl; apoA-I, 28.7 [7.9-59.1] mg/dl. Following nine infusions in 1 month, apoA-I and HDL-c increased directly after infusion by 27.0 and 16.1 mg/dl (P = 0.018). CER-001 induced a 44% relative increase (P = 0.018) in in vitro cellular cholesterol efflux with a trend toward increased FSE (P = 0.068). After nine infusions of CER-001, carotid mean vessel wall area decreased compared with baseline from 25.0 to 22.8 mm(2) (P = 0.043) and target-to-background ratio from 2.04 to 1.81 (P = 0.046). In FHA-subjects, CER-001 stimulates cholesterol mobilization and reduces artery wall dimension and inflammation, supporting further evaluation of CER-001 in FHA patients. Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.

  15. Effect of open-label infusion of an apoA-I-containing particle (CER-001) on RCT and artery wall thickness in patients with FHA[S

    PubMed Central

    Kootte, Ruud S.; Smits, Loek P.; van der Valk, Fleur M.; Dasseux, Jean-Louis; Keyserling, Constance H.; Barbaras, Ronald; Paolini, John F.; Santos, Raul D.; van Dijk, Theo H.; Dallinga-van Thie, Geesje M.; Nederveen, Aart J.; Mulder, Willem J. M.; Hovingh, G. Kees; Kastelein, John J. P.; Groen, Albert K.; Stroes, Erik S.

    2015-01-01

    Reverse cholesterol transport (RCT) contributes to the anti-atherogenic effects of HDL. Patients with the orphan disease, familial hypoalphalipoproteinemia (FHA), are characterized by decreased tissue cholesterol removal and an increased atherogenic burden. We performed an open-label uncontrolled proof-of-concept study to evaluate the effect of infusions with a human apoA-I-containing HDL-mimetic particle (CER-001) on RCT and the arterial vessel wall in FHA. Subjects received 20 infusions of CER-001 (8 mg/kg) during 6 months. Efficacy was assessed by measuring (apo)lipoproteins, plasma-mediated cellular cholesterol efflux, fecal sterol excretion (FSE), and carotid artery wall dimension by MRI and artery wall inflammation by 18F-fluorodeoxyglucose-positron emission tomography/computed tomography scans. We included seven FHA patients: HDL-cholesterol (HDL-c), 13.8 [1.8–29.1] mg/dl; apoA-I, 28.7 [7.9–59.1] mg/dl. Following nine infusions in 1 month, apoA-I and HDL-c increased directly after infusion by 27.0 and 16.1 mg/dl (P = 0.018). CER-001 induced a 44% relative increase (P = 0.018) in in vitro cellular cholesterol efflux with a trend toward increased FSE (P = 0.068). After nine infusions of CER-001, carotid mean vessel wall area decreased compared with baseline from 25.0 to 22.8 mm2 (P = 0.043) and target-to-background ratio from 2.04 to 1.81 (P = 0.046). In FHA-subjects, CER-001 stimulates cholesterol mobilization and reduces artery wall dimension and inflammation, supporting further evaluation of CER-001 in FHA patients. PMID:25561459

  16. Combined "pro-atherosclerotic" variants of the ACE and APOE genes increase the risk of the coronary artery disease associated with the presence of cigarette smoking.

    PubMed

    Zak, Iwona; Niemiec, Pawel; Balcerzyk, Anna; Krauze, Jolanta

    2008-12-01

    Cigarette smoking increases the synthesis of angiotensin-1 converting enzyme (ACE) and induces oxidative modifications of the apolipoprotein E (apo E).Thus we explored the gene-environment interactions between APOE gene epsilon and ACE gene insertion/deletion polymorphisms and cigarette smoking in coronary artery disease (CAD) patients. We analysed 360 subjects: 171 CAD patients and 189 blood donors without a history of cardiovascular diseases. ACE and APOE polymorphisms were genotyped using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methods, respectively. To determine gene-environment interactions, epidemiological methodology was used. The ACE DD genotype was a rather weak risk factor of CAD in the analysed population (OR = 1.87, P = 0.01).The differences in allele and genotype distribution of the APOE polymorphism were not statistically significant.The carriers of the combined genotype ACE(DD) + APOE(epsilon4epsilon4,epsilon3epsilon4,epsilon2epsilon4) were more frequent in patients, however, the differences were on the bound of statistical significance (P = 0.08). Logistic regression analysis showed that the ACE(DD) + apo E(epsilon4epsilon4,epsilon3epsilon4,epsilon2epsilon4) cigarette smokers were much more frequent in the CAD group (OR = 11.68, 95%CI; 1.52-246.43, P = 0.009).We confirmed these results using the 4 x 2 table approach and we found a synergistic effect of the ACE(DD) + APOE(epsilon4epsilon4,epsilon3epsilon4,epsilon2epsilon4) combined genotype and cigarette smoking (SI = 10.52, SIM = 6.09). We demonstrated the existence of the synergistic effect between cigarette smoking and the contemporaneous carrier-state of APOE epsilon4 and ACE D alleles which increased the risk of CAD to a large extent.

  17. Combined orcein and martius scarlet blue (OMSB) staining for qualitative and quantitative analyses of atherosclerotic plaques in brachiocephalic arteries in apoE/LDLR(-/-) mice.

    PubMed

    Gajda, Mariusz; Jasztal, Agnieszka; Banasik, Tomasz; Jasek-Gajda, Ewa; Chlopicki, Stefan

    2017-02-06

    Numerous cellular and extracellular components should be analyzed in sections of atherosclerotic plaques to assess atherosclerosis progression and vulnerability. Here, we combined orcein (O) staining for elastic fibers and martius scarlet blue (MSB) polychrome to visualize various morphological contents of plaque in brachiocephalic arteries (BCA) of apoE/LDLR(-/-) mice. Elastic fibers (including broken elastic laminae and 'buried' fibrous caps) were stained purple and they could be easily distinguished from collagen fibers (blue). Orcein allowed clear identification of even the finest elastic fibers. Erythrocytes were stained yellow and they could easily be discerned from mature fibrin (red). Old fibrin tends to acquire blue color. The method of OMSB staining is simple, takes less than 1 h to perform and can be adapted to automatic stainers. Most importantly, the color separation is good enough to allow digital automatic segmentation of specific components in tissue section and quantitative analysis of the plaque constituents. OMSB was used to compare atherosclerotic plaques in proximal and distal regions of BCA in apoE/LDLR(-/-) mice. In conclusion, OMSB staining represents a novel staining that could be routinely used for qualitative and quantitative microscopic assessments of formaldehyde-fixed and paraffin-embedded sections of arteries with atherosclerotic lesions.

  18. Goal attainments and their discrepancies for low density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apo B) in over 2,000 Chinese patients with known coronary artery disease or type 2 diabetes

    PubMed Central

    Yang, Xiang-Jun; Zhao, Xin; Xu, Hai-Feng

    2015-01-01

    Purpose Low density lipoprotein cholesterol (LDL-C) is primary treatment target for patients with dislipidemia. The apolipoprotein B (apo B), an emerging biomarker for cardiovascular risk prediction, appears to be superior to the LDL-C. However, little is known about goal attainments and their discrepancies for LDL-C and apo B in Chinese patients with known CAD or DM. Methods A total of 2,172 hospitalized patients with known coronary artery disease (CAD) or DM, aged >27 years of old, were enrolled. The success rates for apo B and LDL-C goal attainments were evaluated and compared by categorization and by sex. Results When the success rates for apo B were compared with the ones for LDL-C, the former was higher than the latter across all categorizations, with the statistically significant differences seen in all patients, CAD alone and DM alone (P<0.0001), but not in coexistence of CAD and DM (P=0.190). The trend toward to higher success rates for LDL-C and apo B goal attainments in men than in women were noteworthy across all categorizations although only in all patients and in DM alone patients were the statistically significant differences found (P<0.01). Conclusions The LDL-C lags behind the apo B in goal attainments in Chinese patients. Whether these discrepancies are associated with the occurrence differences for CAD and for stroke between the East Asia and the Western countries warrants further study. PMID:25984449

  19. Goal attainments and their discrepancies for low density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apo B) in over 2,000 Chinese patients with known coronary artery disease or type 2 diabetes.

    PubMed

    He, Yong-Ming; Yang, Xiang-Jun; Zhao, Xin; Xu, Hai-Feng

    2015-04-01

    Low density lipoprotein cholesterol (LDL-C) is primary treatment target for patients with dislipidemia. The apolipoprotein B (apo B), an emerging biomarker for cardiovascular risk prediction, appears to be superior to the LDL-C. However, little is known about goal attainments and their discrepancies for LDL-C and apo B in Chinese patients with known CAD or DM. A total of 2,172 hospitalized patients with known coronary artery disease (CAD) or DM, aged >27 years of old, were enrolled. The success rates for apo B and LDL-C goal attainments were evaluated and compared by categorization and by sex. When the success rates for apo B were compared with the ones for LDL-C, the former was higher than the latter across all categorizations, with the statistically significant differences seen in all patients, CAD alone and DM alone (P<0.0001), but not in coexistence of CAD and DM (P=0.190). The trend toward to higher success rates for LDL-C and apo B goal attainments in men than in women were noteworthy across all categorizations although only in all patients and in DM alone patients were the statistically significant differences found (P<0.01). The LDL-C lags behind the apo B in goal attainments in Chinese patients. Whether these discrepancies are associated with the occurrence differences for CAD and for stroke between the East Asia and the Western countries warrants further study.

  20. Plasmalogen modulation attenuates atherosclerosis in ApoE- and ApoE/GPx1-deficient mice.

    PubMed

    Rasmiena, Aliki A; Barlow, Christopher K; Stefanovic, Nada; Huynh, Kevin; Tan, Ricardo; Sharma, Arpeeta; Tull, Dedreia; de Haan, Judy B; Meikle, Peter J

    2015-12-01

    We previously reported a negative association of circulating plasmalogens (phospholipids with proposed atheroprotective properties) with coronary artery disease. Plasmalogen modulation was previously demonstrated in animals but its effect on atherosclerosis was unknown. We assessed the effect of plasmalogen enrichment on atherosclerosis of murine models with differing levels of oxidative stress. Six-week old ApoE- and ApoE/glutathione peroxidase-1 (GPx1)-deficient mice were fed a high-fat diet with/without 2% batyl alcohol (precursor to plasmalogen synthesis) for 12 weeks. Mass spectrometry analysis of lipids showed that batyl alcohol supplementation to ApoE- and ApoE/GPx1-deficient mice increased the total plasmalogen levels in both plasma and heart. Oxidation of plasmalogen in the treated mice was evident from increased level of plasmalogen oxidative by-product, sn-2 lysophospholipids. Atherosclerotic plaque in the aorta was reduced by 70% (P = 5.69E-07) and 69% (P = 2.00E-04) in treated ApoE- and ApoE/GPx1-deficient mice, respectively. A 40% reduction in plaque (P = 7.74E-03) was also seen in the aortic sinus of only the treated ApoE/GPx1-deficient mice. Only the treated ApoE/GPx1-deficient mice showed a decrease in VCAM-1 staining (-28%, P = 2.43E-02) in the aortic sinus and nitrotyrosine staining (-78%, P = 5.11E-06) in the aorta. Plasmalogen enrichment via batyl alcohol supplementation attenuated atherosclerosis in ApoE- and ApoE/GPx1-deficient mice, with a greater effect in the latter group. Plasmalogen enrichment may represent a viable therapeutic strategy to prevent atherosclerosis and reduce cardiovascular disease risk, particularly under conditions of elevated oxidative stress and inflammation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  1. Coronary Arteries

    MedlinePlus

    ... and animations for grades K-6. The Coronary Arteries Coronary Circulation The heart muscle, like every other ... into two main coronary blood vessels (also called arteries). These coronary arteries branch off into smaller arteries, ...

  2. Cathepsin K Deficiency Prevents the Aggravated Vascular Remodeling Response to Flow Cessation in ApoE-/- Mice.

    PubMed

    Donners, Marjo M P C; Bai, Lili; Lutgens, Suzanne P M; Wijnands, Erwin; Johnson, Jason; Schurgers, Leon J; Liu, Cong-Lin; Daemen, Mat J A P; Cleutjens, Kitty B J M; Shi, Guo-Ping; Biessen, Erik A L; Heeneman, Sylvia

    2016-01-01

    Cathepsin K (catK) is a potent lysosomal cysteine protease involved in extracellular matrix (ECM) degradation and inflammatory remodeling responses. Here we have investigated the contribution of catK deficiency on carotid arterial remodeling in response to flow cessation in apoE-/- and wild type (wt) background. Ligation-induced hyperplasia is considerably aggravated in apoE-/- versus wt mice. CatK protein expression was significantly increased in neointimal lesions of apoE-/- compared with wt mice, suggesting a role for catK in intimal hyperplasia under hyperlipidemic conditions. Surprisingly, CatK deficiency completely blunted the augmented hyperplastic response to flow cessation in apoE-/-, whereas vascular remodeling in wt mice was unaffected. As catK deficiency did neither alter lesion collagen content and elastic laminae fragmentation in vivo, we focused on effects of catK on (systemic) inflammatory responses. CatK deficiency significantly reduced circulating CD3 T-cell numbers, but increased the regulatory T cell subset in apoE-/- but not wt mice. Moreover, catK deficiency changed CD11b+Ly6G-Ly6C high monocyte distribution in apoE-/- but not wt mice and tended to favour macrophage M2a polarization. In conclusion, catK deficiency almost completely blunted the increased vascular remodeling response of apoE-/- mice to flow cessation, possibly by correcting hyperlipidemia-associated pro-inflammatory effects on the peripheral immune response.

  3. Cathepsin K Deficiency Prevents the Aggravated Vascular Remodeling Response to Flow Cessation in ApoE-/- Mice

    PubMed Central

    Lutgens, Suzanne P. M.; Wijnands, Erwin; Johnson, Jason; Schurgers, Leon J.; Liu, Cong-Lin; Daemen, Mat J. A. P.; Cleutjens, Kitty B. J. M.; Shi, Guo-Ping; Biessen, Erik A. L.; Heeneman, Sylvia

    2016-01-01

    Cathepsin K (catK) is a potent lysosomal cysteine protease involved in extracellular matrix (ECM) degradation and inflammatory remodeling responses. Here we have investigated the contribution of catK deficiency on carotid arterial remodeling in response to flow cessation in apoE-/- and wild type (wt) background. Ligation-induced hyperplasia is considerably aggravated in apoE-/- versus wt mice. CatK protein expression was significantly increased in neointimal lesions of apoE-/- compared with wt mice, suggesting a role for catK in intimal hyperplasia under hyperlipidemic conditions. Surprisingly, CatK deficiency completely blunted the augmented hyperplastic response to flow cessation in apoE-/-, whereas vascular remodeling in wt mice was unaffected. As catK deficiency did neither alter lesion collagen content and elastic laminae fragmentation in vivo, we focused on effects of catK on (systemic) inflammatory responses. CatK deficiency significantly reduced circulating CD3 T-cell numbers, but increased the regulatory T cell subset in apoE-/- but not wt mice. Moreover, catK deficiency changed CD11b+Ly6G-Ly6C high monocyte distribution in apoE-/- but not wt mice and tended to favour macrophage M2a polarization. In conclusion, catK deficiency almost completely blunted the increased vascular remodeling response of apoE-/- mice to flow cessation, possibly by correcting hyperlipidemia-associated pro-inflammatory effects on the peripheral immune response. PMID:27636705

  4. Absence of Four-and-a-Half LIM Domain Protein 2 Decreases Atherosclerosis in ApoE-/- Mice.

    PubMed

    Ebrahimian, Talin; Simon, David; Lemarié, Catherine A; Simeone, Stefania; Heidari, Maryam; Mann, Koren K; Wassmann, Sven; Lehoux, Stephanie

    2015-05-01

    Four-and-a-half LIM domain protein-2 (FHL2) is expressed in endothelial cells, vascular smooth muscle cells, and leukocytes. It regulates cell survival, migration, and inflammatory response, but its role in atherogenesis is unknown. To investigate the role of FHL2 in atherosclerosis, FHL2-deficient mice were crossed with ApoE-deficient mice, to generate ApoE/FHL2-/- mice. After high-fat diet, ApoE/FHL2-/- mice had significantly smaller atherosclerotic plaques than ApoE-/- mice in the aortic sinus, the brachiocephalic artery, and the aorta. This was associated with enhanced collagen and smooth muscle cell contents and a 2-fold reduction in macrophage content within the plaques of ApoE/FHL-2-/- versus ApoE-/- mice. This could be explained, in part, by the reduction in aortic ICAM-1 (intracellular adhesion molecule) mRNA and VCAM-1 (vascular cell adhesion molecule) protein expression in the plaque. Aortic gene expression of the chemokines CX3CL1 and CCL5 was increased in ApoE/FHL2-/- versus ApoE-/- mice. Peritoneal thioglycollate injection elicited equivalent numbers of monocytes and macrophages in both groups, but a significantly lower number of proinflammatory Ly6C high monocytes were recruited in ApoE/FHL2-/- versus ApoE-/- mice. Furthermore, mRNA levels of CX3CR1 were 2-fold higher in monocytes from ApoE/FHL2-/- versus ApoE-/- mice. Finally, we investigated the potential importance of myeloid cell FHL2 deficiency in atherosclerosis. After being irradiated, ApoE-/- or ApoE/FHL2-/- mice were transplanted with ApoE-/- or ApoE/FHL2-/- bone marrow. After high-fat diet, both chimeric groups developed smaller plaques than ApoE-/- transplanted with ApoE-/- bone marrow. These results suggest that FHL2 in both myeloid and vascular cells may play an important role in atherosclerosis by promoting proinflammatory chemokine production, adhesion molecule expression, and proinflammatory monocyte recruitment. © 2015 American Heart Association, Inc.

  5. Divergent systemic and local inflammatory response to hind limb demand ischemia in wild-type and ApoE-/- mice.

    PubMed

    Crawford, Robert S; Albadawi, Hassan; Robaldo, Alessandro; Peck, Michael A; Abularrage, Christopher J; Yoo, Hyung-Jin; Lamuraglia, Glenn M; Watkins, Michael T

    2013-08-01

    We designed studies to determine whether the ApoE-/- phenotype modulates the local skeletal muscle and systemic inflammatory (plasma) responses to lower extremity demand ischemia. The ApoE-/- phenotype is an experimental model for atherosclerosis in humans. Aged female ApoE-/- and C57BL6 mice underwent femoral artery ligation, then were divided into sedentary and demand ischemia (exercise) groups on day 14. We assessed baseline and postexercise limb perfusion and hind limb function. On day 14, animals in the demand ischemia group underwent daily treadmill exercise through day 28. Sedentary mice were not exercised. On day 28, we harvested plasma and skeletal muscle from ischemic limbs from sedentary and exercised mice. We assayed muscle for angiogenic and proinflammatory proteins, markers of skeletal muscle regeneration, and evidence of skeletal muscle fiber maturation. Hind limb ischemia was similar in ApoE-/- and C57 mice before the onset of exercise. Under sedentary conditions, plasma vascular endothelial cell growth factor and interleukin-6, but not keratinocyte chemoattractant factor (KC) or macrophage inflammatory protein-2 (MIP-2), were higher in ApoE (P < 0.0001). After exercise, plasma levels of vascular endothelial cell growth factor, KC, and MIP-2, but not IL-6, were lower in ApoE (P < 0.004). The cytokines KC and MIP-2 in muscle were greater in exercised ApoE-/- mice compared with C57BL6 mice (P = 0.01). Increased poly-ADP-ribose activity and mature muscle regeneration were associated with demand ischemia in the C57BL6 mice, compared with the ApoE-/- mice (P = 0.01). Demand limb ischemia in the ApoE-/- phenotype exacerbated the expression of select systemic cytokines in plasma and blunted indices of muscle regeneration. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Arterial insufficiency

    MedlinePlus

    ... is atherosclerosis or "hardening of the arteries." Fatty material (called plaque) builds up on the walls of your arteries. This causes them to become narrow and stiff. As a result, it is hard for blood to flow through your arteries. Blood flow may be suddenly ...

  7. Acute arterial occlusion - kidney

    MedlinePlus

    Acute renal arterial thrombosis; Renal artery embolism; Acute renal artery occlusion; Embolism - renal artery ... kidneys need a good blood supply. The main artery to the kidney is called the renal artery. ...

  8. Brachioradial arteries with anastomotic arteries connecting to brachial arteries bilaterally.

    PubMed

    Hong, Tong; Qiuhong, Dan; Haipeng, Cai

    2010-01-01

    We present a patient with a failed radial coronary angioplasty as a result of bilateral brachioradial arteries, the radial arteries anomalously originating from the axillary arteries. We review the literature concerning abnormal origins of the radial artery and propose the left ulnar artery as optimal access of choice in cases with a right brachioradial artery of relatively small size in its proximal part.

  9. Arterial calcifications

    PubMed Central

    Rennenberg, Roger J M W; Schurgers, Leon J; Kroon, Abraham A; Stehouwer, Coen D A

    2010-01-01

    Abstract Arterial calcifications as found with various imaging techniques, like plain X-ray, computed tomography or ultrasound are associated with increased cardiovascular risk. The prevalence of arterial calcification increases with age and is stimulated by several common cardiovascular risk factors. In this review, the clinical importance of arterial calcification and the currently known proteins involved are discussed. Arterial calcification is the result of a complex interplay between stimulating (bone morphogenetic protein type 2 [BMP-2], RANKL) and inhibitory (matrix Gla protein, BMP-7, osteoprotegerin, fetuin-A, osteopontin) proteins. Vascular calcification is especially prevalent and related to adverse outcome in patients with renal insufficiency and diabetes mellitus. We address the special circumstances and mechanisms in these patient groups. Treatment and prevention of arterial calcification is possible by the use of specific drugs. However, it remains to be proven that reduction of vascular calcification in itself leads to a reduced cardiovascular risk. PMID:20716128

  10. APOE Genotyping, Cardiovascular Disease

    MedlinePlus

    ... tests: Cardiac Risk Assessment ; HDL Cholesterol ; LDL Cholesterol ; Lipid Profile ; Triglycerides Were you looking instead for APOE ... to help in diagnosis and treatment of elevated lipid levels. APOE testing may be used to help ...

  11. Mesenteric artery ischemia

    MedlinePlus

    ... bowel - mesenteric; Dead gut - mesenteric; Atherosclerosis - mesenteric artery; Hardening of the arteries - mesenteric artery ... the aorta, the main artery from the heart. Hardening of the arteries occurs when fat, cholesterol, and ...

  12. Peripheral Artery Disease

    MedlinePlus

    ... Physician Resources Professions Site Index A-Z Peripheral Artery Disease (PAD) Peripheral artery disease (PAD) refers to ... is peripheral artery disease treated? What is peripheral artery disease (PAD)? Peripheral artery disease, or PAD, refers ...

  13. Angioplasty and stent placement - peripheral arteries

    MedlinePlus

    Percutaneous transluminal angioplasty - peripheral artery; PTA - peripheral artery; Angioplasty - peripheral arteries; Iliac artery -angioplasty; Femoral artery - angioplasty; Popliteal artery - angioplasty; Tibial artery - angioplasty; Peroneal artery - ...

  14. Arterial Stiffness.

    PubMed

    Avolio, Alberto

    2013-04-01

    Stiffness of large arteries has been long recognized as a significant determinant of pulse pressure. However, it is only in recent decades, with the accumulation of longitudinal data from large and varied epidemiological studies of morbidity and mortality associated with cardiovascular disease, that it has emerged as an independent predictor of cardiovascular risk. This has generated substantial interest in investigations related to intrinsic causative and associated factors responsible for the alteration of mechanical properties of the arterial wall, with the aim to uncover specific pathways that could be interrogated to prevent or reverse arterial stiffening. Much has been written on the haemodynamic relevance of arterial stiffness in terms of the quantification of pulsatile relationships of blood pressure and flow in conduit arteries. Indeed, much of this early work regarded blood vessels as passive elastic conduits, with the endothelial layer considered as an inactive lining of the lumen and as an interface to flowing blood. However, recent advances in molecular biology and increased technological sophistication for the detection of low concentrations of biochemical compounds have elucidated the highly important regulatory role of the endothelial cell affecting vascular function. These techniques have enabled research into the interaction of the underlying passive mechanical properties of the arterial wall with the active cellular and molecular processes that regulate the local environment of the load-bearing components. This review addresses these emerging concepts.

  15. ApoE derived from adipose tissue does not suppress atherosclerosis or correct hyperlipidemia in apoE knockout mice

    PubMed Central

    Huang, Zhi H.; Reardon, Catherine A.; Subbaiah, Papasani V.; Getz, Godfrey S.; Mazzone, Theodore

    2013-01-01

    The synthesis of apoE by adipocytes has profound effects on adipose tissue lipid flux and gene expression. Using adipose tissue transplantation from wild-type (WT) to apoE knockout (EKO) mice, we show that adipose tissue also contributes to circulating apoE. Different from circulating apoE produced by bone marrow transplantation (BMT), however, adipose tissue-derived apoE does not correct hyperlipidemia or suppress atherosclerosis. ApoE secreted by macrophages has a more acidic isoform distribution, and it increases binding of reconstituted VLDL particles to hepatocytes and fibroblasts more effectively than apoE secreted by adipocytes. The incremental binding can be entirely accounted for by binding to the LDL receptor. After BMT into EKO hosts, plasma cholesterol and macrophage-derived apoE are largely within IDL/LDL- and HDL-sized particles. After adipose tissue transplantation, most cholesterol and adipocyte apoE remain in VLDL. After BMT, circulating apoE no longer demonstrates predominance of acidic isoforms compared with that circulating after fat transplantation. In conclusion, fat transplantation provides circulating apoE levels similar to those provided by bone marrow transplantation, but it does not suppress hyperlipidemia or atherosclerosis. A potential mechanism contributing to this difference is differential binding to cell surface lipoprotein receptors. PMID:23071294

  16. ApoE derived from adipose tissue does not suppress atherosclerosis or correct hyperlipidemia in apoE knockout mice.

    PubMed

    Huang, Zhi H; Reardon, Catherine A; Subbaiah, Papasani V; Getz, Godfrey S; Mazzone, Theodore

    2013-01-01

    The synthesis of apoE by adipocytes has profound effects on adipose tissue lipid flux and gene expression. Using adipose tissue transplantation from wild-type (WT) to apoE knockout (EKO) mice, we show that adipose tissue also contributes to circulating apoE. Different from circulating apoE produced by bone marrow transplantation (BMT), however, adipose tissue-derived apoE does not correct hyperlipidemia or suppress atherosclerosis. ApoE secreted by macrophages has a more acidic isoform distribution, and it increases binding of reconstituted VLDL particles to hepatocytes and fibroblasts more effectively than apoE secreted by adipocytes. The incremental binding can be entirely accounted for by binding to the LDL receptor. After BMT into EKO hosts, plasma cholesterol and macrophage-derived apoE are largely within IDL/LDL- and HDL-sized particles. After adipose tissue transplantation, most cholesterol and adipocyte apoE remain in VLDL. After BMT, circulating apoE no longer demonstrates predominance of acidic isoforms compared with that circulating after fat transplantation. In conclusion, fat transplantation provides circulating apoE levels similar to those provided by bone marrow transplantation, but it does not suppress hyperlipidemia or atherosclerosis. A potential mechanism contributing to this difference is differential binding to cell surface lipoprotein receptors.

  17. Carotid artery surgery

    MedlinePlus

    Carotid endarterectomy; CAS surgery; Carotid artery stenosis - surgery; Endarterectomy - carotid artery ... through the catheter around the blocked area during surgery. Your carotid artery is opened. The surgeon removes ...

  18. MR histology of advanced atherosclerotic lesions of ApoE- knockout mice

    NASA Astrophysics Data System (ADS)

    Naumova, A.; Yarnykh, V.; Ferguson, M.; Rosenfeld, M.; Yuan, C.

    2016-02-01

    The purposes of this study were to examine the feasibility of determining the composition of advanced atherosclerotic plaques in fixed ApoE-knockout mice and to develop a time-efficient microimaging protocol for MR histological imaging on mice. Five formalin-fixed transgenic ApoE-knockout mice were imaged at the 9.4T Bruker BioSpec MR scanner using 3D spoiled gradient-echo sequence with an isotropic field of view of 24 mm3; TR 20.8 ms; TE 2.6 ms; flip angle 20°, resulted voxel size 47 × 63 × 94 pm3. MRI examination has shown that advanced atherosclerotic lesions of aorta, innominate and carotid arteries in ApoE-knockout mice are characterized by high calcification and presence of the large fibrofatty nodules. MRI quantification of atherosclerotic lesion components corresponded to histological assessment of plaque composition with a correlation coefficient of 0.98.

  19. Shear stress-induced atherosclerotic plaque composition in ApoE(-/-) mice is modulated by connexin37.

    PubMed

    Pfenniger, A; Meens, M J; Pedrigi, R M; Foglia, B; Sutter, E; Pelli, G; Rochemont, V; Petrova, T V; Krams, R; Kwak, B R

    2015-11-01

    Shear stress patterns influence atherogenesis and plaque stability; low laminar shear stress (LLSS) promotes unstable plaques whereas oscillatory shear stress (OSS) induces more stable plaques. Endothelial connexin37 (Cx37) expression is also regulated by shear stress, which may contribute to localization of atherosclerotic disease. Moreover, Cx37 reduces initiation of atherosclerosis by inhibiting monocyte adhesion. The present work investigates the effect of Cx37 on the phenotype of plaques induced by LLSS or OSS. Shear stress-modifying casts were placed around the common carotid artery of ApoE(-/-) or ApoE(-/-)Cx37(-/-) mice, and animals were placed on a high-cholesterol diet for 6 or 9 weeks. Atherosclerotic plaque size and composition were assessed by immunohistochemistry. Plaque size in response to OSS was increased in ApoE(-/-)Cx37(-/-) mice compared to ApoE(-/-) animals. Most plaques contained high lipid and macrophage content and a low amount of collagen. In ApoE(-/-) mice, macrophages were more prominent in LLSS than OSS plaques. This difference was reversed in ApoE(-/-)Cx37(-/-) animals, with a predominance of macrophages in OSS plaques. The increase in macrophage content in ApoE(-/-)Cx37(-/-) OSS plaques was mainly due to increased accumulation of M1 and Mox macrophage subtypes. Cx37 expression in macrophages did not affect their proliferation or their polarization in vitro. Cx37 deletion increased the size of atherosclerotic lesions in OSS regions and abrogated the development of a stable plaque phenotype under OSS in ApoE(-/-) mice. Hence, local hemodynamic factors may modify the risk for adverse atherosclerotic disease outcomes associated to a polymorphism in the human Cx37 gene. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. Carotid Artery Screening

    MedlinePlus

    ... Physician Resources Professions Site Index A-Z Carotid Artery Screening What is carotid artery screening? Who should ... information about carotid artery screening? What is carotid artery screening? Screening examinations are tests performed to find ...

  1. Coronary Artery Bypass Grafting

    MedlinePlus

    ... from the NHLBI on Twitter. What Is Coronary Artery Bypass Grafting? Coronary artery bypass grafting (CABG) is ... bypass multiple coronary arteries during one surgery. Coronary Artery Bypass Grafting Figure A shows the location of ...

  2. Arterial embolism

    MedlinePlus

    ... for embolization (especially to the brain) is mitral stenosis . Endocarditis (infection of the inside of the heart) can also cause arterial emboli. A common source for an embolus is from areas of hardening (atherosclerosis) in the aorta and other large blood vessels. These clots can ...

  3. Arterial switch.

    PubMed

    Planche, C; Lacour-Gayet, F; Serraf, A

    1998-01-01

    A relatively large spectra of anatomic variations are found within the unifying features of discordant ventriculoarterial connections. Variants that lend themselves to anatomic repair by the arterial switch operation are discussed, these include transposition of the great arteries with intact ventricular septum (TGA IVS), TGA associated with a ventricular septal defect (TGA VSD), double-outlet right ventricle with subpulmonary VSD (DORV VSD), and TGA or DORV with VSD associated with coarctation. Double discordance with VSD, which is currently treated by double switch or Rastelli and atrial switch and which probably represents, in our department, the only remaining indication for atrial switch, is not discussed. Also, we exclude TGA associated with pulmonary stenosis, which is treated by Rastelli or REV operation.

  4. Parents&apos; Views of Schools&apos; Involvement Efforts

    ERIC Educational Resources Information Center

    Rodriguez, Raymond J.; Blatz, Erin T.; Elbaum, Batya

    2014-01-01

    Individual and focus group interviews were conducted with 96 parents of students with disabilities in 18 schools to explore parents&apos; views of schools&apos; efforts to engage them in their child&apos;s education. A mixed-methods approach was used to identify and evaluate the relative importance of eight themes related to schools&apos; efforts…

  5. Human PCSK9 promotes hepatic lipogenesis and atherosclerosis development via apoE- and LDLR-mediated mechanisms.

    PubMed

    Tavori, Hagai; Giunzioni, Ilaria; Predazzi, Irene M; Plubell, Deanna; Shivinsky, Anna; Miles, Joshua; Devay, Rachel M; Liang, Hong; Rashid, Shirya; Linton, MacRae F; Fazio, Sergio

    2016-05-15

    Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes the degradation of hepatic low-density lipoprotein (LDL) receptors (LDLR), thereby, decreasing hepatocyte LDL-cholesterol (LDL-C) uptake. However, it is unknown whether PCSK9 has effects on atherogenesis that are independent of lipid changes. The present study investigated the effect of human (h) PCSK9 on plasma lipids, hepatic lipogenesis, and atherosclerotic lesion size and composition in transgenic mice expressing hPCSK9 (hPCSK9tg) on wild-type (WT), LDLR⁻/⁻, or apoE⁻/⁻ background. hPCSK9 expression significantly increased plasma cholesterol (+91%), triglycerides (+18%), and apoB (+57%) levels only in WT mice. The increase in plasma lipids was a consequence of both decreased hepatic LDLR and increased hepatic lipid production, mediated transcriptionally and post-transcriptionally by PCSK9 and dependent on both LDLR and apoE. Despite the lack of changes in plasma lipids in mice expressing hPCSK9 and lacking LDLR (the main target for PCSK9) or apoE (a canonical ligand for the LDLR), hPCSK9 expression increased aortic lesion size in the absence of apoE (268 655 ± 97 972 µm² in hPCSK9tg/apoE⁻/⁻ vs. 189 423 ± 65 700 µm(2) in apoE⁻/⁻) but not in the absence of LDLR. Additionally, hPCSK9 accumulated in the atheroma and increased lesion Ly6C(hi) monocytes (by 21%) in apoE⁻/⁻ mice, but not in LDLR⁻/⁻ mice. PCSK9 increases hepatic lipid and lipoprotein production via apoE- and LDLR-dependent mechanisms. However, hPCSK9 also accumulate in the artery wall and directly affects atherosclerosis lesion size and composition independently of such plasma lipid and lipoprotein changes. These effects of hPCSK9 are dependent on LDLR but are independent of apoE. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

  6. ApoCIII enrichment in HDL impairs HDL-mediated cholesterol efflux capacity.

    PubMed

    Luo, Mengdie; Liu, Aiying; Wang, Shuai; Wang, Tianle; Hu, Die; Wu, Sha; Peng, Daoquan

    2017-05-24

    Apolipoprotein CIII (apoCIII) has been reported to be tightly associated with triglyceride metabolism and the susceptibility to coronary artery disease (CAD). Besides, apoCIII has also been found to affect the anti-apoptotic effects of HDL. However, the effect of apoCIII on HDL-mediated cholesterol efflux, the crucial function of HDL, has not been reported. A hospital-based case-control study was conducted to compare the apoCIII distribution in lipoproteins between CAD patients and nonCAD controls and to explore the relationship between HDL-associated apoCIII (apoCIIIHDL) and HDL-mediated cholesterol efflux. One hundred forty CAD patients and nighty nine nonCAD controls were included. Plasma apoCIII, apoCIIIHDL and cholesterol efflux capacity was measured. The apoCIIIHDL ratio (apoCIIIHDL over plasma apoCIII) was significantly higher in CAD patients than that in control group (0.52 ± 0.24 vs. 0.43 ± 0.22, P = 0.004). Both apoCIIIHDL and apoCIIIHDL ratio were inversely correlated with cholesterol efflux capacity (r = -0.241, P = 0.0002; r = -0.318, P < 0.0001, respectively). Stepwise multiple regression analysis revealed that the apoCIIIHDL ratio was an independent contributor to HDL-mediated cholesterol efflux capacity (standardized β = -0.325, P < 0.001). This study indicates that the presence of apoCIII in HDL may affect HDL-mediated cholesterol efflux capacity, implying the alternative role of apoCIII in the atherogenesis.

  7. Carotid Artery Disease

    MedlinePlus

    ... brain with blood. If you have carotid artery disease, the arteries become narrow, usually because of atherosclerosis. ... one of the causes of stroke. Carotid artery disease often does not cause symptoms, but there are ...

  8. Peripheral arterial line (image)

    MedlinePlus

    A peripheral arterial line is a small, short plastic catheter placed through the skin into an artery of the arm or leg. The purpose of a peripheral arterial line is to allow continuous monitoring of blood pressure ...

  9. Social disruption stress increases IL-6 levels and accelerates atherosclerosis in ApoE-/- mice.

    PubMed

    Bernberg, Evelina; Ulleryd, Marcus A; Johansson, Maria E; Bergström, Göran M L

    2012-04-01

    We have previously shown that different forms of stress have distinctive effects on atherogenesis in mice. We showed that social stress increase atherosclerosis in ApoE(-/-) mice, while more physical forms of stress do not. Here we evaluated the effect of social disruption (SDR) stress on atherogenesis and evaluated cytokine release after SDR-stress and five more physical stressors. Male ApoE(-/-) mice were exposed to SDR-stress during 12 weeks, and atherosclerotic plaque area was assessed in aorta, aortic root and innominate artery. Further, male C57BL/6 mice were exposed to SDR-stress or five physical stressors, and cytokine and corticosterone levels were analyzed in plasma/serum samples immediately after stress. We found a correlation between the level of SDR-stress and atherosclerotic plaque area in aorta and a numerical increased plaque area in aortic root. SDR stress did not affect histological features of plaque composition. However, SDR-stress increased levels of corticosterone, IL-6 and CXCL1. Plasma corticosterone increased for all five physical stressors, but IL-6 and CXCL1 only increased in the group exposed to restraint combined with rat odor. These findings suggest that SDR-stress is indeed atherogenic, in contrast to our previous results using the physical stressors. A possible explanation to this difference is that SDR-stress, but not physical stressors, leads to release of the pro-inflammatory cytokines IL-6 and CXCL1. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  10. Towards the modelling of ageing and atherosclerosis effects in ApoE(-/-) mice aortic tissue.

    PubMed

    Waffenschmidt, Tobias; Cilla, Myriam; Sáez, Pablo; Pérez, Marta M; Martínez, Miguel A; Menzel, Andreas; Peña, Estefanía

    2016-08-16

    The goal of this work consists in a quantitative analysis and constitutive modelling of ageing processes associated to plaque formation in mice arteries. Reliable information on the characteristic evolution of pressure-stretch curves due to the ageing effects is extracted from previous inflation test experiments. Furthermore, characteristic age-dependent material parameters are identified on the basis of a continuum-mechanics-based parameter optimisation technique. The results indicate that the aorta-stiffness of the healthy control mice remains basically constant irrespective of the diet-time and age. In contrast, significant differences exist within the material response and in consequence within the material parameters between the ApoE(-/-) and the control mice as well as for the different locations over the aorta which is underlined by our experimental observations. With regard to the temporal evolution of the material parameters, we observe that the material parameters for the ApoE(-/-) mice aortas exhibit a saturation-type increase with respect to age.

  11. Vascular Wall ACE is not required for Atherogenesis in ApoE-/- mice

    PubMed Central

    Weiss, Daiana; Bernstein, Kenneth E.; Fuchs, Sebastian; Adams, Jonathan; Synetos, Andreas; Taylor, W. Robert

    2009-01-01

    Background It has been proposed that elements of the renin angiotensin system expressed in the arterial wall are critical for the development of atherosclerosis. Angiotensin converting enzyme (ACE) is highly expressed by the endothelium and is responsible for a critical enzymatic step in the generation of angiotensin II. However, the functional contribution of ACE expression in the vascular wall in atherogenesis is unknown. Therefore, we made use of unique genetic models in which mice without expression of ACE in the vascular wall were crossed with apoE-/- mice in order to determine the contribution of tissue ACE expression to atherosclerotic lesion formation. Methods and Results Mice expressing either a soluble form of ACE (ACE 2/2) or mice with somatic ACE expression restricted to the liver and kidney (ACE 3/3) on an ApoE-/- background were placed on a standard chow or Western diet for 6 months. Atherosclerotic lesion area in the ACE 2/2 mice was significantly lower than that seen in the ACE 3/3 mice. However, these animals also had significantly lower blood pressure and reduced plasma ACE activity which precluded establishing a specific causal relationship between absent tissue ACE activity and decreased atherosclerotic lesion extent. Therefore, we studied the ACE 3/3 mice which are normotensive and lack vascular ACE expression. In the ACE 3/3 animals, atherosclerotic lesion area was no different from wild type controls despite reduced plasma ACE activity. Conclusions We concluded that under these experimental conditions, expression of ACE in the arterial wall is not required for atherosclerotic lesion formation. PMID:19880118

  12. LDL-apheresis depletes apoE-HDL and pre-β1-HDL in familial hypercholesterolemia: relevance to atheroprotection

    PubMed Central

    Orsoni, Alexina; Saheb, Samir; Levels, Johannes H. M.; Dallinga-Thie, Geesje; Atassi, Marielle; Bittar, Randa; Robillard, Paul; Bruckert, Eric; Kontush, Anatol; Carrié, Alain; Chapman, M. John

    2011-01-01

    Subnormal HDL-cholesterol (HDL-C) and apolipoprotein (apo)AI levels are characteristic of familial hypercholesterolemia (FH), reflecting perturbed intravascular metabolism with compositional anomalies in HDL particles, including apoE enrichment. Does LDL-apheresis, which reduces HDL-cholesterol, apoAI, and apoE by adsorption, induce selective changes in HDL subpopulations, with relevance to atheroprotection? Five HDL subpopulations were fractionated from pre- and post-LDL-apheresis plasmas of normotriglyceridemic FH subjects (n = 11) on regular LDL-apheresis (>2 years). Apheresis lowered both plasma apoE (−62%) and apoAI (−16%) levels, with preferential, genotype-independent reduction in apoE. The mass ratio of HDL2:HDL3 was lowered from ∼1:1 to 0.72:1 by apheresis, reflecting selective removal of HDL2 mass (80% of total HDL adsorbed). Pre-LDL-apheresis, HDL2 subpopulations were markedly enriched in apoE, consistent with ∼1 copy of apoE per 4 HDL particles. Large amounts (50-66%) of apoE-HDL were removed by apheresis, preferentially in the HDL2b subfraction (−50%); minor absolute amounts of apoE-HDL were removed from HDL3 subfractions. Furthermore, pre-β1-HDL particle levels were subnormal following removal (−53%) upon apheresis, suggesting that cellular cholesterol efflux may be defective in the immediate postapheresis period. In LDL-receptor (LDL-R) deficiency, LDL-apheresis may enhance flux through the reverse cholesterol transport pathway and equally attenuate potential biglycan-mediated deposition of apoE-HDL in the arterial matrix. PMID:21957200

  13. Macrophage apolipoprotein A-I expression protects against atherosclerosis in ApoE-deficient mice and up-regulates ABC transporters.

    PubMed

    Su, Yan Ru; Ishiguro, Hiroyuki; Major, Amy S; Dove, Dwayne E; Zhang, Wenwu; Hasty, Alyssa H; Babaev, Vladimir R; Linton, MacRae F; Fazio, Sergio

    2003-10-01

    The antiatherogenic effect of high-density lipoprotein (HDL) and its major protein component apolipoprotein A-I (apoA-I) has been largely attributed to their key roles in reverse cholesterol transport (RCT) and cellular cholesterol efflux. Substantial evidence shows that overexpression of human apoA-I reduces atherosclerosis in animal models. However, it is uncertain whether this protection is due to an increase in plasma HDL level or to a local effect in the artery wall. To test the hypothesis that expression of human apoA-I in macrophages can promote RCT in the artery wall, we used a retroviral construct expressing human apoA-I cDNA (MFG-HAI) to transduce ApoE(-/-) bone marrow cells and then transplanted these cells into ApoE(-/-) mice with preexisting atherosclerosis. ApoE(-/-) mice reconstituted with MFG-HAI marrow had a significant reduction (30%) in atherosclerotic lesions in the proximal aorta compared to control mice that received marrow expressing MFG parental virus. Peritoneal macrophages isolated from MFG-HAI mice showed a four- to fivefold increase in mRNA expression levels of both ATP-binding cassette (ABC) A1 and ABCG1 compared to controls. Our data demonstrate that gene transfer-mediated expression of human apoA-I in macrophages can compensate in part for apoE deficiency and delay the progression of atherosclerotic lesions by stimulating ABC-dependent cholesterol efflux and RCT.

  14. Targeting ApoC-III to Reduce Coronary Disease Risk.

    PubMed

    Khetarpal, Sumeet A; Qamar, Arman; Millar, John S; Rader, Daniel J

    2016-09-01

    Triglyceride-rich lipoproteins (TRLs) are causal contributors to the risk of developing coronary artery disease (CAD). Apolipoprotein C-III (apoC-III) is a component of TRLs that elevates plasma triglycerides (TGs) through delaying the lipolysis of TGs and the catabolism of TRL remnants. Recent human genetics approaches have shown that heterozygous loss-of-function mutations in APOC3, the gene encoding apoC-III, lower plasma TGs and protect from CAD. This observation has spawned new interest in therapeutic efforts to target apoC-III. Here, we briefly review both currently available as well as developing therapies for reducing apoC-III levels and function to lower TGs and cardiovascular risk. These therapies include existing options including statins, fibrates, thiazolidinediones, omega-3-fatty acids, and niacin, as well as an antisense oligonucleotide targeting APOC3 currently in clinical development. We review the mechanisms of action by which these drugs reduce apoC-III and the current understanding of how reduction in apoC-III may impact CAD risk.

  15. Matrix metalloproteinase-9 modulation by resident arterial cells is responsible for injury-induced accelerated atherosclerotic plaque development in apolipoprotein E-deficient mice.

    PubMed

    Choi, Eric T; Collins, Emily T; Marine, Leopoldo A; Uberti, Maria G; Uchida, Hisashi; Leidenfrost, Jeremy E; Khan, M Faisal; Boc, Kenneth P; Abendschein, Dana R; Parks, William C

    2005-05-01

    Although matrix metalloproteinase-9 (MMP-9) has been implicated in atherosclerotic plaque instability, the exact role it plays in the plaque development and progression remains largely unknown. We generated apolipoprotein E (apoE)-deficient (apoE-/-) MMP-9-deficient (MMP-9-/-) mice to determine the mechanisms and the main cell source of MMP-9 responsible for the plaque composition during accelerated atherosclerotic plaque formation. Three weeks after temporary carotid artery ligation revealed that while on a Western-type diet, apoE-/- MMP-9-/- mice had a significant reduction in intimal plaque length and volume compared with apoE-/- MMP-9+/+ mice. The reduction in plaque volume correlated with a significantly lower number of intraplaque cells of resident cells and bone marrow-derived cells. To determine the cellular origin of MMP-9 in plaque development, bone marrow transplantation after total-body irradiation was performed with apoE-/- MMP-9+/+ and apoE-/- MMP-9-/- mice, which showed that only MMP-9 derived from resident arterial cells is required for plaque development. MMP-9 is derived from resident arterial cells and is required for early atherosclerotic plaque development and cellular accumulation in apoE-/- mice.

  16. ApoE and Quality of Life in Nonagenarians

    PubMed Central

    Parsaik, Ajay K; Lapid, Maria I.; Rummans, Teresa A.; Cha, Ruth H.; Boeve, Bradley F.; Pankratz, Vernon (Shane) S.; Tangalos, Eric G.; Petersen, Ronald C.

    2012-01-01

    Objectives ApoE ε4 is associated with adverse health conditions that negatively impact the quality of life (QOL). The relationship between ApoE ε4 and QOL has not been explored in the oldest old. Our study aimed to examine ApoE in the oldest old, and explore its association with QOL. Design Cross-sectional cohort study. Setting A medium sized community in Olmsted County, Minnesota, USA. Participants 90–99 year old individuals living independently or in long term care environments. Measurements We collected demographic information and measured cognitive function (Short Test of Mental Status [STMS], Mini-Mental State Examination [MMSE], Mattis Dementia Rating Scale [DRS]), QOL (Linear Analogue Self Assessment [LASA]) and ApoE distribution. Subjects were classified as cognitively normal, mild cognitive impairment (MCI), dementia (DEM), or dementia with stroke and/or parkinsonism (DEMSP). Regression model was used to assess the predictors of QOL. Results 121 subjects (45 cognitively normal, 13 MCI, 34 DEM, 29 DEMSP) aged 90–99,106 (87.6 %) females, were included. Frequency of ApoE ε3 allele was highest [194 (80.2%): ε2/3 18, ε3/3 77, ε3/4 22] followed by ApoE ε4 [25 (10.3%): ε2/4 3, ε3/4 22] and ApoE ε2 [23 (9.5%; ε2/2 1, ε2/3 18, ε2/4 3]. None of the subjects carried ApoE ε4/4 genotype. QOL was similar between ApoE ε4 carrier and non-carriers. Physical well-being, emotional well-being, intellectual well-being, social connectedness and coping ability were positively associated with QOL, whereas male gender, DEMSP, pain frequency and pain severity were negatively associated. Conclusions The most common ApoE in the oldest old was ε3/3 genotype and ε3 allele. No association was found between ApoE ε4 and QOL. However, those with high physical, emotional and intellectual well being, social connectedness and coping ability had the highest overall QOL. PMID:22863665

  17. Fatty acid-based lipidomics and membrane remodeling induced by apoE3 and apoE4 in human neuroblastoma cells.

    PubMed

    Prasinou, Paraskevi; Dafnis, Ioannis; Giacometti, Giorgia; Ferreri, Carla; Chroni, Angeliki; Chatgilialoglu, Chryssostomos

    2017-10-01

    Apolipoprotein E (apoE) is a major lipid carrier of the lipoprotein transport system that plays critical roles in various pathologies. Human apoE has three common isoforms, the apoE4 being associated with Alzheimer's disease. This is the first study in the literature investigating the effects of apoE (apoE3 and apoE4 isoforms) on membrane fatty acid profile in neuroblastoma SK-N-SH cells. Fatty acid analyses were carried out by gas chromatography of the corresponding methyl esters (FAME). We observed the occurrence of membrane fatty acid remodeling in the presence of each of the two apoE isoforms. ApoE3 increased the membrane level of stearic acid and dihomo-gamma-linolenic acid (DGLA), whereas apoE4 had opposite effects. Both apoE3 and apoE4 increased saturated and monounsaturated fatty acids (SFA and MUFA), omega-6/omega-3 ratio and decreased total polyunsaturated fatty acid (PUFA) amount, but with various intensities. Moreover, both apoE isoforms decreased membrane homeostasis indexes such as PUFA balance, unsaturation index and peroxidation index. Our results highlight membrane property changes connected to the apoE isoforms suggesting membrane lipidomics to be inserted in further model studies of apolipoproteins in health and disease. Copyright © 2017. Published by Elsevier B.V.

  18. Carotid artery anatomy (image)

    MedlinePlus

    There are four carotid arteries, two on each side of the neck: right and left internal carotid arteries, and right and left external carotid arteries. The carotid arteries deliver oxygen-rich blood from the heart to the head and brain.

  19. Genetic Restoration of Plasma ApoE Improves Cognition and Partially Restores Synaptic Defects in ApoE-Deficient Mice.

    PubMed

    Lane-Donovan, Courtney; Wong, Wen Mai; Durakoglugil, Murat S; Wasser, Catherine R; Jiang, Shan; Xian, Xunde; Herz, Joachim

    2016-09-28

    Alzheimer's disease (AD) is the most common form of dementia in individuals over the age of 65 years. The most prevalent genetic risk factor for AD is the ε4 allele of apolipoprotein E (ApoE4), and novel AD treatments that target ApoE are being considered. One unresolved question in ApoE biology is whether ApoE is necessary for healthy brain function. ApoE knock-out (KO) mice have synaptic loss and cognitive dysfunction; however, these findings are complicated by the fact that ApoE knock-out mice have highly elevated plasma lipid levels, which may independently affect brain function. To bypass the effect of ApoE loss on plasma lipids, we generated a novel mouse model that expresses ApoE normally in peripheral tissues, but has severely reduced ApoE in the brain, allowing us to study brain ApoE loss in the context of a normal plasma lipid profile. We found that these brain ApoE knock-out (bEKO) mice had synaptic loss and dysfunction similar to that of ApoE KO mice; however, the bEKO mice did not have the learning and memory impairment observed in ApoE KO mice. Moreover, we found that the memory deficit in the ApoE KO mice was specific to female mice and was fully rescued in female bEKO mice. Furthermore, while the AMPA/NMDA ratio was reduced in ApoE KO mice, it was unchanged in bEKO mice compared with controls. These findings suggest that plasma lipid levels can influence cognition and synaptic function independent of ApoE expression in the brain. One proposed treatment strategy for Alzheimer's disease (AD) is the reduction of ApoE, whose ε4 isoform is the most common genetic risk factor for the disease. A major concern of this strategy is that an animal model of ApoE deficiency, the ApoE knock-out (KO) mouse, has reduced synapses and cognitive impairment; however, these mice also develop dyslipidemia and severe atherosclerosis. Here, we have shown that genetic restoration of plasma ApoE to wild-type levels normalizes plasma lipids in ApoE KO mice. While this does

  20. Vapor resistant arteries

    NASA Technical Reports Server (NTRS)

    Shaubach, Robert M. (Inventor); Dussinger, Peter M. (Inventor); Buchko, Matthew T. (Inventor)

    1989-01-01

    A vapor block resistant liquid artery structure for heat pipes. A solid tube artery with openings is encased in the sintered material of a heat pipe wick. The openings are limited to that side of the artery which is most remote from the heat source. The liquid in the artery can thus exit the artery through the openings and wet the sintered sheath, but vapor generated at the heat source is unlikely to move around the solid wall of the artery and reverse its direction in order to penetrate the artery through the openings. An alternate embodiment uses finer pore size wick material to resist vapor entry.

  1. Coronary Artery Fistula

    DTIC Science & Technology

    2007-04-01

    ascending aorta and pulmonary artery) and congenital coronary artery stenosis . Most coronary artery fistulas are congenital but may also...MILITARY MEDICINE, 172, 4: xi-xii, 2007 Military Medicine, Vol. 172, 4, April 2007 Radiology Corner Case #11 Coronary Artery Fistula...man with a single episode of vague sub- sternal chest pain was referred for evaluation of possible coronary artery disease. His medical history was

  2. Neuroprotective Sirtuin ratio reversed by ApoE4.

    PubMed

    Theendakara, Veena; Patent, Alexander; Peters Libeu, Clare A; Philpot, Brittany; Flores, Sonia; Descamps, Olivier; Poksay, Karen S; Zhang, Qiang; Cailing, Gabriellee; Hart, Matthew; John, Varghese; Rao, Rammohan V; Bredesen, Dale E

    2013-11-05

    The canonical pathogenesis of Alzheimer's disease links the expression of apolipoprotein E ε4 allele (ApoE) to amyloid precursor protein (APP) processing and Aβ peptide accumulation by a set of mechanisms that is incompletely defined. The development of a simple system that focuses not on a single variable but on multiple factors and pathways would be valuable both for dissecting the underlying mechanisms and for identifying candidate therapeutics. Here we show that, although both ApoE3 and ApoE4 associate with APP with nanomolar affinities, only ApoE4 significantly (i) reduces the ratio of soluble amyloid precursor protein alpha (sAPPα) to Aβ; (ii) reduces Sirtuin T1 (SirT1) expression, resulting in markedly differing ratios of neuroprotective SirT1 to neurotoxic SirT2; (iii) triggers Tau phosphorylation and APP phosphorylation; and (iv) induces programmed cell death. We describe a subset of drug candidates that interferes with the APP-ApoE interaction and returns the parameters noted above to normal. Our data support the hypothesis that neuronal connectivity, as reflected in the ratios of critical mediators such as sAPPα:Aβ, SirT1:SirT2, APP:phosphorylated (p)-APP, and Tau:p-Tau, is programmatically altered by ApoE4 and offer a simple system for the identification of program mediators and therapeutic candidates.

  3. Haplotype analysis of Apo AI-CIII-AIV gene cluster and lipids level: Tehran Lipid and Glucose Study.

    PubMed

    Daneshpour, Maryam S; Faam, Bita; Mansournia, Mohamad Ali; Hedayati, Mehdi; Halalkhor, Sohrab; Mesbah-Namin, Seyed Alireza; Shojaei, Shahla; Zarkesh, Maryam; Azizi, Fereidoun

    2012-02-01

    Iranian populations show an increased tendency for abnormal lipid levels and high risk of Coronary artery disease. Considering the important role played by the ApoAI-CIII-AIV gene cluster in the regulation of the level and metabolism of lipids, this study aimed at elucidating the association between five single nucleotide polymorphisms on the Apo11q cluster gene and lipid levels. A cross-sectional study of 823 subjects (340 males and 483 females) from the Tehran lipid and glucose study (TLGS) was conducted. Levels of TG, Chol, HDL-C, Apo AI, Apo AIV, Apo B, and Apo CIII were measured, and the selected segments of the APOAI-CIII-AIV gene cluster were amplified by PCR and the polymorphisms were revealed by RFLP using restriction enzymes. The allele frequencies for each SNP between males and females were not significantly different. The distribution of Genotypes and alleles was in Hardy-Weinberg equilibrium except for Apo AI (+83C>T). The results showed a significant association between TG, HDL-C, HDL(2), Apo AI, and Apo B levels and the presence of some alleles in the polymorphisms studied. After haplotype analysis not only did the association between these variables and SNPs remain but also levels of Chol and LDL-C were added. This study demonstrates that the level of lipids such as TG, HDL-C, HDL(2), Apo AI, and Apo B, maybe regulated partly by genetic factors and their haplotype within the Apo11q gene cluster.

  4. ApoA1, ApoJ and ApoE Plasma Levels and Genotype Frequencies in Cerebral Amyloid Angiopathy.

    PubMed

    Montañola, Alex; de Retana, Sofía Fernández; López-Rueda, Antonio; Merino-Zamorano, Cristina; Penalba, Anna; Fernández-Álvarez, Paula; Rodríguez-Luna, David; Malagelada, Ana; Pujadas, Francesc; Montaner, Joan; Hernández-Guillamon, Mar

    2016-03-01

    The involvement of apolipoproteins, such as the ApoE4 isoform, in Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA) highlights the fact that certain lipid carriers may participate in soluble β-amyloid (Aβ) transport. Our general aim was to characterize the soluble levels of the apolipoproteins apoE, apoA1 and apoJ/clusterin and their genotype status in patients with CAA. We analyzed the genotypes frequency of APOA1 (rs5069, rs670), CLU (rs11136000, rs1532278, rs7012010, rs9331888) and APOE (rs429358, rs7412) in a cohort of patients with CAA-associated intracerebral hemorrhage (ICH) (n = 59) and compared the results with those from hypertension-associated ICH (n = 42), AD patients (n = 73) and controls (n = 88). In a subgroup of patients, we also determined the plasma concentrations of apoE, apoA1 and apoJ/clusterin. We found increased plasma apoJ/clusterin levels in CAA patients compared to AD patients or controls after adjusting for sex and age (CAA vs. controls, p = 0.033; CAA vs. AD, p = 0.013). ApoA1 levels were not altered between groups, although a strong correlation was observed between plasma Aβ(1-40) and apoA1 among CAA patients (r = 0.583, p = 0.007). Regarding plasma apoE concentration, a robust association between circulating levels and genotype status was confirmed (p < 0.001). Whereas the APOE4 frequency was higher in AD (p < 0.001) and CAA (p = 0.013), the APOA1 and CLU genotypes were not different among groups. In the CAA cohort, the risk-linked CLU variant (C) rs11136000 was associated with white matter hyperintensities (p = 0.045) and the presence of lobar microbleeds (p = 0.023) on MRI. In summary, our findings suggest that apoA1 may act as a physiological transporter of Aβ(1-40) and that apoJ/clusterin appears to be a chaperone related to distinctive lesions in CAA brains.

  5. Cooled artery extension

    NASA Technical Reports Server (NTRS)

    Gernert, Nelson J. (Inventor)

    1990-01-01

    An artery vapor trap. A heat pipe artery is constructed with an extension protruding from the evaporator end of the heat pipe beyond the active area of the evaporator. The vapor migrates into the artery extension because of gravity or liquid displacement, and cooling the extension condenses the vapor to liquid, thus preventing vapor lock in the working portion of the artery by removing vapor from within the active artery. The condensed liquid is then transported back to the evaporator by the capillary action of the artery extension itself or by wick located within the extension.

  6. Extracellular Proteolysis of Apolipoprotein E (apoE) by Secreted Serine Neuronal Protease

    PubMed Central

    Tamboli, Irfan Y.; Heo, Dongeun; Rebeck, G. William

    2014-01-01

    Under normal conditions, brain apolipoprotein E (apoE) is secreted and lipidated by astrocytes, then taken up by neurons via receptor mediated endocytosis. Free apoE is either degraded in intraneuronal lysosomal compartments or released. Here we identified a novel way by which apoE undergoes proteolysis in the extracellular space via a secreted neuronal protease. We show that apoE is cleaved in neuronal conditioned media by a secreted serine protease. This apoE cleavage was inhibited by PMSF and α1-antichymotrypsin, but not neuroserpin-1 or inhibitors of thrombin and cathepsin G, supporting its identity as a chymotrypsin like protease. In addition, apoE incubation with purified chymotrypsin produced a similar pattern of apoE fragments. Analysis of apoE fragments by mass spectrometry showed cleavages occuring at the C-terminal side of apoE tryptophan residues, further supporting our identification of cleavage by chymotrypsin like protease. Hippocampal neurons were more efficient in mediating this apoE cleavage than cortical neurons. Proteolysis of apoE4 generated higher levels of low molecular weight fragments compared to apoE3. Primary glial cultures released an inhibitor of this proteolytic activity. Together, these studies reveal novel mechanism by which apoE can be regulated and therefore could be useful in designing apoE directed AD therapeutic approaches. PMID:24675880

  7. Extracellular proteolysis of apolipoprotein E (apoE) by secreted serine neuronal protease.

    PubMed

    Tamboli, Irfan Y; Heo, Dongeun; Rebeck, G William

    2014-01-01

    Under normal conditions, brain apolipoprotein E (apoE) is secreted and lipidated by astrocytes, then taken up by neurons via receptor mediated endocytosis. Free apoE is either degraded in intraneuronal lysosomal compartments or released. Here we identified a novel way by which apoE undergoes proteolysis in the extracellular space via a secreted neuronal protease. We show that apoE is cleaved in neuronal conditioned media by a secreted serine protease. This apoE cleavage was inhibited by PMSF and α1-antichymotrypsin, but not neuroserpin-1 or inhibitors of thrombin and cathepsin G, supporting its identity as a chymotrypsin like protease. In addition, apoE incubation with purified chymotrypsin produced a similar pattern of apoE fragments. Analysis of apoE fragments by mass spectrometry showed cleavages occurring at the C-terminal side of apoE tryptophan residues, further supporting our identification of cleavage by chymotrypsin like protease. Hippocampal neurons were more efficient in mediating this apoE cleavage than cortical neurons. Proteolysis of apoE4 generated higher levels of low molecular weight fragments compared to apoE3. Primary glial cultures released an inhibitor of this proteolytic activity. Together, these studies reveal novel mechanism by which apoE can be regulated and therefore could be useful in designing apoE directed AD therapeutic approaches.

  8. How proteomic ApoE serotyping could impact Alzheimer's disease risk assessment: genetic testing by proteomics.

    PubMed

    Nishimura, Motoi; Satoh, Mamoru; Matsushita, Kazuyuki; Nomura, Fumio

    2014-08-01

    Humans have three major apolipoprotein E (ApoE) alleles (APOE; ε2, ε3 and ε4) that produce three ApoE protein isoforms. The ε2 allele encodes the ApoE2 isoform (Cys112, Cys158), whereas ε3 encodes the wild-type ApoE3 isoform (Cys112, Arg158) and ε4 encodes the ApoE4 isoform (Arg112, Arg158). Because the type of ApoE expressed is related to sporadic Alzheimer's disease risk and familial hyperlipidemia, many clinical studies have utilized ApoE typing in recent years. ApoE serotyping is based on the correlation between ApoE genotype and isoform; it is therefore possible to determine the genotype from the blood ApoE isoform combination. Serotyping ApoE using mass spectrometry promises highly accurate results while requiring minimal amounts of blood and reagents, resulting in lower costs, which suggest that proteomic-based ApoE serotyping may eventually become a routine clinical laboratory test. Not limited to ApoE, proteomic analysis of human samples could be used to intentionally determine - and perhaps unintentionally reveal - personal genetic information.

  9. Coronary Artery Anomalies

    MedlinePlus

    ... Center for Coronary Artery Anomalies Doctors at the Texas Heart Institute's Center for Coronary Artery Anomalies (CCAA) ... comments. Terms of Use and Privacy Policy © Copyright Texas Heart Institute All rights reserved.

  10. Carotid Artery Disease

    MedlinePlus

    ... coronary artery disease: High levels of low-density lipoprotein cholesterol (bad cholesterol) and triglycerides in the blood. High blood pressure Diabetes Smoking Family history of coronary artery disease Obesity ...

  11. Spontaneous Coronary Artery Dissection

    MedlinePlus

    ... artery dissection (SCAD). It's not yet clear what role these factors play in causing the disease. Common factors include: Female sex. Though spontaneous coronary artery dissection (SCAD) can occur ...

  12. Peripheral artery disease - legs

    MedlinePlus

    ... pale. When PAD becomes severe, you may have: Impotence Pain and cramps at night Pain or tingling ... emboli that block small arteries Coronary artery disease Impotence Open sores (ischemic ulcers on the lower legs) ...

  13. Retinal artery occlusion

    MedlinePlus

    ... These blockages are more likely if there is hardening of the arteries ( atherosclerosis ) in the eye. Clots ... Blindness and vision loss Blood clots Diabetes Glaucoma Hardening of the arteries High blood cholesterol levels High ...

  14. Radial Artery Catheterization

    MedlinePlus

    ... of the radial artery for cardiac catheterization procedures. Advantages of Radial Artery Catheterization Any catheter placement into ... walk, and eat immediately. This is a particular advantage for patients with back problems because there is ...

  15. Hardening of the arteries

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/000171.htm Hardening of the arteries To use the sharing features on this page, please enable JavaScript. Hardening of the arteries, also called atherosclerosis, occurs when ...

  16. Carotid artery surgery - slideshow

    MedlinePlus

    ... page: //medlineplus.gov/ency/presentations/100124.htm Carotid artery surgery - series—Normal anatomy To use the sharing ... out of 4 Overview There are four carotid arteries, with a pair located on each side of ...

  17. Peripheral artery bypass - leg

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/007394.htm Peripheral artery bypass - leg To use the sharing features on this page, please enable JavaScript. Peripheral artery bypass is surgery to reroute the blood supply ...

  18. Uterine artery embolization

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/007384.htm Uterine artery embolization To use the sharing features on this page, please enable JavaScript. Uterine artery embolization (UAE) is a procedure to treat fibroids ...

  19. Coronary artery fistula

    MedlinePlus

    Congenital heart defect - coronary artery fistula; Birth defect heart - coronary artery fistula ... attaches to one of the chambers of the heart (the atrium or ventricle) or another blood vessel ( ...

  20. Coronary Artery Disease

    MedlinePlus

    Coronary artery disease (CAD) is the most common type of heart disease. It is the leading cause of death in the United States in both men and women. CAD happens when the arteries that supply blood to ...

  1. Coronary artery disease

    MedlinePlus Videos and Cool Tools

    ... heart muscle itself. Damage to or blockage of a coronary artery can result in injury to the heart. Normally, blood flows through a coronary artery unimpeded. However, a process called atherosclerosis ...

  2. What Is Peripheral Artery Disease?

    MedlinePlus

    ... from the NHLBI on Twitter. What Is Peripheral Artery Disease? Peripheral artery disease (P.A.D.) is ... that affects blood flow to the legs. Normal Artery and Artery With Plaque Buildup The illustration shows ...

  3. ApoE and Aβ in Alzheimer’s disease: accidental encounters or partners?

    PubMed Central

    Kanekiyo, Takahisa; Xu, Huaxi; Bu, Guojun

    2014-01-01

    Among the three human apolipoprotein E (apoE) isoforms, apoE4 increases the risk of Alzheimer’s disease (AD). While transporting cholesterol is a primary function, apoE also regulates amyloid-β (Aβ) metabolism, aggregation and deposition. Although earlier work suggests that different affinities of apoE isoforms to Aβ might account for their effects on Aβ clearance, recent studies indicate that apoE also competes with Aβ for cellular uptake through apoE receptors. Thus, several factors likely determine the variable effects apoE has on Aβ. In this review, we examine biochemical, structural, and functional studies and propose testable models that address the complex mechanisms underlying apoE-Aβ interaction and how apoE4 may increase AD risk and also serve as a target pathway for therapy. PMID:24559670

  4. A novel BET bromodomain inhibitor, RVX-208, shows reduction of atherosclerosis in hyperlipidemic ApoE deficient mice.

    PubMed

    Jahagirdar, Ravi; Zhang, Haiyan; Azhar, Salman; Tobin, Jennifer; Attwell, Sarah; Yu, Raymond; Wu, Jin; McLure, Kevin G; Hansen, Henrik C; Wagner, Gregory S; Young, Peter R; Srivastava, Rai Ajit K; Wong, Norman C W; Johansson, Jan

    2014-09-01

    Despite the benefit of statins in reducing cardiovascular risk, a sizable proportion of patients still remain at risk. Since HDL reduces CVD risk through a process that involves formation of pre-beta particles that facilitates the removal of cholesterol from the lipid-laden macrophages in the arteries, inducing pre-beta particles, may reduce the risk of CVD. A novel BET bromodomain antagonist, RVX-208, was reported to raise apoA-I and increase preβ-HDL particles in non-human primates and humans. In the present study, we investigated the effect of RVX-208 on aortic lesion formation in hyperlipidemic apoE(-/-) mice. Oral treatments of apoE(-/-) mice with 150 mg/kg b.i.d RVX-208 for 12 weeks significantly reduced aortic lesion formation, accompanied by 2-fold increases in the levels of circulating HDL-C, and ∼50% decreases in LDL-C, although no significant changes in plasma apoA-I were observed. Circulating adhesion molecules as well as cytokines also showed significant reduction. Haptoglobin, a proinflammatory protein, known to bind with HDL/apoA-I, decreased >2.5-fold in the RVX-208 treated group. With a therapeutic dosing regimen in which mice were fed Western diet for 10 weeks to develop lesions followed by switching to a low fat diet and concurrent treatment with RVX-208 for 14 weeks, RVX-208 similarly reduced lesion formation by 39% in the whole aorta without significant changes in the plasma lipid parameters. RVX-208 significantly reduced the proinflammatory cytokines IP-10, MIP1(®) and MDC. These results show that the antiatherogenic activity of BET inhibitor, RVX-208, occurs via a combination of lipid changes and anti-inflammatory activities. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  5. ApoE isoform-specific regulation of regeneration in the peripheral nervous system

    PubMed Central

    Comley, Laura H.; Fuller, Heidi R.; Wishart, Thomas M.; Mutsaers, Chantal A.; Thomson, Derek; Wright, Ann K.; Ribchester, Richard R.; Morris, Glenn E.; Parson, Simon H.; Horsburgh, Karen; Gillingwater, Thomas H.

    2011-01-01

    Apolipoprotein E (apoE) is a 34 kDa glycoprotein with three distinct isoforms in the human population (apoE2, apoE3 and apoE4) known to play a major role in differentially influencing risk to, as well as outcome from, disease and injury in the central nervous system. In general, the apoE4 allele is associated with poorer outcomes after disease or injury, whereas apoE3 is associated with better responses. The extent to which different apoE isoforms influence degenerative and regenerative events in the peripheral nervous system (PNS) is still to be established, and the mechanisms through which apoE exerts its isoform-specific effects remain unclear. Here, we have investigated isoform-specific effects of human apoE on the mouse PNS. Experiments in mice ubiquitously expressing human apoE3 or human apoE4 on a null mouse apoE background revealed that apoE4 expression significantly disrupted peripheral nerve regeneration and subsequent neuromuscular junction re-innervation following nerve injury compared with apoE3, with no observable effects on normal development, maturation or Wallerian degeneration. Proteomic isobaric tag for relative and absolute quantitation (iTRAQ) screens comparing healthy and regenerating peripheral nerves from mice expressing apoE3 or apoE4 revealed significant differences in networks of proteins regulating cellular outgrowth and regeneration (myosin/actin proteins), as well as differences in expression levels of proteins involved in regulating the blood–nerve barrier (including orosomucoid 1). Taken together, these findings have identified isoform-specific roles for apoE in determining the protein composition of peripheral nerve as well as regulating nerve regeneration pathways in vivo. PMID:21478199

  6. An Anti-apoE4 Specific Monoclonal Antibody Counteracts the Pathological Effects of apoE4 In Vivo.

    PubMed

    Luz, Ishai; Liraz, Ori; Michaelson, Daniel M

    2016-06-02

    ApolipoproteinE4 (apoE4) is the most prevalent genetic risk factor for Alzheimer's disease (AD) and as such is a promising therapeutic target. This study examined the extent to which the pathological effects of apoE4 can be counteracted in vivo utilizing an immunological approach in which anti-apoE4 antibodies are applied peripherally by i.p. injections into apoE4-targeted replacement mice. Prerequisites for the successful pursuit of this objective are the availability of antibodies that specifically bind brain apoE4 and not apoE3, and demonstrating that direct application of these antibodies into the brain can counteract the effects of apoE4. Accordingly, it was shown that the antiapoE4 monoclonal antibody (mAb) 9D11 binds specifically to brain apoE4 and not apoE3. Direct i.c.v. application of mAb 9D11 prevented the apoE4-driven accumulation of Aβ in hippocampal neurons following activation of the amyloid cascade by inhibiting the Aβ-degrading enzyme neprilysin. These findings provide a proof-of-concept that anti-apoE4 mAb 9D11, when introduced into the brain, can counteract the apoE4 effects in vivo. Subsequent experiments, utilizing repeated i.p. injections of mAb 9D11, resulted in the formation of apoE/IgG complexes specifically in apoE4 mice. This was associated with reversal of the cognitive impairments of apoE4 in the Morris water maze and the novel object recognition test as well as with reversal of key apoE4-driven pathologies including the hyperphosphorylated tau and the reduced levels of the apoER2 receptor. These results indicate that anti-apoE4 immunotherapy counteracts the cognitive and brain pathological effects of apoE4, and suggest that such an approach could also benefit human apoE4 carriers.

  7. Feline immunodeficiency virus and retrovirus-mediated adventitial ex vivo gene transfer to rabbit carotid artery using autologous vascular smooth muscle cells.

    PubMed

    Kankkonen, Hanna M; Turunen, Mikko P; Hiltunen, Mikko O; Lehtolainen, Pauliina; Koponen, Jonna; Leppänen, Pia; Turunen, Anna-Mari; Ylä-Herttuala, Seppo

    2004-03-01

    We have developed an ex vivo gene transfer technique to rabbit arterial wall using autologous smooth muscle cells (SMCs). SMCs were harvested from rabbit ear artery, transduced in vitro with vesicular stomatitis virus G-glycoprotein pseudotyped retrovirus or feline immunodeficiency virus (FIV) and returned to the adventitial surface of the carotid artery using a periadventitial silicone collar or collagen sheet placed around the artery. Beta-galactosidase (lacZ) and human apolipoprotein E3 (apoE3) cDNAs were used as transgenes. After retrovirus-mediated gene transfer of lacZ the selected cells implanted with high efficiency and expressed lacZ marker gene at a very high level 7 and 14 days after the operation. The level of lacZ expression decreased thereafter but was still detectable 12 weeks after the gene transfer, and was exclusively localized to the site of cell implantation inside the collar. Utilizing FIV vector expressing apoE3, low levels of apoE were measured from serum collected from a low-density lipoprotein receptor deficient Watanabe heritable hyperlipidemic rabbits 1 month after the gene transfer. The physiological effect of apoE expression was detected as transiently elevated serum cholesterol levels. The results indicate that the model can be used for high efficiency local gene transfer in arteries, e.g. during vascular surgery. The model is also valuable for studying expression, stability and safety of new gene transfer vectors and their expression products in vivo.

  8. Apolipoprotein E genotype and plasma levels in coronary artery disease. A case-control study in the Italian population.

    PubMed

    Corbo, R M; Vilardo, T; Ruggeri, M; Gemma, A T; Scacchi, R

    1999-04-01

    To investigate the role of the apolipoprotein B and apolipoprotein E polymorphisms in coronary artery disease (CAD) susceptibility in the Italian population and their relation to plasma lipid and apolipoprotein levels. APOB (APOB Xbal, EcoRI, Ins/Del), and APOE (APOE Cfol) polymorphisms were analyzed in 150 male CAD patients and 110 matched controls. In the same subjects plasma lipid, apoB, and apoE levels were measured. No differences in the distribution of the APOB polymorphisms were observed between patients and controls. Among patients the number of e*4-carriers was significantly higher than in controls. e*4-carriers were more frequent among the hypertensive patients and had a higher systolic blood pressure (p = 0.007) than the non-e*4 carriers. The APOB Xbal polymorphism was found to influence the distribution of HDL-cholesterol. Patients showed significantly lower levels of apoE (39.29 mg/L) than controls (54.32 mg/dL) and the lowest concentrations were associated to the E4/E3 and E4/E4 genotypes. Quantitative data are consistent with the hypothesis that apoE has an anti-atherosclerotic role and suggest that the apoE quantitation could be a useful parameter for defining cardiovascular risk. e*4 allele appears to be a risk factor for CAD in the Italian population and could act by its association with low apoE levels.

  9. Renal artery aneurysms.

    PubMed

    González, J; Esteban, M; Andrés, G; Linares, E; Martínez-Salamanca, J I

    2014-01-01

    A renal artery aneurysm is defined as a dilated segment of renal artery that exceeds twice the diameter of a normal renal artery. Although rare, the diagnosis and incidence of this entity have been steadily increasing due to the routine use of cross-sectional imaging. In certain cases, renal artery aneurysms may be clinically important and potentially lethal. However, knowledge of their occurrence, their natural history, and their prognosis with or without treatment is still limited. This article aims to review the recent literature concerning renal artery aneurysms, with special consideration given to physiopathology, indications for treatment, different technical options, post-procedure complications and treatment outcomes.

  10. Extracranial vertebral artery intervention.

    PubMed

    Mukherjee, Debabrata; Pineda, Guillermo

    2007-12-01

    Atherosclerosis is the commonest cause of vertebral artery stenosis and has a predilection for the origin and proximal section of the extracranial portion of the vessel and also the intracranial portion of the vessel. Although it has generally been thought that extracranial vertebral artery (ECVA) disease has a more benign outcome compared to intracranial vertebral artery disease, significant occlusive disease of the proximal vertebral artery is the primary cause of vertebral artery ischemia in a significant proportion of patients. We focus on the interventional management of patients with proximal ECVA disease in this article.

  11. External artery heat pipe

    NASA Technical Reports Server (NTRS)

    Gernert, Nelson J. (Inventor); Ernst, Donald M. (Inventor); Shaubach, Robert M. (Inventor)

    1989-01-01

    An improved heat pipe with an external artery. The longitudinal slot in the heat pipe wall which interconnects the heat pipe vapor space with the external artery is completely filled with sintered wick material and the wall of the external artery is also covered with sintered wick material. This added wick structure assures that the external artery will continue to feed liquid to the heat pipe evaporator even if a vapor bubble forms within and would otherwise block the liquid transport function of the external artery.

  12. Jet pump assisted artery

    NASA Technical Reports Server (NTRS)

    1975-01-01

    A procedure for priming an arterial heat pump is reported; the procedure also has a means for maintaining the pump in a primed state. This concept utilizes a capillary driven jet pump to create the necessary suction to fill the artery. Basically, the jet pump consists of a venturi or nozzle-diffuser type constriction in the vapor passage. The throat of this venturi is connected to the artery. Thus vapor, gas, liquid, or a combination of the above is pumped continuously out of the artery. As a result, the artery is always filled with liquid and an adequate supply of working fluid is provided to the evaporator of the heat pipe.

  13. Transradial artery coronary angioplasty.

    PubMed

    Kiemeneij, F; Laarman, G J; de Melker, E

    1995-01-01

    This study explored the feasibility and safety of percutaneous coronary balloon angioplasty (PTCA) with miniaturized PTCA equipment via the radial artery. Coronary angioplasty (PTCA) via the femoral or brachial arteries may be associated with rare vascular complications such as bleeding and damage to the artery and adjacent structures. It was postulated that PTCA via the radial artery with miniaturized angioplasty equipment is feasible and that no major puncture site-related complications occur because hemostasis is obtained easily and because no major structures are near the radial artery. With double blood supply to the hand, radial artery occlusion is well tolerated. In 100 patients with collateral blood supply to the right hand, PTCA was attempted with 6F guiding catheters and rapid-exchange balloon catheters for exertional angina (87 patients) or nonexertional angina (13 patients). Angioplasty was attempted in 122 lesions (type A n = 67 [55%], Type B n = 37 [30%], and type C n = 18 [15%]). Pre- and post-PTCA computerized quantitative coronary analysis was performed. Radial artery function and structure were assessed clinically and with Doppler and two-dimensional ultrasound on the day of discharge. Coronary catheterization via the radial artery was successful in 94 patients (94%). The 6 remaining patients had successful PTCA via the femoral artery (n = 5) or the brachial artery (n = 1). Procedural success (120 of 122 lesions) was achieved in 92 patients (98%) via the radial artery and in 98 patients of the total study population.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. ApoE genotype: from geographic distribution to function and responsiveness to dietary factors.

    PubMed

    Egert, Sarah; Rimbach, Gerald; Huebbe, Patricia

    2012-08-01

    ApoE is a key protein in lipid metabolism with three major isoforms. ApoE allele frequencies show non-random global distribution especially in Europe with high apoE ε3 frequency in the Mediterranean area, whereas the apoE ε4 genotype is enriched in Northern Europe. The apoE ε4 genotype is one of the most important genetic risk factors for age-dependent chronic diseases, including CVD and Alzheimer's disease (AD). The apoE polymorphism has been shown to impact on blood lipids, biomarkers of oxidative stress and chronic inflammation, which all may contribute to the isoform-dependent disease risk. Studies in mice and human subjects indicate that the apoE ε3 but not the apoE ε4 genotype may significantly benefit from dietary flavonoids (e.g. quercetin) and n-3 fatty acids. Metabolism of lipid soluble vitamins E and D is likewise differentially affected by the apoE genotype. Epidemiological and experimental evidence suggest a better vitamin D status in apoE ε4 than ε3 subjects indicating a certain advantage of ε4 over ε3. The present review aims at evaluation of current data available on interactions between apoE polymorphism and dietary responsiveness to flavonoids, fat soluble vitamins and n-3 fatty acids. Likewise, distinct geographic distribution and chronic disease risk of the different apoE isoforms are addressed.

  15. Central Nervous System Lipoproteins: ApoE and Regulation of Cholesterol Metabolism.

    PubMed

    Mahley, Robert W

    2016-07-01

    ApoE on high-density lipoproteins is primarily responsible for lipid transport and cholesterol homeostasis in the central nervous system (CNS). Normally produced mostly by astrocytes, apoE is also produced under neuropathologic conditions by neurons. ApoE on high-density lipoproteins is critical in redistributing cholesterol and phospholipids for membrane repair and remodeling. The 3 main structural isoforms differ in their effectiveness. Unlike apoE2 and apoE3, apoE4 has markedly altered CNS metabolism, is associated with Alzheimer disease and other neurodegenerative disorders, and is expressed at lower levels in brain and cerebrospinal fluid. ApoE4-expressing cultured astrocytes and neurons have reduced cholesterol and phospholipid secretion, decreased lipid-binding capacity, and increased intracellular degradation. Two structural features are responsible for apoE4 dysfunction: domain interaction, in which arginine-61 interacts ionically with glutamic acid-255, and a less stable conformation than apoE3 and apoE2. Blocking domain interaction by gene targeting (replacing arginine-61 with threonine) or by small-molecule structure correctors increases CNS apoE4 levels and lipid-binding capacity and decreases intracellular degradation. Small molecules (drugs) that disrupt domain interaction, so-called structure correctors, could prevent the apoE4-associated neuropathology by blocking the formation of neurotoxic fragments. Understanding how to modulate CNS cholesterol transport and metabolism is providing important insights into CNS health and disease. © 2016 American Heart Association, Inc.

  16. Deleuze&apos;s Children

    ERIC Educational Resources Information Center

    Hickey-Moody, Anna Catherine

    2013-01-01

    Children, the image of the child, and the gendered figures of the girl and the boy are thematics that run through the work of Deleuze and feature prominently in his joint writing with Guattari. However, there are many different children in Deleuze&apos;s writings. Various child figures do distinct things in Deleuze&apos;s work. In this article, I…

  17. Deleuze&apos;s Children

    ERIC Educational Resources Information Center

    Hickey-Moody, Anna Catherine

    2013-01-01

    Children, the image of the child, and the gendered figures of the girl and the boy are thematics that run through the work of Deleuze and feature prominently in his joint writing with Guattari. However, there are many different children in Deleuze&apos;s writings. Various child figures do distinct things in Deleuze&apos;s work. In this article, I…

  18. Divergent Systemic and Local Inflammatory Response to Hind Limb Demand Ischemia in Wild Type And ApoE−/− Mice

    PubMed Central

    Crawford, Robert S.; Albadawi, Hassan; Robaldo, Alessandro; Peck, Michael A.; Abularrage, Christopher J.; Yoo, Hyung-Jin; LaMuraglia, Glenn M.; Watkins, Michael T.

    2013-01-01

    Introduction Studies were designed to determine whether the ApoE−/− phenotype modulates the local skeletal muscle and systemic inflammatory (plasma) responses to lower extremity demand ischemia. The ApoE−/− phenotype is an experimental model for atherosclerosis in humans. Methods Aged female ApoE −/− and C57BL6 mice underwent femoral artery ligation, then divided into sedentary and demand ischemia (exercise) groups on day 14. Baseline and post exercise limb perfusion and hind limb function were assessed. On day 14, animals in the demand ischemia group underwent daily treadmill exercise through day 28. Sedentary mice were not exercised. On day 28, plasma and skeletal muscle from ischemic limbs were harvested from sedentary and exercised mice. Muscle was assayed for angiogenic and pro-inflammatory proteins, markers of skeletal muscle regeneration, and evidence of skeletal muscle fiber maturation. Results Hind limb ischemia was similar in ApoE −/− and C57 mice prior to the onset of exercise. Under sedentary conditions, plasma VEGF, IL-6, but not KC or MIP-2 were higher in ApoE (P<0.0001). Following exercise, plasma levels of VEGF, KC and MIP-2, but not IL-6 were lower in ApoE (P<0.004). The cytokines KC and MIP-2 in muscle was greater in exercised ApoE−/− mice as compared to C57BL6 mice (p=0.01). Increased PAR activity, and mature muscle regeneration was associated with demand ischemia in the C57BL6 mice as compared to the ApoE −/− mice (p=0.01). Conclusion Demand limb ischemia in the ApoE−/− phenotype exacerbated the expression of select systemic cytokines in plasma and blunted indices of muscle regeneration. PMID:23528286

  19. ApoE influences amyloid-β (Aβ) clearance despite minimal apoE/Aβ association in physiological conditions

    PubMed Central

    Verghese, Philip B.; Castellano, Joseph M.; Garai, Kanchan; Wang, Yinong; Jiang, Hong; Shah, Aarti; Bu, Guojun; Frieden, Carl; Holtzman, David M.

    2013-01-01

    Apolipoprotein E gene (APOE) alleles may shift the onset of Alzheimer’s disease (AD) through apoE protein isoforms changing the probability of amyloid-β (Aβ) accumulation. It has been proposed that differential physical interactions of apoE isoforms with soluble Aβ (sAβ) in brain fluids influence the metabolism of Aβ, providing a mechanism to account for how APOE influences AD risk. In contrast, we provide clear evidence that apoE and sAβ interactions occur minimally in solution and in the cerebrospinal fluid of human subjects, producing apoE3 and apoE4 isoforms as assessed by multiple biochemical and analytical techniques. Despite minimal extracellular interactions with sAβ in fluid, we find that apoE isoforms regulate the metabolism of sAβ by astrocytes and in the interstitial fluid of mice that received apoE infusions during brain Aβ microdialysis. We find that a significant portion of apoE and sAβ compete for the low-density lipoprotein receptor-related protein 1 (LRP1)–dependent cellular uptake pathway in astrocytes, providing a mechanism to account for apoE’s regulation of sAβ metabolism despite minimal evidence of direct interactions in extracellular fluids. We propose that apoE influences sAβ metabolism not through direct binding to sAβ in solution but through its actions with other interacting receptors/transporters and cell surfaces. These results provide an alternative frame work for the mechanistic explanations on how apoE isoforms influence the risk of AD pathogenesis. PMID:23620513

  20. Molecular imaging of inflammation in the ApoE -/- mouse model of atherosclerosis with IodoDPA

    SciTech Connect

    Foss, Catherine A.; Bedja, Djahida; Mease, Ronnie C.; Wang, Haofan; Kass, David A.; Chatterjee, Subroto; Pomper, Martin G.

    2015-05-22

    Background: Atherosclerosis is a common and serious vascular disease predisposing individuals to myocardial infarction and stroke. Intravascular plaques, the pathologic lesions of atherosclerosis, are largely composed of cholesterol-laden luminal macrophage-rich infiltrates within a fibrous cap. The ability to detect those macrophages non-invasively within the aorta, carotid artery and other vessels would allow physicians to determine plaque burden, aiding management of patients with atherosclerosis. Methods and results: We previously developed a low-molecular-weight imaging agent, [{sup 125}I]iodo-DPA-713 (iodoDPA), which selectively targets macrophages. Here we use it to detect both intravascular macrophages and macrophage infiltrates within the myocardium in the ApoE -/- mouse model of atherosclerosis using single photon emission computed tomography (SPECT). SPECT data were confirmed by echocardiography, near-infrared fluorescence imaging and histology. SPECT images showed focal uptake of radiotracer at the aortic root in all ApoE -/- mice, while the age-matched controls were nearly devoid of radiotracer uptake. Focal radiotracer uptake along the descending aorta and within the myocardium was also observed in affected animals. Conclusions: IodoDPA is a promising new imaging agent for atherosclerosis, with specificity for the macrophage component of the lesions involved. - Highlights: • [{sup 125}I]iodoDPA SPECT detects atherosclerotic plaques in ApoE -/- mice with high contrast. • Plaques are detected in ApoE -/- mice regardless of diet with iodoDPA. • iodoDPA has very low uptake in healthy tissue including healthy TSPO + tissues at 24 h.

  1. Duplicated middle cerebral artery.

    PubMed

    Perez, Jesus; Machado, Calixto; Scherle, Claudio; Hierro, Daniel

    2009-01-01

    Duplicated middle cerebral artery (DMCA) is an anomalous vessel arising from the internal carotid artery. The incidence DMCA is relatively law, and an association between this anomaly and cerebral aneurysms has been documented. There is a controversy whether DMCA may have perforating arteries. This is an important fact to consider in aneurysm surgery. We report the case of a 34-year-old black woman who suffered a subarachnoid hemorrhage and the angiography a left DMCA, and an aneurysm in an inferior branch of the main MCA. The DMCA and the MCA had perforating arteries. The aneurysm was clipped without complications. The observation of perforating arteries in our patient confirms that the DMCA may have perforating arteries. This is very important to be considered in cerebral aneurysms surgery. Moreover, the DMCA may potentially serve as a collateral blood supply to the MCA territory in cases of MCA occlusion.

  2. Palmar artery aneurysm

    PubMed Central

    Shutze, Ryan A.; Liechty, Joseph

    2017-01-01

    Aneurysms of the hand are rarely encountered and more rarely reported. The least common locations of these aneurysms are the palmar and digital arteries. The etiologies of these entities are quite varied, although they usually present as a pulsatile mass. Following a thorough evaluation, including arterial anatomic imaging, they should be repaired. The reported results following repair have been good. Herein we report a girl with a spontaneous palmar artery aneurysm and its management. PMID:28127131

  3. Lymphotoxin beta receptor signaling promotes tertiary lymphoid organogenesis in the aorta adventitia of aged ApoE-/- mice.

    PubMed

    Gräbner, Rolf; Lötzer, Katharina; Döpping, Sandra; Hildner, Markus; Radke, Dörte; Beer, Michael; Spanbroek, Rainer; Lippert, Beatrix; Reardon, Catherine A; Getz, Godfrey S; Fu, Yang-Xin; Hehlgans, Thomas; Mebius, Reina E; van der Wall, Michael; Kruspe, Dagmar; Englert, Christoph; Lovas, Agnes; Hu, Desheng; Randolph, Gwendalyn J; Weih, Falk; Habenicht, Andreas J R

    2009-01-16

    Atherosclerosis involves a macrophage-rich inflammation in the aortic intima. It is increasingly recognized that this intimal inflammation is paralleled over time by a distinct inflammatory reaction in adjacent adventitia. Though cross talk between the coordinated inflammatory foci in the intima and the adventitia seems implicit, the mechanism(s) underlying their communication is unclear. Here, using detailed imaging analysis, microarray analyses, laser-capture microdissection, adoptive lymphocyte transfers, and functional blocking studies, we undertook to identify this mechanism. We show that in aged apoE(-/-) mice, medial smooth muscle cells (SMCs) beneath intimal plaques in abdominal aortae become activated through lymphotoxin beta receptor (LTbetaR) to express the lymphorganogenic chemokines CXCL13 and CCL21. These signals in turn trigger the development of elaborate bona fide adventitial aortic tertiary lymphoid organs (ATLOs) containing functional conduit meshworks, germinal centers within B cell follicles, clusters of plasma cells, high endothelial venules (HEVs) in T cell areas, and a high proportion of T regulatory cells. Treatment of apoE(-/-) mice with LTbetaR-Ig to interrupt LTbetaR signaling in SMCs strongly reduced HEV abundance, CXCL13, and CCL21 expression, and disrupted the structure and maintenance of ATLOs. Thus, the LTbetaR pathway has a major role in shaping the immunological characteristics and overall integrity of the arterial wall.

  4. Gremlin-1 is an inhibitor of macrophage migration inhibitory factor and attenuates atherosclerotic plaque growth in ApoE-/- Mice.

    PubMed

    Müller, Iris; Schönberger, Tanja; Schneider, Martina; Borst, Oliver; Ziegler, Melanie; Seizer, Peter; Leder, Christoph; Müller, Karin; Lang, Michael; Appenzeller, Florian; Lunov, Oleg; Büchele, Berthold; Fahrleitner, Manuela; Olbrich, Marcus; Langer, Harald; Geisler, Tobias; Lang, Florian; Chatterjee, Madhumita; de Boer, Jan Freark; Tietge, Uwe J F; Bernhagen, Jürgen; Simmet, Thomas; Gawaz, Meinrad

    2013-11-01

    Monocyte infiltration and macrophage formation are pivotal steps in atherosclerosis and plaque vulnerability. Gremlin-1/Drm is crucial in embryo-/organogenesis and has been shown to be expressed in the adult organism at sites of arterial injury and to inhibit monocyte migration. The purpose of the present study was to evaluate and characterize the role of Gremlin-1 in atherosclerosis. Here we report that Gremlin-1 is highly expressed primarily by monocytes/macrophages in aortic atherosclerotic lesions of ApoE(-/-) mice and is secreted from activated monocytes and during macrophage development in vitro. Gremlin-1 reduces macrophage formation by inhibiting macrophage migration inhibitory factor (MIF), a cytokine critically involved in atherosclerotic plaque progression and vulnerability. Gremlin-1 binds with high affinity to MIF (KD = 54 nm), as evidenced by surface plasmon resonance analysis and co-immunoprecipitation, and reduces MIF-induced release of TNF-α from macrophages. Treatment of ApoE(-/-) mice with a dimeric recombinant fusion protein, mGremlin1-Fc, but not with equimolar control Fc or inactivated mGremlin1-Fc, reduced TNF-α expression, the content of monocytes/macrophages of atherosclerotic lesions, and attenuated atheroprogression. The present data disclose that Gremlin-1 is an endogenous antagonist of MIF and define a role for Gremlin-1/MIF interaction in atherosclerosis.

  5. Arterial waveform analysis.

    PubMed

    Esper, Stephen A; Pinsky, Michael R

    2014-12-01

    The bedside measurement of continuous arterial pressure values from waveform analysis has been routinely available via indwelling arterial catheterization for >50 years. Invasive blood pressure monitoring has been utilized in critically ill patients, in both the operating room and critical care units, to facilitate rapid diagnoses of cardiovascular insufficiency and monitor response to treatments aimed at correcting abnormalities before the consequences of either hypo- or hypertension are seen. Minimally invasive techniques to estimate cardiac output (CO) have gained increased appeal. This has led to the increased interest in arterial waveform analysis to provide this important information, as it is measured continuously in many operating rooms and intensive care units. Arterial waveform analysis also allows for the calculation of many so-called derived parameters intrinsically created by this pulse pressure profile. These include estimates of left ventricular stroke volume (SV), CO, vascular resistance, and during positive-pressure breathing, SV variation, and pulse pressure variation. This article focuses on the principles of arterial waveform analysis and their determinants, components of the arterial system, and arterial pulse contour. It will also address the advantage of measuring real-time CO by the arterial waveform and the benefits to measuring SV variation. Arterial waveform analysis has gained a large interest in the overall assessment and management of the critically ill and those at a risk of hemodynamic deterioration.

  6. Buckling instability in arteries.

    PubMed

    Vandiver, Rebecca M

    2015-04-21

    Arteries can become tortuous in response to abnormal growth stimuli, genetic defects and aging. It is suggested that a buckling instability is a mechanism that might lead to artery tortuosity. Here, the buckling instability in arteries is studied by examining asymmetric modes of bifurcation of two-layer cylindrical structures that are residually stressed. These structures are loaded by an axial force, internal pressure and have nonlinear, anisotropic, hyperelastic responses to stresses. Strain-softening and reduced opening angle are shown to lower the critical internal pressure leading to buckling. In addition, the ratio of the media thickness to the adventitia thickness is shown to have a dramatic impact on arterial instability.

  7. [Platelets and arterial thrombosis].

    PubMed

    Cazenave, Jean-Pierre; Gachet, Christian; Lanza, François; Wiesel, Marie-Louise

    2003-01-01

    The pathological mechanisms involved in arterial thrombus formation are similar to the mechanisms involved in physiological hemostasis. Arterial thrombosis is initiated following lesion of the vessel wall, either through rupture of an atherosclerotic plaque containing lipids, adhesive proteins and tissue factor or after angioplasty exposing the thrombogenic subendothelial matrix. Platelets play a major role in arterial thrombus formation through ADP secretion and thrombin generation on their activated surface. Arterial thrombosis is a frequent complication of atherosclerotic lesions and leads to acute ischemic events. These events are therapeutic emergencies which require administration of antithrombotic drugs inhibiting platelet functions and thrombin.

  8. Single Umbilical Artery

    PubMed Central

    Cairns, J. David; McKee, James

    1964-01-01

    A prospective study of 2000 obstetrical deliveries was undertaken to establish the incidence of single umbilical artery in the newborn and the frequency of congenital malformations reported to be associated with this disorder. Twenty cases of single umbilical artery were discovered; two proved to have an associated congenital malformation. In neither of these cases was medical management affected by the discovery of a single artery. In addition, the vascular arrangement in the cords of 31 concurrently occurring congenitally malformed babies was examined, and in no instance was a single umbilical artery found. PMID:14214230

  9. Immune-modulation by polyclonal IgM treatment reduces atherosclerosis in hypercholesterolemic apoE-/- mice.

    PubMed

    Cesena, Fernando H Y; Dimayuga, Paul C; Yano, Juliana; Zhao, Xiaoning; Kirzner, Jonathan; Zhou, Jianchang; Chan, Lai Fan; Lio, Wai Man; Cercek, Bojan; Shah, Prediman K; Chyu, Kuang-Yuh

    2012-01-01

    Gamma-globulin treatment reduces experimental atherosclerosis by modulating immune function; however the effect of IgM on atherosclerosis is not known. We investigated the effect of serum-derived, non-immune polyclonal IgM (Poly-IgM) on atherosclerosis in mice with advanced disease and also assessed its immune-modulatory effects. Aortic atherosclerosis was assessed in apoE-/- mice fed atherogenic diet starting at 6 weeks of age. In addition, mice were also subjected to perivascular cuff injury to the carotid artery at 25 weeks of age to induce accelerated atherosclerosis. At the time of injury, the mice were treated weekly with a commercially available Poly-IgM (0.4mg/mouse) or PBS for 4 weeks and euthanized at 29 weeks of age. Poly-IgM reduced aortic atherosclerosis, and reduced lesion size in the aortic sinus and injured carotid artery, without significant changes in serum cholesterol levels. Poly-IgM treatment was associated with increased anti-oxLDL IgG titers and a reduction in the % splenic CD4(+) T cells compared to controls. The splenic CD4(+) T cell cultured from the Poly-IgM treated mice had reduced proliferation in vitro compared with controls. Poly-IgM treatment reduced aortic and accelerated carotid atherosclerosis in apoE-/- mice in association with increased anti-oxLDL IgG titers, and reduced number and proliferative function of splenic CD4(+) T cells. Our study identifies a novel athero-protective and immunomodulatory role for non-immune polyclonal IgM. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  10. SAP deficiency mitigated atherosclerotic lesions in ApoE(-/-) mice.

    PubMed

    Zheng, Lingyun; Wu, Teng; Zeng, Cuiling; Li, Xiangli; Li, Xiaoqiang; Wen, Dingwen; Ji, Tianxing; Lan, Tian; Xing, Liying; Li, Jiangchao; He, Xiaodong; Wang, Lijing

    2016-01-01

    Serum amyloid P conpoent (SAP), a member of the pentraxin family, interact with pathogens and cell debris to promote their removal by macrophages and neutrophils and is co-localized with atherosclerotic plaques in patients. However, the exact mechanism of SAP in atherogenesis is still unclear. We investigated whether SAP influence macrophage recruitment and foam cell formation and ultimately affect atherosclerotic progression. we generated apoE(-/-); SAP(-/-) (DKO) mice and fed them western diet for 4 and 8 weeks to characterize atherosclerosis development. SAP deficiency effectively reduced plaque size both in the aorta (p = 0.0006 for 4 wks; p = 0.0001 for 8 wks) and the aortic root (p = 0.0061 for 4 wks; p = 0.0079 for 8wks) compared with apoE(-/-) mice. Meanwhile, SAP deficiency inhibited oxLDL-induced foam cell formation (p = 0.0004) compared with apoE(-/-) mice and SAP treatment increases oxLDL-induced foam cell formation (p = 0.002) in RAW cells. Besides, SAP deficiency reduced macrophages recruitment (p = 0.035) in vivo and in vitro (p = 0.026). Furthermore, SAP treatment enhanced CD36 (p = 0.007) and FcγRI (p = 0.031) expression induced by oxLDL through upregulating JNK and p38 MAPK phosphorylation whereas specific JNK1/2 inhibitor reduced CD36 (p = 0.0005) and FcγRI (P = 0.0007) expression in RAW cell. SAP deficiency also significantly decreased the expression of M1 and M2 macrophage markers and inflammatory cytokines in oxLDL-induced macrophages. SAP deficiency mitigated foam cell formation and atherosclerotic development in apoE(-/-) mice, due to reduction in macrophages recruitment, polarization and pro-inflammatory cytokines and inhibition the CD36/FcγR-dependent signaling pathway. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. Postprandial apoE Isoform and Conformational Changes Associated with VLDL Lipolysis Products Modulate Monocyte Inflammation

    PubMed Central

    den Hartigh, Laura J.; Altman, Robin; Hutchinson, Romobia; Petrlova, Jitka; Budamagunta, Madhu S.; Tetali, Sarada D.; Lagerstedt, Jens O.; Voss, John C.; Rutledge, John C.

    2012-01-01

    Objective Postprandial hyperlipemia, characterized by increased circulating very low-density lipoproteins (VLDL) and circulating lipopolysaccharide (LPS), has been proposed as a mechanism of vascular injury. Our goal was to examine the interactions between postprandial lipoproteins, LPS, and apoE3 and apoE4 on monocyte activation. Methods and Results We showed that apoE3 complexed to phospholipid vesicles attenuates LPS-induced THP-1 monocyte cytokine expression, while apoE4 increases expression. ELISA revealed that apoE3 binds to LPS with higher affinity than apoE4. Electron paramagnetic resonance (EPR) spectroscopy of site-directed spin labels placed on specific amino acids of apoE3 showed that LPS interferes with conformational changes normally associated with lipid binding. Specifically, compared to apoE4, apoE bearing the E3-like R112→Ser mutation displays increased self association when exposed to LPS, consistent with a stronger apoE3-LPS interaction. Additionally, lipolysis of fasting VLDL from normal human donors attenuated LPS-induced TNFα secretion from monocytes to a greater extent than postprandial VLDL, an effect partially reversed by blocking apoE. This effect was reproduced using fasting VLDL lipolysis products from e3/e3 donors, but not from e4/e4 subjects, suggesting that apoE3 on fasting VLDL prevents LPS-induced inflammation more readily than apoE4. Conclusion Postprandial apoE isoform and conformational changes associated with VLDL dramatically modulate vascular inflammation. PMID:23209766

  12. Effects of simulated heat waves on ApoE-/- mice.

    PubMed

    Wang, Chunling; Zhang, Shuyu; Tian, Ying; Wang, Baojian; Shen, Shuanghe

    2014-01-28

    The effects of simulated heat waves on body weight, body temperature, and biomarkers of cardiac function in ApoE-/- mice were investigated. Heat waves were simulated in a meteorological environment simulation chamber according to data from a heat wave that occurred in July 2001 in Nanjing, China. Eighteen ApoE-/- mice were divided into control group, heat wave group, and heat wave BH4 group. Mice in the heat wave and BH4 groups were exposed to simulated heat waves in the simulation chamber. Mice in BH4 group were treated with gastric lavage with BH4 2 h prior to heat wave exposure. Results showed that the heat waves did not significantly affect body weight or ET-1 levels. However, mice in the heat wave group had significantly higher rectal temperature and NO level and lower SOD activity compared with mice in the control group (p < 0.01), indicating that heat wave had negative effects on cardiac function in ApoE-/- mice. Gastric lavage with BH4 prior to heat wave exposure significantly reduced heat wave-induced increases in rectal temperature and decreases in SOD activity. Additionally, pretreatment with BH4 further increased NO level in plasma. Collectively, these beneficial effects demonstrate that BH4 may potentially mitigate the risk of coronary heart disease in mice under heat wave exposure. These results may be useful when studying the effects of heat waves on humans.

  13. Measuring How Elastic Arteries Function.

    ERIC Educational Resources Information Center

    DeMont, M. Edwin; MacGillivray, Patrick S.; Davison, Ian G.; McConnell, Colin J.

    1997-01-01

    Describes a procedure used to measure force and pressure in elastic arteries. Discusses the physics of the procedure and recommends the use of bovine arteries. Explains the preparation of the arteries for the procedure. (DDR)

  14. Living with Carotid Artery Disease

    MedlinePlus

    ... from the NHLBI on Twitter. Living With Carotid Artery Disease If you have carotid artery disease, you can take steps to manage the ... treatment plan, and getting ongoing care. Having carotid artery disease raises your risk of having a stroke . ...

  15. What Is Carotid Artery Disease?

    MedlinePlus

    ... from the NHLBI on Twitter. What Is Carotid Artery Disease? Carotid artery disease is a disease in ... blood to your face, scalp, and neck. Carotid Arteries Figure A shows the location of the right ...

  16. Peripheral Artery Disease and Diabetes

    MedlinePlus

    ... Artery Disease Venous Thromboembolism Aortic Aneurysm More Peripheral Artery Disease & Diabetes Updated:Jan 26,2016 People with ... developing atherosclerosis, the most common cause of peripheral artery disease (PAD) . And individuals with PAD have a ...

  17. Measuring How Elastic Arteries Function.

    ERIC Educational Resources Information Center

    DeMont, M. Edwin; MacGillivray, Patrick S.; Davison, Ian G.; McConnell, Colin J.

    1997-01-01

    Describes a procedure used to measure force and pressure in elastic arteries. Discusses the physics of the procedure and recommends the use of bovine arteries. Explains the preparation of the arteries for the procedure. (DDR)

  18. Screening for Carotid Artery Stenosis

    MedlinePlus

    ... Task Force learned about the potential benefits and harms of screening for carotid artery stenosis: Health professionals ... blood flow through the arteries. Potential Benefits and Harms of Carotid Artery Stenosis Screening and Treatment The ...

  19. Association of Apolipoprotein A1, B with Stenosis of Intracranial and Extracranial Arteries in Patients with Cerebral Infarction.

    PubMed

    Li, Mi-Mi; Lin, You-Yu; Huang, Yin-Hui; Zhuo, Shi-Tu; Yang, Mei-Li; Lin, Hua-Song; Cai, Ruo-Wei

    2015-01-01

    To investigate the distribution of stenosis of intracranial and extracranial arteries of Han population patients suffering from cerebral infarction in the city of Quanzhou in Fujian and to determine the correlation of apolipoprotein A1 and apolipoprotein B with intracranial and extracranial atherosclerosis stenosis. For this study, we enrolled patients with cerebral infarction between December 2009 and October 2012 at the Neurology Department of The Second Affiliated Hospital of Fujian Medical University. All patients were examined by computed tomography angiography (CTA). Past medical history, demographic data, and biochemical markers were collected. Multiple logistic regression analysis was used to study the association between apo A1, apo B, and cerebral atherosclerosis stenosis. A total of 412 patients were included in this study. 137 cases (33.3%) were classified as the intracranial atherosclerosis stenosis (ICAS) group, 74 cases (18.0%) as the combined intracranial and extracranial atherosclerosis stenosis (COAS) group, 44 cases (0.7%) as the extracranial atherosclerosis stenosis (ECAS) group, and 157 cases (38.1%) as the non-cerebral atherosclerosis stenosis (NCAS) group. Middle cerebral arteries (43.8%) were the most common lesions of intracranial arterial atherosclerosis stenosis. Extracranial carotid stenosis (30.7%) were more likely to be stenoses in the extracranial internal carotid arteries. Compared with the NCAS group, apo B was significantly higher (p < 0.001), apo A1 was significantly lower in the ICAS group and COAS group (p = 0.02 and p = 0.030). Compared with the mild atherosclerosis stenosis group, apo B was higher in the severe extracranial atherosclerosis stenosis group (p = 0.03), apo A1 was lower in the severe intracranial atherosclerosis stenosis group (p < 0.001). The multiple logistic regression analyses showed that when apo A1 > 1.28 g/L, it was an independent protective factor of intracranial stenosis (OR, 0.39), apo B was an

  20. Interactive effect of APOE genotype and blood pressure on cognitive decline: the PATH through life study.

    PubMed

    Andrews, Shea; Das, Debjani; Anstey, Kaarin J; Easteal, Simon

    2015-01-01

    The apolipoprotein E (APOE) *ε4 allele and hypertension are two of the most prevalent risk factors for cognitive decline in later life. Here we investigate whether cognitive decline is affected by interaction between these two risk factors. Specifically, we examine whether APOE*ε4 moderates the association between high blood pressure and cognition in later life. Cognitive function was assessed at three time points over a period of 8 years in 1,474 cognitively normal, community-dwelling adults aged 60-64 years at baseline. Blood pressure and APOE genotype were assessed at baseline. Blood pressure was measured categorically as 'Hypertension' and continuously as 'Mean Arterial Pressure' (MAP). Multilevel models were used to investigate main and interactive effects of APOE genotype and both hypertension and MAP on the rate of change of episodic memory, working memory, verbal ability, perceptual speed, and global cognition. The APOE-hypertension interaction was associated with a small but statistically significant increase in the rate of decline of episodic memory, verbal ability, and global cognition. However, its inclusion in the model did not increase the amount of outcome variation explained beyond that already explained by the effect of time. In contrast, the APOE-MAP interaction had no effect on the rate of decline in any of these domains of cognitive performance. These results provide tentative evidence that APOE genotype moderates the association between high blood pressure and cognitive decline in later life.

  1. Genetics in Arterial Calcification

    PubMed Central

    Rutsch, Frank; Nitschke, Yvonne; Terkeltaub, Robert

    2011-01-01

    Artery calcification reflects an admixture of factors such as ectopic osteochondral differentiation with primary host pathological conditions. We review how genetic factors, as identified by human genome-wide association studies, and incomplete correlations with various mouse studies, including knockout and strain analyses, fit into “pieces of the puzzle” in intimal calcification in human atherosclerosis, and artery tunica media calcification in aging, diabetes mellitus, and chronic kidney disease. We also describe in sharp contrast how ENPP1, CD73, and ABCC6 serve as “cogs in a wheel” of arterial calcification. Specifically, each is a minor component in the function of a much larger network of factors that exert balanced effects to promote and suppress arterial calcification. For the network to normally suppress spontaneous arterial calcification, the “cogs” ENPP1, CD73, and ABCC6 must be present and in working order. Monogenic ENPP1, CD73, and ABCC6 deficiencies each drive a molecular pathophysiology of closely related but phenotypically different diseases (generalized arterial calcification of infancy (GACI), pseudoxan-thoma elasticum (PXE) and arterial calcification caused by CD73 deficiency (ACDC)), in which premature onset arterial calcification is a prominent but not the sole feature. PMID:21852556

  2. Coronary artery stent (image)

    MedlinePlus

    ... with a balloon catheter and expands when the balloon is inflated. The stent is then left there to help keep the artery open. ... with a balloon catheter and expands when the balloon is inflated. The stent is then left there to help keep the artery open.

  3. [Pulmonary artery intimal sarcoma].

    PubMed

    Bourry, N; Chabrot, P; Jeannin, G; Filaire, M; Charpy, C; Bay, J O; Kemeny, J L; Caillaud, D; Escande, G; Boyer, L

    2008-02-01

    Pulmonary artery sarcoma is a rare tumor. We present a case of intimal sarcoma arising from right pulmonary artery and left lower pulmonary vein observed in a 44-year-old man with a non-productive cough. Computed tomographic scans and magnetic resonance imaging showing filling defect enhancement contributed early, suggesting the diagnosis of primary vascular tumor, hypothesis confirmed by pathologist findings.

  4. Coronary artery disease (image)

    MedlinePlus

    ... through these arteries is critical for the heart. Coronary artery disease usually results from the build-up of fatty material and plaque, a condition called atherosclerosis. As the ... blood to the heart can slow or stop, causing chest pain (stable ...

  5. Arterial Pressure Analog.

    ERIC Educational Resources Information Center

    Heusner, A. A.; Tracy, M. L.

    1980-01-01

    Describes a simple hydraulic analog which allows students to explore some physical aspects of the cardiovascular system and provides them with a means to visualize and conceptualize these basic principles. Simulates the behavior of arterial pressure in response to changes in heart rate, stroke volume, arterial compliance, and peripheral…

  6. Higher Brain Perfusion May Not Support Memory Functions in Cognitively Normal Carriers of the ApoE ε4 Allele Compared to Non-Carriers

    PubMed Central

    Zlatar, Zvinka Z.; Bischoff-Grethe, Amanda; Hays, Chelsea C.; Liu, Thomas T.; Meloy, M. J.; Rissman, Robert A.; Bondi, Mark W.; Wierenga, Christina E.

    2016-01-01

    Age-related changes in cerebral blood flow (CBF), which carries necessary nutrients to the brain, are associated with increased risk for mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Whether the association between CBF and cognition is moderated by apolipoprotein E (ApoE) ε4 genotype, a known risk factor for AD, remains understudied, with most research focusing on exploring brain regions in which there are diagnostic group differences in CBF (i.e., cognitively normal vs. MCI vs. AD). This study measured resting CBF via arterial spin labeling (ASL) magnetic resonance imaging (MRI) and verbal memory functions using a composite score in 59 older adults with normal cognition (38 ε3; 21 ε4). Linear mixed effect models were employed to investigate if the voxel-wise relationship between verbal memory performance and resting CBF was modified by ApoE genotype. Results indicated that carriers of the ApoE ε4 allele display negative associations between verbal memory functions and CBF in medial frontal cortex, medial and lateral temporal cortex, parietal regions, insula, and the basal ganglia. Contrarily, ε3 carriers exhibited positive associations between verbal memory functions and CBF in medial frontal cortex, thalamus, insula, and basal ganglia. Findings suggest that higher CBF was associated with worse verbal memory functions in cognitively normal ε4 carriers, perhaps reflecting dysregulation within the neurovascular unit, which is no longer supportive of cognition. Results are discussed within the context of the vascular theory of AD risk. PMID:27445794

  7. Human ApoE Isoforms Differentially Modulate Glucose and Amyloid Metabolic Pathways in Female Brain: Evidence of the Mechanism of Neuroprotection by ApoE2 and Implications for Alzheimer's Disease Prevention and Early Intervention.

    PubMed

    Keeney, Jeriel Thomas-Richard; Ibrahimi, Shaher; Zhao, Liqin

    2015-01-01

    Three major genetic isoforms of apolipoprotein E (ApoE), ApoE2, ApoE3, and ApoE4, exist in humans and lead to differences in susceptibility to Alzheimer's disease (AD). This study investigated the impact of human ApoE isoforms on brain metabolic pathways involved in glucose utilization and amyloid-β (Aβ) degradation, two major areas that are significantly perturbed in preclinical AD. Hippocampal RNA samples from middle-aged female mice with targeted human ApoE2, ApoE3, and ApoE4 gene replacement were comparatively analyzed with a qRT-PCR custom array for the expression of 85 genes involved in insulin/insulin-like growth factor (Igf) signaling. Consistent with its protective role against AD, ApoE2 brain exhibited the most metabolically robust profile among the three ApoE genotypes. When compared to ApoE2 brain, both ApoE3 and ApoE4 brains exhibited markedly reduced levels of Igf1, insulin receptor substrates (Irs), and facilitated glucose transporter 4 (Glut4), indicating reduced glucose uptake. Additionally, ApoE4 brain exhibited significantly decreased Pparg and insulin-degrading enzyme (Ide), indicating further compromised glucose metabolism and Aβ dysregulation associated with ApoE4. Protein analysis showed significantly decreased Igf1, Irs, and Glut4 in ApoE3 brain, and Igf1, Irs, Glut4, Pparg, and Ide in ApoE4 brain compared to ApoE2 brain. These data provide the first documented evidence that human ApoE isoforms differentially affect brain insulin/Igf signaling and downstream glucose and amyloid metabolic pathways, illustrating a potential mechanism for their differential risk in AD. A therapeutic strategy that enhances brain insulin/Igf1 signaling activity to a more robust ApoE2-like phenotype favoring both energy production and amyloid homeostasis holds promise for AD prevention and early intervention.

  8. Diagnosis of Intracranial Artery Dissection

    PubMed Central

    KANOTO, Masafumi; HOSOYA, Takaaki

    2016-01-01

    Cerebral arterial dissection is defined as a hematoma in the wall of a cervical or an intracranial artery. Cerebral arterial dissection causes arterial stenosis, occlusion, and aneurysm, resulting in acute infarction and hemorrhage. Image analysis by such methods as conventional angiography, computed tomography, magnetic resonance imaging, and so on plays an important role in diagnosing cerebral arterial dissection. In this study, we explore the methods and findings involved in the diagnosis of cerebral arterial dissection. PMID:27180630

  9. Primary pulmonary artery sarcoma.

    PubMed

    Jin, Tao; Zhang, Chong; Feng, Zhiying; Ni, Yiming

    2008-08-01

    Primary pulmonary artery sarcoma is an uncommon tumor. We report a case of a 73-year-old male patient with a two-week history of palpitations and shortness of breath, aggravated for two days and was believed to be pulmonary hypertension. Emergency heart ultrasound after admission presented a massive pulmonary embolism in the pulmonary artery. The patient's condition was successfully managed with urgent pulmonary artery embolectomy. The patient demonstrated improvement in hemodynamics after the operation. Histologic and immunohistochemical assays were performed and a diagnosis was made as primary pulmonary artery sarcoma arising from the left pulmonary artery. Resection of the tumor is recommended for the treatment of this rare malignant tumor. The corresponding chemotherapy, follow-up and prognosis are described as well in this case report.

  10. ApoA-I mimetics.

    PubMed

    Stoekenbroek, R M; Stroes, E S; Hovingh, G K

    2015-01-01

    A wealth of evidence indicates that plasma levels of high-density lipoprotein cholesterol (HDL-C) are inversely related to the risk of cardiovascular disease (CVD). Consequently, HDL-C has been considered a target for therapy in order to reduce the residual CVD burden that remains significant, even after application of current state-of-the-art medical interventions. In recent years, however, a number of clinical trials of therapeutic strategies that increase HDL-C levels failed to show the anticipated beneficial effect on CVD outcomes. As a result, attention has begun to shift toward strategies to improve HDL functionality, rather than levels of HDL-C per se. ApoA-I, the major protein component of HDL, is considered to play an important role in many of the antiatherogenic functions of HDL, most notably reverse cholesterol transport (RCT), and several therapies have been developed to mimic apoA-I function, including administration of apoA-I, mutated variants of apoA-I, and apoA-I mimetic peptides. Based on the potential anti-inflammatory effects, apoA-I mimetics hold promise not only as anti-atherosclerotic therapy but also in other therapeutic areas.

  11. The Effect of a High-Fat Diet on Brain Plasticity, Inflammation and Cognition in Female ApoE4-Knockin and ApoE-Knockout Mice

    PubMed Central

    Janssen, Carola I. F.; Jansen, Diane; Mutsaers, Martina P. C.; Dederen, Pieter J. W. C.; Geenen, Bram; Mulder, Monique T.; Kiliaan, Amanda J.

    2016-01-01

    Apolipoprotein E4 (ApoE4), one of three common isoforms of ApoE, is a major risk factor for late-onset Alzheimer disease (AD). ApoE-deficient mice, as well as mice expressing human ApoE4, display impaired learning and memory functions and signs of neurodegeneration. Moreover, ApoE protects against high-fat (HF) diet induced neurodegeneration by its role in the maintenance of the integrity of the blood-brain barrier. The influence of a HF diet on the progression of AD-like cognitive and neuropathological changes was assessed in wild-type (WT), human ApoE4 and ApoE-knockout (ApoE-/-) mice to evaluate the modulatory role of ApoE in this process. From 12 months of age, female WT, ApoE4, and ApoE-/- mice were fed either a standard or a HF diet (19% butter, 0.5% cholate, 1.25% cholesterol) throughout life. At 15 months of age mice performed the Morris water maze, evaluating spatial learning and memory. ApoE-/- showed increased spatial learning compared to WT mice (p = 0.009). HF diet improved spatial learning in WT mice (p = 0.045), but did not affect ApoE4 and ApoE-/- mice. Immunohistochemical analyses of the hippocampus demonstrated increased neuroinflammation (CD68) in the cornu ammonis 1 (CA1) region in ApoE4 (p = 0.001) and in ApoE-/- (p = 0.032) mice on standard diet. HF diet tended to increase CD68 in the CA1 in WT mice (p = 0.052), while it decreased in ApoE4 (p = 0.009), but ApoE-/- remained unaffected. A trend towards increased neurogenesis (DCX) was found in both ApoE4 (p = 0.052) and ApoE-/- mice (p = 0.068). In conclusion, these data suggest that HF intake induces different effects in WT mice compared to ApoE4 and ApoE-/- with respect to markers for cognition and neurodegeneration. We propose that HF intake inhibits the compensatory mechanisms of neuroinflammation and neurogenesis in aged female ApoE4 and ApoE-/- mice. PMID:27171180

  12. Macrophage-Specific ApoE Gene Repair Reduces Diet-Induced Hyperlipidemia and Atherosclerosis in Hypomorphic Apoe Mice

    PubMed Central

    Gaudreault, Nathalie; Kumar, Nikit; Olivas, Victor R.; Eberlé, Delphine; Rapp, Joseph H.; Raffai, Robert L.

    2012-01-01

    Background Apolipoprotein (apo) E is best known for its ability to lower plasma cholesterol and protect against atherosclerosis. Although the liver is the major source of plasma apoE, extra-hepatic sources of apoE, including from macrophages, account for up to 10% of plasma apoE levels. This study examined the contribution of macrophage-derived apoE expression levels in diet-induced hyperlipidemia and atherosclerosis. Methodology/Principal Findings Hypomorphic apoE (Apoeh/h) mice expressing wildtype mouse apoE at ∼2–5% of physiological levels in all tissues were derived by gene targeting in embryonic stem cells. Cre-mediated gene repair of the Apoeh/h allele in Apoeh/hLysM-Cre mice raised apoE expression levels by 26 fold in freshly isolated peritoneal macrophages, restoring it to 37% of levels seen in wildtype mice. Chow-fed Apoeh/hLysM-Cre and Apoeh/h mice displayed similar plasma apoE and cholesterol levels (55.53±2.90 mg/dl versus 62.70±2.77 mg/dl, n = 12). When fed a high-cholesterol diet (HCD) for 16 weeks, Apoeh/hLysM-Cre mice displayed a 3-fold increase in plasma apoE and a concomitant 32% decrease in plasma cholesterol when compared to Apoeh/h mice (602.20±22.30 mg/dl versus 888.80±24.99 mg/dl, n = 7). On HCD, Apoeh/hLysM-Cre mice showed increased apoE immunoreactivity in lesional macrophages and liver-associated Kupffer cells but not hepatocytes. In addition, Apoeh/hLysM-Cre mice developed 35% less atherosclerotic lesions in the aortic root than Apoeh/h mice (167×103±16×103 µm2 versus 259×103±56×103 µm2, n = 7). This difference in atherosclerosis lesions size was proportional to the observed reduction in plasma cholesterol. Conclusions/Significance Macrophage-derived apoE raises plasma apoE levels in response to diet-induced hyperlipidemia and by such reduces atherosclerosis proportionally to the extent to which it lowers plasma cholesterol levels. PMID:22606237

  13. Mesenteric Artery Insufficiency

    PubMed Central

    Coles, John C.; Walker, John B.; Gergely, N. F.; Buttigliero, Jorge

    1963-01-01

    The syndromes of superior mesenteric artery insufficiency are briefly reviewed. Three cases associated with infarction of bowel which were treated with restoration of arterial flow and resection of residual irretrievable bowel are reported. In two patients an embolectomy and in one patient a bypass graft were used to restore arterial continuity. The importance of the recognition and removal of irretrievable bowel at the time of vascular reconstruction is emphasized. Success is not necessarily predicated by the time factor alone, although the importance of early diagnosis and surgical intervention cannot be denied. PMID:14042788

  14. Ruptured visceral artery aneurysms.

    PubMed

    Chiaradia, M; Novelli, L; Deux, J-F; Tacher, V; Mayer, J; You, K; Djabbari, M; Luciani, A; Rahmouni, A; Kobeiter, H

    2015-01-01

    Visceral artery aneurysms are rare but their estimated mortality due to rupture ranges between 25 and 70%. Treatment of visceral artery aneurysm rupture is usually managed by interventional radiology. Specific embolization techniques depend on the location, affected organ, locoregional arterial anatomy, and interventional radiologist skill. The success rate following treatment by interventional radiology is greater than 90%. The main complication is recanalization of the aneurysm, showing the importance of post-therapeutic monitoring, which should preferably be performed using MR imaging. Copyright © 2015 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.

  15. Bilateral variant testicular arteries with double renal arteries

    PubMed Central

    2009-01-01

    Background The testicular arteries normally arise from the abdominal aorta. There are reports about the variant origin of these arteries. Accessory renal arteries are also a common finding but their providing origin to testicular arteries is an important observation. The variations described here are unique and provide significant information to surgeons dissecting the abdominal cavity. Case presentation During routine dissection classes of abdominal region of a 60-year-old male cadaver, we observed bilateral variant testicular arteries and double renal arteries. Conclusion Awareness of variations of the testicular arteries such as those presented here becomes important during surgical procedures like varicocele and undescended testes. PMID:19187540

  16. Postoperative internal thoracic artery spasm after coronary artery bypass grafting.

    PubMed

    Harskamp, Ralf E; McNeil, Jeffrey D; van Ginkel, Margreet W; Bastos, Renata B; Baisden, Clinton E; Calhoon, John H

    2008-02-01

    Spasm of the left internal thoracic artery in the perioperative period represents a life-threatening complication after coronary artery bypass grafting. We present a case in which graft spasm was treated with the administration of intra-arterial nitroglycerin and verapamil. Although vasospasm is more often seen in radial artery grafts, this case demonstrates that left internal thoracic artery grafts are also prone to spasm.

  17. Anomalous left coronary artery from pulmonary artery with mitral stenosis.

    PubMed

    Das, Mrinalendu; Mahindrakar, Pallavi; Das, Debasis; Behera, Sukanta Kumar; Chowdhury, Saibal Roy; Bandyopadhyay, Biswajit

    2011-08-01

    The usual presentation of anomalous left coronary artery from pulmonary artery is severe left-sided heart failure and mitral valve insufficiency presenting during the first months of life. The manifestations of left heart failure may be masked if pulmonary artery pressure remains high. We believe this is a rarest of rare case of anomalous left coronary artery from pulmonary artery with severe mitral stenosis and pulmonary hypertension in which pulmonary hypertension, along with good collateral circulation helped to preserve left ventricular function.

  18. ApoE4-specific Misfolded Intermediate Identified by Molecular Dynamics Simulations

    PubMed Central

    Williams II, Benfeard; Convertino, Marino; Das, Jhuma; Dokholyan, Nikolay V.

    2015-01-01

    The increased risk of developing Alzheimer’s disease (AD) is associated with the APOE gene, which encodes for three variants of Apolipoprotein E, namely E2, E3, E4, differing only by two amino acids at positions 112 and 158. ApoE4 is known to be the strongest risk factor for AD onset, while ApoE3 and ApoE2 are considered to be the AD-neutral and AD-protective isoforms, respectively. It has been hypothesized that the ApoE isoforms may contribute to the development of AD by modifying the homeostasis of ApoE physiological partners and AD-related proteins in an isoform-specific fashion. Here we find that, despite the high sequence similarity among the three ApoE variants, only ApoE4 exhibits a misfolded intermediate state characterized by isoform-specific domain-domain interactions in molecular dynamics simulations. The existence of an ApoE4-specific intermediate state can contribute to the onset of AD by altering multiple cellular pathways involved in ApoE-dependent lipid transport efficiency or in AD-related protein aggregation and clearance. We present what we believe to be the first structural model of an ApoE4 misfolded intermediate state, which may serve to elucidate the molecular mechanism underlying the role of ApoE4 in AD pathogenesis. The knowledge of the structure for the ApoE4 folding intermediate provides a new platform for the rational design of alternative therapeutic strategies to fight AD. PMID:26506597

  19. Differential Effects of apoE4 and Activation of ABCA1 on Brain and Plasma Lipoproteins

    PubMed Central

    Harats, Dror; Shaish, Aviv; Levkovitz, Hana; Bielicki, John K.; Johansson, Jan O.; Michaelson, Daniel M.

    2016-01-01

    Apolipoprotein E4 (apoE4), the leading genetic risk factor for Alzheimer's disease (AD), is less lipidated compared to the most common and AD-benign allele, apoE3. We have recently shown that i.p. injections of the ATP-binding cassette A1 (ABCA1) agonist peptide CS-6253 to apoE mice reverse the hypolipidation of apoE4 and the associated brain pathology and behavioral deficits. While in the brain apoE is the main cholesterol transporter, in the periphery apoE and apoA-I both serve as the major cholesterol transporters. We presently investigated the extent to which apoE genotype and CS-6253 treatment to apoE3 and apoE4-targeted replacement mice affects the plasma levels and lipid particle distribution of apoE, and those of plasma and brain apoA-I and apoJ. This revealed that plasma levels of apoE4 were lower and eluted faster following FPLC than plasma apoE3. Treatment with CS-6253 increased the levels of plasma apoE4 and rendered the elution profile of apoE4 similar to that of apoE3. Similarly, the levels of plasma apoA-I were lower in the apoE4 mice compared to apoE3 mice, and this effect was partially reversed by CS-6253. Conversely, the levels of apoA-I in the brain which were higher in the apoE4 mice, were unaffected by CS-6253. The plasma levels of apoJ were higher in apoE4 mice than apoE3 mice and this effect was abolished by CS-6253. Similar but less pronounced effects were obtained in the brain. In conclusion, these results suggest that apoE4 affects the levels of apoA-I and apoJ and that the anti-apoE4 beneficial effects of CS-6253 may be related to both central and peripheral mechanisms. PMID:27824936

  20. The Role of APOE in Cerebrovascular Dysfunction

    PubMed Central

    Tai, Leon M; Thomas, Riya; Marottoli, Felecia M; Koster, Kevin P; Kanekiyo, Takahisa; Morris, Alan WJ; Bu, Guojun

    2016-01-01

    The ε4 allele of the apolipoprotein E gene (APOE4) is associated with cognitive decline during aging, is the greatest genetic risk factor for Alzheimer’s disease and has links to other neurodegenerative conditions that affect cognition. Increasing evidence indicates that APOE genotypes differentially modulate the function of the cerebrovasculature (CV), with apoE and its receptors expressed by different cell types at the CV interface (astrocytes, pericytes, smooth muscle cells, brain endothelial cells). However, research on the role of apoE in CV dysfunction has not advanced as quickly as other apoE-modulated pathways. This review will assess what aspects of the CV are modulated by APOE genotypes during aging and under disease states, discuss potential mechanisms, and summarize the therapeutic significance of the topic. We propose that APOE4 induces CV dysfunction through direct signaling at the CV, and indirectly via modulation of peripheral and central pathways. Further, that APOE4 predisposes the CV to damage by, and exacerbates the effects of, additional risk factors (such as sex, hypertension, and diabetes). ApoE4-induced detrimental CV changes include reduced cerebral blood flow (CBF), modified neuron-CBF coupling, increased blood-brain barrier leakiness, cerebral amyloid angiopathy (CAA), hemorrhages and disrupted transport of nutrients and toxins. The apoE4-induced detrimental changes may be linked to pericyte migration/activation, astrocyte activation, smooth muscle cell damage, basement membrane degradation and alterations in brain endothelial cells. PMID:26884068

  1. Peripheral Arterial Disease

    MedlinePlus

    Peripheral arterial disease (PAD) happens when there is a narrowing of the blood vessels outside of your heart. The cause of ... smoking. Other risk factors include older age and diseases like diabetes, high blood cholesterol, high blood pressure, ...

  2. Uterine artery embolization - discharge

    MedlinePlus

    ... your uterus (uterine artery). Small plastic or gelatin particles were injected into the blood vessels that carry blood to the fibroids. These particles block the blood supply to the fibroids. Without ...

  3. Carotid artery disease

    MedlinePlus

    ... a stroke recover most or all of their functions. Others die of the stroke itself or from complications. About half of people ... patients with extracranial carotid and vertebral artery disease: executive summary: ... American Association of Neuroscience Nurses, American Association ...

  4. Peripheral Artery Disease

    MedlinePlus

    ... needed to restore blood flow: Angioplasty : In an angioplasty procedure, an interventional radiologist threads a catheter through a blood vessel to the affected artery and inflates a small balloon to reopen it. In some cases, the insertion ...

  5. Renal arteries (image)

    MedlinePlus

    A renal angiogram is a test used to examine the blood vessels of the kidneys. The test is performed ... main vessel of the pelvis, up to the renal artery that leads into the kidney. Contrast medium ...

  6. Coronary artery spasm

    MedlinePlus

    ... blocker or a long-acting nitrate long-term. Beta-blockers are another type of medicine that is used with other coronary artery problems. However, beta-blockers may make this problem worse. They should be ...

  7. Median artery revisited

    PubMed Central

    RODRÍGUEZ-NIEDENFÜHR, M.; SAÑUDO, J. R.; VÁZQUEZ, T.; NEARN, L.; LOGAN, B.; PARKIN, I.

    1999-01-01

    This study confirms that the median artery may persist in adult life in 2 different patterns, palmar and antebrachial, based on their vascular territory. The palmar type, which represents the embryonic pattern, is large, long and reaches the palm. The antebrachial type, which represents a partial regression of the embryonic artery is slender, short, and terminates before reaching the wrist. These 2 arterial patterns appear with a different incidence. The palmar pattern was studied in the whole sample (120 cadavers) and had an incidence of 20%, being more frequent in females than in males (1.3∶1), occurring unilaterally more often than bilaterally (4∶1) and slightly more frequently on the right than on the left (1.1∶1). The antebrachial pattern was studied in only 79 cadavers and had an incidence of 76%, being more frequent in females than in males (1.6∶1); it was commoner unilaterally than bilaterally (1.5∶1) and was again slightly more prevalent on the right than on the left (1.2∶1). The origin of the median artery was variable in both patterns. The palmar type most frequently arose from the caudal angle between the ulnar artery and its common interosseous trunk (59%). The antebrachial pattern most frequently originated from the anterior interosseous artery (55%). Other origins, for both patterns, were from the ulnar artery or from the common interosseous trunk. The median artery in the antebrachial pattern terminated in the upper third (74%) or in the distal third of the forearm (26%). However, the palmar pattern ended as the 1st, 2nd or 1st and 2nd common digital arteries (65%) or joined the superficial palmar arch (35%). The median artery passed either anterior (67%) or posterior (25%) to the anterior interosseous nerve. It pierced the median nerve in the upper third of the forearm in 41% of cases with the palmar pattern and in none of the antebrachial cases. In 1 case the artery pierced both the anterior interosseous and median nerves. PMID

  8. ApoE and the role of very low density lipoproteins in adipose tissue inflammation Wang: ApoE and adipose tissue inflammation

    PubMed Central

    Wang, Jiali; Perrard, Xiaoyuan Dai; Perrard, Jerry L.; Mukherjee, Aparna; Rosales, Corina; Chen, Yuguo; Smith, C. Wayne; Pownall, Henry J.; Ballantyne, Christie M.; Wu, Huaizhu

    2012-01-01

    Objective To identify the role of triglyceride-rich lipoproteins (TGRLs) and apoE, a major apolipoprotein in TGRLs, in adipose tissue inflammation with high-fat diet (HFD)–induced obesity. Methods Male apoE−/− and C57BL/6J wild-type (WT) mice fed HFD for 12 weeks were assessed for metabolic and inflammatory parameters. ApoE−/− and WT mice were orally gavaged with [3H]palmitic acid to examine the role of apoE in fat delivery to adipose tissue. VLDL from obese apoE−/− mice were intravenously injected into lean WT or apoE−/− mice to test potential contribution of TGRLs-derived fat delivery to inflammation in adipose tissue and the role of apoE. Results ApoE−/− mice gained less body weight, and had less fat mass and lower triglyceride levels in skeletal muscle than WT. ApoE−/− mice on HFD had better insulin sensitivity than WT even when comparing body weight–matched mice. Compared to WT mice, apoE−/− mice on HFD had lower levels of inflammatory cytokines/chemokines and CD11c in adipose tissue, and lower levels of inflammatory markers in skeletal muscle. At 6 hours after oral gavage with [3H]palmitic acid, incorporation of [3H]palmitic acid into adipose tissue and skeletal muscle was lower in apoE−/− mice. After repeated daily injection for 3 days, VLDL from obese apoE−/− mice induced inflammation in adipose tissue of recipient WT but not apoE−/− mice. Conclusion In HFD-induced obesity, apoE plays an important role in inflammation in adipose tissue and skeletal muscle, likely by mediating TGRL-derived fat delivery to these tissues. PMID:22770993

  9. Internal mammary artery.

    PubMed

    Calafiore, Antonio M; Weltert, Luca; Mauro, Michele Di; Actis-Dato, Guglielmo; Iacò, Angela L; Centofanti, Paolo; Torre, Michele La; Patanè, Francesco

    2005-01-01

    The internal mammary artery (IMA) has been already used in some pioneering experiences since the middle of last century but it became the graft of choice only in the 1980s, after widespread angiographic and clinical demonstration of its superiority over the saphenous vein graft (SVG). The use of both mammary arteries was then explored in order to achieve better long-term results when compared to single IMA and SVG. The IMA can be harvested pedicled or skeletonized and used as an in situ graft or as a source for composite graft (Y-graft, lengthened graft). When the bilateral internal mammary artery (BIMA) is grafted in situ, the left internal mammary artery (LIMA) is generally used for the left descending artery (LAD) and the RIMA for the right coronary artery (RCA), or for the lateral wall, usually going through the transverse sinus. In the case of Y-graft, the left coronary system is more frequently chosen as the target site of revascularization. Our experience shows that: (1) The use of IMA provides better 15-year clinical results when compared to SVG. (2) The use of BIMA in patients younger than 75 years can produce higher 10-year freedom from cardiac-related events than the single one, even in diabetic patients.

  10. Mercury, APOE, and child behavior.

    PubMed

    Ng, Sharon; Lin, Ching-Chun; Jeng, Suh-Fang; Hwang, Yaw-Huei; Hsieh, Wu-Shiun; Chen, Pau-Chung

    2015-02-01

    Methylmercury (MeHg) is a neurotoxicant and may have an adverse impact on child behavior. However, this impact was found to be inconsistent in fish-eating populations. Although the positive effects of the nutrients provided by a fish diet may overcome the effect of MeHg, the possibility of genetic variants influencing an individual's response to MeHg has also been discussed. The role of the Apolipoprotein E (APOE) epsilon 4 allele (ε4) on MeHg related neurotoxicity is still unclear. In the present study, we investigated the role of APOE variants in the relationship between cord blood mercury (Hg) and child behavior. A total of 166 subjects were recruited at delivery, and their cord blood was collected for laboratory analyses of Hg and the APOE genotype. The Child Behavior Checklist (CBCL) was administered to the subjects when they reached the age of two years. An increase in cord blood Hg concentrations in APOE ε4 carriers was consistently associated with an increased score for all CBCL syndromes. After controlling for potential confounding factors, the group of ε4 carriers with an elevated cord blood Hg concentration had significantly higher scores in the syndrome categories of general internalizing, emotionally reactive, and anxiety/depression as well as CBCL total scores. Furthermore, general externalizing and aggressive syndromes were borderline significantly higher in this group. In conclusion, we suggest that APOE may modify the toxicity of MeHg. APOE ε4 carriers may be more vulnerable to the effects of MeHg on child behavior at the age of two years. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Arterial stump pressure: a determinant of arterial patency?

    PubMed

    Nunley, J A; Goldner, R D; Koman, L A; Gelberman, R; Urbaniak, J R

    1987-03-01

    Twenty-seven patients with acute injuries to the radial or ulnar arteries had arterial repairs using microvascular techniques. No patient had an ischemic hand secondary to his arterial injury. The overall patency rate for all repaired vessels was 56%. For sharp, clean lacerations, the success rate for repairs was 55%. Repairs of acute, sharp lacerations yielded no better results than delayed reconstructions. The average distal end arterial stump pressure for patent arteries was 66% of mean, while for thrombosed vessels it was 76% of mean; this was not a statistically significant difference (p = 0.9). There was no statistical correlation between forearm arterial patency, age, sex, vessel injured, mechanism of injury, time of repair, or clinically measured distal arterial stump pressure. At the present time, it does not appear to be possible to predict arterial patency by measuring arterial stump pressure at the time of definitive repair.

  12. Evolution of complete arterial grafting. For coronary artery disease.

    PubMed Central

    Buxton, B F; Fuller, J A; Tatoulis, J

    1998-01-01

    Arterial grafting for the correction of coronary artery disease preceded the use of saphenous vein grafts, but the overwhelming popularity of the saphenous vein from 1970 to 1985 left the development of arterial grafting dormant. Excellent graft patency results from pedicled internal thoracic artery grafting and continued saphenous vein graft failure prompted our unit to explore complete arterial grafting with internal thoracic artery and radial artery grafts. One thousand and fifty-three patients who received a combination of internal thoracic artery and radial artery grafts were compared with 1,156 patients who received internal thoracic artery and saphenous vein grafts. All patients underwent primary coronary artery bypass surgery between 1995 and 1998. The early mortality and morbidity and the probability of survival at 2 years were similar in both groups of patients. Early graft patency studies of 35 radial artery grafts showed 33 (94%) were patent at a mean of 12 months. Complete arterial grafting using internal thoracic and radial arteries is safe and may provide a long-term benefit. Images PMID:9566058

  13. Resting-state functional connectivity changes in aging apoE4 and apoE-KO mice.

    PubMed

    Zerbi, Valerio; Wiesmann, Maximilian; Emmerzaal, Tim L; Jansen, Diane; Van Beek, Maarten; Mutsaers, Martina P C; Beckmann, Christian F; Heerschap, Arend; Kiliaan, Amanda J

    2014-10-15

    It is well established that the cholesterol-transporter apolipoprotein ε (APOE) genotype is associated with the risk of developing neurodegenerative diseases. Recently, brain functional connectivity (FC) in apoE-ε4 carriers has been investigated by means of resting-state fMRI, showing a marked differentiation in several functional networks at different ages compared with carriers of other apoE isoforms. The causes of such hampered FC are not understood. We hypothesize that vascular function and synaptic repair processes, which are both impaired in carriers of ε4, are the major contributors to the loss of FC during aging. To test this hypothesis, we integrated several different MRI techniques with immunohistochemistry and investigated FC changes in relation with perfusion, diffusion, and synaptic density in apoE4 and apoE-knock-out (KO) mice at 12 (adult) and 18 months of age. Compared with wild-type mice, we detected FC deficits in both adult and old apoE4 and apoE-KO mice. In apoE4 mice, these changes occurred concomitant with increased mean diffusivity in the hippocampus, whereas perfusion deficits appear only later in life, together with reduced postsynaptic density levels. Instead, in apoE-KO mice FC deficits were mirrored by strongly reduced brain perfusion since adulthood. In conclusion, we provide new evidence for a relation between apoE and brain connectivity, possibly mediated by vascular risk factors and by the efficiency of APOE as synaptic modulator in the brain. Our results show that multimodal MR neuroimaging is an excellent tool to assess brain function and to investigate early neuropathology and aging effects in translational research. Copyright © 2014 the authors 0270-6474/14/3413963-13$15.00/0.

  14. Effects of ApoE on intracellular calcium levels and apoptosis of neurons after mechanical injury.

    PubMed

    Jiang, L; Zhong, J; Dou, X; Cheng, C; Huang, Z; Sun, X

    2015-08-20

    The current study aimed to explore the effects of apolipoprotein e (ApoE) on intracellular calcium ([Ca(2+)]i) and apoptosis of neurons after mechanical injury in vitro. A neuron mechanical injury model was established after primary neurons obtained from APOE knockout and wild-type (WT) mice, and four experimental groups were generated: Group-ApoE4, Group-ApoE3, Group-ApoE(-) and Group-WT. Recombinant ApoE4 and ApoE3 were added to Group-ApoE4 and Group-ApoE3 respectively, and Group-ApoE(-) and Group-WT were control groups. Intracellular calcium was labeled by fluo-3/AM and examined using laser scanning confocal microscope and flow cytometry, and the apoptosis of neurons was also evaluated. The intracellular calcium levels and apoptosis rates of mice neurons were significantly higher in Group-ApoE4 than in Group-ApoE3 and Group-WT after mechanical injury. However, without mechanical injury on neurons, no significant differences in intracellular calcium levels and apoptosis rates were found among all four experimental groups. The effects of ApoE4 on intracellular calcium levels and apoptosis rates of injured neurons were partly decreased by EGTA treatment. Compared with ApoE3-treatment and WT neurons, ApoE4 caused higher intracellular calcium levels and apoptosis rates of neurons after mechanical injury. This suggested APOE polymorphisms may affect neuron apoptosis after mechanical injury through different influences on intracellular calcium levels. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  15. 56Fe accelerates development of atherosclerosis in apoE -/-mice

    NASA Astrophysics Data System (ADS)

    Kucik, Dennis; Yu, Tao; Parks, Brian; Yu, Shaohua; Srivastava, Roshni; Gupta, Kiran; Wu, Xing; Khaled, Saman; Chang, Polly; Kabarowski, Janusz

    Exposure to radiation from a variety of sources is associated with increased risk of heart disease and stroke. For example, for women with early breast cancer, the benefit of radiotherapy can be nearly offset by the increased risk of mortality from cardiovascular disease. Head and neck cancer patients who undergo radiation treatment are at significantly elevated risk of stroke, even in a relatively young patient population that would not normally be at risk for atheroscle-rosis. Similarly, atomic bomb survivors had an increased incidence of mortality from coronary artery disease and stroke. Even radiation technologists working before 1950 (when occupational exposure was higher) had increased mortality due to circulatory diseases. Although much is known about the cardiovascular consequences these exposures to X-raus and gamma radiation, the response to the type of radiation likely to be encountered in prolonged space flight has not been determined. A key component of this cosmic radiation is 56Fe, which is particularly damaging to tissues. Using collimated beams, we selectively irradiated aortic arches and carotids (only) of the well-established apoE -/-atherosclerosis mouse model to test directly whether 56Fe exposure is a cardiovascular risk factor. Mice were sacrificed at 13 weeks post-irradiation and dissected, and aortas were divided into areas that had been targeted by the ion beam and those that were not. The area that was covered by plaques was then quantified. Plaque area at 13 weeks post-irradiation was significantly greater in targeted areas of mice that had received 5 Gy of 56Fe as compared to age-and sex-matched un-irradiated controls. In the carotid arteries and aortic roots, significantly greater atherosclerosis was apparent for a 2Gy exposure as well (the lowest dose tested). This demonstrates that even a single exposure to heavy ion radiation is capable of triggering events that culminate in cardiovascular disease, even long after the exposure has

  16. Blood Flow in Arteries

    NASA Astrophysics Data System (ADS)

    Ku, David N.

    Blood flow in arteries is dominated by unsteady flow phenomena. The cardiovascular system is an internal flow loop with multiple branches in which a complex liquid circulates. A nondimensional frequency parameter, the Womersley number, governs the relationship between the unsteady and viscous forces. Normal arterial flow is laminar with secondary flows generated at curves and branches. The arteries are living organs that can adapt to and change with the varying hemodynamic conditions. In certain circumstances, unusual hemodynamic conditions create an abnormal biological response. Velocity profile skewing can create pockets in which the direction of the wall shear stress oscillates. Atherosclerotic disease tends to be localized in these sites and results in a narrowing of the artery lumena stenosis. The stenosis can cause turbulence and reduce flow by means of viscous head losses and flow choking. Very high shear stresses near the throat of the stenosis can activate platelets and thereby induce thrombosis, which can totally block blood flow to the heart or brain. Detection and quantification of stenosis serve as the basis for surgical intervention. In the future, the study of arterial blood flow will lead to the prediction of individual hemodynamic flows in any patient, the development of diagnostic tools to quantify disease, and the design of devices that mimic or alter blood flow. This field is rich with challenging problems in fluid mechanics involving three-dimensional, pulsatile flows at the edge of turbulence.

  17. Attributional Gender Bias: Teachers&apos; Ability and Effort Explanations for Students&apos; Math Performance

    ERIC Educational Resources Information Center

    Espinoza, Penelope; Arêas da Luz Fontes, Ana B.; Arms-Chavez, Clarissa J.

    2014-01-01

    Research is presented on the attributional gender bias: the tendency to generate different attributions (explanations) for female versus male students&apos; performance in math. Whereas boys&apos; successes in math are attributed to ability, girls&apos; successes are attributed to effort; conversely, boys&apos; failures in math are attributed to a…

  18. Caspase-3 Deletion Promotes Necrosis in Atherosclerotic Plaques of ApoE Knockout Mice.

    PubMed

    Grootaert, Mandy O J; Schrijvers, Dorien M; Hermans, Marthe; Van Hoof, Viviane O; De Meyer, Guido R Y; Martinet, Wim

    2016-01-01

    Apoptosis of macrophages and vascular smooth muscle cells (VSMCs) in advanced atherosclerotic plaques contributes to plaque progression and instability. Caspase-3, a key executioner protease in the apoptotic pathway, has been identified in human and mouse atherosclerotic plaques but its role in atherogenesis is not fully explored. We therefore investigated the impact of caspase-3 deletion on atherosclerosis by crossbreeding caspase-3 knockout (Casp3(-/-)) mice with apolipoprotein E knockout (ApoE(-/-)) mice. Bone marrow-derived macrophages and VSMCs isolated from Casp3(-/-)ApoE(-/-) mice were resistant to apoptosis but showed increased susceptibility to necrosis. However, caspase-3 deficiency did not sensitize cells to undergo RIP1-dependent necroptosis. To study the effect on atherosclerotic plaque development, Casp3(+/+)ApoE(-/-) and Casp3(-/-)ApoE(-/-) mice were fed a western-type diet for 16 weeks. Though total plasma cholesterol, triglycerides, and LDL cholesterol levels were not altered, both the plaque size and percentage necrosis were significantly increased in the aortic root of Casp3(-/-)ApoE(-/-) mice as compared to Casp3(+/+)ApoE(-/-) mice. Macrophage content was significantly decreased in plaques of Casp3(-/-)ApoE(-/-) mice as compared to controls, while collagen content and VSMC content were not changed. To conclude, deletion of caspase-3 promotes plaque growth and plaque necrosis in ApoE(-/-) mice, indicating that this antiapoptotic strategy is unfavorable to improve atherosclerotic plaque stability.

  19. Attributional Gender Bias: Teachers&apos; Ability and Effort Explanations for Students&apos; Math Performance

    ERIC Educational Resources Information Center

    Espinoza, Penelope; Arêas da Luz Fontes, Ana B.; Arms-Chavez, Clarissa J.

    2014-01-01

    Research is presented on the attributional gender bias: the tendency to generate different attributions (explanations) for female versus male students&apos; performance in math. Whereas boys&apos; successes in math are attributed to ability, girls&apos; successes are attributed to effort; conversely, boys&apos; failures in math are attributed to a…

  20. ApoE and the role of very low density lipoproteins in adipose tissue inflammation

    USDA-ARS?s Scientific Manuscript database

    Our goal was too identify the role of triglyceride-rich lipoproteins and apoE, a major apolipoprotein in triglyceride-rich lipoproteins, in adipose tissue inflammation with high-fat diet induced obesity. Male apoE-/- and C57BL/6J wild-type mice fed high fat diets for 12 weeks were assessed for metab...

  1. Plasma apolipoprotein C-III levels, triglycerides, and coronary artery calcification in type 2 diabetics.

    PubMed

    Qamar, Arman; Khetarpal, Sumeet A; Khera, Amit V; Qasim, Atif; Rader, Daniel J; Reilly, Muredach P

    2015-08-01

    Triglyceride-rich lipoproteins have emerged as causal risk factors for developing coronary heart disease independent of low-density lipoprotein cholesterol levels. Apolipoprotein C-III (ApoC-III) modulates triglyceride-rich lipoprotein metabolism through inhibition of lipoprotein lipase and hepatic uptake of triglyceride-rich lipoproteins. Mutations causing loss-of-function of ApoC-III lower triglycerides and reduce coronary heart disease risk, suggestive of a causal role for ApoC-III. Little data exist about the relationship of ApoC-III, triglycerides, and atherosclerosis in patients with type 2 diabetes mellitus (T2DM). Here, we examined the relationships between plasma ApoC-III, triglycerides, and coronary artery calcification in patients with T2DM. Plasma ApoC-III levels were measured in a cross-sectional study of 1422 subjects with T2DM but without clinically manifest coronary heart disease. ApoC-III levels were positively associated with total cholesterol (Spearman r=0.36), triglycerides (r=0.59), low-density lipoprotein cholesterol (r=0.16), fasting glucose (r=0.16), and glycosylated hemoglobin (r=0.12; P<0.0001 for all). In age, sex, and race-adjusted analysis, ApoC-III levels were positively associated with coronary artery calcification (Tobit regression ratio, 1.78; 95% confidence interval, 1.27-2.50 per SD increase in ApoC-III; P<0.001). As expected for an intermediate mediator, these findings were attenuated when adjusted for both triglycerides (Tobit regression ratio, 1.43; 95% confidence interval, 0.94-2.18; P=0.086) and separately for very low-density lipoprotein cholesterol (Tobit regression ratio, 1.14; 95% confidence interval, 0.75-1.71; P=0.53). In persons with T2DM, increased plasma ApoC-III is associated with higher triglycerides, less favorable cardiometabolic phenotypes, and higher coronary artery calcification, a measure of subclinical atherosclerosis. Therapeutic inhibition of ApoC-III may thus be a novel strategy for reducing plasma

  2. Jack Michael&apos;s Motivation

    ERIC Educational Resources Information Center

    Miguel, Caio F.

    2013-01-01

    Among many of Jack Michael&apos;s contributions to the field of behavior analysis is his behavioral account of motivation. This paper focuses on the concept of "motivating operation" (MO) by outlining its development from Skinner&apos;s (1938) notion of "drive." Conceptually, Michael&apos;s term helped us change our focus on…

  3. Childrens&apos; Conceptions of Nature

    ERIC Educational Resources Information Center

    Payne, Phillip

    2014-01-01

    This paper describes a study of sixth grade children&apos;s conceptions of nature and the environment. In so doing, it asks that environmental educators pay more attention to children&apos;s preconceived notions of environment and nature. Should this occur the theory-practice gap in environmental education may be diminished. Learners&apos; concept…

  4. Jack Michael&apos;s Motivation

    ERIC Educational Resources Information Center

    Miguel, Caio F.

    2013-01-01

    Among many of Jack Michael&apos;s contributions to the field of behavior analysis is his behavioral account of motivation. This paper focuses on the concept of "motivating operation" (MO) by outlining its development from Skinner&apos;s (1938) notion of "drive." Conceptually, Michael&apos;s term helped us change our focus on…

  5. Coronary artery imaging in children.

    PubMed

    Goo, Hyun Woo

    2015-01-01

    Coronary artery problems in children usually have a significant impact on both short-term and long-term outcomes. Early and accurate diagnosis, therefore, is crucial but technically challenging due to the small size of the coronary artery, high heart rates, and limited cooperation of children. Coronary artery visibility on CT and MRI in children is considerably improved with recent technical advancements. Consequently, CT and MRI are increasingly used for evaluating various congenital and acquired coronary artery abnormalities in children, such as coronary artery anomalies, aberrant coronary artery anatomy specific to congenital heart disease, Kawasaki disease, Williams syndrome, and cardiac allograft vasculopathy.

  6. Coronary Artery Imaging in Children

    PubMed Central

    2015-01-01

    Coronary artery problems in children usually have a significant impact on both short-term and long-term outcomes. Early and accurate diagnosis, therefore, is crucial but technically challenging due to the small size of the coronary artery, high heart rates, and limited cooperation of children. Coronary artery visibility on CT and MRI in children is considerably improved with recent technical advancements. Consequently, CT and MRI are increasingly used for evaluating various congenital and acquired coronary artery abnormalities in children, such as coronary artery anomalies, aberrant coronary artery anatomy specific to congenital heart disease, Kawasaki disease, Williams syndrome, and cardiac allograft vasculopathy. PMID:25741188

  7. Traumatic Distal Ulnar Artery Thrombosis

    PubMed Central

    Karaarslan, Ahmet A.; Karakaşlı, Ahmet; Mayda, Aslan; Karcı, Tolga; Aycan, Hakan; Kobak, Şenol

    2014-01-01

    This paper is about a posttraumatic distal ulnar artery thrombosis case that has occurred after a single blunt trauma. The ulnar artery thrombosis because of chronic trauma is a frequent condition (hypothenar hammer syndrome) but an ulnar artery thrombosis because of a single direct blunt trauma is rare. Our patient who has been affected by a single blunt trauma to his hand and developed ulnar artery thrombosis has been treated by resection of the thrombosed ulnar artery segment. This report shows that a single blunt trauma can cause distal ulnar artery thrombosis in the hand and it can be treated merely by thrombosed segment resection in suitable cases. PMID:25276455

  8. Redox reactions of apo mammalian ferritin.

    PubMed

    Watt, R K; Frankel, R B; Watt, G D

    1992-10-13

    Apo horse spleen ferritin undergoes a 6.3 +/- 0.5 electron redox reaction at -310 mV at pH 6.0-8.5 and 25 degrees C to form reduced apoferritin (apoMFred). Reconstituted ferritin containing up to 50 ferric ions undergoes reduction at the same potential, taking up one electron per ferric ion and six additional electrons by the protein. We propose that apo mammalian ferritin (apoMF) contains six redox centers that can be fully oxidized forming oxidized apoferritin (apoMFox) or fully reduced forming apoMFred. ApoMFred can be prepared conveniently by dithionite or methyl viologen reduction. ApoMFred is slowly oxidized by molecular oxygen but more rapidly by Fe(CN)6(3-) to apoMFox. Fe(III)-cytochrome c readily oxidizes apoMFred to apoMFox with a stoichiometry of 6 Fe(III)-cytochrome c per apoMFred, demonstrating a rapid interprotein electron-transfer reaction. Both redox states of apoMF react with added Fe3+ and Fe2+. Addition of eight Fe2+ to apoMFox under anaerobic conditions produced apoMFred and Fe3+, as evidenced by the presence of a strong g = 4.3 EPR signal. Subsequent addition of bipyridyl produced at least six Fe(bipyd)3(2+) per MF, establishing the reversibility of this internal electron-transfer process between the redox centers of apoMF and bound iron. Incubation of apoMFred with the Fe(3+)-ATP complex under anaerobic conditions resulted in the formation and binding of two Fe2+ and four Fe3+ by the protein. The various redox states formed by the binding of Fe2+ and Fe3+ to apoMFox and apoMFred are proposed and discussed. The yellow color of apoMF appears to be an integral characteristic of the apoMF and is possibly associated with its redox activity.

  9. A 1D model of the arterial circulation in mice.

    PubMed

    Aslanidou, Lydia; Trachet, Bram; Reymond, Philippe; Fraga-Silva, Rodrigo A; Segers, Patrick; Stergiopulos, Nikolaos

    2016-01-01

    At a time of growing concern over the ethics of animal experimentation, mouse models are still an indispensable source of insight into the cardiovascular system and its most frequent pathologies. Nevertheless, reference data on the murine cardiovascular anatomy and physiology are lacking. In this work, we developed and validated an in silico, one dimensional model of the murine systemic arterial tree consisting of 85 arterial segments. Detailed aortic dimensions were obtained in vivo from contrast-enhanced micro-computed tomography in 3 male, C57BL/6J anesthetized mice and 3 male ApoE(-/-) mice, all 12-weeks old. Physiological input data were gathered from a wide range of literature data. The integrated form of the Navier-Stokes equations was solved numerically to yield pressures and flows throughout the arterial network. The resulting model predictions have been validated against invasive pressure waveforms and non-invasive velocity and diameter waveforms that were measured in vivo on an independent set of 47 mice. In conclusion, we present a validated one-dimensional model of the anesthetized murine cardiovascular system that can serve as a versatile tool in the field of preclinical cardiovascular research.

  10. Ruptured jejunal artery aneurysm

    PubMed Central

    Costa, Sílvia; Costa, Alexandre; Pereira, Tiago; Maciel, Jorge

    2013-01-01

    Visceral artery aneurysms (VAAs), unlike aortic aneurysms, are very rare, but are also a potentially lethal vascular disease. Jejunal artery aneurysms only account for less than 3% of VAAs, but have a 30% risk of rupture, with 20% death rate, presenting with only few and vague symptoms. We report the case of a 76-year-old man presenting at the emergency department (ED) with a crampy epigastric pain and vomiting. An ultrasound performed diagnosed free abdominal fluid and immediate CT scan diagnosed jejunal artery aneurysm spontaneously rupturing, followed by hypovolaemic shock. Emergent surgery was undertaken, and aneurysmectomy, followed by partial enterectomy with primary anastomosis were performed, because of segmentary jejunal ischaemia. The patient's recovery was unremarkable. High level of suspicion, rapid diagnosis capability and prompt surgical or endovascular intervention, as well as an effective teamwork in the ED are critical to avoid the devastating consequences of ruptured VAAs. PMID:23771962

  11. ApoE enhances nanodisk-mediated curcumin delivery to glioblastoma multiforme cells

    PubMed Central

    Ghosh, Mistuni; Ryan, Robert O

    2013-01-01

    Aim To evaluate the effect of incorporating the polyphenol, curcumin, into nanodisk (ND) particles on its biological activity. Materials & methods Curcumin-NDs formulated with different scaffold proteins were incubated with cultured glioblastoma multiforme cells. Results When ApoE was employed as the ND scaffold protein, enhanced curcumin uptake was observed. Furthermore, ApoE curcumin-NDs induced greater cell death than either free curcumin or ApoAI curcumin-NDs. A total of 1 h after exposure of glioblastoma multiforme cells to ApoE curcumin-NDs, significant curcumin uptake was detected while ApoE was localized at the cell surface. After 2 h, a portion of the curcumin had migrated to the nucleus, giving rise to enhanced fluorescence intensity in discrete intranuclear sites. Conclusion ApoE-mediated interaction of curcumin-NDs with glioblastoma multiforme cells leads to enhanced curcumin uptake and increased biological activity. PMID:23879635

  12. Transcatheter Arterial Embolization for Spontaneous Rupture of the Omental Artery

    SciTech Connect

    Matsumoto, Tomohiro; Yamagami, Takuji; Morishita, Hiroyuki; Iida, Shigeharu; Tazoe, Jun; Asai, Shunsuke; Masui, Koji; Ikeda, Jun; Nagata, Akihiro; Sato, Osamu; Nishimura, Tsunehiko

    2011-02-15

    We encountered a rare case of spontaneous rupture of the omental artery. A 25-year-old man without any episode of abdominal trauma or bleeding disorders came to the emergency unit with left upper abdominal pain. Hematoma with extravasation of the greater omentum and a hemoperitoneum was confirmed on abdominal contrast-enhanced computed tomography. Bleeding from the omental artery was suspected based on these findings. Transcatheter arterial embolization was successfully performed after extravasation of the omental artery, which arises from the left gastroepiploic artery, was confirmed on arteriography. Partial ometectomy was performed 10 days after transcatheter arterial embolization, revealing that the hematoma measured 10 cm in diameter in the greater omentum. Pathological examination showed rupture of the branch of an omental artery without abnormal findings, such as an aneurysm or neoplasm. Thus, we diagnosed him with spontaneous rupture of the omental artery. The patient recovered and was discharged from the hospital 10 days after the surgery, with a favorable postoperative course.

  13. Splenic artery aneurysm.

    PubMed

    Tcbc-Rj, Rui Antônio Ferreira; Ferreira, Myriam Christina Lopes; Ferreira, Daniel Antônio Lopes; Ferreira, André Gustavo Lopes; Ramos, Flávia Oliveira

    2016-01-01

    Splenic artery aneurysms - the most common visceral artery aneurysms - are found most often in multiparous women and in patients with portal hypertension. Indications for treatment of splenic artery aneurysm or pseudoaneurysm include specific symptoms, female gender and childbearing age, presence of portal hypertension, planned liver transplantation, a pseudoaneurysm of any size, and an aneurysm with a diameter of more than 2.5cm. Historically, the treatment of splenic artery aneurysm has been surgical ligation of the splenic artery, ligation of the aneurysm, or aneurysmectomy with or without splenectomy, depending on the aneurysm location. There are other percutaneous interventional techniques. The authors present a case of a splenic artery aneurysm in a 51-year-old woman, detected incidentally. RESUMO Aneurismas da artéria esplênica - os aneurismas arteriais viscerais mais comuns - são encontrados mais frequentemente em mulheres multíparas e em pacientes com hipertensão portal. As indicações para o seu tratamento incluem sintomas específicos, sexo feminino e idade fértil, presença de hipertensão portal, paciente em fila de transplante hepático, um pseudoaneurisma de qualquer tamanho, e um aneurisma com um diâmetro superior a 2,5cm. Historicamente, o tratamento do aneurisma da artéria esplênica tem sido a ligadura cirúrgica da artéria esplênica, a ligadura do aneurisma ou a aneurismectomia, com ou sem esplenectomia, dependendo do local do aneurisma. Existem outras técnicas intervencionistas percutâneas. Os autores apresentam o caso de um aneurisma de artéria esplênica em uma mulher de 51 anos de idade, diagnosticado incidentalmente.

  14. Idiopathic pulmonary artery aneurysm.

    PubMed

    Kotwica, Tomasz; Szumarska, Joanna; Staniszewska-Marszalek, Edyta; Mazurek, Walentyna; Kosmala, Wojciech

    2009-05-01

    Pulmonary artery aneurysm (PAA) is an uncommon lesion, which may be associated with different etiologies including congenital cardiovascular diseases, systemic vasculitis, connective tissue diseases, infections, and trauma. Idiopathic PAA is sporadically diagnosed by exclusion of concomitant major pathology. We report a case of a 56-year-old female with an idiopathic pulmonary artery dilatation identified fortuitously by echocardiography and confirmed by contrast-enhanced computed tomography. Neither significant pulmonary valve dysfunction nor pulmonary hypertension and other cardiac abnormalities which might contribute to the PAA development were found. Here, we describe echocardiographic and computed tomography findings and review the literature on PAA management.

  15. Pulmonary Artery Sarcoma

    PubMed Central

    Shomaf, Maha; Obeidat, Nathir; Najjar, Saleh

    2014-01-01

    Pulmonary artery sarcomas (PAS) are extremely rare sarcomas of uncertain histogenesis that often mimic pulmonary thromboemboli. This is a report of a 60-year-old female patient who presented with recurrent chest pain and cough. The patient was first diagnosed with pulmonary embolism but she did not improve on anticoagulant therapy. Follow-up imaging studies revealed a mass in the left hilar region extending into the pulmonary trunk and branches of the left pulmonary artery. The tru-cut biopsy revealed an undifferentiated sarcoma. The patient died 10 months after her initial presentation. PMID:26425600

  16. Harvesting the radial artery

    PubMed Central

    Osterday, Robert M.; Brodman, Richard F.

    2013-01-01

    The radial artery (RA) has emerged as an important arterial graft for coronary bypass surgery. With improving five-year patency rates and increasing uptake, great attention has been focused on the optimal conduit harvesting technique. We herein present our approach to RA harvesting. Prerequisites of a successful harvest include adherence to important anatomical landmarks, protection of the sensory innervation to the volar forearm, and meticulous handling of the RA branches. Regardless of the harvesting methodology chosen, adherence to a “no-touch” technique will optimize the patency and durability of the RA conduit. PMID:23977633

  17. VPO1 mediates ApoE oxidation and impairs the clearance of plasma lipids.

    PubMed

    Yang, Youfeng; Cao, Zehong; Tian, Ling; Garvey, W Timothy; Cheng, Guangjie

    2013-01-01

    ApoE is an abundant component of chylomicron, VLDL, IDL, and HDL. It binds to multiple types of lipids and is implicated in cholesterol and triglyceride homeostasis. Oxidation of ApoE plays a crucial role in the genesis of atherosclerosis. It is proposed that heme-containing peroxidases (hPx) are major mediators of lipoprotein oxidization. Vascular peroxidase 1 (VPO1) is a recently-discovered hPx, which is expressed in cardiovascular system, lung, liver etc. and secreted into plasma. Its plasma concentration is three orders of magnitude of that of myeloperoxidase. If VPO1 mediates ApoE oxidation and affects the lipid metabolism remains to be elucidated. Recombinant ApoE and VPO1 were expressed and purified from stably-expressing cell lines deriving from HEK293 cells. ApoE oxidation was carried out by VPO1 in the presence of H2O2 and chloride. ApoE oxidation was verified by a variety of approaches including immunoblot and amino acid analyses. To evaluate the functional changes in VPO1-oxidized ApoE, lipid emulsion particle binding assays were employed. Oxidized ApoE binds weaker to lipid emulsion particles, which mimic the large lipid complexes in vivo. In lipid efflux assay, oxidized ApoE showed reduced capability in efflux of lipids from foam cells. Mice administrated with oxidized ApoE via blood exhibited weaker clearance ability of plasma lipids. Our data suggest that VPO1 is a new mediator regulating lipid homeostasis, implying a role in genesis and development of atherosclerosis.

  18. VPO1 Mediates ApoE Oxidation and Impairs the Clearance of Plasma Lipids

    PubMed Central

    Yang, Youfeng; Cao, Zehong; Tian, Ling; Garvey, W. Timothy; Cheng, Guangjie

    2013-01-01

    Objective ApoE is an abundant component of chylomicron, VLDL, IDL, and HDL. It binds to multiple types of lipids and is implicated in cholesterol and triglyceride homeostasis. Oxidation of ApoE plays a crucial role in the genesis of atherosclerosis. It is proposed that heme-containing peroxidases (hPx) are major mediators of lipoprotein oxidization. Vascular peroxidase 1 (VPO1) is a recently-discovered hPx, which is expressed in cardiovascular system, lung, liver etc. and secreted into plasma. Its plasma concentration is three orders of magnitude of that of myeloperoxidase. If VPO1 mediates ApoE oxidation and affects the lipid metabolism remains to be elucidated. Methods Recombinant ApoE and VPO1 were expressed and purified from stably-expressing cell lines deriving from HEK293 cells. ApoE oxidation was carried out by VPO1 in the presence of H2O2 and chloride. ApoE oxidation was verified by a variety of approaches including immunoblot and amino acid analyses. To evaluate the functional changes in VPO1-oxidized ApoE, lipid emulsion particle binding assays were employed. Results Oxidized ApoE binds weaker to lipid emulsion particles, which mimic the large lipid complexes in vivo. In lipid efflux assay, oxidized ApoE showed reduced capability in efflux of lipids from foam cells. Mice administrated with oxidized ApoE via blood exhibited weaker clearance ability of plasma lipids. Conclusions Our data suggest that VPO1 is a new mediator regulating lipid homeostasis, implying a role in genesis and development of atherosclerosis. PMID:23451244

  19. Modulation of autoimmune arthritis severity in mice by apolipoprotein E (ApoE) and cholesterol.

    PubMed

    Alvarez, P; Genre, F; Iglesias, M; Augustin, J J; Tamayo, E; Escolà-Gil, J C; Lavín, B; Blanco-Vaca, F; Merino, R; Merino, J

    2016-12-01

    Apolipoprotein E (ApoE) deficiency promoted an exacerbation of autoimmune arthritis in mice by inducing proinflammatory immune responses. In this study we analysed the contribution of hypercholesterolaemia and/or the absence of ApoE anti-inflammatory properties, unrelated to its function in the control of cholesterol metabolism, towards the acceleration of arthritis in these mutant animals. The induction and severity of collagen type II-induced arthritis (CIA) were compared for B10.RIII wild-type (WT), B10.RIII.ApoE(+/-) , B10.RIII.ApoE(-/-) and B10.RIII.low-density lipoprotein receptor (LDLR(-/-) ) mice with different concentrations of circulating ApoE and cholesterol. A 50-70% reduction in serum levels of ApoE was observed in heterozygous B10.RIII.ApoE(+/-) mice in comparison to B10.RIII.WT, although both strains of mice exhibited similar circulating lipid profiles. This ApoE reduction was associated with an increased CIA severity that remained lower than in homozygous B10.RIII.ApoE(-/-) mice. An important rise in circulating ApoE concentration was observed in hypercholesterolaemic B10.RIII.LDLR(-/-) mice fed with a normal chow diet, and both parameters increased further with an atherogenic hypercholesterolaemic diet. However, the severity of CIA in B10.RIII.LDLR(-/-) mice was similar to that of B10.RIII.WT controls. In conclusion, by comparing the evolution of CIA between several strains of mutant mice with different levels of serum ApoE and cholesterol, our results demonstrate that both hypercholesterolaemia and ApoE regulate the intensity of in-vivo systemic autoimmune responses. © 2016 British Society for Immunology.

  20. Understanding Arteries | Coronary Artery Disease | NIH MedlinePlus the Magazine

    MedlinePlus

    ... this page please turn Javascript on. Feature: Coronary Artery Disease Understanding Arteries Past Issues / Fall 2010 Table of Contents Below: ... the arteries and veins are healthy. A Healthy Artery An artery is a muscular tube. It has ...

  1. Reconstructive surgery for segmental arterial mediolysis involving both the internal carotid artery and visceral arteries.

    PubMed

    Obara, Hideaki; Matsumoto, Kenji; Narimatsu, Yoshiaki; Sugiura, Hitoshi; Kitajima, Masaki; Kakefuda, Toshihiro

    2006-03-01

    Segmental arterial mediolysis (SAM) is a rare, nonatherosclerotic, noninflammatory arteriopathy. A 52-year-old man with sudden hemiparesis of the right side was found to have an aneurysm of the left internal carotid artery and concomitant multiple aneurysms of the extrahepatic, celiac, and superior mesenteric arteries. Reconstructive operations using autologous vein graft were performed to treat the aneurysms. The histopathology analyses of resected arterial and aneurysmal specimens showed characteristics consistent with SAM. To our knowledge, a successfully treated case of SAM affecting both the carotid artery and visceral arteries has not previously been described.

  2. Thrombospondin1 Deficiency Attenuates Obesity-Associated Microvascular Complications in ApoE-/- Mice

    PubMed Central

    Maimaitiyiming, Hasiyeti; Clemons, Kate; Zhou, Qi; Norman, Heather; Wang, Shuxia

    2015-01-01

    Obesity is associated with insulin resistance and the increased development of vascular complications. Previously, we have demonstrated that thrombospondin1 (TSP1) regulates macrophage function and contributes to obesity associated inflammation and insulin resistance. However, the role of TSP1 in the development of obesity associated vascular complications is not clear. Therefore, in the current study, we investigated whether TSP1 deficiency protects mice from obesity associated micro as well as macro-vascular complications in ApoE-/- mice. In this study, male ApoE-/- mice and ApoE-/-TSP1-/- mice were fed with a low-fat (LF) or a high-fat (HF) diet for 16 weeks. We found that body weight and fat mass increased similarly between the ApoE-/-TSP1-/- mice and ApoE-/- mice under HF feeding conditions. However, as compared to obese ApoE-/- mice, obese ApoE-/-TSP1-/- mice had improved glucose tolerance, increased insulin sensitivity, and reduced systemic inflammation. Aortic atherosclerotic lesion formation was similar in these two groups of mice. In contrast, albuminuria was attenuated and kidney fibrosis was reduced in obese ApoE-/-TSP1-/- mice compared to obese ApoE-/- mice. The improved kidney function in obese ApoE-/-TSP1-/- mice was associated with decreased renal lipid accumulation. Together, these data suggest that TSP1 deficiency did not affect the development of obesity associated macro-vascular complication, but attenuated obesity associated micro-vascular complications. PMID:25803585

  3. Thrombospondin1 deficiency attenuates obesity-associated microvascular complications in ApoE-/- mice.

    PubMed

    Maimaitiyiming, Hasiyeti; Clemons, Kate; Zhou, Qi; Norman, Heather; Wang, Shuxia

    2015-01-01

    Obesity is associated with insulin resistance and the increased development of vascular complications. Previously, we have demonstrated that thrombospondin1 (TSP1) regulates macrophage function and contributes to obesity associated inflammation and insulin resistance. However, the role of TSP1 in the development of obesity associated vascular complications is not clear. Therefore, in the current study, we investigated whether TSP1 deficiency protects mice from obesity associated micro as well as macro-vascular complications in ApoE-/- mice. In this study, male ApoE-/- mice and ApoE-/-TSP1-/- mice were fed with a low-fat (LF) or a high-fat (HF) diet for 16 weeks. We found that body weight and fat mass increased similarly between the ApoE-/-TSP1-/- mice and ApoE-/- mice under HF feeding conditions. However, as compared to obese ApoE-/- mice, obese ApoE-/-TSP1-/- mice had improved glucose tolerance, increased insulin sensitivity, and reduced systemic inflammation. Aortic atherosclerotic lesion formation was similar in these two groups of mice. In contrast, albuminuria was attenuated and kidney fibrosis was reduced in obese ApoE-/-TSP1-/- mice compared to obese ApoE-/- mice. The improved kidney function in obese ApoE-/-TSP1-/- mice was associated with decreased renal lipid accumulation. Together, these data suggest that TSP1 deficiency did not affect the development of obesity associated macro-vascular complication, but attenuated obesity associated micro-vascular complications.

  4. Phospholipid dysregulation contributes to ApoE4-associated cognitive deficits in Alzheimer’s disease pathogenesis

    PubMed Central

    Zhu, Li; Zhong, Minghao; Elder, Gregory A.; Sano, Mary; Holtzman, David M.; Gandy, Sam; Cardozo, Christopher; Haroutunian, Vahram; Robakis, Nikolaos K.; Cai, Dongming

    2015-01-01

    The apolipoprotein E4 (ApoE4) allele is the strongest genetic risk factor for developing sporadic Alzheimer’s disease (AD). However, the mechanisms underlying the pathogenic nature of ApoE4 are not well understood. In this study, we have found that ApoE proteins are critical determinants of brain phospholipid homeostasis and that the ApoE4 isoform is dysfunctional in this process. We have found that the levels of phosphoinositol biphosphate (PIP2) are reduced in postmortem human brain tissues of ApoE4 carriers, in the brains of ApoE4 knock-in (KI) mice, and in primary neurons expressing ApoE4 alleles compared with those levels in ApoE3 counterparts. These changes are secondary to increased expression of a PIP2-degrading enzyme, the phosphoinositol phosphatase synaptojanin 1 (synj1), in ApoE4 carriers. Genetic reduction of synj1 in ApoE4 KI mouse models restores PIP2 levels and, more important, rescues AD-related cognitive deficits in these mice. Further studies indicate that ApoE4 behaves similar to ApoE null conditions, which fails to degrade synj1 mRNA efficiently, unlike ApoE3 does. These data suggest a loss of function of ApoE4 genotype. Together, our data uncover a previously unidentified mechanism that links ApoE4-induced phospholipid changes to the pathogenic nature of ApoE4 in AD. PMID:26372964

  5. Interaction of ApoE3 and ApoE4 isoforms with an ITM2b/BRI2 mutation linked to the Alzheimer disease-like Danish dementia: Effects on learning and memory.

    PubMed

    Biundo, Fabrizio; Ishiwari, Keita; Del Prete, Dolores; D'Adamio, Luciano

    2015-12-01

    Mutations in Amyloid β Precursor Protein (APP) and in genes that regulate APP processing--such as PSEN1/2 and ITM2b/BRI2--cause familial dementia, such Familial Alzheimer disease (FAD), Familial Danish (FDD) and British (FBD) dementias. The ApoE gene is the major genetic risk factor for sporadic AD. Three major variants of ApoE exist in humans (ApoE2, ApoE3, and ApoE4), with the ApoE4 allele being strongly associated with AD. ITM2b/BRI2 is also a candidate regulatory node genes predicted to mediate the common patterns of gene expression shared by healthy ApoE4 carriers and late-onset AD patients not carrying ApoE4. This evidence provides a direct link between ITM2b/BRI2 and ApoE4. To test whether ApoE4 and pathogenic ITM2b/BRI2 interact to modulate learning and memory, we crossed a mouse carrying the ITM2b/BRI2 mutations that causes FDD knocked-in the endogenous mouse Itm2b/Bri2 gene (FDDKI mice) with human ApoE3 and ApoE4 targeted replacement mice. The resultant ApoE3, FDDKI/ApoE3, ApoE4, FDDKI/ApoE4 male mice were assessed longitudinally for learning and memory at 4, 6, 12, and 16-17 months of age. The results showed that ApoE4-carrying mice displayed spatial working/short-term memory deficits relative to ApoE3-carrying mice starting in early middle age, while long-term spatial memory of ApoE4 mice was not adversely affected even at 16-17 months, and that the FDD mutation impaired working/short-term spatial memory in ApoE3-carrying mice and produced impaired long-term spatial memory in ApoE4-carrying mice in middle age. The present results suggest that the FDD mutation may differentially affect learning and memory in ApoE4 carriers and non-carriers.

  6. Peripheral Arterial Disease and Claudication

    MedlinePlus

    ... of fatty deposits inside them. This is called atherosclerosis. If you have PAD, your arms, and more ... also more likely in people who already have atherosclerosis in other arteries, such as the arteries in ...

  7. A rare case report of subscapular artery.

    PubMed

    Khaki, Amir Afshin; Shoja, M A Mohagjel; Khaki, Arash

    2011-01-01

    Axillary artery is one of the most important arteries of the upper limb, which is a continua- tion of the subclavian artery. It begins at the lateral border of the first rib and ends at the inferior border of the teres major where it becomes the brachial artery. Axillary artery has six important branches included: 1) Superior thoracic artery 2) Thoracoacromial artery 3) Lateral thoracic artery 4) Subscapular artery 5) Posterior circumflex humeral artery 6) Anterior circumflex humeral artery. Subscapular artery arises from the third part of axillary artery normally and then divides into cir- cumflex scapular artery that extremely enters the triangular space. The other branch of subscapular artery, the thoracodorsal artery, accompanies thracodorsal nerve to lateral border of scapula and supplies and innervates that region. In this case the subscapular artery was absent in both sides and instead of that the circumflex scapular artery was directly derived from axillary artery and the thoracodorsal artery is separated from circumflex scapular artery as a thin and short branch, too. It seemed that the lateral thoracic artery, which was thicker than its normal condition, supplied the muscles of the lateral part of scapula and the thoracodorsal muscle. Other branches of the axillary artery demonstrated without any abnormally. Since axillary artery has the highest rate of rapture and damage coming after the popliteal artery, knowing the variations is important and essential for surgeons, radiologist and anatomist.

  8. ApoE knockout rabbits: A novel model for the study of human hyperlipidemia.

    PubMed

    Niimi, Manabu; Yang, Dongshan; Kitajima, Shuji; Ning, Bo; Wang, Chuan; Li, Shen; Liu, Enqi; Zhang, Jifeng; Eugene Chen, Y; Fan, Jianglin

    2016-02-01

    Rabbits are one of the best animal models for the study of hyperlipidemia and atherosclerosis. Although many transgenic rabbits have been created, the development of gene knockout (KO) rabbits has been impossible due to the lack of rabbit embryonic stem cells. We along with others recently generated KO rabbits using genome editing techniques. In the current study, we characterized the lipoprotein profiles of apoE KO rabbits on both chow and cholesterol diets and investigated their susceptibility to a diet-induced atherosclerosis. We analyzed plasma lipids and lipoproteins of apoE KO rabbits and compared them with those of wild-type rabbits. On a chow diet, homozygous (but not heterozygous) apoE KO rabbits showed mild hyperlipidemia and, when challenged with a cholesterol diet, they showed greater susceptibility to diet-induced hyperlipidemia than did the wild-type rabbits and their plasma total cholesterol levels were remarkably increased (1070 ± 61 mg/dL in apoE KO vs. 169 ± 79 mg/dL in the wild type, p < 0.001). Hyperlipidemia in apoE KO rabbits was caused by elevated remnant lipoproteins. Interestingly, increased remnant lipoproteins in apoE KO rabbits were predominated by apoB-48 and rich in both apoA-I and apoA-IV contents. Furthermore, apoE KO rabbits developed greater aortic atherosclerosis than wild-type rabbits when fed with a cholesterol diet for 10 weeks. To our knowledge, this is the first report of generating KO rabbits for the study of lipid and lipoprotein metabolism. ApoE KO rabbits should be a useful model for the study of human hyperlipidemia and atherosclerosis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  9. Traumatic Brachial Artery Injuries

    PubMed Central

    Ergunes, Kazim; Yilik, Levent; Ozsoyler, Ibrahim; Kestelli, Mert; Ozbek, Cengiz; Gurbuz, Ali

    2006-01-01

    We performed this retrospective study to analyze our strategies for managing and surgically treating brachial artery injuries. Fifty-seven patients with a total of 58 traumatic brachial artery injuries underwent surgery at our institution, from August 1996 through November 2004. Fifty-four patients were male and 3 were female (age range, 7 to 75 years; mean, 29.4 years). Forty-four of the patients had penetrating injuries (18 had stab wounds; 16, window glass injuries; and 10, industrial accidents), 10 had blunt trauma injuries (traffic accidents), and 3 had gunshot injuries. Fourteen patients (24.6%) had peripheral nerve injury. All patients underwent Doppler ultrasonographic examination. The repair of the 58 arterial injuries involved end-to-end anastomosis for 32 injuries (55.2%), reverse saphenous vein graft interpositional grafts for 18 (31%), and primary repair for 8 (13.8%). Venous continuity was achieved in 11 (84.6%) of 13 patients who had major venous injuries. Nine of the 57 patients (15.8%) required primary fasciotomy. Follow-up showed that 5 of the 14 patients with peripheral nerve injury had apparent disabilities due to nerve injury. One patient underwent amputation. There were no deaths. We believe that good results can be achieved in patients with brachial artery injuries by use of careful physical examination, Doppler ultrasonography, and restoration of viability with vascular repair and dbridement of nonviable tissues. Traumatic neurologic injury frequently leads to disability of the extremities. PMID:16572866

  10. Pancreaticoduodenal arterial aneurysms.

    PubMed Central

    Verta, M J; Dean, R H; Yao, J S; Conn, J; Mehn, W H; Bergan, J J

    1977-01-01

    Experience with four aneurysms of the pancreaticoduodenal artery is reviewed and compared to the reported experience of 19 other cases. In view of the common presentation of such lesions as intra-abdominal hemorrhage preceded by non-specific abdominal pain and other digestive symptoms, it is suggested that angiography perfomed preoperatively or intraoperatively allows definitive diagnosis and leads to specific therapy. PMID:406863

  11. Hepatic Artery Infusion Chemotherapy

    PubMed Central

    Schüller, J.; Kroiss, A.; Dinstl, K.

    1990-01-01

    Hepatic artery chemotherapy was given to 36 patients, using totally implantable devices consisting of a port and external pump. Twenty-seven patients had inoperable liver metastases of colorectal origin. The infusion system was inserted by laparotomy into the hepatic artery via the gastroduodenal artery. There was no operative mortality. Thirteen infusion systems could not be used for chemotherapy due to dislodgement, early death and lack of follow-up. FUdR was infused every two weeks. There were minor local complications like thrombosis of the system and dislodgement of the port. Toxic effects could be managed by reducing the dose. Response to chemotherapy was evaluated by survival, clinical condition, CEA, ultrasound and CT six months after onset of arterial chemotherapy. Ten/twenty-three patients (43%) responded to therapy, eight of them died on the average 19 months after initial chemotherapy. Six patients were non-responders, seven had stable disease. Five/ten patients developed extrahepatic metastases. Mean survival time was 13.1 months, mean interval until relapse 10.6 months. PMID:2149279

  12. Absent or occult pulmonary artery.

    PubMed Central

    Presbitero, P; Bull, C; Haworth, S G; de Leval, M R

    1984-01-01

    Of 12 patients with angiographically absent pulmonary artery, 11 were investigated surgically. The previously occult pulmonary artery was found in 10 patients, in five of whom a vestige of an intrapericardial artery was present and in five the artery was patent only at the hilus, a gap existing between the main pulmonary artery and the hilar vessel, and no artery was found in one. All patients with an intrapericardial artery had right ventricular outflow tract obstruction and a ductus descending vertically from underneath the aortic arch. In those without an intrapericardial vessel the occult artery was on the side opposite the aortic arch, and there was evidence of a ductus coming from the innominate artery on the side of the interruption. The occult pulmonary artery, where identified at operation, was usually joined initially to the systemic circulation. Ultimately, continuity between the hilar and main pulmonary artery may be established surgically. Where no intrapericardial vessel exists, however, a conduit may be required to bridge the gap. It seems advisable to search for the occult artery as early in life as is feasible in the hope that providing a blood supply will ensure development of the vessel and normal lung growth. Images PMID:6743435

  13. Intravital live cell triggered imaging system reveals monocyte patrolling and macrophage migration in atherosclerotic arteries

    NASA Astrophysics Data System (ADS)

    McArdle, Sara; Chodaczek, Grzegorz; Ray, Nilanjan; Ley, Klaus

    2015-02-01

    Intravital multiphoton imaging of arteries is technically challenging because the artery expands with every heartbeat, causing severe motion artifacts. To study leukocyte activity in atherosclerosis, we developed the intravital live cell triggered imaging system (ILTIS). This system implements cardiac triggered acquisition as well as frame selection and image registration algorithms to produce stable movies of myeloid cell movement in atherosclerotic arteries in live mice. To minimize tissue damage, no mechanical stabilization is used and the artery is allowed to expand freely. ILTIS performs multicolor high frame-rate two-dimensional imaging and full-thickness three-dimensional imaging of beating arteries in live mice. The external carotid artery and its branches (superior thyroid and ascending pharyngeal arteries) were developed as a surgically accessible and reliable model of atherosclerosis. We use ILTIS to demonstrate Cx3cr1GFP monocytes patrolling the lumen of atherosclerotic arteries. Additionally, we developed a new reporter mouse (Apoe-/-Cx3cr1GFP/+Cd11cYFP) to image GFP+ and GFP+YFP+ macrophages "dancing on the spot" and YFP+ macrophages migrating within intimal plaque. ILTIS will be helpful to answer pertinent open questions in the field, including monocyte recruitment and transmigration, macrophage and dendritic cell activity, and motion of other immune cells.

  14. Cerebral Arterial Fenestrations

    PubMed Central

    Cooke, Daniel L; Stout, Charles E; Kim, Warren T; Kansagra, Akash P; Yu, John Paul; Gu, Amy; Jewell, Nicholas P; Hetts, Steven W; Higashida, Randall T; Dowd, Christopher F; Halbach, Van V

    2014-01-01

    Summary Arterial fenestrations are an anatomic variant with indeterminate significance. Given the controversy surrounding fenestrations we sought their prevalence within our practice along with their association with other cerebrovascular anomalies. We retrospectively reviewed 10,927 patients undergoing digital subtraction angiography between 1992 and 2011. Dictated reports were searched for the terms “fenestration” or “fenestrated” with images reviewed for relevance, yielding 228 unique cases. A Medline database search from February 1964 to January 2013 generated 304 citations, 127 cases of which were selected for analysis. Cerebral arterial fenestrations were identified in 228 patients (2.1%). At least one aneurysm was noted in 60.5% of patients, with an aneurysm arising from the fenestration in 19.6% of patients. Aneurysmal subarachnoid hemorrhage or non-aneurysmal subarachnoid hemorrhage were present in 60.1% and 15.8%, respectively. For the subset of patients with an aneurysm arising directly from a fenestration relative to those patients with an aneurysm not immediately associated with a fenestration, the prevalence of aneurysmal subarachnoid hemorrhage was 66.7% vs. 58.6% (p = 0.58). Fenestrations were more often within the posterior circulation (73.2%) than the anterior circulation (24.6%), though there was no difference in the prevalence of aneurysms within these groups (61.1% vs. 60.7%, p = 1.0). Cerebral arterial fenestrations are an anatomic variant more often manifesting at the anterior communicating arterial complex and basilar artery and with no definite pathological relationship with aneurysms. PMID:24976087

  15. Successful small diameter arterial grafting using cryopreserved allograft arteries.

    PubMed

    Eskew, T D; Ollerenshaw, J D; Philpott, J M; Dennis, K; Dawson, P; Sun, Y S; Chitwood, W R; Lust, R M

    1997-01-01

    Intimal hyperplasia (IH) limits the long-term success of veins as arterial grafts. IH occurs in veins partly as an adaptive process to arterial pressure conditions. The authors have previously reported early success with cryopreserved (CP) saphenous veins as aortocoronary bypass grafts, and they have hypothesized that CP arterial segments were already structurally adapted for arterial conditions. Six femoral arterial segments were harvested from three adult donor dogs, and cryopreserved. The segments were thawed and implanted into six recipient dogs, in end-to-end fashion, as interpositional grafts in the femoral artery. A similar length of native femoral artery was removed from the implant site and grafted in the contralateral femoral artery of the same animal to serve as native autograft-matched controls. Grafts were harvested bilaterally after 2 (n = 3) and 4 weeks (n = 3), perfusion fixed (80 mmHg, 15 min), and analyzed histologically. All grafts were patent at harvest, and flows distal to the grafted segments were not significantly different between grafts within an animal either at implant or subsequent harvest. Although CP arterial grafts still showed slight but significant dilation compared with native autograft, the dilation was much less than seen previously with either CP or native venous segments. No evidence of inflammation or IH was seen in CP arterial grafts. The absence of early IH or inflammation suggests that CP small diameter arteries may perform better than many currently available allograft tissues and synthetic prosthetics.

  16. Spasm in Arterial Grafts in Coronary Artery Bypass Grafting Surgery.

    PubMed

    He, Guo-Wei; Taggart, David P

    2016-03-01

    Spasm of arterial grafts in coronary artery bypass grafting surgery is still a clinical problem, and refractory spasm can occasionally be lethal. Perioperative spasm in bypass grafts and coronary arteries has been reported in 0.43% of all coronary artery bypass grafting surgery, but this may be an underestimate. Spasm can develop not only in the internal mammary artery but more frequently in the right gastroepiploic and radial artery. The mechanism of spasm can involve many pathways, particularly those involving regulation of the intracellular calcium concentration. Endothelial dysfunction also plays a role in spasm. Depending on the clinical scenario, the possibility of spasm during and after coronary artery bypass grafting should be confirmed by angiography. If present, immediate intraluminal injection of vasodilators is often effective, although other procedures such as an intraaortic balloon pump or extracorporeal membrane oxygenation may also become necessary to salvage the patient. Prevention of spasm involves many considerations, and the principles are discussed in this review article.

  17. Hormonal modulators of glial ABCA1 and apoE levels.

    PubMed

    Fan, Jianjia; Shimizu, Yoko; Chan, Jeniffer; Wilkinson, Anna; Ito, Ayaka; Tontonoz, Peter; Dullaghan, Edie; Galea, Liisa A M; Pfeifer, Tom; Wellington, Cheryl L

    2013-11-01

    Apolipoprotein E (apoE) is the major lipid carrier in the central nervous system. As apoE plays a major role in the pathogenesis of Alzheimer disease (AD) and also mediates repair pathways after several forms of acute brain injury, modulating the expression, secretion, or function of apoE may provide potential therapeutic approaches for several neurological disorders. Here we show that progesterone and a synthetic progestin, lynestrenol, significantly induce apoE secretion from human CCF-STTG1 astrocytoma cells, whereas estrogens and the progesterone metabolite allopregnanolone have negligible effects. Intriguingly, lynestrenol also increases expression of the cholesterol transporter ABCA1 in CCF-STTG1 astrocytoma cells, primary murine glia, and immortalized murine astrocytes that express human apoE3. The progesterone receptor inhibitor RU486 attenuates the effect of progestins on apoE expression in CCF-STTG1 astrocytoma cells but has no effect on ABCA1 expression in all glial cell models tested, suggesting that the progesterone receptor (PR) may participate in apoE but does not affect ABCA1 regulation. These results suggest that selective reproductive steroid hormones have the potential to influence glial lipid homeostasis through liver X receptor-dependent and progesterone receptor-dependent pathways.

  18. Hormonal modulators of glial ABCA1 and apoE levels[S

    PubMed Central

    Fan, Jianjia; Shimizu, Yoko; Chan, Jeniffer; Wilkinson, Anna; Ito, Ayaka; Tontonoz, Peter; Dullaghan, Edie; Galea, Liisa A. M.; Pfeifer, Tom; Wellington, Cheryl L.

    2013-01-01

    Apolipoprotein E (apoE) is the major lipid carrier in the central nervous system. As apoE plays a major role in the pathogenesis of Alzheimer disease (AD) and also mediates repair pathways after several forms of acute brain injury, modulating the expression, secretion, or function of apoE may provide potential therapeutic approaches for several neurological disorders. Here we show that progesterone and a synthetic progestin, lynestrenol, significantly induce apoE secretion from human CCF-STTG1 astrocytoma cells, whereas estrogens and the progesterone metabolite allopregnanolone have negligible effects. Intriguingly, lynestrenol also increases expression of the cholesterol transporter ABCA1 in CCF-STTG1 astrocytoma cells, primary murine glia, and immortalized murine astrocytes that express human apoE3. The progesterone receptor inhibitor RU486 attenuates the effect of progestins on apoE expression in CCF-STTG1 astrocytoma cells but has no effect on ABCA1 expression in all glial cell models tested, suggesting that the progesterone receptor (PR) may participate in apoE but does not affect ABCA1 regulation.These results suggest that selective reproductive steroid hormones have the potential to influence glial lipid homeostasis through liver X receptor-dependent and progesterone receptor-dependent pathways. PMID:23999864

  19. [Digital subtract arteriographic characteristics of carotid artery, vertebral artery, subclavian artery and renal artery in type 2 diabetic patients with lower extremities peripheral arterial disease].

    PubMed

    Chen, Da-Wei; Lu, Wu-Sheng; Wang, Chun; Jiao, He; Tian, Hao-Ming; Ran, Xing-Wu

    2012-09-01

    To investigate angiographical characteristics of carotid, vertebral, subclavian, and renal arteries in the type 2 diabetic patients with lower extremities peripheral arterial disease (LEPAD). There were 104 type 2 diabetic patients with LEPAD recruited in this study, who received digital subtract arteriography (DSA). Ankle-brachial index (ABI) assessment was also performed in 50 participants. Dependent upon the stenosis degree of vertebral artery, subclavian artery and renal artery measured by DSA, the patients were divided into normal group (stenosis < or = 50%) or pathological group(stenosis > 50% or blocked lesions). The angiographic features of carotid, vertebral, subclavian, and renal arteries were analyzed and the relationship between arterial stenosis and ABI was explored. DSA results of 104 patients showed that the most common lesion in the arteries was plaque. The stenosis degrees of 51%-74% and 75%-99% were most commonly observed in renal artery, with incidence of 22.1% and 5.8%, respectively. Arterial occlusion was most commonly observed in vertebral artery, with incidence of 27.9%. The patients with stenosis or occlusion of arteries had lower ABI (P = 0.000), and the patients with stenosis or occlusion of vertebral and renal arteries also had lower ABI (P = 0.003 and 0.02, respectively), compared with those without stenosis. ABI < 0.9 indicated higher risk of stenosis or occlusion of vertebral and renal arteries (P = 0.008 and 0.047 respectively). Between the patients with subclavian arterial stenosis and those without this artery stenosis, there was no statistical significant difference observed in ABI level. Type 2 diabetic patients with LEPAD can affect multiple arteries, showing plaque formation, multi-segmental stenosis and occlusion of arteries. The patients with ABI < 0.9 have higher risk of multiple arterial stenosis or occlusion lesions.

  20. Impact of ApoE genotypes variations on Toxoplasma patients with dementia.

    PubMed

    Yahya, Raida S; Awad, Soha I; El-Baz, Hatim A; Saudy, Niveen; Abdelsalam, Osama A; Al-Din, Mohamed S Shehab

    2017-05-01

    Toxoplasma deprives host neuron cells from cholesterol and leads to its ability to potentiate dementia. ApoE intermediates neuronal transmission of cholesterol, which is a key constituent for axonal development, redesigning occasions that are important for education and synaptic arrangement, development of memory and repair of neuron. The aim of this work is to investigate the effect of ApoE genotypes on dementia associated with neurodegeneration in latent Toxoplasma gondii in elderly population. This study comprised: 133 patients with dementia (78 were positive for toxoplasma IgG and 55 were negative) and 95 subjects as control group without dementia (30 were positive for toxoplasma IgG and 65 were negative). All of them were subjected to a cognitive assessment, T. gondii seropositivity (ELISA) and determination of ApoE allelic forms (PCR). The ApoE genotype distribution shows that the most predominant genotype is ApoE3/3 and the most widely recognized allele is E3. Both patients and control were further divided into Toxoplasma IgG positive group (n=108) and Toxoplasma IgG negative group (n=120). ApoE4 non carrier, ApoE 2/3 and ApoE 3/3 alleles have highly significant differences (P<0.001) between dementia and non-dementia patients in Toxoplasma infected patients in comparison to non-infected ones. Toxoplasma positive patients have more risk to develop dementia regardless ApoE4 carriage. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Apolipoprotein A-I mimetic peptide reverses impaired arterial healing after injury by reducing oxidative stress.

    PubMed

    Rosenbaum, Michael A; Chaudhuri, Pinaki; Abelson, Benjamin; Cross, Brandy N; Graham, Linda M

    2015-08-01

    Endothelial cell (EC) migration is essential for healing of arterial injuries caused by angioplasty, but a high cholesterol diet inhibits endothelial repair. In vivo studies suggest that apolipoprotein A-I (apoA-I), the major protein constituent of HDL, is essential for normal healing of arterial injuries. ApoA-I mimetics, including 4F, have been designed to mimic the amphipathic portion of the apoA-I molecule. This study was undertaken to determine if 4F improves endothelial migration and healing. A razor scrape assay was used to analyze the effect of 4F on EC migration in vitro. Endothelial healing in vivo was assessed following electrical injury of carotid arteries in mice. Markers of oxidative stress were also examined. Lipid oxidation products inhibited EC migration in vitro, but preincubation with L-4F preserved EC migration. Endothelial healing of carotid arterial injuries in mice on a high cholesterol diet was delayed compared with mice on a chow diet with 27.8% vs. 48.2% healing, respectively, at 5 days. Administration of D-4F improved endothelial healing in mice on a high cholesterol diet to 43.4%. D-4F administration had no effect on lipid levels but decreased markers of oxidation. In vivo, there was a significant inverse correlation between endothelial healing and plasma markers of oxidative stress. These studies suggested that an apoA-I mimetic can improve endothelial healing of arterial injuries by decreasing oxidative stress. Published by Elsevier Ireland Ltd.

  2. C1-esterase inhibitor protects against early vein graft remodeling under arterial blood pressure.

    PubMed

    Krijnen, Paul A J; Kupreishvili, Koba; de Vries, Margreet R; Schepers, Abbey; Stooker, Wim; Vonk, Alexander B A; Eijsman, Leon; Van Hinsbergh, Victor W M; Zeerleder, Sacha; Wouters, Diana; van Ham, Marieke; Quax, Paul H A; Niessen, Hans W M

    2012-01-01

    Arterial pressure induced vein graft injury can result in endothelial loss, accelerated atherosclerosis and vein graft failure. Inflammation, including complement activation, is assumed to play a pivotal role herein. Here, we analyzed the effects of C1-esterase inhibitor (C1inh) on early vein graft remodeling. Human saphenous vein graft segments (n=8) were perfused in vitro with autologous blood either supplemented or not with purified human C1inh at arterial pressure for 6h. The vein segments and perfusion blood were analyzed for cell damage and complement activation. In addition, the effect of purified C1inh on vein graft remodeling was analyzed in vivo in atherosclerotic C57Bl6/ApoE3 Leiden mice, wherein donor caval veins were interpositioned in the common carotid artery. Application of C1inh in the in vitro perfusion model resulted in significantly higher blood levels and significantly more depositions of C1inh in the vein wall. This coincided with a significant reduction in endothelial loss and deposition of C3d and C4d in the vein wall, especially in the circular layer, compared to vein segments perfused without supplemented C1inh. Administration of purified C1inh significantly inhibited vein graft intimal thickening in vivo in atherosclerotic C57Bl6/ApoE3 Leiden mice, wherein donor caval veins were interpositioned in the common carotid artery. C1inh significantly protects against early vein graft remodeling, including loss of endothelium and intimal thickening. These data suggest that it may be worth considering its use in patients undergoing coronary artery bypass grafting. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  3. Arterial versus venous endothelial cells.

    PubMed

    dela Paz, Nathaniel G; D'Amore, Patricia A

    2009-01-01

    Vascular endothelial cells (ECs) form the inner lining of all blood vessels from the largest artery and veins, viz., the aorta and venae cavae, respectively, to the capillaries that connect the arterial and venous systems. Because these two major conducting systems of the cardiovasculature differ functionally, it is not surprising that the physical makeup of arteries and veins, including the ECs that line their lumina, are also distinct. Although few would argue that the local environment contributes to the differences between arteries and veins, recent evidence has shown that the specification of arterial and venous identity is largely genetically determined.

  4. Impact of a multi-nutrient diet on cognition, brain metabolism, hemodynamics, and plasticity in apoE4 carrier and apoE knockout mice.

    PubMed

    Jansen, Diane; Zerbi, Valerio; Janssen, Carola I F; van Rooij, Daan; Zinnhardt, Bastian; Dederen, Pieter J; Wright, Alan J; Broersen, Laus M; Lütjohann, Dieter; Heerschap, Arend; Kiliaan, Amanda J

    2014-09-01

    Lipid metabolism and genetic background together strongly influence the development of both cardiovascular and neurodegenerative diseases like Alzheimer's disease (AD). A non-pharmacological way to prevent the genotype-induced occurrence of these pathologies is given by dietary behavior. In the present study, we tested the effects of long-term consumption of a specific multi-nutrient diet in two models for atherosclerosis and vascular risk factors in AD: the apolipoprotein ε4 (apoE4) and the apoE knockout (apoE ko) mice. This specific multi-nutrient diet was developed to support neuronal membrane synthesis and was expected to contribute to the maintenance of vascular health. At 12 months of age, both genotypes showed behavioral changes compared to control mice and we found increased neurogenesis in apoE ko mice. The specific multi-nutrient diet decreased anxiety-related behavior in the open field, influenced sterol composition in serum and brain tissue, and increased the concentration of omega-3 fatty acids in the brain. Furthermore, we found that wild-type and apoE ko mice fed with this multi-nutrient diet showed locally increased cerebral blood volume and decreased hippocampal glutamate levels. Taken together, these data suggest that a specific dietary intervention has beneficial effects on early pathological consequences of hypercholesterolemia and vascular risk factors for AD.

  5. ApoE4 markedly exacerbates tau-mediated neurodegeneration in a mouse model of tauopathy.

    PubMed

    Shi, Yang; Yamada, Kaoru; Liddelow, Shane Antony; Smith, Scott T; Zhao, Lingzhi; Luo, Wenjie; Tsai, Richard M; Spina, Salvatore; Grinberg, Lea T; Rojas, Julio C; Gallardo, Gilbert; Wang, Kairuo; Roh, Joseph; Robinson, Grace; Finn, Mary Beth; Jiang, Hong; Sullivan, Patrick M; Baufeld, Caroline; Wood, Michael W; Sutphen, Courtney; McCue, Lena; Xiong, Chengjie; Del-Aguila, Jorge L; Morris, John C; Cruchaga, Carlos; Fagan, Anne M; Miller, Bruce L; Boxer, Adam L; Seeley, William W; Butovsky, Oleg; Barres, Ben A; Paul, Steven M; Holtzman, David M

    2017-09-28

    APOE4 is the strongest genetic risk factor for late-onset Alzheimer disease. ApoE4 increases brain amyloid-β pathology relative to other ApoE isoforms. However, whether APOE independently influences tau pathology, the other major proteinopathy of Alzheimer disease and other tauopathies, or tau-mediated neurodegeneration, is not clear. By generating P301S tau transgenic mice on either a human ApoE knock-in (KI) or ApoE knockout (KO) background, here we show that P301S/E4 mice have significantly higher tau levels in the brain and a greater extent of somatodendritic tau redistribution by three months of age compared with P301S/E2, P301S/E3, and P301S/EKO mice. By nine months of age, P301S mice with different ApoE genotypes display distinct phosphorylated tau protein (p-tau) staining patterns. P301S/E4 mice develop markedly more brain atrophy and neuroinflammation than P301S/E2 and P301S/E3 mice, whereas P301S/EKO mice are largely protected from these changes. In vitro, E4-expressing microglia exhibit higher innate immune reactivity after lipopolysaccharide treatment. Co-culturing P301S tau-expressing neurons with E4-expressing mixed glia results in a significantly higher level of tumour-necrosis factor-α (TNF-α) secretion and markedly reduced neuronal viability compared with neuron/E2 and neuron/E3 co-cultures. Neurons co-cultured with EKO glia showed the greatest viability with the lowest level of secreted TNF-α. Treatment of P301S neurons with recombinant ApoE (E2, E3, E4) also leads to some neuronal damage and death compared with the absence of ApoE, with ApoE4 exacerbating the effect. In individuals with a sporadic primary tauopathy, the presence of an ε4 allele is associated with more severe regional neurodegeneration. In individuals who are positive for amyloid-β pathology with symptomatic Alzheimer disease who usually have tau pathology, ε4-carriers demonstrate greater rates of disease progression. Our results demonstrate that ApoE affects tau

  6. ApoE gene delivery inhibits severe hypercholesterolemia in newborn ApoE-KO mice.

    PubMed

    Signori, Emanuela; Rinaldi, Monica; Fioretti, Daniela; Iurescia, Sandra; Seripa, Davide; Perrone, Giuseppe; Norata, Giuseppe Danilo; Catapano, Alberico Luigi; Fazio, Vito Michele

    2007-09-21

    Apolipoprotein E, a key regulator in cholesterol-rich lipoprotein metabolism, is considered a strong candidate for treating hypercholesterolemia and cardiovascular disease. Inherited deficiency of this protein results in type III hyperlipoproteinemia in humans. ApoE-knockout mice, which develop spontaneous hypercholesterolemia, are an excellent model of human atherosclerosis. Here we investigated the therapeutic effects of a plasmid vector encoding human APOE3 sequence intramuscularly injected in hypercholesterolemic newborn mice at the ages of 5 and 14 days. We further explored the possibility of inducing tolerance in newborns when injected early. Our data show that direct i.m. naked DNA injection reduces severe hypercholesterolemia in newborn mice. Moreover, when naked DNA is administrated early, no immune response is generated against the human APOE, allowing repeated administrations. Neonatal therapies are important for the treatment of many genetic childhood diseases where early administration is required to prevent developmental damage. We propose the use of direct i.m. naked gene transfer in newborns to prevent long-term damages arising from hypercholesterolemic conditions.

  7. Attenuated atherosclerotic lesions in apoE-Fcγ chain-deficient hyperlipidemic mouse model is associated with inhibition of Th17 cells and promotion of Tregs1

    PubMed Central

    Pong Ng, Hang; Burris, Ramona L.; Nagarajan, Shanmugam

    2011-01-01

    Though the presence of anti-oxLDL IgG is well documented in clinical and animal studies, the role for FcγRs to the progression of atherosclerosis has not been studied in detail. In the present study, we investigated the role for activating FcγR in the progression of atherosclerosis using apoE-Fcγ chain double knockout (DKO) mice. Relative to apoE KO mice, arterial lesion formation was significantly decreased in apoE-Fcγ chain DKO mice. Bone marrow chimera studies showed reduced lesions in apoE KO mice receiving the bone marrow of apoE-Fcγ chain DKO mice. Compared to apoE KO mice, anti-oxLDL IgG1 (Th2) and IgG2a (Th1), IL-10, and IFN-γ secretion by activated T cells were increased in apoE-Fc γ chain DKO mice. These findings suggest that reduced atherosclerotic lesion in apoE-Fcγ chain DKO mice is not due to Th1/Th2 imbalance. Interestingly, number of Th17 cells and the secretion of IL-17 by activated CD4+ cells were decreased in apoE-Fcγ chain DKO mice. Notably, the number of T-regulatory cells, expression of mRNA, and secretion of TGF-β and IL-10 were increased in apoE-Fcγ chain DKO mice. Furthermore, secretions of IL-6 and STAT-3 phosphorylation essential for Th17 cell genesis were reduced in apoE-Fcγ chain DKO mice. Importantly, decrease in Th17 cells in apoE-Fcγ chain DKO mice was due to reduced IL-6 release by antigen presenting cells of apoE-Fcγ chain DKO mice. Collectively, our data suggest that activating FcγR promotes atherosclerosis by inducing Th17 response in the hyperlipidemic apoE KO mouse model. PMID:22043015

  8. Pediatric nonaortic arterial aneurysms.

    PubMed

    Davis, Frank M; Eliason, Jonathan L; Ganesh, Santhi K; Blatt, Neal B; Stanley, James C; Coleman, Dawn M

    2016-02-01

    Pediatric arterial aneurysms are extremely uncommon. Indications for intervention remain poorly defined and treatments vary. The impetus for this study was to better define the contemporary surgical management of pediatric nonaortic arterial aneurysms. A retrospective analysis was conducted of 41 children with 61 aneurysms who underwent surgical treatment from 1983 to 2015 at the University of Michigan. Arteries affected included: renal (n = 26), femoral (n = 7), iliac (n = 7), superior mesenteric (n = 4), brachial (n = 3), carotid (n = 3), popliteal (n = 3), axillary (n = 2), celiac (n = 2), ulnar (n = 2), common hepatic (n = 1), and temporal (n = 1). Intracranial aneurysms and aortic aneurysms treated during the same time period were not included in this study. Primary outcomes analyzed were postoperative complications, mortality, and freedom from reintervention. The study included 27 boys and 14 girls, with a median age of 9.8 years (range, 2 months-18 years) and a weight of 31.0 kg (range, 3.8-71 kg). Multiple aneurysms existed in 14 children. Obvious factors that contributed to aneurysmal formation included: proximal juxta-aneurysmal stenoses (n = 14), trauma (n = 12), Kawasaki disease (n = 4), Ehlers-Danlos type IV syndrome (n = 1), and infection (n = 1). Preoperative diagnoses were established using arteriography (n = 23), magnetic resonance angiography (n = 6), computed tomographic arteriography (n = 5), or ultrasonography (n = 7), and confirmed during surgery. Indications for surgery included risk of expansion and rupture, potential thrombosis or embolization of aneurysmal thrombus, local soft tissue and nerve compression, and secondary hypertension in the case of renal artery aneurysms. Primary surgical techniques included: aneurysm resection with reanastomsis, reimplantation, or angioplastic closure (n = 16), interposition (n = 10) or bypass grafts (n = 2), ligation (n = 9), plication (n = 8), endovascular occlusion (n = 3), and nephrectomy (n = 4) in

  9. Measuring Beliefs in Centimeters: Private Knowledge Biases Preschoolers&apos; and Adults&apos; Representation of Others&apos; Beliefs

    ERIC Educational Resources Information Center

    Sommerville, Jessica A.; Bernstein, Daniel M.; Meltzoff, Andrew N.

    2013-01-01

    A novel task, using a continuous spatial layout, was created to investigate the degree to which (in centimeters) 3-year-old children&apos;s ("N" = 63), 5-year-old children&apos;s ("N" = 60), and adults&apos; ("N" = 60) own privileged knowledge of the location of an object biased their representation of a…

  10. Measuring Beliefs in Centimeters: Private Knowledge Biases Preschoolers&apos; and Adults&apos; Representation of Others&apos; Beliefs

    ERIC Educational Resources Information Center

    Sommerville, Jessica A.; Bernstein, Daniel M.; Meltzoff, Andrew N.

    2013-01-01

    A novel task, using a continuous spatial layout, was created to investigate the degree to which (in centimeters) 3-year-old children&apos;s ("N" = 63), 5-year-old children&apos;s ("N" = 60), and adults&apos; ("N" = 60) own privileged knowledge of the location of an object biased their representation of a…

  11. Thromboembolism in pulmonary artery sarcoma.

    PubMed

    Farsad, Mohsen; Pernter, Patrizia; Triani, Antonio; Osele, Luzian; Wiedermann, Christian J

    2009-04-01

    Pulmonary artery sarcoma, although rare, must be considered in the differential diagnosis of pulmonary thromboembolism. Clinically and radiologically, it may imitate pulmonary embolism, making diagnosis difficult and delaying treatment. Patients often have no symptom resolution despite therapeutic anticoagulation. Visualization of filling defects within a pulmonary artery on contrast-enhanced CT cannot reliably differentiate between pulmonary thromboembolism and malignant lesions like leiomyosarcoma. FDG PET-CT offers the potential for identification of malignant lesions. The authors report a case with pulmonary artery thromboembolism due to thrombi formed on a pulmonary artery leiomyosarcoma. Integrated FDG PET-CT showed no FDG-uptake along the major part of the filling defect within the right main pulmonary artery suggesting blood clot and increased uptake along the posterior wall of the right main pulmonary artery and the left lower lobar artery suggesting malignancy.

  12. Prenatal Exposure to apoE Deficiency and Postnatal Hypercholesterolemia Are Associated with Altered Cell-Specific Lysine Methyltransferase and Histone Methylation Patterns in the Vasculature

    PubMed Central

    Alkemade, Fanneke E.; van Vliet, Patrick; Henneman, Peter; van Dijk, Ko Willems; Hierck, Beerend P.; van Munsteren, J. Conny; Scheerman, Joyce A.; Goeman, Jelle J.; Havekes, Louis M.; Gittenberger-de Groot, Adriana C.; van den Elsen, Peter J.; DeRuiter, Marco C.

    2010-01-01

    We recently demonstrated that neointima formation of adult heterozygous apolipoprotein E (apoE+/−) offspring from hypercholesterolemic apoE−/− mothers was significantly increased as compared with genetically identical apoE+/− offspring from normocholesterolemic wild-type mothers. Since atherosclerosis is the consequence of a complex microenvironment and local cellular interactions, the effects of in utero programming and type of postnatal diet on epigenetic histone modifications in the vasculature were studied in both groups of offspring. An immunohistochemical approach was used to detect cell-specific histone methylation modifications and expression of accompanying lysine methyltransferases in the carotid arteries. Differences in histone triple-methylation modifications in vascular endothelial and smooth muscle cells revealed that the offspring from apoE−/− mothers had significantly different responses to a high cholesterol diet when compared with offspring from wild-type mothers. Our results suggest that both in utero programming and postnatal hypercholesterolemia affect epigenetic patterning in the vasculature, thereby providing novel insights regarding initiation and progression of vascular disease in adults. PMID:20035052

  13. Liver-specific deletion of the Plpp3 gene alters plasma lipid composition and worsens atherosclerosis in apoE(-/-) mice.

    PubMed

    Busnelli, Marco; Manzini, Stefano; Hilvo, Mika; Parolini, Cinzia; Ganzetti, Giulia S; Dellera, Federica; Ekroos, Kim; Jänis, Minna; Escalante-Alcalde, Diana; Sirtori, Cesare R; Laaksonen, Reijo; Chiesa, Giulia

    2017-03-14

    The PLPP3 gene encodes for a ubiquitous enzyme that dephosphorylates several lipid substrates. Genome-wide association studies identified PLPP3 as a gene that plays a role in coronary artery disease susceptibility. The aim of the study was to investigate the effect of Plpp3 deletion on atherosclerosis development in mice. Because the constitutive deletion of Plpp3 in mice is lethal, conditional Plpp3 hepatocyte-specific null mice were generated by crossing floxed Plpp3 mice with animals expressing Cre recombinase under control of the albumin promoter. The mice were crossed onto the athero-prone apoE(-/-) background to obtain Plpp3(f/f)apoE(-/-)Alb-Cre(+) and Plpp3(f/f)apoE(-/-)Alb-Cre(-) offspring, the latter of which were used as controls. The mice were fed chow or a Western diet for 32 or 12 weeks, respectively. On the Western diet, Alb-Cre(+) mice developed more atherosclerosis than Alb-Cre(-) mice, both at the aortic sinus and aorta. Lipidomic analysis showed that hepatic Plpp3 deletion significantly modified the levels of several plasma lipids involved in atherosclerosis, including lactosylceramides, lysophosphatidic acids, and lysophosphatidylinositols. In conclusion, Plpp3 ablation in mice worsened atherosclerosis development. Lipidomic analysis suggested that the hepatic Plpp3 deletion may promote atherosclerosis by increasing plasma levels of several low-abundant pro-atherogenic lipids, thus providing a molecular basis for the observed results.

  14. Arterial conduits for hepatic artery revascularisation in adult liver transplantation.

    PubMed

    Muralidharan, Vijayaragavan; Imber, Charles; Leelaudomlipi, Surasak; Gunson, Bridget K; Buckels, John A C; Mirza, Darius F; Mayer, A David; Bramhall, Simon R

    2004-05-01

    Arterial complications after orthotopic liver transplantation (OLT), including hepatic artery thrombosis (HAT), are important causes of early graft failure. The use of an arterial conduit is an accepted alternative to the utilisation of native recipient hepatic artery for specific indications. This study aims to determine the efficacy of arterial conduits and the outcome in OLT. We retrospectively reviewed 1,575 cadaveric adult OLTs and identified those in which an arterial conduit was used for hepatic revascularisation. Data on the primary disease, indication for using arterial conduit, type of vascular graft, operative technique and outcome were obtained. Thirty-six (2.3%) patients underwent OLT in which arterial conduits were used for hepatic artery (HA) revascularisation. Six of these were performed on the primary transplant, while the rest (n=30) were performed in patients undergoing re-transplantation, including six who had developed hepatic artery aneurysms. The incidence of arterial conduits was 0.4% (6/1,426 cases) in all primary OLTs and 20.1% (30/149 cases) in all re-transplants. Twenty-nine procedures utilised iliac artery grafts from the same donor as the liver, six used iliac artery grafts from a different donor, and a single patient underwent a polytetrafluoroethylene (PTFE) graft. Two techniques were used: infra-renal aorto-hepatic artery conduit and interposition between the donor and recipient native HAs, or branches of the HAs. The 30-day mortality rate for operations using an arterial conduit was 30.6%. Three conduits thrombosed at 9, 25 and 155 months, respectively, but one liver graft survived without re-transplantation. The arterial conduits had 1- and 5-year patency rates of 88.5% and 80.8%. The 1- and 5-year patient survival rates were 66.7% and 44%. We can thus conclude that an arterial conduit is a viable alternative option for hepatic revascularisation in both primary and re-transplantation. Despite a lower patency rate than that of

  15. Association of apolipoprotein A5 concentration with serum insulin and triglyceride levels and coronary artery disease in Korean men

    USDA-ARS?s Scientific Manuscript database

    OBJECTIVE: Whereas the relation between apolipoprotein A5 (APOA5) gene polymorphisms and triglycerides (TG) levels is well established, the associations between apoA5 concentrations, TG and coronary artery disease (CAD) remain controversial. Therefore, we investigated these relations in the setting ...

  16. The APO*E3-Leiden mouse as an animal model for basal laminar deposit

    PubMed Central

    Kliffen, M.; Lutgens, E.; Daemen, M.; de Muinck, E. D; Mooy, C.; de Jong, P. T V M

    2000-01-01

    AIM—To investigate the APO*E3-Leiden mouse as an animal model for age related maculopathy (ARM) related extracellular deposits.
METHODS—Eyes were obtained from APO*E3-Leiden transgenic mice on a high fat/cholesterol (HFC) diet (n=12) or on a normal mouse chow (n=6), for 9 months. As controls, eyes were collected from APO-E knockout mice on the same diets. From each mouse one eye was processed for microscopic evaluation and immunohistochemistry with a polyclonal antibody directed against human apo-E. Electron microscopy was also performed.
RESULTS—All 12 eyes of the APO*E3-Leiden mice on an HFC diet contained basal laminar deposit (BLD; class 1 to class 3), whereas two of six APO*E3-Leiden mice on normal chow showed BLD class 1. The ultrastructural aspects of this BLD were comparable with those seen in early BLD in humans, and BLD showed immunoreaction with anti-human-apo-E antibodies. No BLD was found in any of the control mice. Drusen were not detected in any of the mice.
CONCLUSION—These results indicate that APO*E3-Leiden mice can be used as animal model for the pathogenesis of BLD, and that a HFC diet enhances the accumulation of this deposit. Furthermore, this study supports the previously suggested involvement of dysfunctional apo-E in the accumulation of extracellular deposits in ARM.

 PMID:11090485

  17. Evaluation of Anomalous Coronary Arteries from the Pulmonary Artery

    PubMed Central

    Guzeltas, Alper; Ozturk, Erkut; Tanidir, Ibrahim Cansaran; Kasar, Taner; Haydin, Sertac

    2017-01-01

    Objective This study evaluated clinical and diagnostic findings, treatment methods, and follow-up of cases of anomalous coronary arteries from the pulmonary artery. Methods The study included all cases diagnosed with anomalous coronary arteries from the pulmonary artery between January 2012 and January 2016. Data from patients’ demographic characteristics, electrocardiography, echocardiography, angiographic findings, operation, intensive care unit stay, and follow-up were evaluated. Results The study included 12 patients (8 male, 4 female), 10 with anomalous left coronary artery from the pulmonary artery (ALCAPA) and 2 with anomalous right coronary artery from the pulmonary artery (ARCAPA). Median age at diagnosis was 4 months (range, 1 month - 10 years old) and median weight was 5.5 kg (range, 3-30 kg). The most common complaints were murmur (n=7) and respiratory distress (n=5). In 4 cases, the initial diagnosis was dilated cardiomyopathy. Electrocardiographs were pathologic in all cases. Echocardiographic examination revealed medium to severe mitral valve regurgitation in 4 cases and reduced (< 40%) ejection fraction in 6 patients. Of the 12 patients, 8 underwent direct implantation of the left coronary artery into the aorta, 2 underwent implantation of the right coronary artery into the aorta, and the remaining 2 underwent a Takeuchi procedure. There were no early mortalities. Median hospital stay was 20 days (range, 5-35 days). Median follow-up duration was 18 months (range, 5-36 months), and no cases required further surgery during follow-up. Conclusions Anomalous coronary arteries from the pulmonary artery can be successfully repaired providing there is early diagnosis and effective, appropriate intensive care unit follow-up. Therefore, coronary artery origins should be evaluated carefully, especially in cases with dilated cardiomyopathies.

  18. Caliber-Persistent Artery

    PubMed Central

    Costa, Sabrina Araújo Pinho; Ruiz, Marcelo Martinson; Kaba, Shajadi Pardo; Florezi, Giovanna Piacenza; Lemos Júnior, Celso Augusto; Witzel, Andréa Lusvarghi

    2015-01-01

    Caliber-persistent artery (CPLA) of the lip is a common vascular anomaly in which a main arterial branch extends to the surface of the mucous tissue with no reduction in its diameter. It usually manifests as pulsatile papule, is easily misdiagnosed, and is observed more frequently among older people, suggesting that its development may involve a degenerative process associated with aging; CPLA is also characterized by the loss of tone of the adjacent supporting connective tissue. Although the diagnosis is clinical, high-resolution Doppler ultrasound is a useful noninvasive tool for evaluating the lesion. This report describes the case of a 58-year-old male patient who complained of a lesion of the lower lip with bleeding and recurrent ulceration. The patient was successfully treated in our hospital after a diagnosis of CPLA and is currently undergoing a clinical outpatient follow-up with no complaints. PMID:26448884

  19. Coronary artery fistulas

    PubMed Central

    Said, S.A.M.; Thiadens, A.A.H.J.; Fieren, M.J.C.H.; Meijboom, E.J.; van der Werf, T.; Bennink, G.B.W.E.

    2002-01-01

    The aetiology of congenital coronary artery fistulas remains a challenging issue. Coronary arteries with an anatomically normal origin may, for obscure reasons, terminate abnormally and communicate with different single or multiple cardiac chambers or great vessels. When this occurs, the angiographic morphological appearance may vary greatly from discrete channels to plexiform network of vessels. Coronary arteriovenous fistulas (CAVFs) have neither specific signs nor pathognomonic symptoms; the spectrum of clinical features varies considerably. The clinical presentation of symptomatic cases can include angina pectoris, myocardial infarction, fatigue, dyspnoea, CHF, SBE, ventricular and supraventricular tachyarrhythmias or even sudden cardiac death. CAVFs may, however, be a coincidental finding during diagnostic coronary angiography (CAG). CAG is considered the gold standard for diagnosing and delineating the morphological anatomy and pathway of CAVFs. There are various tailored therapeutic modalities for the wide spectrum of clinical manifestations of CAVFs, including conservative pharmacological strategy, percutaneous transluminal embolisation and surgical ligation. ImagesFigure 1Figure 2Figure 3Figure 4 PMID:25696067

  20. Segmental arterial mediolysis.

    PubMed

    Chao, Christine P

    2009-09-01

    Segmental arterial mediolysis (SAM) is a nonatherosclerotic, noninflammatory arteriopathy, which is characterized by dissecting aneurysms resulting from lysis of the outer media of the arterial wall. The most common presentation is abdominal pain and hemorrhage in the elderly. Computed tomography (CT) and angiography imaging findings overlap with various vasculitides and include segmental changes of aneurysm and stenosis. A key distinguishing feature is the presence of dissections, the principle morphologic expression of SAM. Differentiation and exclusion of an inflammatory arteritis is crucial in appropriate management, as immunosuppressants generally used for treatment of vasculitis may be ineffective or even worsen the vasculopathy. Although the disease can be self-limiting without treatment or with conservative medical therapy, the acute process carries a 50% mortality rate and may necessitate urgent surgical and/or endovascular therapy. Prompt recognition and diagnosis are therefore of utmost importance in appropriate management of this rare entity.

  1. Renal Artery Embolization

    PubMed Central

    Sauk, Steven; Zuckerman, Darryl A.

    2011-01-01

    Renal artery embolization (RAE) is an effective minimally invasive alternative procedure for the treatment of a variety of conditions. Since the 1970s when RAE was first developed, technical advances and growing experience have expanded the indications to not only include treatment of conditions such as symptomatic hematuria and palliation for metastatic renal cancer, but also preoperative infarction of renal tumors, treatment of angiomyolipomas, vascular malformations, medical renal disease, and complications following renal transplantation. With the drastically improved morbidity associated with this technique in part due to the introduction of more precise embolic agents and smaller delivery catheters, RAE continues to gain popularity for various urologic conditions. The indications and techniques for renal artery embolization are reviewed in the following sections. PMID:23204638

  2. Renal Artery Stent Outcomes

    PubMed Central

    Murphy, Timothy P.; Cooper, Christopher J.; Matsumoto, Alan H.; Cutlip, Donald E.; Pencina, Karol M.; Jamerson, Kenneth; Tuttle, Katherine R.; Shapiro, Joseph I.; D’Agostino, Ralph; Massaro, Joseph; Henrich, William; Dworkin, Lance D.

    2016-01-01

    BACKGROUND Multiple randomized clinical trials comparing renal artery stent placement plus medical therapy with medical therapy alone have not shown any benefit of stent placement. However, debate continues whether patients with extreme pressure gradients, stenosis severity, or baseline blood pressure benefit from stent revascularization. OBJECTIVES The study sought to test the hypothesis that pressure gradients, stenosis severity, and/or baseline blood pressure affects outcomes after renal artery stent placement. METHODS Using data from 947 patients with a history of hypertension or chronic kidney disease from the largest randomized trial of renal artery stent placement, the CORAL (Cardiovascular Outcomes in Renal Atherosclerotic Lesions) study, we performed exploratory analyses to determine if subsets of patients experienced better outcomes after stent placement than the overall cohort. We examined baseline stenosis severity, systolic blood pressure, and translesion pressure gradient (peak systolic and mean) and performed interaction tests and Cox proportional hazards analyses for the occurrence of the primary endpoint through all follow-up, to examine the effect of these variables on outcomes by treatment group. RESULTS There were no statistically significant differences in outcomes based on the examined variables nor were there any consistent nonsignificant trends. CONCLUSIONS Based on data from the CORAL randomized trial, there is no evidence of a significant treatment effect of the renal artery stent procedure compared with medical therapy alone based on stenosis severity, level of systolic blood pressure elevation, or according to the magnitude of the transstenotic pressure gradient. (Benefits of Medical Therapy Plus Stenting for Renal Atherosclerotic Lesions [CORAL]; NCT00081731) PMID:26653621

  3. Coronary artery disease.

    PubMed

    Hanson, Michele A; Fareed, Mohammad Tariq; Argenio, Sandra L; Agunwamba, Akochi O; Hanson, Teresa R

    2013-03-01

    Coronary artery disease (CAD) is the leading cause of death worldwide. There are several presenting clinical syndromes, including sudden cardiac death. Risk factor analysis can help the primary care provider identify patients who may need more extensive evaluation or treatment. Treatment may be medical or surgical and depends on the individual patient's comorbidities and preferences. In the future, growth of new blood vessels or cardiac cells may aid in the treatment of CAD. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Endothelial Protective Monocyte Patrolling in Large Arteries Intensified by Western Diet and Atherosclerosis.

    PubMed

    Quintar, Amado; McArdle, Sara; Wolf, Dennis; Marki, Alex; Ehinger, Erik; Vassallo, Melanie; Miller, Jacqueline F; Mikulski, Zbigniew; Ley, Klaus; Buscher, Konrad

    2017-03-16

    Rationale: Non-classical mouse monocyte (CX3CR1(high), Ly-6C(low)) patrolling along the vessels of the microcirculation is critical for endothelial homeostasis and inflammation. Due to technical challenges it is currently not established how patrolling occurs in large arteries. Objective: This study was undertaken to elucidate the molecular, migratory and functional phenotype of patrolling monocytes in the high shear and pulsatile environment of large arteries in healthy, hyperlipidemic and atherosclerotic conditions. Methods and Results: Applying a new method for stable, long-term two-photon intravital microscopy of unrestrained large arteries in live CX3CR1-GFP mice, we show that non-classical monocytes patrol inside healthy carotid arteries at a velocity of 36 μm/min, three times faster than in microvessels. The tracks are less straight but lead preferentially downstream. The number of patrolling monocytes is increased 9-fold by feeding wildtype mice a western diet or by applying topical TLR7/8 agonists. A similar increase is seen in CX3CR1(+/GFP)/apoE(-/-) mice on chow diet, with a further 2-3-fold increase on western diet (22-fold over healthy). In plaque conditions, monocytes are readily captured onto the endothelium from free flow. Stable patrolling is unaffected in CX3CR1-deficient mice and involves the contribution of LFA-1 and α4 integrins. The endothelial damage in atherosclerotic carotid arteries was assessed by electron microscopy and correlates with the number of intraluminal patrollers. Abolishing patrolling monocytes in Nr4a1(-/-) apoE(-/-) mice leads to pronounced endothelial apoptosis. Conclusions: Arterial patrolling is a prominent new feature of non-classical monocytes with unique molecular and kinetic properties. It is highly upregulated in hyperlipidemia and atherosclerosis in an CX3CR1-independent fashion, and plays a potential role in endothelial protection.

  5. Peripheral arterial disease

    PubMed Central

    2011-01-01

    Introduction Up to 20% of adults aged over 55 years have detectable peripheral arterial disease of the legs, but this may cause symptoms of intermittent claudication in only a small proportion of affected people. The main risk factors are smoking and diabetes mellitus, but other risk factors for cardiovascular disease are also associated with peripheral arterial disease. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for people with chronic peripheral arterial disease? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2010. Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review. We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 70 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review, we present information relating to the effectiveness and safety of the following interventions: antiplatelet agents, bypass surgery, cilostazol, exercise, pentoxifylline, percutaneous transluminal angioplasty (PTA), prostaglandins, smoking cessation, and statins. PMID:21477401

  6. Peripheral arterial disease

    PubMed Central

    2009-01-01

    Introduction Up to 20% of adults aged over 55 years have detectable peripheral arterial disease of the legs, but this may cause symptoms of intermittent claudication in only a small proportion of affected people. The main risk factors are smoking and diabetes mellitus, but other risk factors for cardiovascular disease are also associated with peripheral arterial disease. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for people with chronic peripheral arterial disease? We searched: Medline, Embase, The Cochrane Library, and other important databases up to March 2009. (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 59 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: antiplatelet agents; bypass surgery; cilostazol; exercise; pentoxifylline; percutaneous transluminal angioplasty (PTA); prostaglandins; smoking cessation; and statins. PMID:19454099

  7. LATENT LIFE OF ARTERIES.

    PubMed

    Carrel, A

    1910-07-23

    When a segment of artery, killed by heat, formalin or glycerin is transplanted, it undergoes a rapid degeneration. Its muscle fibers disappear while the tissue of the host reacts by building a new wall of connective tissue. When the transplanted vessel has been preserved in a condition of latent life, no degeneration of the wall occurs, or the wall undergoes only partial degeneration. The muscle fibers can keep their normal appearance, even for a long time after the operation. It is, therefore, demonstrated that arteries can be preserved outside of the body in a condition of unmanifested actual life. The best method of preservation consists of placing the vessels, immersed in vaselin, in an ice box, the temperature of which is slightly above the freezing point. From a surgical standpoint, the transplantation of preserved vessels can be used with some safety. When the arteries were kept in defibrinated blood or vaselin and in cold storage, the proportion of positive results was 75 and 80 per cent., and this can probably be increased.

  8. [Innominate artery war injury].

    PubMed

    Ilic, Radoje; Kronja, Goran; Markovic, Zoran; Tisma, Svetislav

    2005-04-01

    A case is reported of successfully surgically treated explosive war injury to the innominate artery. A 26-year-old soldier was injured in combat by a fragment of mortar shell. In the field hospital, the wound gauze packing was applied, followed by orotracheal intubation and thoracic drainage. The soldier was admitted to MMA six hours later. Physical examination, on admission, revealed huge swelling of the neck, the absence of pulse in the right arm and the right common carotid artery. Chest x-ray revealed hemopneumothorax of the right side and the foreign metal body in the projection of the right sternoclavicular joint. Due to the suspicion of large vessel injury, a median sternotomy was immediately performed. Surgery revealed disrupted bifurcation of the right innominate artery, so the ligation was performed. Aortography was performed postoperatively, followed by the reconstruction of innominate bifurcation with synthetic grafts. Control aortography showed good graft patency, and the patient was discharged from the hospital in good general condition with palpable pulses and mild anisocoria as a sole neurological sequela. A rare and life-threatening injury was successfully managed, mainly due to the rational treatment carried out in the field hospital that helped the injured to survive and arrive to the institution capable of performing the most sophisticated diagnostic and therapeutic procedures.

  9. Segmental arterial mediolysis.

    PubMed

    Pillai, Anil Kumar; Iqbal, Shams I; Liu, Raymond W; Rachamreddy, Niranjan; Kalva, Sanjeeva P

    2014-06-01

    Segmental arterial mediolysis (SAM) is an uncommon, nonatherosclerotic, noninflammatory, large- to medium-sized arteriopathy first described in 1976. It is characterized histologically by vacuolization and lysis of the outer arterial media leading to dissecting aneurysms and vessel rupture presenting clinically with self-limiting abdominal pain or catastrophic hemorrhages in the abdomen. Patients of all ages are affected with a greater incidence at the fifth and sixth decades. There is a slight male predominance. Imaging findings overlap with inflammatory vasculitis, collagen vascular disease, and fibromuscular dysplasia. The presence of segmental dissections involving the celiac, mesenteric, and/or renal arteries is the key distinguishing features of SAM. Inflammatory markers, genetic tests for collagen vascular disorders, and hypercoagulable studies are negative. Anti-inflammatory agents and immunosuppressants are not effective. A mortality rate of 50 % has been attributed to the acute presentation with aneurysmal rupture necessitating urgent surgical or endovascular treatments; in the absence of the acute presentation, SAM is a self-limiting disease and is treated conservatively. There are no established guidelines on medical therapy, although optimal control of blood pressure is considered the main cornerstone of medical therapy. The long-term prognosis is not known.

  10. ABCA1/ApoE/HDL Pathway Mediates GW3965-Induced Neurorestoration After Stroke.

    PubMed

    Cui, Xu; Chopp, Michael; Zhang, Zhenggang; Li, Rongwen; Zacharek, Alex; Landschoot-Ward, Julie; Venkat, Poornima; Chen, Jieli

    2017-02-01

    ATP-binding cassette transporter A1 (ABCA1) is a major reverse cholesterol transporter and plays critical role in the formation of brain high-density lipoprotein (HDL) cholesterol. Apolipoprotein E (ApoE) is the most abundant apolipoprotein and transports cholesterol into cells in brain. ABCA1 and ApoE are upregulated by liver-X receptors. Activation of liver-X receptors has neurorestorative benefit for stroke. The current study investigates whether ABCA1/ApoE/HDL pathway mediates GW3965, a synthetic dual liver-X receptor agonist, induced neurorestoration after stroke. Middle-aged male specific brain ABCA1-deficient (ABCA1(-B/-B)) and floxed-control (ABCA1(fl/fl)) mice were subjected to distal middle-cerebral artery occlusion (dMCAo) and gavaged with saline or GW3965 (10 mg/kg) or intracerebral infusion of artificial cerebrospinal fluid or human plasma HDL3 in ABCA1(-B/-B) stroke mice, starting 24 hours after dMCAo and daily until euthanization 14 days after dMCAo. No differences in the blood level of total cholesterol and triglyceride and lesion volume were found among the groups. Compared with ABCA1(fl/fl) ischemic mice, ABCA1(-B/-B) ischemic mice exhibited impairment functional outcome and decreased ABCA1/ApoE expression and decreased gray/white matter densities in the ischemic boundary zone 14 days after dMCAo. GW3965 treatment of ABCA1(fl/fl) ischemic mice led to increased brain ABCA1/ApoE expression, concomitantly to increased blood HDL, gray/white matter densities and oligodendrocyte progenitor cell numbers in the ischemic boundary zone, as well as improved functional outcome 14 days after dMCAo. GW3965 treatment had negligible beneficial effects in ABCA1(-B/-B) ischemic mice. However, intracerebral infusion of human plasma HDL3 significantly attenuated ABCA1(-B/-B)-induced deficits. In vitro, GW3965 treatment (5 μM) increased ABCA1/synaptophysin level and neurite/axonal outgrowth in primary cortical neurons derived from ABCA1(fl/fl) embryos, but not in

  11. Epilepsy: neuroinflammation, neurodegeneration, and APOE genotype.

    PubMed

    Aboud, Orwa; Mrak, Robert E; Boop, Frederick A; Griffin, W Sue T

    2013-07-29

    Precocious development of Alzheimer-type neuropathological changes in epilepsy patients, especially in APOE ϵ4,4 carriers is well known, but not the ways in which other APOE allelic combinations influence this outcome. Frozen and paraffin-embedded tissue samples resected from superior temporal lobes of 92 patients undergoing temporal lobectomies as a treatment for medication-resistant temporal lobe epilepsy were used in this study. To determine if epilepsy-related changes reflect those in another neurological condition, analogous tissue samples harvested from 10 autopsy-verified Alzheimer brains, and from 10 neurologically and neuropathologically normal control patients were analyzed using immunofluorescence histochemistry, western immunoblot, and real-time PCR to determine genotype effects on neuronal number and size, neuronal and glial expressions of amyloid β (Aβ) precursor protein (βAPP), Aβ, apolipoprotein E (ApoE), S100B, interleukin-1α and β, and α and β secretases; and on markers of neuronal stress, including DNA/RNA damage and caspase 3 expression. Allelic combinations of APOE influenced each epilepsy-related neuronal and glial response measured as well as neuropathological change. APOE ϵ3,3 conferred greatest neuronal resilience denoted as greatest production of the acute phase proteins and low neuronal stress as assessed by DNA/RNA damage and caspase-3 expression. Among patients having an APOE ϵ2 allele, none had Aβ plaques; their neuronal sizes, like those with APOE ϵ3,3 genotype were larger than those with other genotypes. APOE ϵ4,4 conferred the weakest neuronal resilience in epilepsy as well as in Alzheimer patients, but there were no APOE genotype-dependent differences in these parameters in neurologically normal patients. Our findings provide evidence that the strength of the neuronal stress response is more related to patient APOE genotype than to either the etiology of the stress or to the age of the patient, suggesting that APOE

  12. HSP90 inhibition suppresses inflammatory response and reduces carotid atherosclerotic plaque formation in ApoE mice.

    PubMed

    Mu, Hongmei; Wang, Liyong; Zhao, Lei

    2017-04-01

    Emerging evidences indicate that heat-shock protein 90 (HSP90) is associated with atherogenesis. However, the effect of HSP90 on plaque stability is largely unknown. In this study, we explored the role of HSP90 in plaque development and its regulatory mechanisms on vasculature. Heat-shock protein90-overexpression lentivirus (Lenti-HSP90) was used to transfect apoE(-/-) mice after constrictive collars were planted at the right common carotid arteries. As a result, HSP90 gene overexpression led to reduction in en face plaque area and increase in unstable plaque with heavier accumulation of lipids. Concomitantly, more macrophages, less smooth muscle cells, and collagen were generated, suggesting aggravated inflammation. However, inhibition of HSP90 with 17-AAG, a HSP90-inhibitor, induced opposing effects. Moreover, HSP90 upregulated plaque MMP-8, which might be the underlying mechanism of the change in plaque vulnerability index. Further, the translocation of NF-κB was promoted by HSP90, while inhibition of NF-κB significantly reduced MMP-8 production, which is upregulated by HSP90. These findings suggested that HSP90 governs plaque development and vulnerability, as well as inflammation, at least in part via MMP-8 and NF-κB signaling pathways. © 2016 John Wiley & Sons Ltd.

  13. A novel CCR2 antagonist inhibits atherogenesis in apoE deficient mice by achieving high receptor occupancy.

    PubMed

    Bot, Ilze; Ortiz Zacarías, Natalia V; de Witte, Wilhelmus E A; de Vries, Henk; van Santbrink, Peter J; van der Velden, Daniël; Kröner, Mara J; van der Berg, Dirk-Jan; Stamos, Dean; de Lange, Elizabeth C M; Kuiper, Johan; IJzerman, Adriaan P; Heitman, Laura H

    2017-12-01

    CC Chemokine Receptor 2 (CCR2) and its endogenous ligand CCL2 are involved in a number of diseases, including atherosclerosis. Several CCR2 antagonists have been developed as potential therapeutic agents, however their in vivo clinical efficacy was limited. In this report, we aimed to determine whether 15a, an antagonist with a long residence time on the human CCR2, is effective in inhibiting the development of atherosclerosis in a mouse disease model. First, radioligand binding assays were performed to determine affinity and binding kinetics of 15a on murine CCR2. To assess the in vivo efficacy, western-type diet fed apoE(-/-) mice were treated daily with 15a or vehicle as control. Treatment with 15a reduced the amount of circulating CCR2(+) monocytes and the size of the atherosclerotic plaques in both the carotid artery and the aortic root. We then showed that the long pharmacokinetic half-life of 15a combined with the high drug concentrations ensured prolonged CCR2 occupancy. These data render 15a a promising compound for drug development and confirms high receptor occupancy as a key parameter when targeting chemokine receptors.

  14. ApoL1 levels in high density lipoprotein and cardiovascular event presentation in patients with familial hypercholesterolemia[S

    PubMed Central

    Cubedo, Judit; Padró, Teresa; Alonso, Rodrigo; Mata, Pedro; Badimon, Lina

    2016-01-01

    HDL composition rather than HDL-cholesterol (HDL-C) levels seems to be a key determinant of HDL-induced atheroprotection. Heterozygous familial hypercholesterolemia (FH) patients, with lifelong exposure to high LDL levels, show a high prevalence of premature coronary artery disease. We hypothesized that HDL of FH patients might have a modified protein composition and investigated the proteomic signature of HDL obtained from FH patients and their unaffected relatives. HDLs were characterized by 2D electrophoresis/MS in 10 families from the SAFEHEART cohort (3 individuals/family: 2 with genetic FH diagnosis and 1 non-FH relative) clinically characterized and treated as per guidelines. FH patients had lower apoA-I levels and a differential HDL distribution profile of apoL1 and apoA-IV. ELISA validation revealed decreased apoL1 serum levels in FH patients. ApoL1 levels were able to predict presentation of an ischemic cardiac event, and apoL1/HDL-C ratio was associated with the survival rate after the event. FH patients who died because of a fatal cardiac event had lower apoL1 and LCAT content in HDL3 an average of 3.5 years before the event than those who survived. Changes in HDL protein composition could affect patients’ prognosis. The proteomic profile of apoL1 is modified in HDLs of high cardiovascular risk patients, and apoL1 plasma levels are significantly lower in serum and in HDL3 of patients that will suffer an adverse cardiac event within 3 years. PMID:27112635

  15. ApoL1 levels in high density lipoprotein and cardiovascular event presentation in patients with familial hypercholesterolemia.

    PubMed

    Cubedo, Judit; Padró, Teresa; Alonso, Rodrigo; Mata, Pedro; Badimon, Lina

    2016-06-01

    HDL composition rather than HDL-cholesterol (HDL-C) levels seems to be a key determinant of HDL-induced atheroprotection. Heterozygous familial hypercholesterolemia (FH) patients, with lifelong exposure to high LDL levels, show a high prevalence of premature coronary artery disease. We hypothesized that HDL of FH patients might have a modified protein composition and investigated the proteomic signature of HDL obtained from FH patients and their unaffected relatives. HDLs were characterized by 2D electrophoresis/MS in 10 families from the SAFEHEART cohort (3 individuals/family: 2 with genetic FH diagnosis and 1 non-FH relative) clinically characterized and treated as per guidelines. FH patients had lower apoA-I levels and a differential HDL distribution profile of apoL1 and apoA-IV. ELISA validation revealed decreased apoL1 serum levels in FH patients. ApoL1 levels were able to predict presentation of an ischemic cardiac event, and apoL1/HDL-C ratio was associated with the survival rate after the event. FH patients who died because of a fatal cardiac event had lower apoL1 and LCAT content in HDL3 an average of 3.5 years before the event than those who survived. Changes in HDL protein composition could affect patients' prognosis. The proteomic profile of apoL1 is modified in HDLs of high cardiovascular risk patients, and apoL1 plasma levels are significantly lower in serum and in HDL3 of patients that will suffer an adverse cardiac event within 3 years. Copyright © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.

  16. Map3k8 Modulates Monocyte State and Atherogenesis in ApoE-/- Mice.

    PubMed

    Sanz-Garcia, Carlos; Sánchez, Ángela; Contreras-Jurado, Constanza; Cales, Carmela; Barranquero, Cristina; Muñoz, Marta; Merino, Ramón; Escudero, Paula; Sanz, Maria-Jesús; Osada, Jesús; Aranda, Ana; Alemany, Susana

    2017-02-01

    Map3k8 (Cot/Tpl2) activates the MKK1/2-ERK1/2, MAPK pathway downstream from interleukin-1R, tumor necrosis factor-αR, NOD-2R (nucleotide-binding oligomerization domain-like 2R), adiponectinR, and Toll-like receptors. Map3k8 plays a key role in innate and adaptive immunity and influences inflammatory processes by modulating the functions of different cell types. However, its role in atherogenesis remains unknown. In this study, we analyzed the role of this kinase in this pathology. We show here that Map3k8 deficiency results in smaller numbers of Ly6C(high)CD11c(low) and Ly6C(low)CD11c(high) monocytes in ApoE(-)(/-) mice fed a high-fat diet (HFD). Map3k8(-/-)ApoE(-/-) monocytes displayed high rates of apoptosis and reduced amounts of Nr4a1, a transcription factor known to modulate apoptosis in Ly6C(low)CD11c(high) monocytes. Map3k8(-/-)ApoE(-/-) splenocytes and macrophages showed irregular patterns of cytokine and chemokine expression. Map3k8 deficiency altered cell adhesion and migration in vivo and decreased CCR2 expression, a determinant chemokine receptor for monocyte mobilization, on circulating Ly6C(high)CD11c(low) monocytes. Map3k8(-/-)ApoE(-/-) mice fed an HFD showed decreased cellular infiltration in the atherosclerotic plaque, with low lipid content. Lesions had similar size after Map3k8(+/+)ApoE(-/-) bone marrow transplant into Map3k8(-/-)ApoE(-/-) and Map3k8(+/+)ApoE(-/-) mice fed an HFD, whereas smaller plaques were observed after the transplantation of bone marrow lacking both ApoE and Map3k8. Map3k8 decreases apoptosis of monocytes and enhances CCR2 expression on Ly6C(high)CD11c(low) monocytes of ApoE(-/-) mice fed an HFD. These findings explain the smaller aortic lesions in ApoE(-/-) mice with Map3k8(-/-)ApoE(-/-) bone marrow cells fed an HFD, supporting further studies of Map3k8 as an antiatherosclerotic target. © 2016 American Heart Association, Inc.

  17. Why Was Kelvin&apos;s Estimate of the Earth&apos;s Age Wrong?

    ERIC Educational Resources Information Center

    Lovatt, Ian; Syed, M. Qasim

    2014-01-01

    This is a companion to our previous paper in which we give a published example, based primarily on Perry&apos;s work, of a graph of ln "y" versus "t" when "y" is an exponential function of "t". This work led us to the idea that Lord Kelvin&apos;s (William Thomson&apos;s) estimate of the Earth&apos;s age was…

  18. Why Was Kelvin&apos;s Estimate of the Earth&apos;s Age Wrong?

    ERIC Educational Resources Information Center

    Lovatt, Ian; Syed, M. Qasim

    2014-01-01

    This is a companion to our previous paper in which we give a published example, based primarily on Perry&apos;s work, of a graph of ln "y" versus "t" when "y" is an exponential function of "t". This work led us to the idea that Lord Kelvin&apos;s (William Thomson&apos;s) estimate of the Earth&apos;s age was…

  19. Capillary isotachophoresis study of lipoprotein network sensitive to apolipoprotein E phenotype. 1. ApoE distribution between lipoproteins.

    PubMed

    Dergunov, Alexander D; Ponthieux, Anne; Mel'kin, Maxim V; Lambert, Daniel; Visvikis-Siest, Sophie; Siest, Gerard

    2009-05-01

    Sixteen patients differing widely in plasma triglyceride content were divided into three groups by their apolipoprotein E (apoE) phenotype-E33 homozygotes, E23, and E34 heterozygotes. The plasma lipid and apoE distribution between individual lipoproteins was followed by capillary isotachophoresis (CITP) of plasma samples pre-stained with lipid fluorescent probe NBD-C6-ceramide and by fluorescein-labeled apoE, respectively. Among 12 peaks visualized by ceramide staining, an individual peak with very low density lipoproteins (VLDL) was identified. The VLDL cholesterol and apoE content determined by CITP directly in whole plasma were significantly related to their content as determined by conventional analysis with isolated VLDL. The ceramide distribution among lipoprotein pools was insensitive to apoE phenotype (49-53 : 7-11 : 39-43% for HDL, VLDL, and IDL/LDL, respectively) while the preferential binding of apoE to VLDL was observed in E34 patients compared to E33 (62 : 19 : 20 vs. 70 : 9 : 22%). In a study of apoE/F displacement from lipoproteins at plasma titration by apoC-III in vitro, apoE was found to bind more tightly to VLDL from E34 compared to E33 patients as evidenced by both the increased non-displaceable apoE pool, the increased VLDL sorbtion capacity for apoE, and the decreased displacement parameter in a "container" model of lipoprotein binding. Two different types of apoE package in a whole lipoprotein profile were observed. ApoE structure in a particular lipoprotein may underlie the phenotype-sensitive apoE distribution and apoC-III interference in hypertriglyceridemia.

  20. Teaching Laura Kipnis&apos;s "Love&apos;s Labors" in "Ways of Reading"

    ERIC Educational Resources Information Center

    Fike, Matthew A.

    2013-01-01

    This essay describes a method of teaching a very challenging anthology piece: Laura Kipnis&apos;s "Love&apos;s Labors" (chapter 1 of her 2003 "Against Love: A Polemic"). The method, although designed for a critical thinking course, should also provide resources for those who teach Kipnis&apos;s work in writing courses. Using…

  1. The Impact of Adolescents&apos; Dyslexia on Parents&apos; and Their Own Educational Expectations

    ERIC Educational Resources Information Center

    Rimkute, Laura; Torppa, Minna; Eklund, Kenneth; Nurmi, Jari-Erik; Lyytinen, Heikki

    2014-01-01

    The present study examined the role that adolescents&apos; dyslexia plays in their educational expectations, as well as their parents&apos; expectations concerning their offspring&apos;s future education. To investigate this, 170 adolescents were asked to report their educational expectations on two occasions while they were still attending…

  2. Individual Differences in Children&apos;s and Parents&apos; Generic Language

    ERIC Educational Resources Information Center

    Gelman, Susan A.; Ware, Elizabeth A.; Kleinberg, Felicia; Manczak, Erika M.; Stilwell, Sarah M.

    2014-01-01

    Generics ("&apos;Dogs&apos; bark") convey important information about categories and facilitate children&apos;s learning. Two studies with parents and their 2- or 4-year-old children (N = 104 dyads) examined whether individual differences in generic language use are as follows: (a) stable over time, contexts, and domains, and (b) linked…

  3. SIRT1 reduces endothelial activation without affecting vascular function in ApoE-/- mice.

    PubMed

    Stein, Sokrates; Schäfer, Nicola; Breitenstein, Alexander; Besler, Christian; Winnik, Stephan; Lohmann, Christine; Heinrich, Kathrin; Brokopp, Chad E; Handschin, Christoph; Landmesser, Ulf; Tanner, Felix C; Lüscher, Thomas F; Matter, Christian M

    2010-06-01

    Excessive production of reactive oxygen species (ROS) contributes to progression of atherosclerosis, at least in part by causing endothelial dysfunction and inflammatory activation. The class III histone deacetylase SIRT1 has been implicated in extension of lifespan. In the vasculature,SIRT1 gain-of-function using SIRT1 overexpression or activation has been shown to improve endothelial function in mice and rats via stimulation of endothelial nitric oxide (NO) synthase (eNOS). However, the effects of SIRT1 loss-of-function on the endothelium in atherosclerosis remain to be characterized. Thus, we have investigated the endothelial effects of decreased endogenous SIRT1 in hypercholesterolemic ApoE-/- mice. We observed no difference in endothelial relaxation and eNOS (Ser1177) phosphorylation between 20-week old male atherosclerotic ApoE-/- SIRT1+/- and ApoE-/- SIRT1+/+ mice. However, SIRT1 prevented endothelial superoxide production, inhibited NF-kappaB signaling, and diminished expression of adhesion molecules. Treatment of young hypercholesterolemic ApoE-/- SIRT1+/- mice with lipopolysaccharide to boost NF-kappaB signaling led to a more pronounced endothelial expression of ICAM-1 and VCAM-1 as compared to ApoE-/- SIRT1+/+ mice. In conclusion, endogenous SIRT1 diminishes endothelial activation in ApoE-/- mice, but does not affect endothelium-dependent vasodilatation.

  4. ApoE: the role of conserved residues in defining function.

    PubMed

    Frieden, Carl

    2015-01-01

    The amino acid sequences of apolipoprotein E (apoE) from 63 different mammalian species have been downloaded from the protein database. The sequences were compared to human apoE4 to determine conserved and non-conserved sequences of amino acids. ApoE4 is the major risk factor for the development of late onset Alzheimer's disease while apoE3, which differs from apoE4 by a single amino acid change at position 112, poses little or no risk for the development of this disease. Thus, the two proteins appear to be structurally and functionally different. Seven highly conserved regions, representing approximately 47 amino acids (of 299) have been found. These regions are distributed throughout the protein and reflect ligand binding sites as well as regions proposed to be involved in the propagation of the cysteine-arginine change at position 112 to distant regions of the protein in the N- and C-terminal domains. Highly non-conserved regions are at the N- and C-terminal ends of the apoE protein. © 2014 The Protein Society.

  5. James Baldwin&apos;s "Everybody&apos;s Protest Novel": Educating Our Responses to Racism

    ERIC Educational Resources Information Center

    Frank, Jeff

    2014-01-01

    The aim of this article is to establish--and explore--James Baldwin&apos;s significance for educational theory. Through a close reading of "Everybody&apos;s Protest Novel", I show that Baldwin&apos;s thinking is an important (if unrecognized) precursor to the work of Stanley Cavell and Cora Diamond, and is relevant to a number of…

  6. Calculus Students&apos; and Instructors&apos; Conceptualizations of Slope: A Comparison across Academic Levels

    ERIC Educational Resources Information Center

    Nagle, Courtney; Moore-Russo, Deborah; Viglietti, Janine; Martin, Kristi

    2013-01-01

    This study considers tertiary calculus students&apos; and instructors&apos; conceptualizations of slope. Qualitative techniques were employed to classify responses to 5 items using conceptualizations of slope identified across various research settings. Students&apos; responses suggest that they rely on procedurally based conceptualizations of…

  7. James Baldwin&apos;s "Everybody&apos;s Protest Novel": Educating Our Responses to Racism

    ERIC Educational Resources Information Center

    Frank, Jeff

    2014-01-01

    The aim of this article is to establish--and explore--James Baldwin&apos;s significance for educational theory. Through a close reading of "Everybody&apos;s Protest Novel", I show that Baldwin&apos;s thinking is an important (if unrecognized) precursor to the work of Stanley Cavell and Cora Diamond, and is relevant to a number of…

  8. Calculus Students&apos; and Instructors&apos; Conceptualizations of Slope: A Comparison across Academic Levels

    ERIC Educational Resources Information Center

    Nagle, Courtney; Moore-Russo, Deborah; Viglietti, Janine; Martin, Kristi

    2013-01-01

    This study considers tertiary calculus students&apos; and instructors&apos; conceptualizations of slope. Qualitative techniques were employed to classify responses to 5 items using conceptualizations of slope identified across various research settings. Students&apos; responses suggest that they rely on procedurally based conceptualizations of…

  9. Critical Pedagogy&apos;s Problem with Changing Teachers&apos; Dispositions towards Critical Teaching

    ERIC Educational Resources Information Center

    Neumann, Jacob W.

    2013-01-01

    Increasing teachers&apos; dispositions towards critical teaching is a fundamental goal for critical pedagogy. Because critical educational change cannot occur without teachers&apos; "buy-in," developing teachers&apos; inclination to implement critical teaching into their classrooms is a prerequisite for any successful critical pedagogy…

  10. SIRT1 reduces endothelial activation without affecting vascular function in ApoE-/- mice

    PubMed Central

    Stein, Sokrates; Schäfer, Nicola; Breitenstein, Alexander; Besler, Christian; Winnik, Stephan; Lohmann, Christine; Heinrich, Kathrin; Brokopp, Chad E.; Handschin, Christoph; Landmesser, Ulf; Tanner, Felix C.; Lüscher, Thomas F.; Matter, Christian M.

    2010-01-01

    Excessive production of reactive oxygen species (ROS) contributes to progression of atherosclerosis, at least in part by causing endothelial dysfunction and inflammatory activation. The class III histone deacetylase SIRT1 has been implicated in extension of lifespan. In the vasculature,SIRT1 gain-of-function using SIRT1 overexpression or activation has been shown to improve endothelial function in mice and rats via stimulation of endothelial nitric oxide (NO) synthase (eNOS). However, the effects of SIRT1 loss-of-function on the endothelium in atherosclerosis remain to be characterized. Thus, we have investigated the endothelial effects of decreased endogenous SIRT1 in hypercholesterolemic ApoE-/- mice. We observed no difference in endothelial relaxation and eNOS (Ser1177) phosphorylation between 20-week old male atherosclerotic ApoE-/- SIRT1+/- and ApoE-/- SIRT1+/+ mice. However, SIRT1 prevented endothelial superoxide production, inhibited NF-κB signaling, and diminished expression of adhesion molecules. Treatment of young hypercholesterolemic ApoE-/- SIRT1+/- mice with lipopolysaccharide to boost NF-κB signaling led to a more pronounced endothelial expression of ICAM-1 and VCAM-1 as compared to ApoE-/- SIRT1+/+ mice. In conclusion, endogenous SIRT1 diminishes endothelial activation in ApoE-/- mice, but does not affect endothelium-dependent vasodilatation. PMID:20606253

  11. The Impact of Adolescents&apos; Dyslexia on Parents&apos; and Their Own Educational Expectations

    ERIC Educational Resources Information Center

    Rimkute, Laura; Torppa, Minna; Eklund, Kenneth; Nurmi, Jari-Erik; Lyytinen, Heikki

    2014-01-01

    The present study examined the role that adolescents&apos; dyslexia plays in their educational expectations, as well as their parents&apos; expectations concerning their offspring&apos;s future education. To investigate this, 170 adolescents were asked to report their educational expectations on two occasions while they were still attending…

  12. On the Relations between Parents&apos; Ideals and Children&apos;s Autonomy

    ERIC Educational Resources Information Center

    de Ruyter, Doret J.; Schinkel, Anders

    2013-01-01

    In this article Doret J. de Ruyter and Anders Schinkel argue that parents&apos; ideals can enhance children&apos;s autonomy, but that they may also have a detrimental effect on the development of children&apos;s autonomy. After describing the concept of "ideals" and elucidating a systems theoretical conception of autonomy, de Ruyter and…

  13. On the Relations between Parents&apos; Ideals and Children&apos;s Autonomy

    ERIC Educational Resources Information Center

    de Ruyter, Doret J.; Schinkel, Anders

    2013-01-01

    In this article Doret J. de Ruyter and Anders Schinkel argue that parents&apos; ideals can enhance children&apos;s autonomy, but that they may also have a detrimental effect on the development of children&apos;s autonomy. After describing the concept of "ideals" and elucidating a systems theoretical conception of autonomy, de Ruyter and…

  14. The association between serum ApoE genetic polymorphism and serum lipid level in hemodialysis patients.

    PubMed

    Zhang, Yong; Zhang, Linlin; Cao, Bo

    2015-02-01

    Growing evidence indicates that apolipoprotein E (ApoE) is one of the most important candidate genes for influencing the development of hemodialysis (HD). This study aims to detect the potential association between serum ApoE genetic polymorphism and serum lipid level in HD. A total of 485 subjects were enrolled in this case-control study. The created restriction site polymerase chain reaction and DNA sequencing methods were used to investigate ApoE c.109G>A genetic polymorphism. Our data suggested that there were significant differences in the distribution of allelic and genotypic frequencies between HD patients and healthy controls. The levels of total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, ApoA-I, ApoB, ApoE, and lipoprotein (a) for genotype AA were different from genotype GG in HD patients and healthy controls. Our findings support that the ApoE c.109G>A genetic polymorphism might influence the development of HD and could be a risk factor for assessing HD.

  15. Developing Preschool Teachers&apos; Knowledge of Students&apos; Number Conceptions

    ERIC Educational Resources Information Center

    Tsamir, Pessia; Tirosh, Dina; Levenson, Esther; Tabach, Michal; Barkai, Ruthi

    2014-01-01

    This article describes a study that investigates preschool teachers&apos; knowledge of their young students&apos; number conceptions and the teachers&apos; related self-efficacy beliefs. It also presents and illustrates elements of a professional development program designed explicitly to promote this knowledge among preschool teachers. Results…

  16. Gene-Environment Interaction of ApoE Genotype and Combat Exposure on PTSD

    PubMed Central

    Lyons, Michael J.; Genderson, Margo; Grant, Michael D.; Logue, Mark; Zink, Tyler; McKenzie, Ruth; Franz, Carol E.; Panizzon, Matthew; Lohr, James B.; Jerskey, Beth; Kremen, William S.

    2015-01-01

    Factors determining who develops PTSD following trauma are not well understood. The €4 allele of the apolipoprotein E (apoE) gene is associated with dementia and unfavorable outcome following brain insult. PTSD is also associated with dementia. Given evidence that psychological trauma adversely affects the brain, we hypothesized that the apoE genotype moderates effects of psychological trauma on PTSD pathogenesis. To investigate the moderation of the relationship between PTSD symptoms and combat exposure, we used 172 participants with combat trauma sustained during the Vietnam War. PTSD symptoms were the dependent variable and number of combat experiences, apoE genotype, and the combat experiences × apoE genotype interaction were predictors. We also examined the outcome of a diagnosis of PTSD (n = 39) versus no PTSD diagnosis (n = 131). The combat × apoE genotype interaction was significant for both PTSD symptoms (P = .014) and PTSD diagnosis (P = .009). ApoE genotype moderates the relationship between combat exposure and PTSD symptoms. Although the pathophysiology of PTSD is not well understood, the €4 allele is related to reduced resilience of the brain to insult. Our results are consistent with the €4 allele influencing the effects of psychological trauma on the brain, thereby affecting the risk of PTSD. PMID:24132908

  17. Residual strains in conduit arteries.

    PubMed

    Rachev, A; Greenwald, S E

    2003-05-01

    Residual strains and stresses are those that exist in a body when all external loads are removed. Residual strains in arteries can be characterized by the opening angle of the sector-like cross-section which arises when an unloaded ring segment is radially cut. A review of experimental methods for measuring residual strains and the main results about the variation of the opening angle with arterial localization, age, smooth muscle activity, mechanical environment and certain vascular pathologies are presented and discussed. It is shown that, in addition to their well-established ability to homogenize the stress field in the arterial wall, residual strains make arteries more compliant and thereby improve their performance as elastic reservoirs and ensure more effective local control of the arterial lumen by smooth muscle cells. Finally, evidence that, in some cases, residual strains remain in arteries even after they have been cut radially is discussed.

  18. Noninvasive assessment of arterial compliance of human cerebral arteries with short inversion time arterial spin labeling

    PubMed Central

    Warnert, Esther AH; Murphy, Kevin; Hall, Judith E; Wise, Richard G

    2015-01-01

    A noninvasive method of assessing cerebral arterial compliance (AC) is introduced in which arterial spin labeling (ASL) is used to measure changes in arterial blood volume (aBV) occurring within the cardiac cycle. Short inversion time pulsed ASL (PASL) was performed in healthy volunteers with inversion times ranging from 250 to 850 ms. A model of the arterial input function was used to obtain the cerebral aBV. Results indicate that aBV depends on the cardiac phase of the arteries in the imaging volume. Cerebral AC, estimated from aBV and brachial blood pressure measured noninvasively in systole and diastole, was assessed in the flow territories of the basal cerebral arteries originating from the circle of Willis: right and left middle cerebral arteries (RMCA and LMCA), right and left posterior cerebral arteries (RPCA and LPCA), and the anterior cerebral artery (ACA). Group average AC values calculated for the RMCA, LMCA, ACA, RPCA, and LPCA were 0.56%±0.2%, 0.50%±0.3%, 0.4%±0.2%, 1.1%±0.5%, and 1.1%±0.3% per mm Hg, respectively. The current experiment has shown the feasibility of measuring AC of cerebral arteries with short inversion time PASL. PMID:25515216

  19. Pulmonary Arterial Hypertension and Neonatal Arterial Switch Surgery for Correction of Transposition of the Great Arteries.

    PubMed

    Domínguez Manzano, Paula; Mendoza Soto, Alberto; Román Barba, Violeta; Moreno Galdó, Antonio; Galindo Izquierdo, Alberto

    2016-09-01

    There are few reports of the appearance of pulmonary arterial hypertension following arterial switch surgery in the neonatal period to correct transposition of the great arteries. We assessed the frequency and clinical pattern of this complication in our series of patients. Our database was reviewed to select patients with transposition of the great arteries corrected by neonatal arterial switch at our hospital and who developed pulmonary hypertension over time. We identified 2 (1.3%) patients with transposition of the great arteries successfully repaired in the first week of life who later experienced pulmonary arterial hypertension. The first patient was a 7-year-old girl diagnosed with severe pulmonary hypertension at age 8 months who did not respond to medical treatment and required lung transplantation. The anatomic pathology findings were consistent with severe pulmonary arterial hypertension. The second patient was a 24-month-old boy diagnosed with severe pulmonary hypertension at age 13 months who did not respond to medical therapy. Pulmonary hypertension is a rare but very severe complication that should be investigated in all patients with transposition of the great arteries who have undergone neonatal arterial switch, in order to start early aggressive therapy for affected patients, given the poor therapeutic response and poor prognosis involved. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  20. [Pathology of coronary arterial calcification].

    PubMed

    Yutani, Chikao

    2007-03-01

    Calcification is an invariable component of advanced coronary artery atherosclerosis. Recent study showed that genetic variations such as matrix inhibitory proteins, polymorphisms for tumor necrosis factor, and inflammatory cytokines may influence coronary artery calcification. And also there have been numerous studies on screening patients for coronary artery disease using electron beam computed tomography, but details of mechanism on calcification have still been unclear. An example of coronary calcification in diabetic patients disclosed that its diffuse distribution might be metabolic on calcification mechanism.

  1. Arterial spasm during renal angioplasty

    SciTech Connect

    Beinart, C.; Sos, T.A.; Saddekni, S.; Weiner, M.A.; Sniderman, K.W.

    1983-10-01

    Spasm of the renal arteries during transluminal angioplasty is a well-documented phenomenon with serious potential sequelae, particularly in young patients with fibromusclar dysplasia. The authors report their experience in 98 cases (105 arteries). Tolazoline, lidocaine, nitrates (or calcium blockers, if available), and heparin should be administered either directly into the renal artery or systemically prior to angioplasty to decrease the incidence and severity of spasm.

  2. Apolipoprotein E (ApoE) polymorphism is related to differences in potential fertility in women: a case of antagonistic pleiotropy?

    PubMed

    Jasienska, Grazyna; Ellison, Peter T; Galbarczyk, Andrzej; Jasienski, Michal; Kalemba-Drozdz, Malgorzata; Kapiszewska, Maria; Nenko, Ilona; Thune, Inger; Ziomkiewicz, Anna

    2015-03-22

    The alleles that are detrimental to health, especially in older age, are thought to persist in populations because they also confer some benefits for individuals (through antagonistic pleiotropy). The ApoE4 allele at the ApoE locus, encoding apolipoprotein E (ApoE), significantly increases risk of poor health, and yet it is present in many populations at relatively high frequencies. Why has it not been replaced by natural selection with the health-beneficial ApoE3 allele? ApoE is a major supplier of cholesterol precursor for the production of ovarian oestrogen and progesterone, thus ApoE has been suggested as the potential candidate gene that may cause variation in reproductive performance. Our results support this hypothesis showing that in 117 regularly menstruating women those with genotypes with at least one ApoE4 allele had significantly higher levels of mean luteal progesterone (144.21 pmol l(-1)) than women with genotypes without ApoE4 (120.49 pmol l(-1)), which indicates higher potential fertility. The hormonal profiles were based on daily data for entire menstrual cycles. We suggest that the finding of higher progesterone in women with ApoE4 allele could provide first strong evidence for an evolutionary mechanism of maintaining the ancestral and health-worsening ApoE4 allele in human populations.

  3. Apolipoprotein E (ApoE) polymorphism is related to differences in potential fertility in women: a case of antagonistic pleiotropy?

    PubMed Central

    Jasienska, Grazyna; Ellison, Peter T.; Galbarczyk, Andrzej; Jasienski, Michal; Kalemba-Drozdz, Malgorzata; Kapiszewska, Maria; Nenko, Ilona; Thune, Inger; Ziomkiewicz, Anna

    2015-01-01

    The alleles that are detrimental to health, especially in older age, are thought to persist in populations because they also confer some benefits for individuals (through antagonistic pleiotropy). The ApoE4 allele at the ApoE locus, encoding apolipoprotein E (ApoE), significantly increases risk of poor health, and yet it is present in many populations at relatively high frequencies. Why has it not been replaced by natural selection with the health-beneficial ApoE3 allele? ApoE is a major supplier of cholesterol precursor for the production of ovarian oestrogen and progesterone, thus ApoE has been suggested as the potential candidate gene that may cause variation in reproductive performance. Our results support this hypothesis showing that in 117 regularly menstruating women those with genotypes with at least one ApoE4 allele had significantly higher levels of mean luteal progesterone (144.21 pmol l−1) than women with genotypes without ApoE4 (120.49 pmol l−1), which indicates higher potential fertility. The hormonal profiles were based on daily data for entire menstrual cycles. We suggest that the finding of higher progesterone in women with ApoE4 allele could provide first strong evidence for an evolutionary mechanism of maintaining the ancestral and health-worsening ApoE4 allele in human populations. PMID:25673673

  4. Plasma proteomic analysis of stable coronary artery disease indicates impairment of reverse cholesterol pathway

    PubMed Central

    Basak, Trayambak; Tanwar, Vinay Singh; Bhardwaj, Gourav; Bhardwaj, Nitin; Ahmad, Shadab; Garg, Gaurav; V, Sreenivas; Karthikeyan, Ganesan; Seth, Sandeep; Sengupta, Shantanu

    2016-01-01

    Coronary artery disease (CAD) is one of the largest causes of death worldwide yet the traditional risk factors, although useful in identifying people at high risk, lack the desired predictive accuracy. Techniques like quantitative plasma proteomics holds immense potential to identify newer markers and this study (conducted in three phases) was aimed to identify differentially expressed proteins in stable CAD patients. In the first (discovery) phase, plasma from CAD cases (angiographically proven) and controls were subjected to iTRAQ based proteomic analysis. Proteins found to be differentially expressed were then validated in the second and third (verification and validation) phases in larger number of (n = 546) samples. After multivariate logistic regression adjusting for confounding factors (age, diet, etc.), four proteins involved in the reverse cholesterol pathway (Apo A1, ApoA4, Apo C1 and albumin) along with diabetes and hypertension were found to be significantly associated with CAD and could account for approximately 88% of the cases as revealed by ROC analysis. The maximum odds ratio was found to be 6.70 for albumin (p < 0.0001), followed by Apo AI (5.07, p < 0.0001), Apo CI (4.03, p = 0.001), and Apo AIV (2.63, p = 0.003). Down-regulation of apolipoproteins and albumin implicates the impairment of reverse cholesterol pathway in CAD. PMID:27350024

  5. Plasma proteomic analysis of stable coronary artery disease indicates impairment of reverse cholesterol pathway.

    PubMed

    Basak, Trayambak; Tanwar, Vinay Singh; Bhardwaj, Gourav; Bhardwaj, Nitin; Ahmad, Shadab; Garg, Gaurav; V, Sreenivas; Karthikeyan, Ganesan; Seth, Sandeep; Sengupta, Shantanu

    2016-06-28

    Coronary artery disease (CAD) is one of the largest causes of death worldwide yet the traditional risk factors, although useful in identifying people at high risk, lack the desired predictive accuracy. Techniques like quantitative plasma proteomics holds immense potential to identify newer markers and this study (conducted in three phases) was aimed to identify differentially expressed proteins in stable CAD patients. In the first (discovery) phase, plasma from CAD cases (angiographically proven) and controls were subjected to iTRAQ based proteomic analysis. Proteins found to be differentially expressed were then validated in the second and third (verification and validation) phases in larger number of (n = 546) samples. After multivariate logistic regression adjusting for confounding factors (age, diet, etc.), four proteins involved in the reverse cholesterol pathway (Apo A1, ApoA4, Apo C1 and albumin) along with diabetes and hypertension were found to be significantly associated with CAD and could account for approximately 88% of the cases as revealed by ROC analysis. The maximum odds ratio was found to be 6.70 for albumin (p < 0.0001), followed by Apo AI (5.07, p < 0.0001), Apo CI (4.03, p = 0.001), and Apo AIV (2.63, p = 0.003). Down-regulation of apolipoproteins and albumin implicates the impairment of reverse cholesterol pathway in CAD.

  6. Radiative transport in large arteries

    PubMed Central

    Ruh, Dominic; Subramanian, Sivaraman; Theodor, Michael; Zappe, Hans; Seifert, Andreas

    2013-01-01

    A refined model for the photon energy distribution in a living artery is established by solving the radiative transfer equation in a cylindrical geometry, using the Monte Carlo method. Combining this model with the most recent experimental values for the optical properties of flowing blood and the biomechanics of a blood-filled artery subject to a pulsatile pressure, we find that the optical intensity transmitted through large arteries decreases linearly with increasing arterial distension. This finding provides a solid theoretical foundation for measuring photoplethysmograms. PMID:24466476

  7. Utilization of laser arterial angioplasty.

    PubMed

    Steg, P G; Ménasché, P

    1989-01-01

    Arterial angioplasty with continuous wave laser radiation is now available in clinical practice and, coupled with balloon catheter angioplasty, has been successful in the treatment of lower limb arterial disease. It appears premature to apply laser angioplasty to coronary artery lesions because of the high incidence of severe complications observed in clinical trials. Experimental studies suggest that some of these complications are related to thermal injury induced by continuous wave laser energy and that they could be minimized by the utilization of pulsed laser sources. Because of recent technologic advances, pulsed laser sources coupled with flexible fiberoptic devices will soon be available for peripheral arterial angioplasty in clinical practice.

  8. Intracranial Arteries - Anatomy and Collaterals.

    PubMed

    Liebeskind, David S; Caplan, Louis R

    2016-01-01

    Anatomy, physiology, and pathophysiology are inextricably linked in patients with intracranial atherosclerosis. Knowledge of abnormal or pathological conditions such as intracranial atherosclerosis stems from detailed recognition of the normal pattern of vascular anatomy. The vascular anatomy of the intracranial arteries, both at the level of the vessel wall and as a larger structure or conduit, is a reflection of physiology over time, from in utero stages through adult life. The unique characteristics of arteries at the base of the brain may help our understanding of atherosclerotic lesions that tend to afflict specific arterial segments. Although much of the knowledge regarding intracranial arteries originates from pathology and angiography series over several centuries, evolving noninvasive techniques have rapidly expanded our perspective. As each imaging modality provides a depiction that combines anatomy and flow physiology, it is important to interpret each image with a solid understanding of typical arterial anatomy and corresponding collateral routes. Compensatory collateral perfusion and downstream flow status have recently emerged as pivotal variables in the clinical management of patients with atherosclerosis. Ongoing studies that illustrate the anatomy and pathophysiology of these proximal arterial segments across modalities will help refine our knowledge of the interplay between vascular anatomy and cerebral blood flow. Future studies may help elucidate pivotal arterial factors far beyond the degree of stenosis, examining downstream influences on cerebral perfusion, artery-to-artery thromboembolic potential, amenability to endovascular therapies and stent conformation, and the propensity for restenosis due to biophysical factors. © 2016 S. Karger AG, Basel.

  9. Arterial pulse wave pressure transducer

    NASA Technical Reports Server (NTRS)

    Kim, C.; Gorelick, D.; Chen, W. (Inventor)

    1974-01-01

    An arterial pulse wave pressure transducer is introduced. The transducer is comprised of a fluid filled cavity having a flexible membrane disposed over the cavity and adapted to be placed on the skin over an artery. An arterial pulse wave creates pressure pulses in the fluid which are transduced, by a pressure sensitive transistor in direct contact with the fluid, into an electric signal. The electrical signal is representative of the pulse waves and can be recorded so as to monitor changes in the elasticity of the arterial walls.

  10. Arterial stiffness in diabetes mellitus.

    PubMed

    Prenner, Stuart B; Chirinos, Julio A

    2015-02-01

    Arterial stiffness is an age-related process that is a shared consequence of numerous diseases including diabetes mellitus (DM), and is an independent predictor of mortality both in this population and in the general population. While much has been published about arterial stiffness in patients with DM, a thorough review of the current literature is lacking. Using a systematic literature search strategy, we aimed to summarize our current understanding related to arterial stiffness in DM. We review key studies demonstrating that, among patients with established DM, arterial stiffness is closely related to the progression of complications of DM, including nephropathy, retinopathy, and neuropathy. It is also becoming clear that arterial stiffness can be increased even in pre-diabetic populations with impaired glucose tolerance, and in those with the metabolic syndrome (METS), well before the onset of overt DM. Some data suggests that arterial stiffness can predict the onset of DM. However, future work is needed to further clarify whether large artery stiffness and the pulsatile hemodynamic changes that accompany it are involved in the pathogenesis of DM, and whether interventions targeting arterial stiffness are associated with improved clinical outcomes in DM. We also review of the potential mechanisms of arterial stiffness in DM, with particular emphasis on the role of advanced glycation endproducts (AGEs) and nitric oxide dysregulation, and address potential future directions for research.

  11. Arterial Abnormalities Leading to Tinnitus.

    PubMed

    Miller, Timothy R; Serulle, Yafell; Gandhi, Dheeraj

    2016-05-01

    Tinnitus is a common symptom that usually originates in the middle ear. Vascular causes of pulsatile tinnitus are categorized by the location of the source of the noise within the cerebral-cervical vasculature: arterial, arteriovenous, and venous. Arterial stenosis secondary to atherosclerotic disease or dissection, arterial anatomic variants at the skull base, and vascular skull base tumors are some of the more common causes of arterial and arteriovenous pulsatile tinnitus. Noninvasive imaging is indicated to evaluate for possible causes of pulsatile tinnitus, and should be followed by catheter angiography if there is a strong clinical suspicion for a dural arteriovenous fistula.

  12. Idiopathic dilatation of pulmonary artery

    PubMed Central

    Sharma, Rahul Kumar; Talwar, Deepak; Gupta, Sameer K; Bansal, Shobhit

    2016-01-01

    Idiopathic dilatation of pulmonary arteries (IDPA) is a rare abnormality of pulmonary arteries, the reported incidence in literature being as low as 0.007% in autopsy samples. With the improvement in diagnostic modalities, antemortem diagnosis of IDPA has been increasingly established by excluding diseases that induce pulmonary arterial enlargement. Here, we present a rare case of idiopathic dilatation of the pulmonary artery admitted with shortness of breath where IDPA was diagnosed as an incidental finding using computed tomography pulmonary angiography and cardiac catheterization. PMID:27891002

  13. Arterial wall thermography.

    PubMed

    Diamantopoulos, Leonidas

    2003-06-01

    An atherosclerotic plaque is considered vulnerable when it is at higher risk of inducing acute cardiac events. The early detection and follow-up of the vulnerable plaque are crucial to prevent these events from happening. To date there are no proven techniques to detect such a plaque. Arterial wall thermography, tracing the heat signature of the activated macrophages, is a new and promising method in this direction. However, the difficulties of applying such a method in vivo should not be neglected. Current science proposes several potential thermographic methods. They can be generally categorized as noninvasive and invasive. Magnetic resonance thermometry (MRT) is the most important noninvasive method. It is novel, accurate, and reproducible, but is unfortunately hampered by resolution limitations due to the size and motion of the target vessels. The "infrared" and the "contact-sensor" are the most important invasive thermographic methods. Mainly due to the difficulties of infrared radiation in penetrating the flowing blood, the contact thermographic methods seem to be the most feasible at present. The superiority of thermal mapping of the arterial wall versus the localized temperature measurements is clear. The use of multiple thermal sensors arranged around the vessel's circumference and the application of motorized catheter pullback, not only ensure a large area of coverage, but also enable us to build thermal maps and vascular thermoanatomical reconstructions by using modern computer technology. It is expected that arterial thermography will undoubtedly initiate debate, mainly concerning the most appropriate therapy for the vulnerable plaque. Data collection and correct interpretation are expected to lead us into making wise decisions.

  14. Right hepatic artery aneurysm.

    PubMed

    Bernal, Astrid Del Pilar Ardila; Loures, Paulo; Calle, Juan Cristóbal Ospina; Cunha, Beatriz; Córdoba, Juan Camilo

    2016-01-01

    We report a case of an aneurysm of the right hepatic artery and its multidisciplinary management by general surgery, endoscopy and radiology services. Being a case of extremely low incidence, it is important to show its diagnostic and therapeutic approach. RESUMO Relatamos um caso de aneurisma da artéria hepática direita conduzido de forma multidisciplinar pelos Serviços de Cirurgia Geral, Endoscopia e Radiologia. Em se tratando de caso de incidência baixíssima, é importante mostrar o enfoque diagnóstico e terapêutico usado em seu manejo.

  15. Artery of Percheron Infarction

    PubMed Central

    Vinod, K.V.; Kaaviya, R.; Arpita, Bhaumik

    2016-01-01

    Artery of Percheron (AOP) occlusion is a rare cause of ischemic stroke characterized by bilateral paramedian thalamic infarcts, with or without mesencephalic infarction. Clinically it presents with mental state disturbances, hypersomnolence, aphasia/dysarthria, amnesia and ocular movement disorders, including vertical gaze palsy. Here, we report a case of cardioembolic AOP infarction in a 37-year-old woman with rheumatic mitral valvular stenosis. This case is being reported to highlight the interesting clinical and neuroimaging features of this rare condition, and the differential diagnosis of AOP infarction on imaging have been discussed. PMID:27647964

  16. Exploring Students&apos; Patterns of Reasoning

    ERIC Educational Resources Information Center

    Matloob Haghanikar, Mojgan

    2012-01-01

    As part of a collaborative study of the science preparation of elementary school teachers, we investigated the quality of students&apos; reasoning and explored the relationship between sophistication of reasoning and the degree to which the courses were considered inquiry oriented. To probe students&apos; reasoning, we developed open-ended written…

  17. Teaching the Writer&apos;s Craft

    ERIC Educational Resources Information Center

    Kittle, Penny

    2014-01-01

    "Writing is a core skill for living, not just for school," writes high school English teacher Penny Kittle. Although it&apos;s important to teach students the conventions of grammar, punctuation, and sentence structure, teachers don&apos;t need to approach this task "like scolds, red pens in hand, stamping out sin, and punishing…

  18. Testing Bernoulli&apos;s Law

    ERIC Educational Resources Information Center

    Ivanov, Dragia; Nikolov, Stefan; Petrova, Hristina

    2014-01-01

    In this paper we present three different methods for testing Bernoulli&apos;s law that are different from the standard "tube with varying cross-section." They are all applicable to high-school level physics education, with varying levels of theoretical and experimental complexity, depending on students&apos; skills, and may even be…

  19. Teaching the Writer&apos;s Craft

    ERIC Educational Resources Information Center

    Kittle, Penny

    2014-01-01

    "Writing is a core skill for living, not just for school," writes high school English teacher Penny Kittle. Although it&apos;s important to teach students the conventions of grammar, punctuation, and sentence structure, teachers don&apos;t need to approach this task "like scolds, red pens in hand, stamping out sin, and punishing…

  20. Testing Bernoulli&apos;s Law

    ERIC Educational Resources Information Center

    Ivanov, Dragia; Nikolov, Stefan; Petrova, Hristina

    2014-01-01

    In this paper we present three different methods for testing Bernoulli&apos;s law that are different from the standard "tube with varying cross-section." They are all applicable to high-school level physics education, with varying levels of theoretical and experimental complexity, depending on students&apos; skills, and may even be…

  1. Life Psychosocial Stresses and Coronary Artery Disease

    PubMed Central

    Bagheri, Babak; Meshkini, Fatemeh; Dinarvand, Kolsoum; Alikhani, Zahra; Haysom, Mal; Rasouli, Mehdi

    2016-01-01

    Background: It is hypothesized that the impacts of life events accumulate and can trigger and promote atherosclerosis in susceptible individuals. In the current study, the correlation of total life stressors during 1 year was investigated relative to coronary artery disease (CAD). Methods: The study population consisted of 148 males and 152 females aged 35–76 years. The subjects were classified as CAD cases and controls according to the results of coronary angiography. The severity of CAD was scored on the basis of the number and the extent of lesions at coronary arteries. The stressful events of life were assessed using Holmes-Rahe Questionnaire and was presented as total psychological stress scores per year (TPSS). Results: The frequency of cigarette smoking, diabetes mellitus, and hypertension was more prevalent in CAD cases than control subjects. The levels of TPSS were increased in patients with CAD compared to the controls (160.3 ± 71.3 vs. 139.8 ± 66.5, P = 0.020). TPSS was also associated positively with the levels of uric acid, erythrocytes counts, erythrocyte sedimentation rate, aspirin consumption, and negatively with high-density lipoprotein-cholesterol and apo-AI. In logistic regression analysis, TPSS correlated with the occurrence of CAD by the odds ratio of 1.773 (1.073–2.930), P = 0.025, but the association was weakened after adjustment for classical risk factors, especially hypertension. TPSS exhibited significant association with the severity of CAD [F (3,274) = 2.6, P = 0.051]. Conclusions: The results suggest that TPSS are associated with the occurrence and severity of CAD significantly, but the association is not independent. PMID:27833720

  2. Influence of metformin on mitochondrial subproteome in the brain of apoE knockout mice.

    PubMed

    Suski, Maciej; Olszanecki, Rafał; Chmura, Łukasz; Stachowicz, Aneta; Madej, Józef; Okoń, Krzysztof; Adamek, Dariusz; Korbut, Ryszard

    2016-02-05

    Neurodegenerative diseases are the set of progressive, age-related brain disorders, characterized by an excessive accumulation of mutant proteins in the certain regions of the brain. Such changes, collectively identified as causal factors of neurodegeneration, all impact mitochondria, imminently leading to their dysfunction. These observations predestine mitochondria as an attractive drug target for counteracting degenerative brain damage. The aim of this study was to use a differential proteomic approach to comprehensively assess the changes in mitochondrial protein expression in the brain of apoE-knockout mice (apoE(-/-)) and to investigate the influence of prolonged treatment with metformin - an indirect activator of AMP-activated protein kinase (AMPK) on the brain mitoproteome in apoE(-/-) mice. The quantitative assessment of the brain mitoproteome in apoE(-/-) revealed the changes in 10 proteins expression as compared to healthy C57BL/6J mice and 25 proteins expression in metformin-treated apoE(-/-) mice. Identified proteins mainly included apoptosis regulators, metabolic enzymes and structural proteins. In summary, our study provided proteomic characteristics suggesting the decrease of antioxidant defense and structural disturbances in the brain mitochondria of apoE(-/-) mice as compared to healthy controls. In this setting, the use of metformin changed the expression of several proteins primarily involved in metabolic processes, the regulation of apoptosis and the structural maintenance of mitochondria, what could potentially restore their native functionalities.

  3. Inferior pancreaticoduodenal artery aneurysm associated with common hepatic artery occlusion.

    PubMed

    Bracale, G; Porcellini, M; Bernardo, B; Selvetella, L; Renda, A

    1996-12-01

    A unique case of true inferior pancreaticoduodenal artery aneurysm (IPDA) associated with occlusion of common hepatic artery is reported. Radiological and MRI findings are described. Because of high risk of visceral ischemia that contraindicated a percutaneous transluminal embolization, a successful tangential resection of aneurysm was performed.

  4. Double right coronary artery or split right coronary artery?

    PubMed

    Chen, Ying-Fu; Chien, Tsu-Ming; Chen, Chih-Wei; Lin, Ching-Cheng; Lee, Chee-Siong

    2012-02-09

    The prevalence of congenital anomalies of the coronary arteries (CAAs) is reported to be approximately 0.2-1.4% of the general population. Of them, The double right coronary artery (RCA) is one of the rarest coronary anomalies. Nonetheless, there is no consensus of the definition of a double RCA until now. Several concepts have been proposed in order to define what is and is not a double RCA. So far, it was been reported 37 times and in 44 cases after a comprehensive literature search through the PubMed database, using the keywords "double right coronary artery," "duplicated right coronary artery," "dual right coronary artery" and "split right coronary artery." Most of the published articles (28 of 37 articles) used the name "double right coronary artery." Nevertheless, some investigators contended that a split RCA is anatomically the same anomaly as the improperly named "double right coronary artery". The debate between those who favor "double RCA" and those who favor "split RCA" indicate the need for a consensus regarding the nomenclature as well diagnostic criteria of such coronary anomalies. It is the time we need to reach a consensus of the nomenclature of this congenital coronary anomaly. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  5. Coronary artery ectasia in Egyptian patients with coronary artery disease.

    PubMed Central

    Waly, H M; Elayda, M A; Lee, V V; el-Said, G; Reul, G J; Hall, R J

    1997-01-01

    We conducted a retrospective study of 45 Egyptian patients with coronary artery ectasia who underwent coronary bypass grafting at our institution between 1980 and 1995. We examined the anatomic distribution and type of coronary ectasia and its association with coronary risk factors in these patients, and evaluated the severity of their coronary artery disease. We compared these findings with those from a group of 230 Egyptian patients who did not have coronary ectasia. These patients also underwent coronary artery bypass grafting between 1980 and 1995 at our institution. Obesity was present in 60% of the patients who had coronary artery ectasia, compared with 42% of patients who did not have ectasia (P < 0.01). Coronary artery ectasia was not related to any coronary risk factors other than obesity. However, patients who had ectasia did have a higher rate of triple-vessel coronary artery disease than did patients without ectasia (82% vs 67%, P < 0.05). Of the coronary vessels affected by ectasia, 43% were left anterior descending arteries. Diffuse disease was noted in 84% of all ectatic segments. We conclude that in this patient population, 2 conditions had a positive correlation with coronary ectasia: obesity and the severity of coronary artery disease. Images PMID:9456489

  6. Gene-Environment Interplay in the Link of Friends&apos; and Nonfriends&apos; Behaviors with Children&apos;s Social Reticence in a Competitive Situation

    ERIC Educational Resources Information Center

    Guimond, Fanny-Alexandra; Brendgen, Mara; Vitaro, Frank; Forget-Dubois, Nadine; Dionne, Ginette; Tremblay, Richard E.; Boivin, Michel

    2014-01-01

    This study used a genetically informed design to assess the effects of friends&apos; and nonfriends&apos; reticent and dominant behaviors on children&apos;s observed social reticence in a competitive situation. Potential gene-environment correlations (rGE) and gene-environment interactions (GxE) in the link between (a) friends&apos; and…

  7. The Influence of Teachers&apos; Conceptions on Their Students&apos; Learning: Children&apos;s Understanding of Sheet Music

    ERIC Educational Resources Information Center

    López-Íñiguez, Guadalupe; Pozo, Juan Ignacio

    2014-01-01

    Background: Despite increasing interest in teachers&apos; and students&apos; conceptions of learning and teaching, and how they influence their practice, there are few studies testing the influence of teachers&apos; conceptions on their students&apos; learning. Aims: This study tests how teaching conception (TC; with a distinction between…

  8. The Influence of Teachers&apos; Conceptions on Their Students&apos; Learning: Children&apos;s Understanding of Sheet Music

    ERIC Educational Resources Information Center

    López-Íñiguez, Guadalupe; Pozo, Juan Ignacio

    2014-01-01

    Background: Despite increasing interest in teachers&apos; and students&apos; conceptions of learning and teaching, and how they influence their practice, there are few studies testing the influence of teachers&apos; conceptions on their students&apos; learning. Aims: This study tests how teaching conception (TC; with a distinction between…

  9. Gene-Environment Interplay in the Link of Friends&apos; and Nonfriends&apos; Behaviors with Children&apos;s Social Reticence in a Competitive Situation

    ERIC Educational Resources Information Center

    Guimond, Fanny-Alexandra; Brendgen, Mara; Vitaro, Frank; Forget-Dubois, Nadine; Dionne, Ginette; Tremblay, Richard E.; Boivin, Michel

    2014-01-01

    This study used a genetically informed design to assess the effects of friends&apos; and nonfriends&apos; reticent and dominant behaviors on children&apos;s observed social reticence in a competitive situation. Potential gene-environment correlations (rGE) and gene-environment interactions (GxE) in the link between (a) friends&apos; and…

  10. Association of apolipoprotein E (ApoE) polymorphisms with risk of primary hyperuricemia in Uygur men, Xinjiang, China.

    PubMed

    Sun, Yu-Ping; Zhang, Bei; Miao, Lei; Wang, Xian-Min; Yu, Jia-Hui; Luo, Li; Ying, Lu; Xin, Gao; Haliakpaer, Gulinizha; Xia, He; Yao, Hua

    2015-04-12

    Apolipoprotein E (ApoE) participates in lipoprotein metabolism and immune regulation. This study assessed association between ApoE polymorphisms with hyperuricemia and uric acid metabolism in Uygur men, Xinjiang, China. A total of 474 hyperuricemia patients and 518 healthy male controls were recruited from the Health Screening Center, Uygur region of Xinjiang, China and subjected to ApoE genotyping using a multiplex amplification refractory mutation system PCR. Apolipoprotein E3/3 genotype was the predominant type with a frequency of 67.7%, while E2/2 was lower than E4/4 in Uygur males. The frequencies of ApoE2, E3, and E4 alleles were 8.5%, 80.1% and 11.4%, respectively. Distribution of ApoE genotypes was significantly different in hyperuricemia patients from the healthy controls (p<0.001). Particularly, the frequency of ApoE E3/3 was 71.7%, E2/3 9.3%, E3/4 9.3%, E4/4 3.2%, E2/4 2.3%, and E2/2 0.2% in patients vs. 68.1%, 4.6%, 2.9%, 12%, 0.6%, and 4.6% in controls, respectively. Moreover, frequency of ApoE E2 allele was greater in the healthy controls than in patients (p<0.001) and the highest level of uric acid occurred in those with ApoE2/4 and E3/4 genotypes, whereas the lowest uric acid level occurred in those with ApoE E2/2 genotype. In addition, the subjects with the ApoE2 allele had a lower uric acid and LDL-C level than those with the ApoE3 allele and ApoE4 allele (p<0.05). The risk of developing hyperuricemia in subjects without the ApoE2 allele was 1.7 fold higher than those subjects with the ApoE2 allele. This study revealed frequencies and distributions of ApoE alleles and genotypes in Uygur males, which are different from Han Chinese. ApoE E4 was associated with a slightly higher risk of primary hyperuricemia, whereas ApoE E2 was associated with reduced risk of primary hyperuricemia and LDL-C level.

  11. Xiaoxianggou attenuates atherosclerotic plaque formation in endogenous high Ang II ApoE(-/-) mice via the inhibition of miR-203 on the expression of Ets-2 in endothelial cells.

    PubMed

    Nie, Wencheng; Zhang, Xiaoqun; Yan, Hui; Li, Shan; Zhu, Weiguo; Fan, Fangyan; Zhu, Jianhua

    2016-08-01

    Atherosclerosis is a chronic immune-inflammatory disorder and one of the leading causes responsible for cardiovascular morbidity and mortality. Traditional Chinese medicine treatment with multi-targets has shown prospects for the therapeutic effect on atherosclerosis. Thus, this study aims to investigate whether xiaoxianggou has benefit for reducing the atherosclerotic plaque area in endogenous high Ang II ApoE(-/-) mice and investigated the underlying mechanisms. Endogenous high Ang II ApoE(-/-) mice model was generated by using two kidney one clip (2K1C). All mice were treated by intragastric administration with xiaoxianggou two times a week for 16 weeks. En face plaque area was analyzed by oil-red O staining. Serum anti-OxLDL antibodies were measured by ELISA assay. Expression of miR-203 and Ets-2 were evaluated using qRT-RCR and western blotting analysis, respectively. This study revealed that xiaoxianggou treatment dose-dependently reduced the atherosclerotic plaque area and serum autoantibodies against oxLDL, elevated miR-203 expression and reduced Ets-2 expression in endogenous high Ang II ApoE(-/-) mice. In primary arterial ECs, Xiaoxianggou reverses the reduced miR-203 expression and the elevated Ets-2 expression induced by AngII, which was further recovered by miR-203 inhibitor. Additionally, miR-203 regulated the expression of Ets-2 by targeting Ets-2-3' UTR. Moreover, miR-203 inhibitor reversed the reduction of atherosclerotic lesion area induced by Xiaoxianggou. These findings present that xiaoxianggou plays an anti-atherosclerotic role in endogenous high Ang II ApoE(-/-) mice model, which is partly due to its antioxidant actions against atherosclerosis and the inhibition of miR-203 on the expression of Ets-2 in endothelial cells. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  12. Pulmonary artery sarcoma mimicking a pulmonary artery aneurysm.

    PubMed

    Terra, Ricardo M; Fernandez, Angelo; Bammann, Ricardo H; Junqueira, Jader J M; Capelozzi, Vera L

    2008-10-01

    Pulmonary artery sarcoma is an uncommon neoplasm, and its clinical and radiological presentation usually simulates chronic thromboembolic disease. We present the case of a 77-year-old woman admitted with dyspnea, chest pain, and hemoptysis. A chest computed tomographic scan showed moderate right-sided pleural effusion and a saccular dilatation of the interlobar portion of the right pulmonary artery, which was filled with contrast and surrounded by an irregular soft-tissue attenuation mass, suggesting a ruptured pulmonary artery aneurysm. The patient was operated on. Intraoperatively, a pseudoaneurysm and a solid mass were identified within the oblique fissure around the interlobar artery. Therefore, a right pneumonectomy was performed. Definitive pathologic examination was consistent with pulmonary artery sarcoma. The patient had a good outcome and is free of disease 2 years after surgery.

  13. Newer perspectives of coronary artery disease in young

    PubMed Central

    Aggarwal, Amitesh; Srivastava, Saurabh; Velmurugan, M

    2016-01-01

    Coronary artery disease (CAD) occurring in less than 45 years of age is termed as young CAD. Recent studies show a prevalence of 1.2% of CAD cases in this age group. Ethnic wise south Asians especially Indians are more vulnerable to have CAD in young age group with a prevalence of 5% to 10%. Conventional risk factors such as smoking, diabetes, hypertension, obesity and family history seems to be as important as in older CAD subjects. But the prevalence of these risk factors seems to vary in younger subjects. By far the most commonly associated risk factor is smoking in young CAD. Several genes associated with lipoprotein metabolism are now found to be associated with young CAD like cholesterol ester transfer protein (CETP) gene, hepatic lipase gene, lipoprotein lipase gene, apo A1 gene, apo E gene and apo B. Biomarkers such as lipoprotein (a), fibrinogen, D-dimer, serum Wnt, gamma glutamyl transferase, vitamin D2 and osteocalcin are seems to be associated with premature CAD in some newer studies. In general CAD in young has better prognosis than older subjects. In terms of prognosis two risk factors obesity and current smoking are associated with poorer outcomes. Angiographic studies shows predominance of single vessel disease in young CAD patients. Like CAD in older person primary and secondary prevention plays an important role in prevention of new and further coronary events. PMID:28070240

  14. Popliteal artery aneurysms.

    PubMed

    Davidovic, L B; Lotina, S I; Kostic, D M; Cinara, I S; Cvetkovic, S D; Markovic, D M; Vojnovic, B R

    1998-08-01

    Altogether 59 patients with 76 popliteal artery aneurysms were treated during the last 36 years. There were 50 (85%) male and 9 (15%) female patients with an average age of 61 years. Nineteen (32%) patients had bilateral aneurysms. The clinical manifestations of the aneurysms included ruptures 4 (5.3%); deep venous thrombosis 4 (5.3%); sciatic nerve compression 1 (1.3%); leg ischemia 52 (68.4%), and asymptomatic pulsatile masses 15 (19.7%). Seventy (92%) aneurysms were atherosclerotic, one (1.3%) mycotic, and four (5.3%) traumatic; one (1.3%) developed owing to fibromuscular displasia. Seven (9.2%) small, asymptomatic aneurysms were not operated on. Reconstructive procedures end-to-end anastomosis, graft interposition, bypass) after aneurysmal resection or exclusion using a medial or posterior approach were done in 59 cases. An autologous saphenous vein graft was used in 49 cases, polytetrafluoroethylene (PTFE) in 5, and heterograft in 2 cases. The in-hospital mortality rate was 2.9%, the early patency rate 93.3%, and limb salvage 95%. The long-term patency rate after a mean follow-up of 4 years was 78% and long-term limb salvage 89%. The total limb salvage was 73%, and the total amputation rate was 27%. The dangerous complications associated with popliteal artery aneurysms and the good results after elective procedures suggest that operative treatment is appropriate.

  15. Spontaneous Arterial Dissection.

    PubMed

    Brandt, Tobias; Caplan, Louis

    2001-09-01

    There is no controlled study for the best treatment or management of cervico-cerebral artery dissection (CAD). Rationale initial empiric treatment in acute CAD to prevent secondary embolism is partial thromboplastin time (PTT)-guided anticoagulation by intravenous heparin followed by anticoagulation with warfarin. Carotid surgery for treatment of CAD is not recommended anymore with the possible exception of persisting severe stenosis of the proximal internal carotid artery (ICA). There could be use of carotid angioplasty by balloon dilatation and stenting in selected cases of severe cerebral hemodynamic impairment by bilateral CAD. Duration of secondary prophylaxis by anticoagulation is best guided by Doppler sonography follow-up, and should be continued until normalization of blood flow or until at least 1 year after the vessel is occluded. There is no evidence that pseudoaneurysms increase the risk for embolic complication, and there is no evidence for surgery or continuation of anticoagulation in patients with pseudoaneurysms. Caution should be recommended for exercises that involve excessive head movements (eg, bungee jumping, trampoline jumping, and chiropractic maneuvers). The patient should be informed that recurrent rate is low in nonfamilial cases. Doppler sonography is a low-cost and high-sensitivity method for patients at risk.

  16. Effect of chronic ethanol on hepatic apolipoprotein (Apo)E glycosylation

    SciTech Connect

    Ghosh, P.; Okoh, C.; Chirtel, S.J.; Liu, Q.H.; Lakshman, M.R. George Washington Univ., Washington, DC )

    1991-03-15

    The authors have previously shown that chronic ethanol feeding significantly inhibits the secretion of ApoE in rats. Since many carbohydrate precursors are essential for the synthesis of mature ApoE before it is secreted, the authors have investigated the effects of chronic ethanol on the incorporation of these precursors into ApoE. Male Wistar rats were divided into groups and were pair-fed with Control and Ethanol liquid diets for a period of 8 weeks. At the end, hepatocytes were isolated from each group and {approximately}400 mg cells were incubated in 8 ml final volume of Krebs bicarbonate buffer, pH 7.4 for 30 min. at 37C with the following labeled precursors individually: (2-{sup 3}H)mannose, (6-{sup 3}H)N-acetyl mannosamine, (4,5-{sup 3}H)galactose, (5,6-{sup 3}H)fucose, and (4,5-{sup 3}H)leucine. The incorporation of each precursor into immunoprecipitable ApoE was measured in cell homogenate, microsome and the Golgi fractions. The results showed that chronic ethanol treatment did not significantly inhibit the incorporation of leucine, fucose and galactose into ApoE at any of the subcellular levels. In contrast, chronic ethanol inhibited the incorporation of: (a) mannose into ApoE by 38% both at whole cell and at microsomal level and (b) N-acetyl mannosamine by 26% at the whole cell level and at the Golgi level. Based on these results, it is concluded that chronic ethanol feeding impairs the mannosylation and sialylation of ApoE in rat liver probably by altering the structure and functions of hepatic microsome and Golgi.

  17. Lack of association of apoE ε4 allele with insulin resistance.

    PubMed

    Ragogna, Francesca; Lattuada, Guido; Ruotolo, Giacomo; Luzi, Livio; Perseghin, Gianluca

    2012-02-01

    ApoE is a polymorphic protein involved in the metabolism of plasma lipoproteins; the ε4 allele was shown to be associated with coronary and aortic atherosclerosis in age-dependent fashion mediated by unknown mechanisms. This study was undertaken to assess whether the apoE isoforms in humans were associated with normal glucose tolerance and with metabolic and inflammatory risk factors of CVD. ApoE genotype was assessed in 365 individuals. Of those, 309 were studied in the postabsorptive conditions and 142 of them also underwent a 3h-OGTT; 56 additional subjects were studied by means of the insulin clamp in combination with [6,6-2H2] glucose infusion. ApoE genotype frequencies were similar to those previously reported and were not influenced by age and BMI. Fasting plasma glucose, insulin, FFA, the lipid profile, surrogate markers (HOMA-IR, OGTT-derived index) as well as the clamp-derived parameters or insulin sensitivity and insulin secretion were not different by apoE genotypes. Serum adipokines concentrations (leptin, adiponectin, resistin) and markers of inflammation (serum fasting hsCRP and MCP1/CCL2) were also not different by apoE genotypes. In the subgroup of young ε4 carriers which underwent the clamp procedure, a higher fasting endogenous glucose production was detected. ApoE genotype was not associated with insulin resistance or altered insulin secretion, and no abnormalities in the typical circulating endocrine, metabolic, and inflammatory features of the insulin resistance syndrome were detected.

  18. In utero arsenic exposure induces early onset of atherosclerosis in ApoE−/− mice

    PubMed Central

    Srivastava, Sanjay; D’Souza, Stanley E.; Sen, Utpal; States, J. Christopher

    2007-01-01

    Consumption of arsenic contaminated drinking water has been linked to higher rates of coronary disease, stroke, and peripheral arterial disease. Recent evidence suggests that early life exposures may play a significant role in the onset of chronic adult diseases. To investigate the potential for in utero exposure to accelerate the onset of cardiovascular disease we exposed pregnant ApoE-knockout (ApoE−/−) mice to arsenic in their drinking water and examined the aortic trees of their male offspring for evidence of early disease 10 and 16 weeks after birth. Mice were maintained on normal chow after weaning. ApoE−/− mice are a commonly used model for atherogenesis and spontaneously develop atherosclerotic disease. Mice exposed to arsenic in utero showed a >2-fold increase in lesion formation in the aortic roots as well as the aortic arch compared to control mice at both 10 and 16 weeks of age. The mice exposed to arsenic also had a 20 – 40% decrease in total triglycerides, but no change in total cholesterol, phospholipids and total abundance of VLDL or HDL particles. Subfractionation of VLDL particles showed a decrease in large VLDL particles. In addition, the arsenic exposed mice showed a vasorelaxation defect in response to acetylcholine suggesting disturbance of endothelial cell signalling. These results indicate that in utero arsenic exposure induces an early onset of atherosclerosis in ApoE−/− mice without a hyperlipidemic diet and support the hypothesis that in utero arsenic exposure may be atherogenic in humans. PMID:17317095

  19. How Is Carotid Artery Disease Treated?

    MedlinePlus

    ... from the NHLBI on Twitter. How Is Carotid Artery Disease Treated? Treatments for carotid artery disease may ... plaque removed and normal blood flow restored. Carotid Artery Angioplasty and Stenting Doctors use a procedure called ...

  20. How Can Carotid Artery Disease Be Prevented?

    MedlinePlus

    ... from the NHLBI on Twitter. How Can Carotid Artery Disease Be Prevented? Taking action to control your risk factors can help prevent or delay carotid artery disease and stroke . Your risk for carotid artery ...

  1. Huge idiopathic pulmonary artery aneurysm.

    PubMed

    Sa-Kong, Heon; Seol, Sang-Hoon; No, Tae-Hoon; Park, Dong-Hee; Jeong, Na-Ri; Jeong, Su-Jin; Kim, Doo-Il

    2017-06-01

    A pulmonary artery aneurysm is an uncommon anomaly. The clinical manifestations are mostly nonspecific, and management is controversial. We report a case of a 67-year-old woman with a main pulmonary artery aneurysm who did not take surgical intervention. Subsequently, there was no increase in size for 3 years.

  2. Huge traumatic pulmonary artery pseudoaneurysm.

    PubMed

    Shnayderman, Dmitriy; Baginski, Scott G; Lea, William B; Erickson, Scott J

    2017-09-01

    Pulmonary artery pseudoaneurysm is a very rare complication of penetrating thoracic trauma. We present a case of a 27-year-old woman who developed a 6.5-cm traumatic pulmonary artery pseudoaneurysm after suffering multiple stab wounds to the chest and the abdomen. The pseudoaneurysm was successfully treated endovascularly with vascular plug occlusion and coil embolization.

  3. Epigenetics and Peripheral Artery Disease.

    PubMed

    Golledge, Jonathan; Biros, Erik; Bingley, John; Iyer, Vikram; Krishna, Smriti M

    2016-04-01

    The term epigenetics is usually used to describe inheritable changes in gene function which do not involve changes in the DNA sequence. These typically include non-coding RNAs, DNA methylation and histone modifications. Smoking and older age are recognised risk factors for peripheral artery diseases, such as occlusive lower limb artery disease and abdominal aortic aneurysm, and have been implicated in promoting epigenetic changes. This brief review describes studies that have associated epigenetic factors with peripheral artery diseases and investigations which have examined the effect of epigenetic modifications on the outcome of peripheral artery diseases in mouse models. Investigations have largely focused on microRNAs and have identified a number of circulating microRNAs associated with human peripheral artery diseases. Upregulating or antagonising a number of microRNAs has also been reported to limit aortic aneurysm development and hind limb ischemia in mouse models. The importance of DNA methylation and histone modifications in peripheral artery disease has been relatively little studied. Whether circulating microRNAs can be used to assist identification of patients with peripheral artery diseases and be modified in order to improve the outcome of peripheral artery disease will require further investigation.

  4. Computer measurement of arterial disease

    NASA Technical Reports Server (NTRS)

    Armstrong, J.; Selzer, R. H.; Barndt, R.; Blankenhorn, D. H.; Brooks, S.

    1980-01-01

    Image processing technique quantifies human atherosclerosis by computer analysis of arterial angiograms. X-ray film images are scanned and digitized, arterial shadow is tracked, and several quantitative measures of lumen irregularity are computed. In other tests, excellent agreement was found between computer evaluation of femoral angiograms on living subjects and evaluation by teams of trained angiographers.

  5. Coronary artery wall imaging in mice using osmium tetroxide and micro-computed tomography (micro-CT)

    SciTech Connect

    Pai, Vinay M.; Kozlowski, Megan; Donahue, Danielle; Miller, Elishiah; Xiao, Xianghui; Chen, Marcus Y.; Yu, Zu-Xi; Connelly, Patricia; Jeffries, Kenneth; Wen, Han

    2012-05-10

    The high spatial resolution of micro-computed tomography (micro-CT) is ideal for 3D imaging of coronary arteries in intact mouse heart specimens. Previously, micro-CT of mouse heart specimens utilized intravascular contrast agents that hardened within the vessel lumen and allowed a vascular cast to be made. However, for mouse coronary artery disease models, it is highly desirable to image coronary artery walls and highlight plaques. For this purpose, we describe an ex vivo contrast-enhanced micro-CT imaging technique based on tissue staining with osmium tetroxide (OsO{sub 4}) solution. As a tissue-staining contrast agent, OsO{sub 4} is retained in the vessel wall and surrounding tissue during the fixation process and cleared from the vessel lumens. Its high X-ray attenuation makes the artery wall visible in CT. Additionally, since OsO{sub 4} preferentially binds to lipids, it highlights lipid deposition in the artery wall. We performed micro-CT of heart specimens of 5- to 25-week-old C57BL/6 wild-type mice and 5- to 13-week-old apolipoprotein E knockout (apoE{sup -/-}) mice at 10 {mu}m resolution. The results show that walls of coronary arteries as small as 45 {mu}m in diameter are visible using a table-top micro-CT scanner. Similar image clarity was achieved with 1/2000th the scan time using a synchrotron CT scanner. In 13-week-old apoE mice, lipid-rich plaques are visible in the aorta. Our study shows that the combination of OsO{sub 4} and micro-CT permits the visualization of the coronary artery wall in intact mouse hearts.

  6. Multiple arterial phase MRI of arterial hypervascular hepatic lesions: improved arterial phase capture and lesion enhancement.

    PubMed

    Ikram, Nabia S; Yee, Judy; Weinstein, Stefanie; Yeh, Benjamin M; Corvera, Carlos U; Monto, Alexander; Hope, Thomas A

    2017-03-01

    To establish if triple-phase arterial imaging improves the detection of arterial phase hyperintense lesions based on arterial phase capture, motion artifact degradation, and lesion enhancement when compared to single-phase imaging. Patients at risk for hepatocellular carcinoma were imaged at 3.0T. Seventy-three consecutive patients with a standard single-phase MRI and eighty-five consecutive patients were imaged using extracellular contrast with triple arterial phase MRI using three sequential accelerated acquisitions of 8 s. Arterial phase capture and image quality were qualitatively categorized. Forty single-phase and forty-four triple-phase studies contained arterially enhancing lesions > 1 cm with washout appearance. The contrast-to-noise ratio (CNR) of the lesions was calculated. We compared the differences in means with Student t-tests and those in arterial phase capture with a Chi squared test with Yates correction. The triple-phase acquisitions captured the early or late arterial phases more frequently than did the single-phase acquisition (99% vs 86%; P value = 0.006). Triple-phase also provided greater number of patients with early or late arterial phase imaging without motion artifact (92% vs 79%, P-value = 0.05). The lesion analysis revealed increased maximum CNR in the triple-phase imaging (704.4) vs. single-phase imaging (517.2), P-value < 0.001. Triple-phase acquisition provides more robust arterial phase imaging for hepatic lesions, with increased lesion CNR, compared to standard single-phase arterial phase imaging.

  7. Arterial anatomy of the thumb.

    PubMed

    Ames, E L; Bissonnette, M; Acland, R; Lister, G; Firrell, J

    1993-08-01

    The anatomical literature has indicated that the arterial supply to the thumb comes from the princeps pollicis artery. However, this simplified description does not often correlate with intraoperative findings. The purpose of this study was to investigate and clarify this important area of anatomy by dissection of fresh cadaver hands. 40 dissections were completed on 35 intravascularly injected and five non-injected hands. Five patterns were identified. The most common pattern showed both a superficial and deep vessel to the first web space in 54% of specimens. Dominant vessels included the superficial palmar branch of the radial artery in 8%, first palmar metacarpal artery in 18% and dorsal metacarpal artery in 8%. Only three specimens correlated with the textbook description. We conclude that the term "princeps pollicis" is actually a misnomer.

  8. Arterial Stiffness: Recommendations and Standardization

    PubMed Central

    Townsend, Raymond R.

    2017-01-01

    The use of arterial stiffness measurements in longitudinal cohorts of normal populations, hypertensive patients, diabetic patients, healthy elderly, and patients on hemodialysis have confirmed the value of this important measure of arterial health, and established its complementary role to measures of blood pressure. Its contribution to understanding cardiovascular and mortality risk beyond blood pressure measurements has moved measures of arterial stiffness into the ranks of factors such as elevated cholesterol, diabetes, and left ventricular hypertrophy in considering cardiovascular risk. The recent international collaboration's publication of reference ranges for normal people and those with hypertension, along with the American Heart Association's recent scientific statement on standardizing arterial stiffness measurements are important aspects to consider in future studies employing these valuable methods, particularly as interventions that not only lower blood pressure but improve arterial function are tested in the clinical arena. PMID:28275588

  9. [Progestins and arterial disease].

    PubMed

    Rozenbaum, H

    1985-01-01

    The role of estrogens in the etiology of vascular accidents was identified soon after oral contraceptives (OCs) came into use over 2 decades ago, but the role of progestins was only identified on the basis of systematic study. Reduction in the estrogen dose of OCs was accompained by a steady decline in venous accidents, but the rate of arterial accidents changed little. It is important to remember that the actual occurrence of vascular accidents in OC users is rare. Available statistics indicate that age and smoking are important risk factors for vascular accidents. Among nonsmokers and smokers respectively, the annual risk of death due to vascular accidents is 1 in 77,000 and 1 in 10,000 for women under 35, 1 in 67,000 and 1 in 2000 for women 35-44, and 1 in 2500 and 1 in 500 for women 45 and over. Some isolated cases of arterial vascular accidents in users of progestin only OCs have been published. The death rate from vascular accidents is 3 times as high when the levonorgestrel dose increases from 150 to 250 mcg, and twice as high when the norethisterone acetate dose increases from 1 to 4 mg. It is not known precisely how synthetic progestins can induce an arterial accident, but the factors involved may include elevation of blood pressure by potentiation of the modifications in renin-angiotensin system caused by ethinyl estradiol, reducing the level of high density lipoprotein (HDL) cholesterol, impairing glucose tolerance, altering the vascular walls directly, or modifying certain coagulation factors. Little data is available on progestin-caused modifications in coagulation factors, but a recent study reported that the effects of combined OCs on coagulation factors increased with the progestin dose. 2 groups of 19-norsteroids are currently used in contraception, the estranes including norethisterone and some prohormones that metabolize to norethisterone before becoming active, and the gonanes including norgestrel, levonorgestrel, and desogestrel. Early optimism

  10. Apolipoprotein E – Low Density Lipoprotein Receptor Interaction Affects Spatial Memory Retention and Brain ApoE Levels in an Isoform-Dependent Manner

    PubMed Central

    Johnson, Lance A.; Olsen, Reid H.J.; Merkens, Louise S.; DeBarber, Andrea; Steiner, Robert D.; Sullivan, Patrick M.; Maeda, Nobuyo; Raber, Jacob

    2014-01-01

    Human apolipoprotein E (apoE) exists in three isoforms: apoE2, apoE3 and apoE4. APOE ε4 (E4) is a major genetic risk factor for cardiovascular disease (CVD) and Alzheimer's disease (AD). ApoE mediates cholesterol metabolism by binding various receptors. The low-density lipoprotein receptor (LDLR) has a high affinity for apoE, and is the only member of its receptor family to demonstrate an apoE isoform specific binding affinity (E4>E3>>E2). Evidence suggests that a functional interaction between apoE and LDLR influences the risk of CVD and AD. We hypothesize that the differential cognitive effects of the apoE isoforms are a direct result of their varying interactions with LDLR. To test this hypothesis, we have employed transgenic mice that express human apoE2, apoE3, or apoE4, and either human LDLR (hLDLR) or no LDLR (LDLR−/−). Our results show that plasma and brain apoE levels, cortical cholesterol, and spatial memory are all regulated by isoform-dependent interactions between apoE and LDLR. Conversely, both anxiety-like behavior and cued associative memory are strongly influenced by APOE genotype, but these processes appear to occur via an LDLR-independent mechanism. Both the lack of LDLR and the interaction between E4 and the LDLR were associated with significant impairments in the retention of long term spatial memory. Finally, levels of hippocampal apoE correlate with long term spatial memory retention in mice with human LDLR. In summary, we demonstrate that the apoE-LDLR interaction affects regional brain apoE levels, brain cholesterol, and cognitive function in an apoE isoform-dependent manner. PMID:24412220

  11. Apolipoprotein E-low density lipoprotein receptor interaction affects spatial memory retention and brain ApoE levels in an isoform-dependent manner.

    PubMed

    Johnson, Lance A; Olsen, Reid H J; Merkens, Louise S; DeBarber, Andrea; Steiner, Robert D; Sullivan, Patrick M; Maeda, Nobuyo; Raber, Jacob

    2014-04-01

    Human apolipoprotein E (apoE) exists in three isoforms: apoE2, apoE3 and apoE4. APOE ε4 is a major genetic risk factor for cardiovascular disease (CVD) and Alzheimer's disease (AD). ApoE mediates cholesterol metabolism by binding various receptors. The low-density lipoprotein receptor (LDLR) has a high affinity for apoE, and is the only member of its receptor family to demonstrate an apoE isoform specific binding affinity (E4>E3>E2). Evidence suggests that a functional interaction between apoE and LDLR influences the risk of CVD and AD. We hypothesize that the differential cognitive effects of the apoE isoforms are a direct result of their varying interactions with LDLR. To test this hypothesis, we have employed transgenic mice that express human apoE2, apoE3, or apoE4, and either human LDLR (hLDLR) or no LDLR (LDLR(-/-)). Our results show that plasma and brain apoE levels, cortical cholesterol, and spatial memory are all regulated by isoform-dependent interactions between apoE and LDLR. Conversely, both anxiety-like behavior and cued associative memory are strongly influenced by APOE genotype, but these processes appear to occur via an LDLR-independent mechanism. Both the lack of LDLR and the interaction between E4 and the LDLR were associated with significant impairments in the retention of long term spatial memory. Finally, levels of hippocampal apoE correlate with long term spatial memory retention in mice with human LDLR. In summary, we demonstrate that the apoE-LDLR interaction affects regional brain apoE levels, brain cholesterol, and cognitive function in an apoE isoform-dependent manner. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. ApoE is required for maintenance of the dentate gyrus neural progenitor pool

    PubMed Central

    Yang, Cui-Ping; Gilley, Jennifer A.; Zhang, Gui; Kernie, Steven G.

    2011-01-01

    Many genes regulating adult neurogenesis have been identified and are known to play similar roles during early neuronal development. We recently identified apolipoprotein E (ApoE) as a gene the expression of which is essentially absent in early brain progenitors but becomes markedly upregulated in adult dentate gyrus stem/progenitor cells. Here, we demonstrate that ApoE deficiency impairs adult dentate gyrus development by affecting the neural progenitor pool over time. We utilized ApoE-deficient mice crossed to a nestin-GFP reporter to demonstrate that dentate gyrus progenitor cells proliferate more rapidly at early ages, which is subsequently accompanied by an overall decrease in neural progenitor cell number at later time points. This appears to be secondary to over-proliferation early in life and ultimate depletion of the Type 1 nestin- and GFAP-expressing neural stem cells. We also rescue the proliferation phenotype with an ApoE-expressing retrovirus, demonstrating that ApoE works directly in this regard. These data provide novel insight into late hippocampal development and suggest a possible role for ApoE in neurodegenerative diseases. PMID:21880781

  13. Aβ immunotherapy for Alzheimer's disease: effects on apoE and cerebral vasculopathy.

    PubMed

    Sakai, Kenji; Boche, Delphine; Carare, Roxana; Johnston, David; Holmes, Clive; Love, Seth; Nicoll, James A R

    2014-12-01

    Aβ immunotherapy for Alzheimer's disease (AD) results in the removal of Aβ plaques and increased cerebral amyloid angiopathy (CAA). In current clinical trials, amyloid-related imaging abnormalities (ARIAs), putatively due to exacerbation of CAA, are concerning side effects. We aimed to assess the role of the Aβ transporter apolipoprotein E (apoE) in the exacerbation of CAA and development of CAA-associated vasculopathy after Aβ immunotherapy. 12 Aβ42-immunized AD (iAD; AN1792, Elan Pharmaceuticals) cases were compared with 28 unimmunized AD (cAD) cases. Immunohistochemistry was quantified for Aβ42, apoE, apoE E4 and smooth muscle actin, and CAA-associated vasculopathy was analyzed. Aβ immunotherapy was associated with redistribution of apoE from cortical plaques to cerebral vessel walls, mirroring the altered distribution of Aβ42. Concentric vessel wall splitting was increased threefold in leptomeningeal vessels after immunotherapy (cAD 6.3 vs iAD 20.6 %, P < 0.001), but smooth muscle cell abnormalities did not differ. The findings suggest that apoE is involved in the removal of plaques and transport of Aβ to the cerebral vasculature induced by Aβ immunotherapy. Immunotherapy was not associated with CAA-related vascular smooth muscle damage, but was accompanied by increased splitting of the vessel wall, perhaps reflecting enhanced deposition and subsequent removal of Aβ. ARIA occurring in some current trials of Aβ immunotherapy may reflect an extreme form of these vascular changes.

  14. [ApoE polymorphisms and dopaminergic replacement therapy in Parkinson's disease].

    PubMed

    Cervantes-Arriaga, Amin; Rodríguez-Violante, Mayela; González-Latapí, Paulina; Dávila-Ortiz de Montellano, David José; Yescas, Petra; Alonso-Vilatela, Elisa

    2014-01-01

    INTRODUCCIÓN: se ha propuesto que la expresión de los polimorfismos de la apolipoproteína E (apoE) es un factor predisponente para el desarrollo temprano de psicosis en los pacientes con enfermedad de Parkinson. La relación entre el genotipo de la apoE y el desarrollo de complicaciones motoras es controvertida. El objetivo de esta investigación fue determinar la relación entre los polimorfismos de la apoE y su frecuencia alélica y el desarrollo de complicaciones secundarias al reemplazo dopaminérgico. MÉTODOS: se evaluaron 231 pacientes con diagnóstico de enfermedad de Parkinson. La presencia de complicaciones fue determinada por un neurólogo y se realizó la genotipificación de los polimorfismos de la apoE. Se utilizó la chi cuadrada para determinar la relación entre la presencia o ausencia de las complicaciones estudiadas y el genotipo de la apoE.

  15. Endothelial NADPH oxidase 4 protects ApoE-/- mice from atherosclerotic lesions.

    PubMed

    Craige, Siobhan M; Kant, Shashi; Reif, Michaella; Chen, Kai; Pei, Yongmei; Angoff, Rebecca; Sugamura, Koichi; Fitzgibbons, Timothy; Keaney, John F

    2015-12-01

    Vascular reactive oxygen species (ROS) are known to be involved in atherosclerosis development and progression. NADPH oxidase 4 (Nox4) is a constitutively active ROS-producing enzyme that is highly expressed in the vascular endothelium. Nox4 is unique in its biology and has been implicated in vascular repair, however, the role of Nox4 in atherosclerosis is unknown. Therefore, to determine the effect of endothelial Nox4 on development of atherosclerosis, Apoe E-/- mice +/- endothelial Nox4 (ApoE-/- + EC Nox4) were fed a high cholesterol/high fat (Western) diet for 24 weeks. Significantly fewer atherosclerotic lesions were observed in the ApoE-/- + EC Nox4 mice as compared to the ApoE-/- littermates, which was most striking in the abdominal region of the aorta. In addition, markers of T cell populations were markedly different between the groups; T regulatory cell marker (FoxP3) was increased whereas T effector cell marker (T-bet) was decreased in aorta from ApoE-/- + EC Nox4 mice compared to ApoE-/- alone. We also observed decreased monokine induced by gamma interferon (MIG; CXCL9), a cytokine known to recruit and activate T cells, in plasma and tissue from ApoE-/- + EC Nox4 mice. To further investigate the link between endothelial Nox4 and MIG expression, we utilized cultured endothelial cells from our EC Nox4 transgenic mice and human cells with adenoviral overexpression of Nox4. In these cultured cells, upregulation of Nox4 attenuated endothelial cell MIG expression in response to interferon-gamma. Together these data suggest that endothelial Nox4 expression reduces MIG production and promotes a T cell distribution that favors repair over inflammation, leading to protection from atherosclerosis. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. [Grafting of carotid arteries].

    PubMed

    Belov, Iu V; Stepanenko, A B; Gens, A P; Bazylev, V V; Seleznev, M N; Savichev, D D

    2005-01-01

    Over 5-years, 167 reconstructive surgeries for stenosis of internal carotid arteries (ICA) were performed in 124 patients. Mean age of the patients was 63.5 years. One hundred and twenty-nine carotid endarterectomies (CEAE) in 86 patients and 38 reconstructive operations of ICA in 38 patients were performed. There were no lethal outcomes in short- and long-term postoperative period. In short-term period after prosthesis of ICA restenosis was revealed in 3% patients, after eversion CEAE in 3% patients the embolism was seen, after standard CEAE restenosis were diagnosed in 8% patients and thrombosis -- in 3%. In long-term period after grafting of ICA the strokes were seen in 3%, stenosis -- in 6% patients, after eversion endarterectomy -- in 0 and 3% patients, and after standard CEAE -- in 3 and 24% patients, respectively. It is concluded that grafting of ICA is adequate surgical method of reconstruction and stroke prevention in specific variants of carotid atherosclerosis.

  17. Spontaneous coronary artery dissection.

    PubMed

    Giacoppo, Daniele; Capodanno, Davide; Dangas, George; Tamburino, Corrado

    2014-07-15

    Spontaneous coronary artery dissection (SCAD) is a relatively rare and unexplored type of coronary disease. Although atherosclerosis, hormonal changes during pregnancy and connective tissue disorders might represent a sufficiently convincing explanation for some patients with SCAD, the many remaining cases display only a weak relationship with these causes. While on one side the clinical heterogeneity of SCAD masks a full understanding of their underlying pathophysiologic process, on the other side paucity of data and misleading presentations hamper the quick diagnosis and optimal management of this condition. A definite diagnosis of SCAD can be significantly facilitated by endovascular imaging techniques. In fact, intravascular ultrasound (IVUS) and optical coherence tomography (OCT) overcome the limitations of coronary angiography providing detailed endovascular morphologic information. In contrast, optimal treatment strategies for SCAD still represent a burning controversial question. Herein, we review the published data examining possible causes and investigating the best therapy for SCAD in different clinical scenarios.

  18. Epilepsy: neuroinflammation, neurodegeneration, and APOE genotype

    PubMed Central

    2013-01-01

    Background Precocious development of Alzheimer-type neuropathological changes in epilepsy patients, especially in APOE ϵ4,4 carriers is well known, but not the ways in which other APOE allelic combinations influence this outcome. Frozen and paraffin-embedded tissue samples resected from superior temporal lobes of 92 patients undergoing temporal lobectomies as a treatment for medication-resistant temporal lobe epilepsy were used in this study. To determine if epilepsy-related changes reflect those in another neurological condition, analogous tissue samples harvested from 10 autopsy-verified Alzheimer brains, and from 10 neurologically and neuropathologically normal control patients were analyzed using immunofluorescence histochemistry, western immunoblot, and real-time PCR to determine genotype effects on neuronal number and size, neuronal and glial expressions of amyloid β (Aβ) precursor protein (βAPP), Aβ, apolipoprotein E (ApoE), S100B, interleukin-1α and β, and α and β secretases; and on markers of neuronal stress, including DNA/RNA damage and caspase 3 expression. Results Allelic combinations of APOE influenced each epilepsy-related neuronal and glial response measured as well as neuropathological change. APOE ϵ3,3 conferred greatest neuronal resilience denoted as greatest production of the acute phase proteins and low neuronal stress as assessed by DNA/RNA damage and caspase-3 expression. Among patients having an APOE ϵ2 allele, none had Aβ plaques; their neuronal sizes, like those with APOE ϵ3,3 genotype were larger than those with other genotypes. APOE ϵ4,4 conferred the weakest neuronal resilience in epilepsy as well as in Alzheimer patients, but there were no APOE genotype-dependent differences in these parameters in neurologically normal patients. Conclusions Our findings provide evidence that the strength of the neuronal stress response is more related to patient APOE genotype than to either the etiology of the stress or to the age of the

  19. Superior mesenteric artery syndrome

    PubMed Central

    Giedrius, Bernotavičius; Kęstutis, Saniukas; Irena, Karmonaitė; Rimantas, Zagorskis

    2016-01-01

    Background. An obstruction of the distal part of the duodenum can occur because of the superior mesenteric artery syndrome (SMAS) after a surgical correction of scoliosis. It is essential to evaluate the risk factors and diagnose the SMAS in time because complications of this condition are life-threatening and it is associated with a high rate of morbidity. Diagnostics of the SMAS is challenging, because it is rare and its symptoms are non-specific. Therefore, in order to better understand the essence of this pathology and to make diagnosis easier we present a rare clinical case of the superior mesenteric artery syndrome after a surgical correction of neuromuscular scoliosis. The clinical case. A 12-year-old girl with a specific development disorder, sensory neuropathy and progressive kypho-scoliosis was admitted to Vilnius University Children’s Hospital. The patient had right side 50-degree thoracic scoliosis and an 80-degree thoracic kyphosis. She underwent posterior spinal fusion with hooks and screws from Th1 to L2. On the fourth day after the surgery the patient developed nausea and began to vomit each day 1-2 times per day, especially after meals. The SMAS was suspected and a nasogastric tube was inserted, stomach decompression and the correction of electrolytes disbalance were made. After the treatment, the symptoms did not recur and a satisfactory correction and balance of the spine were made in coronal and sagittal planes. Conclusions. It is extremely important to identify the risk factors of the SMAS and begin preoperative diet supplements before surgical correction of scoliosis for patients with a low body mass index. After the first episode of vomiting following the surgery, we recommend to investigate these patients for a gastrointestinal obstruction as soon as possible. Decompression of the stomach, enteral or parenteral nutrition, and fluid therapy are essential in treating the SMAS. PMID:28356803

  20. Linking immune-mediated arterial inflammation and cholesterol-induced atherosclerosis in a transgenic mouse model

    PubMed Central

    Ludewig, Burkhard; Freigang, Stefan; Jäggi, Martin; Kurrer, Michael O.; Pei, Yao-Chang; Vlk, Lenka; Odermatt, Bernhard; Zinkernagel, Rolf M.; Hengartner, Hans

    2000-01-01

    Arterial inflammatory responses are thought to be a significant component of atherosclerotic disease. We describe here, using a transgenic approach, the mutual perpetuation of immune-mediated arterial inflammation and cholesterol-induced atherosclerosis. Mice expressing the bacterial transgene β-galactosidase exclusively in cardiomyocytes and in smooth muscle cells in lung arteries and the aorta (SM-LacZ), and hypercholesterolemic apolipoprotein E-deficient SM-LacZ mice (SM-LacZ/apoE−/−) developed myocarditis and arteritis after immunization with dendritic cells presenting a β-galactosidase-derived immunogenic peptide. Hypercholesterolemia amplified acute arteritis and perpetuated chronic arterial inflammation in SM-LacZ/apoE−/− mice, but had no major impact on acute myocarditis or the subsequent development of dilated cardiomyopathy. Conversely, arteritis significantly accelerated cholesterol-induced atherosclerosis. Taken together, these data demonstrate that the linkage of immune-mediated arteritis and hypercholesterolemia favors initiation and maintenance of atherosclerotic lesion formation. Therapeutic strategies to prevent or disrupt such self-perpetuating vicious circles may be crucial for the successful treatment of atherosclerosis. PMID:11050173

  1. Reduced Atherosclerosis in apoE-inhibitory FcγRIIb-Deficient Mice Is Associated With Increased Anti-Inflammatory Responses by T Cells and Macrophages.

    PubMed

    Ng, Hang Pong; Zhu, Xinmei; Harmon, Erin Y; Lennartz, Michelle R; Nagarajan, Shanmugam

    2015-05-01

    Fcγ receptors (FcγRs) are classified as activating (FcγRI, III, and IV) and inhibitory (FcγRII) receptors. We have reported that deletion of activating FcγRs in apolipoprotein E (apoE) single knockout mice attenuated atherosclerosis. In this report, we investigated the hypothesis that deficiency of inhibitory FcγRIIb exacerbates atherosclerosis. ApoE-FcγRIIb double knockout mice, congenic to the C57BL/6 (apoE-FcγRIIbB6 (-/-)), were generated and atherosclerotic lesions were assessed. In contrary to our hypothesis, when compared with apoE single knockout mice, arterial lesions were significantly decreased in apoE-FcγRIIbB6 (-/-) male and female mice fed chow or high-fat diets. Chimeric mice generated by transplanting apoE-FcγRIIbB6 (-/-) marrow into apoE single knockout mice also developed reduced lesions. CD4(+) T cells from apoE-FcγRIIbB6 (-/-) mice produced higher levels of interleukin-10 and transforming growth factor-β than their apoE single knockout counterparts. As our findings conflict with a previous report using apoE-FcγRIIb129/B6 (-/-) mice on a mixed genetic background, we investigated whether strain differences contributed to the anti-inflammatory response. Macrophages from FcγRIIb129/B6 (-/-) mice on a mixed genetic background produced more interleukin-1β and MCP-1 (monocyte chemoattractant protein-1) in response to immune complexes, whereas congenic FcγRIIbB6 (-/-) mice generated more interleukin-10 and significantly less interleukin-1β. Interestingly, the expression of lupus-associated slam genes, located in proximity to fcgr2b in mouse chromosome 1, is upregulated only in mixed FcγRIIb129/B6 (-/-) mice. Our findings demonstrate a detrimental role for FcγRIIb signaling in atherosclerosis and the contribution of anti-inflammatory cytokine responses in the attenuated lesions observed in apoE-FcγRIIbB6 (-/-) mice. As 129/sv genome-derived lupus-associated genes have been implicated in lupus phenotype in FcγRIIb129/B6 (-/-) mice, our

  2. ApoE knockout and knockin mice: the history of their contribution to the understanding of atherogenesis.

    PubMed

    Getz, Godfrey S; Reardon, Catherine A

    2016-05-01

    ApoE is a multifunctional protein that is expressed by many cell types that influences many aspects of cardiovascular physiology. In humans, there are three major allelic variants that differentially influence lipoprotein metabolism and risk for the development of atherosclerosis. Apoe-deficient mice and human apoE isoform knockin mice, as well as hypomorphic Apoe mice, have significantly contributed to our understanding of the role of apoE in lipoprotein metabolism, monocyte/macrophage biology, and atherosclerosis. This brief history of these mouse models will highlight their contribution to the understanding of the role of apoE in these processes. These Apoe(-/-) mice have also been extensively utilized as an atherosensitive platform upon which to assess the impact of modulator genes on the development and regression of atherosclerosis. Copyright © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.

  3. Arterial injuries during inguinal herniorrhaphy.

    PubMed Central

    Shamberger, R C; Ottinger, L W; Malt, R A

    1984-01-01

    In all common forms of inguinal herniorrhaphy, stitches pass either just superficial to the internal iliac artery and vein or through their sheath. Despite the potential for arterial injury, documented cases seem to exist only in the foreign-language literature. We report four cases of arterial injury following inguinal herniorrhaphy in adults. The artery is placed in jeopardy when the transversalis fascia is incorporated in the stitches used to close the medial aspect of the internal inguinal ring. The depth of penetration of the needle and the proximity of the external iliac artery must be accurately judged. Injury can result from direct puncture of the artery or avulsion of one of its branches. Immediate repair of any arterial injury is paramount, and newly subnormal pulses below the inguinal injury are unacceptable. Exposure must be adequate, and division of the floor of the inguinal canal may be necessary for this purpose. Repair may require a simple hemostatic suture, a patch graft, or an interposition graft. PMID:6732332

  4. Left Main Coronary Artery Aneurysm

    PubMed Central

    Doustkami, Hossein; Maleki, Nasrollah; Tavosi, Zahra

    2016-01-01

    Aneurysms of the left main coronary artery are exceedingly rare clinical entities, encountered incidentally in approximately 0.1% of patients who undergo routine angiography. The most common cause of coronary artery aneurysms is atherosclerosis. Angiography is the gold standard for diagnosis and treatment. Depending on the severity of the coexisting coronary stenosis, patients with left main coronary artery aneurysms can be effectively managed either surgically or pharmacologically. We herein report a case of left main coronary artery aneurysm in a 72-year-old man with a prior history of hypertension presenting to our hospital because of unstable angina. The electrocardiogram showed ST-segment depression and T-wave inversion in the precordial leads. All the data of blood chemistry were normal. Echocardiography showed akinetic anterior wall, septum, and apex, mild mitral regurgitation and ejection fraction of 45%. Coronary angiography revealed a saccular aneurysm of the left main coronary artery with significant stenosis in the left anterior descending, left circumflex, and right coronary artery. The patient immediately underwent coronary artery bypass grafting and ligation of the aneurysm. At six months’ follow-up, he remained asymptomatic. PMID:27403190

  5. Development of a method to measure preβHDL and αHDL apoA-I enrichment for stable isotopic studies of HDL kinetics.

    PubMed

    Li, Xuefei; Stolinski, Michael; Umpleby, A Margot

    2012-10-01

    Our understanding of HDL metabolism would be enhanced by the measurement of the kinetics of preβHDL, the nascent form of HDL, since elevated levels have been reported in patients with coronary artery disease. Stable isotope methodology is an established technique that has enabled the determination of the kinetics (production and catabolism) of total HDL apoA-I in vivo. The development of separation procedures to obtain a preβHDL fraction, the isotopic enrichment of which could then be measured, would enable further understanding of the pathways in vivo for determining the fate of preβHDL and the formation of αHDL. A method was developed and optimised to separate and measure preβHDL and αHDL apoA-I enrichment. Agarose gel electrophoresis was first used to separate lipoprotein subclasses, and then a 4-10 % discontinuous SDS-PAGE used to isolate apoA-I. Measures of preβHDL enrichment in six healthy subjects were undertaken following an infusion of L-[1-¹³C-leucine]. After isolation of preβ and αHDL, the isotopic enrichment of apoA-I for each fraction was measured by gas chromatography-mass spectrometry. PreβHDL apoA-I enrichment was measured with a CV of 0.51 % and αHDL apoA-I with a CV of 0.34 %. The fractional catabolic rate (FCR) of preβHDL apoA-I was significantly higher than the FCR of αHDL apoA-I (p < 0.005). This methodology can be used to selectively isolate preβ and αHDL apoA-I for the measurement of apoA-I isotopic enrichment for kinetics studies of HDL subclass metabolism in a research setting.

  6. Selective suppression of adipose tissue apoE expression impacts systemic metabolic phenotype and adipose tissue inflammation.

    PubMed

    Huang, Zhi H; Reardon, Catherine A; Getz, Godfrey S; Maeda, Nobuyo; Mazzone, Theodore

    2015-02-01

    apoE is a multi-functional protein expressed in several cell types and in several organs. It is highly expressed in adipose tissue, where it is important for modulating adipocyte lipid flux and gene expression in isolated adipocytes. In order to investigate a potential systemic role for apoE that is produced in adipose tissue, mice were generated with selective suppression of adipose tissue apoE expression and normal circulating apoE levels. These mice had less adipose tissue with smaller adipocytes containing fewer lipids, but no change in adipocyte number compared with control mice. Adipocyte TG synthesis in the presence of apoE-containing VLDL was markedly impaired. Adipocyte caveolin and leptin gene expression were reduced, but adiponectin, PGC-1, and CPT-1 gene expression were increased. Mice with selective suppression of adipose tissue apoE had lower fasting lipid, insulin, and glucose levels, and glucose and insulin tolerance tests were consistent with increased insulin sensitivity. Lipid storage in muscle, heart, and liver was significantly reduced. Adipose tissue macrophage inflammatory activation was markedly diminished with suppression of adipose tissue apoE expression. Our results establish a novel effect of adipose tissue apoE expression, distinct from circulating apoE, on systemic substrate metabolism and adipose tissue inflammatory state. Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.

  7. Glycation of Apoprotein A-I Is Associated With Coronary Artery Plaque Progression in Type 2 Diabetic Patients

    PubMed Central

    Pu, Li Jin; Lu, Lin; Zhang, Rui Yan; Du, Run; Shen, Ying; Zhang, Qi; Yang, Zheng Kun; Chen, Qiu Jing; Shen, Wei Feng

    2013-01-01

    OBJECTIVE To investigate whether glycation level of apoprotein (apo)A-I is associated with coronary artery disease (CAD) and plaque progression in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Among 375 consecutive type 2 diabetic patients undergoing quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS), 82 patients with nonsignificant stenosis (luminal diameter narrowing <30% [group I]) and 190 patients with significant CAD (luminal diameter stenosis ≥70% [group II]) were included for analysis of apoA-I glycation level and serum activity of lecithin: cholesterol acyltransferase (LCAT). The control group had 136 healthy subjects. At the 1-year follow-up, angiography and IVUS were repeated mainly in group II patients for plaque progression assessment. RESULTS Relative intensity of apoA-I glycation by densitometry was increased, and serum LCAT activity was decreased stepwise across groups control, I, and II. These two measurements were associated with the number of diseased coronary arteries and extent index in group II. During 1-year follow-up, QCA detected 45 patients with plaque progression in 159 subjects, and IVUS found 38 patients with plaque progression in 127 subjects. Baseline relative intensity of apoA-I glycation was significantly increased in patients with plaque progression compared with those without, with values associated with changes in QCA and IVUS measurements. Multivariable regression analysis revealed that baseline relative intensity of apoA-I glycation was an independent determinant of CAD and plaque progression in type 2 diabetic patients. CONCLUSIONS ApoA-I glycation level is associated with the severity of CAD and coronary artery plaque progression in type 2 diabetic patients. PMID:23230102

  8. ApoE2 Exaggerates PTSD-Related Behavioral, Cognitive, and Neuroendocrine Alterations.

    PubMed

    Johnson, Lance A; Zuloaga, Damian G; Bidiman, Erin; Marzulla, Tessa; Weber, Sydney; Wahbeh, Helane; Raber, Jacob

    2015-09-01

    Apolipoprotein E (apoE) is an essential component of lipoprotein particles in both the brain and periphery, and exists in three isoforms in the human population: E2, E3, and E4. ApoE has numerous, well-established roles in neurobiology. Most notably, E4 is associated with earlier onset and increased risk of Alzheimer's disease (AD). Although possession of E2 is protective in the context of AD, E2 appears to confer an increased incidence and severity of posttraumatic stress disorder (PTSD). However, the biological processes underlying this link remain unclear. In this study, we began to elucidate these associations by examining the effects of apoE on PTSD severity in combat veterans, and on PTSD-like behavior in mice with human apoE. In a group of 92 veterans with PTSD, we observed significantly higher Clinician-Administered PTSD Scale and PTSD Checklist scores in E2+ individuals, as well as alterations in salivary cortisol levels. Furthermore, we measured behavioral and biological outcomes in mice expressing human apoE after a single stressful event as well as following a period of chronic variable stress, a model of combat-related trauma. Mice with E2 showed impairments in fear extinction, and behavioral, cognitive, and neuroendocrine alterations following trauma. To the best of our knowledge, these data constitute the first translational demonstration of PTSD severity in men and PTSD-like symptoms in mice with E2, and point to apoE as a novel biomarker of susceptibility, and potential therapeutic target, for PTSD.

  9. Map kinase and PKC signaling pathways modulate NGF-mediated apoE transcription.

    PubMed

    Strachan-Whaley, Megan R; Reilly, Kate; Dobson, James; Kalisch, Bettina E

    2015-05-19

    The present study assessed the mechanisms by which nerve growth factor (NGF) increased the level of apolipoprotein E (apoE) in PC12 cells. NGF (50ng/mL) significantly increased apoE protein levels following 72h of treatment. Similarly NGF increased luciferase activity in cells transfected with a luciferase reporter construct containing a 500bp fragment of the apoE promoter, indicating NGF-induced apoE expression is regulated, at least in part, at the level of transcription. The non-selective nitric oxide synthase (NOS) inhibitor N(ɷ)-nitro-L-arginine methylester (L-NAME; 20mM) did not attenuate the NGF-mediated increase in luciferase activity, while the inducible NOS inhibitor s-methylisothiourea (S-MIU; 2mM) partially attenuated this action of NGF. Inhibition of MAP kinase activation with 50μM U0126 or pre-treatment with the PKC inhibitor bisindolylmaleimide 1 (BIS-1; 10μM) prevented the NGF-mediated activation of the apoE promoter. Pre-treatment with the phospholipase C (PLC) inhibitor U73122 (5μM) partially inhibited the NGF-induced increase in luciferase activity while the Akt inhibitor LY294002 (10μM) had no effect. These data suggest NGF-induced apoE transcription requires MAP kinase and PKC activation and that these TrkA signaling pathways may be modulated by NO. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  10. ApoE2 Exaggerates PTSD-Related Behavioral, Cognitive, and Neuroendocrine Alterations

    PubMed Central

    Johnson, Lance A; Zuloaga, Damian G; Bidiman, Erin; Marzulla, Tessa; Weber, Sydney; Wahbeh, Helane; Raber, Jacob

    2015-01-01

    Apolipoprotein E (apoE) is an essential component of lipoprotein particles in both the brain and periphery, and exists in three isoforms in the human population: E2, E3, and E4. ApoE has numerous, well-established roles in neurobiology. Most notably, E4 is associated with earlier onset and increased risk of Alzheimer's disease (AD). Although possession of E2 is protective in the context of AD, E2 appears to confer an increased incidence and severity of posttraumatic stress disorder (PTSD). However, the biological processes underlying this link remain unclear. In this study, we began to elucidate these associations by examining the effects of apoE on PTSD severity in combat veterans, and on PTSD-like behavior in mice with human apoE. In a group of 92 veterans with PTSD, we observed significantly higher Clinician-Administered PTSD Scale and PTSD Checklist scores in E2+ individuals, as well as alterations in salivary cortisol levels. Furthermore, we measured behavioral and biological outcomes in mice expressing human apoE after a single stressful event as well as following a period of chronic variable stress, a model of combat-related trauma. Mice with E2 showed impairments in fear extinction, and behavioral, cognitive, and neuroendocrine alterations following trauma. To the best of our knowledge, these data constitute the first translational demonstration of PTSD severity in men and PTSD-like symptoms in mice with E2, and point to apoE as a novel biomarker of susceptibility, and potential therapeutic target, for PTSD. PMID:25857685

  11. Local versus global aortic pulse wave velocity in early atherosclerosis: An animal study in ApoE-/--mice using ultrahigh field MRI

    PubMed Central

    Gotschy, Alexander; Bauer, Wolfgang R.; Winter, Patrick; Nordbeck, Peter; Rommel, Eberhard; Jakob, Peter M.; Herold, Volker

    2017-01-01

    Increased aortic stiffness is known to be associated with atherosclerosis and has a predictive value for cardiovascular events. This study aims to investigate the local distribution of early arterial stiffening due to initial atherosclerotic lesions. Therefore, global and local pulse wave velocity (PWV) were measured in ApoE-/- and wild type (WT) mice using ultrahigh field MRI. For quantification of global aortic stiffness, a new multi-point transit-time (TT) method was implemented and validated to determine the global PWV in the murine aorta. Local aortic stiffness was measured by assessing the local PWV in the upper abdominal aorta, using the flow/area (QA) method. Significant differences between age matched ApoE-/- and WT mice were determined for global and local PWV measurements (global PWV: ApoE-/-: 2.7±0.2m/s vs WT: 2.1±0.2m/s, P<0.03; local PWV: ApoE-/-: 2.9±0.2m/s vs WT: 2.2±0.2m/s, P<0.03). Within the WT mouse group, the global PWV correlated well with the local PWV in the upper abdominal aorta (R2 = 0.75, P<0.01), implying a widely uniform arterial elasticity. In ApoE-/- animals, however, no significant correlation between individual local and global PWV was present (R2 = 0.07, P = 0.53), implying a heterogeneous distribution of vascular stiffening in early atherosclerosis. The assessment of global PWV using the new multi-point TT measurement technique was validated against a pressure wire measurement in a vessel phantom and showed excellent agreement. The experimental results demonstrate that vascular stiffening caused by early atherosclerosis is unequally distributed over the length of large vessels. This finding implies that assessing heterogeneity of arterial stiffness by multiple local measurements of PWV might be more sensitive than global PWV to identify early atherosclerotic lesions. PMID:28207773

  12. The apo riboswitch as a molecular hydra.

    PubMed

    Wedekind, Joseph E

    2010-07-14

    Riboswitches "sense" metabolites but knowledge is sparse for structures without bound ligand. Stoddard et al. (2010) determined an apo riboswitch structure "closed" to metabolite binding. Further SAXS, biochemical, and computational analyses support ensemble behavior with interconverting open and closed conformations.

  13. The role of accessory obturator arteries in prostatic arterial embolization.

    PubMed

    Bilhim, Tiago; Pisco, Joao; Pinheiro, Luís Campos; Rio Tinto, Hugo; Fernandes, Lúcia; Pereira, José A

    2014-06-01

    In 9 of 491 patients (1.8%) who underwent prostatic arterial embolization (PAE) for benign prostatic hyperplasia from March 2009-November 2013, prostatic arteries arose from the external iliac artery via an accessory obturator artery (AOA). Computed tomography angiography performed before the procedure identified the variant and allowed planning before the procedure. The nine AOAs were catheterized from a contralateral femoral approach. Bilateral PAE was technically successful in the nine patients. There was a mean decrease in international prostate symptom score of 6.5 points and a mean prostate volume reduction of 15.1% (mean follow-up, 4.8 mo) in the nine patients. Copyright © 2014 SIR. Published by Elsevier Inc. All rights reserved.

  14. Endothelial Protective Monocyte Patrolling in Large Arteries Intensified by Western Diet and Atherosclerosis

    PubMed Central

    Quintar, Amado; McArdle, Sara; Wolf, Dennis; Marki, Alex; Ehinger, Erik; Vassallo, Melanie; Miller, Jacqueline; Mikulski, Zbigniew; Ley, Klaus

    2017-01-01

    Rationale: Nonclassical mouse monocyte (CX3CR1high, Ly-6Clow) patrolling along the vessels of the microcirculation is critical for endothelial homeostasis and inflammation. Because of technical challenges, it is currently not established how patrolling occurs in large arteries. Objective: This study was undertaken to elucidate the molecular, migratory, and functional phenotypes of patrolling monocytes in the high shear and pulsatile environment of large arteries in healthy, hyperlipidemic, and atherosclerotic conditions. Methods and Results: Applying a new method for stable, long-term 2-photon intravital microscopy of unrestrained large arteries in live CX3CR1-GFP (green fluorescent protein) mice, we show that nonclassical monocytes patrol inside healthy carotid arteries at a velocity of 36 μm/min, 3× faster than in microvessels. The tracks are less straight but lead preferentially downstream. The number of patrolling monocytes is increased 9-fold by feeding wild-type mice a Western diet or by applying topical TLR7/8 (Toll-like receptor) agonists. A similar increase is seen in CX3CR1+/GFP/apoE−/− mice on chow diet, with a further 2- to 3-fold increase on Western diet (22-fold over healthy). In plaque conditions, monocytes are readily captured onto the endothelium from free flow. Stable patrolling is unaffected in CX3CR1-deficient mice and involves the contribution of LFA-1 (lymphocyte-associated antigen 1) and α4 integrins. The endothelial damage in atherosclerotic carotid arteries was assessed by electron microscopy and correlates with the number of intraluminal patrollers. Abolishing patrolling monocytes in Nr4a1−/− apoE−/− mice leads to pronounced endothelial apoptosis. Conclusions: Arterial patrolling is a prominent new feature of nonclassical monocytes with unique molecular and kinetic properties. It is highly upregulated in hyperlipidemia and atherosclerosis in a CX3CR1-independent fashion and plays a potential role in endothelial protection

  15. Elevated Ratio of Maternal Plasma ApoCIII to ApoCII in Preeclampsia

    DTIC Science & Technology

    2011-05-01

    Elevated Ratio of Maternal Plasma ApoCIII to ApoCII in Preeclampsia Shannon K. Flood-Nichols, DO1, Jonathan D. Stallings, PhD2, Jennifer L. Gotkin...DO1, Deborah Tinnemore, BS2, Peter G. Napolitano, MD1, and Danielle L. Ippolito, PhD2 Abstract Preeclampsia is a hypertensive disorder unique to...cardiovascular disease and preeclampsia , we hypothesized that the ratio of ApoCIII to ApoCII in maternal first trimester plasma would predict preeclampsia

  16. [Relationship between accelerated artherosclerosis and Treg/Teff balance in uremic apoE-/- mice].

    PubMed

    Shen, Yan; Yuan, Zu-yi; Liu, Yan; Xiao, Yan; Wu, Yue; Zhao, Yan; Tian, Yu-ling; Liu, Wei-min; Wang, Li-jun; Liang, Xiao; Chen, Tao; Geng, Tao

    2010-02-01

    To establish a uremic apolipoprotein E knockout (apoE-/-) mouse model and explore the relationship between accelerated atherosclerosis and Treg/Teff balance. Using apoE-/- mice with C57BL/6J background, uremic apoE-/- mice were created by electrocautery of the right kidney and nephrectomy of the left, and the control apoE-/- mice received a sham-operation. Two weeks after inducing uremia, the renal function of the mice were evaluated to assess the validity of the model. Ten weeks after the operation, blood samples were obtained from the mice to assess the renal function and serum total cholesterol (TCH); the serum concentrations of transforming growth factor-beta(1) (TGF-beta(1)) and interferon-gamma (IFN-gamma) were detected by ELISA, and CD4(+)CD25(+)Foxp3(+)Treg ratio in the spleen was determined by flow cytometry. RT-PCR was used to detect the expression of Foxp3 and IFN-gamma mRNA in the aorta, and oil red O staining used to investigate the relative atherosclerotic area on the frozen sections of the aortic root. The correlation between the renal function parameters and Treg quantity was analyzed. Renal function detection confirmed successful establishment of the uremic apoE-/- mouse model. Ten weeks after the operation, the relative atherosclerotic plaque area in the aortic root plaque increased significantly, the spleen Treg ratio decreased, the serum concentrations of TGF-beta(1) decreased and IFN-gamma and TCH increased, the expression of aortic Foxp3 mRNA decreased and IFN-gamma mRNA increased as compared with those in the control apoE-/- mice. A significant inverse correlation was found between the renal function parameters and Treg quantity in uremic apoE-/- mice. In uremic apoE-/- mice, accelerated aortic atherosclerosis is correlated to the T cell subset (Treg/Teff) imbalance shown by decreased quantity and impaired function of Treg and enhanced activity of Teff.

  17. Neurometabolic roles of ApoE and Ldl-R in mouse brain.

    PubMed

    Lee, Jieun; Choi, Joseph; Wong, G William; Wolfgang, Michael J

    2016-02-01

    Polymorphisms in ApoE are highly correlated with the progression of neurodegenerative disease, in particular Alzheimer's disease. Little is known, however, about the role of ApoE or cholesterol metabolism on brain neurochemistry in general. To better understand the role of lipoprotein and cholesterol metabolism in the brain, we profiled 6 and 12-week old Apoe KO and Ldlr KO mouse models via unbiased metabolomics to determine which metabolites were affected at an early age to identify those that may play a role in triggering pathology later in life. Steady-state metabolomics revealed only subtle differences among Apoe KO, Ldlr KO and WT mouse brains. Ldlr KO mice exhibited alterations in metabolites involved in neurotransmitter, amino acid and cholesterol metabolism. In contrast, Apoe KO mice only showed subtle changes in amino acid and neurotransmitter metabolism. These subtle changes in a broad range of metabolites indicate that ApoE and Ldl-R alone may not play a significant role in these mouse models at an early age, but instead require the cumulative effect from different pathways that lead to dysfunction at a much later stage of life.

  18. Neurometabolic Roles of ApoE and Ldl-R in Mouse Brain

    PubMed Central

    Lee, Jieun; Choi, Joseph; Wong, G. William; Wolfgang, Michael J.

    2015-01-01

    Polymorphisms in ApoE are highly correlated with the progression of neurodegenerative disease, in particular Alzheimer’s disease. Little is known, however, about the role of ApoE or cholesterol metabolism on brain neurochemistry in general. To better understand the role of lipoprotein and cholesterol metabolism in the brain, we profiled 6-week and 12-week old Apoe KO and Ldlr KO mouse models via unbiased metabolomics to determine which metabolites were affected at an early age to identify those that may play a role in triggering pathology later in life. Steady-state metabolomics revealed only subtle differences among Apoe KO, Ldlr KO and WT mouse brains. Ldlr KO mice exhibited alterations in metabolites involved in neurotransmitter, amino acid and cholesterol metabolism. In contrast, Apoe KO mice only showed subtle changes in amino acid and neurotransmitter metabolism. These subtle changes in a broad range of metabolites indicate that ApoE and Ldl-R alone may not play a significant role in these mouse models at an early age, but instead require the cumulative effect from different pathways that lead to dysfunction at a much later stage of life. PMID:26686234

  19. Infants&apos; Discrimination of Female Singing Voices

    ERIC Educational Resources Information Center

    Costa-Giomi, Eugenia; Davila, Yvonne

    2014-01-01

    There&apos;s extensive research on infant&apos;s discrimination of speaking voices but few studies have focused on infant&apos;s discrimination of singing voices. Most investigations on infants&apos; perception of timbre in music have been based on instrumental sounds. We completed an experiment with 7-and 13-month-olds (n = 16 and n = 17…

  20. Infants&apos; Discrimination of Female Singing Voices

    ERIC Educational Resources Information Center

    Costa-Giomi, Eugenia; Davila, Yvonne

    2014-01-01

    There&apos;s extensive research on infant&apos;s discrimination of speaking voices but few studies have focused on infant&apos;s discrimination of singing voices. Most investigations on infants&apos; perception of timbre in music have been based on instrumental sounds. We completed an experiment with 7-and 13-month-olds (n = 16 and n = 17…

  1. Middle-colic artery aneurysm associated with segmental arterial mediolysis, successfully managed by transcatheter arterial embolization: report of a case.

    PubMed

    Hirokawa, Takahisa; Sawai, Hirozumi; Yamada, Koji; Wakasugi, Takehiro; Takeyama, Hiromitsu; Ogino, Hiroyuki; Tsurusaki, Masakatsu; Arai, Yasuaki

    2009-01-01

    An aneurysm of the middle-colic artery, associated with segmental arterial mediolysis (SAM), is a rare condition. This report describes a case of a middle-colic artery aneurysm that was associated with SAM. A 57-year-old man was admitted to our hospital because of severe abdominal pain. A rupture of a middle-colic artery aneurysm was diagnosed by computed tomography, and angiography showed that it may have been associated with SAM. The ruptured aneurysm was successfully treated with transcatheter arterial embolization. Transcatheter arterial embolization might be one of the best treatments for such a complicated aneurysm occurring in a visceral artery.

  2. Pulmonary arterial hypertension

    PubMed Central

    2013-01-01

    Pulmonary arterial hypertension (PAH) is a chronic and progressive disease leading to right heart failure and ultimately death if untreated. The first classification of PH was proposed in 1973. In 2008, the fourth World Symposium on PH held in Dana Point (California, USA) revised previous classifications. Currently, PH is devided into five subgroups. Group 1 includes patients suffering from idiopathic or familial PAH with or without germline mutations. Patients with a diagnosis of PAH should systematically been screened regarding to underlying mutations of BMPR2 gene (bone morphogenetic protein receptor type 2) or more rarely of ACVRL1 (activine receptor-like kinase type 1), ENG (endogline) or Smad8 genes. Pulmonary veno occusive disease and pulmonary capillary hemagiomatosis are individualized and designated as clinical group 1'. Group 2 'Pulmonary hypertension due to left heart diseases' is divided into three sub-groups: systolic dysfonction, diastolic dysfonction and valvular dysfonction. Group 3 'Pulmonary hypertension due to respiratory diseases' includes a heterogenous subgroup of respiratory diseases like PH due to pulmonary fibrosis, COPD, lung emphysema or interstitial lung disease for exemple. Group 4 includes chronic thromboembolic pulmonary hypertension without any distinction of proximal or distal forms. Group 5 regroup PH patients with unclear multifactorial mechanisms. Invasive hemodynamic assessment with right heart catheterization is requested to confirm the definite diagnosis of PH showing a resting mean pulmonary artery pressure (mPAP) of ≥ 25 mmHg and a normal pulmonary capillary wedge pressure (PCWP) of ≤ 15 mmHg. The assessment of PCWP may allow the distinction between pre-capillary and post-capillary PH (PCWP > 15 mmHg). Echocardiography is an important tool in the management of patients with underlying suspicion of PH. The European Society of Cardiology and the European Respiratory Society (ESC-ERS) guidelines specify its role

  3. Pulmonary arterial hypertension.

    PubMed

    Montani, David; Günther, Sven; Dorfmüller, Peter; Perros, Frédéric; Girerd, Barbara; Garcia, Gilles; Jaïs, Xavier; Savale, Laurent; Artaud-Macari, Elise; Price, Laura C; Humbert, Marc; Simonneau, Gérald; Sitbon, Olivier

    2013-07-06

    Pulmonary arterial hypertension (PAH) is a chronic and progressive disease leading to right heart failure and ultimately death if untreated. The first classification of PH was proposed in 1973. In 2008, the fourth World Symposium on PH held in Dana Point (California, USA) revised previous classifications. Currently, PH is devided into five subgroups. Group 1 includes patients suffering from idiopathic or familial PAH with or without germline mutations. Patients with a diagnosis of PAH should systematically been screened regarding to underlying mutations of BMPR2 gene (bone morphogenetic protein receptor type 2) or more rarely of ACVRL1 (activine receptor-like kinase type 1), ENG (endogline) or Smad8 genes. Pulmonary veno occusive disease and pulmonary capillary hemagiomatosis are individualized and designated as clinical group 1'. Group 2 'Pulmonary hypertension due to left heart diseases' is divided into three sub-groups: systolic dysfonction, diastolic dysfonction and valvular dysfonction. Group 3 'Pulmonary hypertension due to respiratory diseases' includes a heterogenous subgroup of respiratory diseases like PH due to pulmonary fibrosis, COPD, lung emphysema or interstitial lung disease for exemple. Group 4 includes chronic thromboembolic pulmonary hypertension without any distinction of proximal or distal forms. Group 5 regroup PH patients with unclear multifactorial mechanisms. Invasive hemodynamic assessment with right heart catheterization is requested to confirm the definite diagnosis of PH showing a resting mean pulmonary artery pressure (mPAP) of ≥ 25 mmHg and a normal pulmonary capillary wedge pressure (PCWP) of ≤ 15 mmHg. The assessment of PCWP may allow the distinction between pre-capillary and post-capillary PH (PCWP > 15 mmHg). Echocardiography is an important tool in the management of patients with underlying suspicion of PH. The European Society of Cardiology and the European Respiratory Society (ESC-ERS) guidelines specify its role

  4. Arterial function of carotid and brachial arteries in postmenopausal vegetarians

    PubMed Central

    Su, Ta-Chen; Torng, Pao-Ling; Jeng, Jiann-Shing; Chen, Ming-Fong; Liau, Chiau-Suong

    2011-01-01

    Background: Vegetarianism is associated with a lower risk of cardiovascular disease. However, studies of arterial function in vegetarians are limited. Methods: This study investigated arterial function in vegetarianism by comparing 49 healthy postmenopausal vegetarians with 41 age-matched omnivores. The arterial function of the common carotid artery was assessed by carotid duplex, while the pulse dynamics method was used to measure brachial artery distensibility (BAD), compliance (BAC), and resistance (BAR). Fasting blood levels of glucose, lipids, lipoprotein (a), high-sensitivity C-reactive protein, homocysteine, and vitamin B12 were also measured. Results: Vegetarians had significantly lower serum cholesterol, high-density and low-density lipoprotein, and glucose compared with omnivores. They also had lower vitamin B12 but higher homocysteine levels. Serum levels of lipoprotein (a) and high-sensitivity C-reactive protein were no different between the two groups. There were no significant differences in carotid beta stiffness index, BAC, and BAD between the two groups even after adjustment for associated covariates. However, BAR was significantly lower in vegetarians than in omnivores. Multiple linear regression analysis revealed that age and pulse pressure were two important determinants of carotid beta stiffness index and BAD. Vegetarianism is not associated with better arterial elasticity. Conclusion: Apparently healthy postmenopausal vegetarians are not significantly better in terms of carotid beta stiffness index, BAC, and BAD, but have significantly decreased BAR than omnivores. Prevention of vitamin B12 deficiency might be beneficial for cardiovascular health in vegetarians. PMID:21915169

  5. Arterial function of carotid and brachial arteries in postmenopausal vegetarians.

    PubMed

    Su, Ta-Chen; Torng, Pao-Ling; Jeng, Jiann-Shing; Chen, Ming-Fong; Liau, Chiau-Suong

    2011-01-01

    Vegetarianism is associated with a lower risk of cardiovascular disease. However, studies of arterial function in vegetarians are limited. This study investigated arterial function in vegetarianism by comparing 49 healthy postmenopausal vegetarians with 41 age-matched omnivores. The arterial function of the common carotid artery was assessed by carotid duplex, while the pulse dynamics method was used to measure brachial artery distensibility (BAD), compliance (BAC), and resistance (BAR). Fasting blood levels of glucose, lipids, lipoprotein (a), high-sensitivity C-reactive protein, homocysteine, and vitamin B12 were also measured. Vegetarians had significantly lower serum cholesterol, high-density and low-density lipoprotein, and glucose compared with omnivores. They also had lower vitamin B12 but higher homocysteine levels. Serum levels of lipoprotein (a) and high-sensitivity C-reactive protein were no different between the two groups. There were no significant differences in carotid beta stiffness index, BAC, and BAD between the two groups even after adjustment for associated covariates. However, BAR was significantly lower in vegetarians than in omnivores. Multiple linear regression analysis revealed that age and pulse pressure were two important determinants of carotid beta stiffness index and BAD. Vegetarianism is not associated with better arterial elasticity. Apparently healthy postmenopausal vegetarians are not significantly better in terms of carotid beta stiffness index, BAC, and BAD, but have significantly decreased BAR than omnivores. Prevention of vitamin B12 deficiency might be beneficial for cardiovascular health in vegetarians.

  6. Coronary artery problems late after arterial switch operation for transposition of the great arteries.

    PubMed

    Tsuda, Takeshi; Bhat, Abdul M; Robinson, Bradley W; Baffa, Jeanne M; Radtke, Wolfgang

    2015-01-01

    The incidence of late coronary artery abnormalities after arterial switch operation (ASO) for d-loop transposition of the great arteries may be underestimated. We retrospectively reviewed coronary artery morphology in 40 of 97 patients who survived the first year after ASO. Seven asymptomatic patients developed significant late coronary artery abnormalities. One patient died suddenly at home with severe left coronary artery (LCA) ostial stenosis at age 3.8 years. The second patient collapsed during exercise at age 9.6 years due to ventricular fibrillation and severe LCA ostial stenosis despite prior negative exercise stress test (EST) and myocardial perfusion imaging (MPI). The third patient was found to have moderate ostial stenosis of the LCA with negative EST and MPI. The fourth patient with exercise-induced ST-T depression and myocardial perfusion defect was shown to have complete LCA occlusion with collateral vessel formation. Three other patients had complete proximal obliteration of either of the coronary arteries with collateral supply. An additional 4 asymptomatic patients had trivial-mild narrowing of the LCA on routine selective coronary angiogram. Incidence of late coronary stenosis or occlusion was not infrequent after ASO (11.3%) and presented usually without preceding symptoms and often after negative non-invasive screening. We advocate routine coronary imaging in all patients after ASO before they participate in competitive sports.

  7. Mutilocus genetic determinants of LDL particle size in coronary artery disease families

    SciTech Connect

    Rotter, J.I.; Bu, X.; Cantor, R.M.

    1996-03-01

    Recent interest in atherosclerosis has focused on the genetic determinants of low-density lipoprotein (LDL) particle size, because of (1) the association of small dense LDL particles with a three-fold increased risk for coronary artery disease (CAD) and (2) the recent report of linkage of the trait to the LDL receptor (chromosome 19). By utilizing nonparametric quantitative sib-pair and relative-pair-analysis methods in CAD families, we tested for linkage of a gene or genes controlling LDL particle sizes with the genetic loci for the major apolipoproteins and enzymes participating in lipoprotein metabolism. We confirmed evidence for linkage to the LDL receptor locus (P = .008). For six candidate gene loci, including apolipoprotein(apo)B, apoAII, apo(a), apoE-CI-CII, lipoprotein lipase, and high-density lipoprotein-binding protein, no evidence for linkage was observed by sib-pair linkage analyses (P values ranged from .24 to .81). However, in addition, we did find tentative evidence for linkage with the apoAI-CIII-AIV locus (chromosome 11) (P = .06) and significant evidence for linkage of the cholesteryl ester transfer protein locus (chromosome 16) (P = .01) and the manganese superoxide dismutase locus (chromosome 6) (P = .001), thus indicating multilocus determination of this atherogenic trait. 73 refs., 3 figs., 4 tabs.

  8. Coronary artery disease and plasma apolipoprotein E4 in mild cognitive impairment

    PubMed Central

    Barekatain, Majid; Zahedian, Faezeh; Askarpour, Hedyeh; Maracy, Mohammad Reza; Hashemi-Jazi, Mohammad; Aghaye-Ghazvini, Mohammad Reza

    2014-01-01

    BACKGROUND Atherosclerosis and apolipoprotein E4 (APOE4) are known risks for Dementia. We sought to evaluate the relationship between coronary atherosclerosis and APOE4 with mild cognitive impairment (MCI). METHODS In a case-control study, subjects with age more than 60 years and recent coronary angiography were evaluated by mini-mental state examination and neuropsychiatry unit cognitive assessment tool (NUCOG) to find the patients with MCI (n = 40) and the controls with normal cognition (n = 40). Coronary angiography records were re-assessed to find the severity of coronary artery disease by the Gensini scores. Plasma levels of APOE4 were measured. RESULTS There were no-significant difference between the 2 groups regarding the plasma APOE4 levels (P = 0.706) and the Gensini scores (P = 0.236). Associations between the Gensini scores and the NUCOG scores in the MCI group (r = −0.196, P = 0.225) and the control group (r = 0.189, P = 0.243) were not significant. However, the interaction effect between the Gensini and the NUCOG scores based on allocation to the control or the patient groups showed statistically significant difference (F(1,67) = 4.84, P = 0.031). CONCLUSION Although atherosclerosis has been considered as known risk factor for dementia and MCI, this study could not reveal that coronary atherosclerosis-related to declining in cognitive functioning. There was no significant association between plasma APOE4 levels and MCI. PMID:25477981

  9. A log-linearized arterial viscoelastic model for evaluation of the carotid artery.

    PubMed

    Hirano, Harutoyo; Horiuchi, Tetsuya; Kutluk, Abdugheni; Kurita, Yuichi; Ukawa, Teiji; Nakamura, Ryuji; Saeki, Noboru; Higashi, Yukihito; Kawamoto, Masashi; Yoshizumi, Masao; Tsuji, Toshio

    2013-01-01

    This paper proposes a method for qualitatively estimating the mechanical properties of arterial walls on a beat-to-beat basis through noninvasive measurement of continuous arterial pressure and arterial diameter using an ultrasonic device. First, in order to describe the nonlinear relationships linking arterial pressure waveforms and arterial diameter waveforms as well as the viscoelastic characteristics of arteries, we developed a second-order nonlinear model (called the log-linearized arterial viscoelastic model) to allow estimation of arterial wall viscoelasticity. Next, to verify the validity of the proposed method, the viscoelastic indices of the carotid artery were estimated. The results showed that the proposed model can be used to accurately approximate the mechanical properties of arterial walls. It was therefore deemed suitable for qualitative evaluation of arterial viscoelastic properties based on noninvasive measurement of arterial pressure and arterial diameter.

  10. Heart Attack Coronary Artery Disease

    MedlinePlus

    ... our e-newsletter! Aging & Health A to Z Heart Attack Coronary Artery Disease, Angina Basic Facts & Information What ... and oxygen supply; this is what causes a heart attack. If the damaged area is small, however, your ...

  11. Update in pulmonary arterial hypertension.

    PubMed

    Mejía Chew, C R; Alcolea Batres, S; Ríos Blanco, J J

    2016-11-01

    Pulmonary arterial hypertension is a rare and progressive disease that mainly affects the pulmonary arterioles (precapillary), regardless of the triggering aetiology. The prevalence of pulmonary hypertension and pulmonary arterial hypertension in Spain is estimated at 19.2 and 16 cases per million inhabitants, respectively. The diagnosis of pulmonary arterial hypertension is based on haemodynamic criteria (mean pulmonary artery pressure ≥25mmHg, pulmonary capillary wedge pressure ≤15mmHg and pulmonary vascular resistance >3 Wood units) and therefore requires the implementation of right cardiac catheterisation. Sequential therapy with a single drug has been used in clinical practice. However, recent European guidelines recommend combined initial therapy in some situations. This review conducts a critical update of our knowledge of this disease according to the latest guidelines and recommendations.

  12. About Peripheral Artery Disease (PAD)

    MedlinePlus

    ... CAD). Both PAD and CAD are caused by atherosclerosis that narrows and blocks arteries in various critical ... can be managed with lifestyle changes and medication . Atherosclerosis and PAD Atherosclerosis is a disease in which ...

  13. The Problem of Character Education and Kohlberg&apos;s Moral Education: Critique from Dewey&apos;s Moral Deliberation

    ERIC Educational Resources Information Center

    Liu, Xiangdong

    2014-01-01

    In this article, the author examines Dewey&apos;s moral deliberation. Liu argues that Dewey&apos;s work will enrich both character education and Kohlberg&apos;s moral education. Liu focuses on character education and on Kohlberg&apos;s moral education because these are the two dominant approaches. Character education seeks to cultivate good…

  14. Applications of Dweck&apos;s Model of Implicit Theories to Teachers&apos; Self-Efficacy and Emotional Experiences

    ERIC Educational Resources Information Center

    Williams, Alexis Ymon

    2012-01-01

    The current study explored Dweck&apos;s (1999; Dweck & Leggett, 1988) model of implicit theories in the context of teaching in order to establish its usefulness for describing teachers&apos; beliefs about students&apos; ability and social behavior. Further it sought to explain the connections between teachers&apos; implicit beliefs and their…

  15. Plaque Size Is Decreased but M1 Macrophage Polarization and Rupture Related Metalloproteinase Expression Are Maintained after Deleting T-Bet in ApoE Null Mice

    PubMed Central

    Tsaousi, Aikaterini; Hayes, Elaine M.; Di Gregoli, Karina; Bond, Andrew R.; Bevan, Laura

    2016-01-01

    Background Thelper1 (Th1) lymphocytes have been previously implicated in atherosclerotic plaque growth but their role in plaque vulnerability to rupture is less clear. We investigated whether T-bet knockout that prevents Th1 lymphocyte differentiation modulates classical (M1) macrophage activation or production of matrix degrading metalloproteinases (MMPs) and their tissue inhibitors, TIMPs. Methods & Results We studied the effect of T-bet deletion in apolipoproteinE (ApoE) knockout mice fed a high fat diet (HFD) or normal chow diet (ND). Transcript levels of M1/M2 macrophage polarization markers, selected MMPs and TIMPs were measured by RT-qPCR in macrophages isolated from subcutaneous granulomas or in whole aortae. Immunohistochemistry of aortic sinus (AS) and brachiocephalic artery (BCA) plaques was conducted to quantify protein expression of the same factors. Deletion of T-bet decreased mRNA for the M1 marker NOS-2 in granuloma macrophages but levels of M2 markers (CD206, arginase-1 and Ym-1), MMPs-2, -9, -12, -13, -14 and -19 or TIMPs-1 to -3 were unchanged. No mRNA differences were observed in aortic extracts from mice fed a HFD for 12 weeks. Moreover, AS and BCA plaques were similarly sized between genotypes, and had similar areas stained for NOS-2, COX-2, MMP-12 and MMP-14 proteins. T-bet deletion increased MMP-13, MMP-14 and arginase-1 in AS plaques. After 35 weeks of ND, T-bet deletion reduced the size of AS and BCA plaques but there were no differences in the percentage areas stained for M1 or M2 markers, MMPs-12, -13, -14, or TIMP-3. Conclusions Absence of Th1 lymphocytes is associated with reduced plaque size in ApoE knockout mice fed a normal but not high fat diet. In either case, M1 macrophage polarization and expression of several MMPs related to plaque instability are either maintained or increased. PMID:26886778

  16. Determinants of ApoB, ApoA1, and the ApoB/ApoA1 ratio in healthy schoolgirls, prospectively studied from mean ages 10 to 19 years: the Cincinnati National Growth and Health Study.

    PubMed

    Morrison, John A; Glueck, Charles J; Daniels, Stephen R; Horn, Paul S; Wang, Ping

    2012-10-01

    The objectives were to prospectively assess determinants of apolipoproteins B (ApoB), A1 (ApoA1), and the ApoB/ApoA1 ratio in 797 healthy black and white schoolgirls from mean ages 10 to 19. There was prospective 9-year follow-up, with measures of ApoB at mean ages 10, 12, 14, 16 and 19, ApoA1 at mean ages 12, 14, 16, and 19, and assessment of annual reports of delayed menstrual cyclicity (≥42 days) from ages 14 to 19. Studies of 402 black and 395 white healthy schoolgirls were done in public and private schools, in urban and suburban Cincinnati. Black girls had lower ApoB, higher ApoA1, and lower ApoB/ApoA1. SHBG at age 14 in white and black girls was inversely correlated with the ApoB/ApoA1. At age 19, ≥3 annual reports of menstrual delay ≥42 days and metabolic syndrome were associated with higher ApoB and a higher ApoB/ApoA1 ratio. From ages 14 to 19, BMI and TG were independently positively associated with ApoB. Menstrual cyclicity ≥42 days, metabolic syndrome, BMI, and TG were independently positively associated with ApoB/ApoA1 ratios, while black race was negatively associated. The atherogenic ApoB/ApoA1 ratio from ages 14 to 19 is lower in black girls, and positively associated with hyperandrogenism, menstrual cyclicity ≥42 days, BMI, TG, and the metabolic syndrome, facilitating an adolescent approach to primary prevention of cardiovascular disease.

  17. Comparative Effects of Diet-Induced Lipid Lowering Versus Lipid Lowering Along With Apo A-I Milano Gene Therapy on Regression of Atherosclerosis.

    PubMed

    Wang, Lai; Tian, Fang; Arias, Ana; Yang, Mingjie; Sharifi, Behrooz G; Shah, Prediman K

    2016-05-01

    Apolipoprotein A-1 (Apo A-I) Milano, a naturally occurring Arg173to Cys mutant of Apo A-1, has been shown to reduce atherosclerosis in animal models and in a small phase 2 human trial. We have shown the superior atheroprotective effects of Apo A-I Milano (Apo A-IM) gene compared to wild-type Apo A-I gene using transplantation of retrovirally transduced bone marrow in Apo A-I/Apo E null mice. In this study, we compared the effect of dietary lipid lowering versus lipid lowering plus Apo A-IM gene transfer using recombinant adeno-associated virus (rAAV) 8 as vectors on atherosclerosis regression in Apo A-I/Apo E null mice. All mice were fed a high-cholesterol diet from age of 6 weeks until week 20, and at 20 weeks, 10 mice were euthanized to determine the extent of atherosclerosis. After 20 weeks, an additional 20 mice were placed on either a low-cholesterol diet plus empty rAAV (n = 10) to serve as controls or low-cholesterol diet plus 1 single intravenous injection of 1.2 × 10(12)vector genomes of adeno-associated virus (AAV) 8 vectors expressing Apo A-IM (n = 10). At the 40 week time point, intravenous AAV8 Apo A-IM recipients showed a significant regression of atherosclerosis in the whole aorta (P< .01), aortic sinuses (P< .05), and brachiocephalic arteries (P< .05) compared to 20-week-old mice, whereas low-cholesterol diet plus empty vector control group showed no significant regression in lesion size. Immunostaining showed that compared to the 20-week-old mice, there was a significantly reduced macrophage content in the brachiocephalic (P< .05) and aortic sinus plaques (P< .05) of AAV8 Apo A-IM recipients. These data show that although dietary-mediated cholesterol lowering halts progression of atherosclerosis, it does not induce regression, whereas combination of low-cholesterol diet and AAV8 mediated Apo A-I Milano gene therapy induces rapid and significant regression of atherosclerosis in mice. These data provide support for the potential feasibility of this

  18. Family history and apoE genotype interaction in Alzheimer`s disease (AD)

    SciTech Connect

    Jarvik, G.P.; Kukull, W.A.; Goddards, K.

    1994-09-01

    The apoE {epsilon}4 allele is associated with increased risk and decreased age of onset of AD. The {epsilon}4 allele may have opposing effects. We determined that family history of a parent or sib with memory problems (famhx+) modified the effect of apoE genotype in a population-based, case (n=165, 72 famhx+)-control (n=233, 73 famhx+) sample. Logistic regression analyses detected a significant apoE genotype (E) by family history (F) by age (A) interaction (ExFxA, p=0.003) and ExF interaction (p=0.0001) in the prediction of AD. ExFxA remained significant when only {epsilon}4+ genotypes were included (p<0.01). ExFxSex (p=0.04) and ExF (p<0.0001) were significant when only {epsilon}4- genotypes were included. Similary, multiple regression detected significant ExF interaction in the prediction of age of AD onset for {epsilon}4+ genotypes (p=0.04) or {epsilon}4- genotypes (p=0.04). Sex did not interact in the prediction of age of onset. Famhx+ increased risk of AD differentially and reduced age of onset except in {epsilon}2+ genotypes. Family history modifies the apoE genotype influence on risk and onset age of AD, suggesting that non-apoE genetic effects interact with apoE in AD. It is most predictive of risk in those with the {epsilon}2{epsilon}3 genotype. Variation in risk and onset among both {epsilon}4+ and {epsilon}4- genotypes demonstrate that {epsilon}2 and {epsilon}3 mediate {epsilon}4 allele effects in AD.

  19. ApoE genotype, past adult lead exposure, and neurobehavioral function.

    PubMed

    Stewart, Walter F; Schwartz, Brian S; Simon, David; Kelsey, Karl; Todd, Andrew C

    2002-05-01

    Our objective in this study was to determine if the known relation between tibia bone lead levels and neurobehavioral test scores are influenced by the apolipoprotein E (ApoE) genotype. We collected data on 20 neurobehavioral tests in 529 former organolead workers who had an average of 16 years since last occupational exposure to lead. We used linear regression to model the relations between each of 20 neurobehavioral test scores and tibia lead, a binary variable for ApoE genotype (i.e., at least one Epsilon4 allele vs. none), and an interaction term between tibia lead and the binary term for ApoE genotype. At the time of testing, former lead workers were an average of 57.6 years of age; 82% were younger than 65 years. In regression analysis, we observed one statistically significant and one borderline significant coefficient for ApoE genotype alone. Coefficients for the ApoE and tibia lead interaction term were negative in 19 of the 20 regression models. This indicates that the slope for the relation between tibia lead and each neurobehavioral test was more negative for individuals with at least one Epsilon4 allele than for those who did not have an Epsilon4 allele. Four of 19 negative coefficients for the interaction term were statistically significant (digit symbol, Purdue pegboard assembly, Purdue pegboard-dominant hand, complex reaction time); another three of the remaining 16 coefficients (symbol digit, trail-making A, Stroop) were borderline significant (i.e., p < 0.10). This study suggests that individuals may vary in susceptibility to the long-term effects of lead on the central nervous system (CNS). In particular, the persistent CNS effect of lead may be more toxic in individuals who have at least one ApoE-Epsilon4 allele.

  20. Twist Buckling Behavior of Arteries

    PubMed Central

    Garcia, Justin R.; Lamm, Shawn D.; Han, Hai-Chao

    2012-01-01

    Arteries are often subjected to torsion due to body movement and surgical procedures. While it is essential that arteries remain stable and patent under twisting loads, the stability of arteries under torsion is poorly understood. The goal of this work was to experimentally investigate the buckling behavior of arteries under torsion and to determine the critical buckling torque, the critical buckling twist angle, and the buckling shape. Porcine common carotid arteries were slowly twisted in vitro until buckling occurred while subjected to a constant axial stretch ratio (1.1, 1.3, 1.5 (in vivo level), and 1.7) and lumen pressure (20, 40, 70, and 100 mmHg). Upon buckling, the arteries snapped to form a kink. For a group of six arteries, the axial stretch ratio significantly affected the critical buckling torque (p < 0.002) and the critical buckling twist angle (p < 0.001). Lumen pressure also significantly affected the critical buckling torque (p < 0.001) but had no significant effect on the critical twist angle (p = 0.067). Convex material constants for a Fung strain energy function were determined and fit well with the axial force, lumen pressure, and torque data measured pre-buckling. The material constants are valid for axial stretch ratios, lumen pressures, and rotation angles of 1.3 – 1.5, 20 – 100 mmHg, and 0 – 270 degrees, respectively. The current study elucidates the buckling behavior of arteries under torsion and provides new insight into mechanical instability of blood vessels. PMID:23160845

  1. Twist buckling behavior of arteries.

    PubMed

    Garcia, Justin R; Lamm, Shawn D; Han, Hai-Chao

    2013-10-01

    Arteries are often subjected to torsion due to body movement and surgical procedures. While it is essential that arteries remain stable and patent under twisting loads, the stability of arteries under torsion is poorly understood. The goal of this work was to experimentally investigate the buckling behavior of arteries under torsion and to determine the critical buckling torque, the critical buckling twist angle, and the buckling shape. Porcine common carotid arteries were slowly twisted in vitro until buckling occurred while subjected to a constant axial stretch ratio (1.1, 1.3, 1.5 (in vivo level) and 1.7) and lumen pressure (20, 40, 70 and 100 mmHg). Upon buckling, the arteries snapped to form a kink. For a group of six arteries, the axial stretch ratio significantly affected the critical buckling torque ([Formula: see text]) and the critical buckling twist angle ([Formula: see text]). Lumen pressure also significantly affected the critical buckling torque ([Formula: see text]) but had no significant effect on the critical twist angle ([Formula: see text]). Convex material constants for a Fung strain energy function were determined and fit well with the axial force, lumen pressure, and torque data measured pre-buckling. The material constants are valid for axial stretch ratios, lumen pressures, and rotation angles of 1.3-1.5, 20-100 mmHg, and 0-270[Formula: see text], respectively. The current study elucidates the buckling behavior of arteries under torsion and provides new insight into mechanical instability of blood vessels.

  2. [Ageing of the arterial wall].

    PubMed

    Hanon, O

    2006-11-01

    Several mechanisms are implicated in the arterial wall changes due to ageing: ageing, hypertension and atherosclerosis. Although the changes related to ageing (arteriosclerosis) have many factors in common with those induced by hypertension, they differ from those caused by atherosclerosis although commonly associated. Arteriosclerosis causes a diffuse increase of the rigidity of the large arteries by disease of the media, the main clinical manifestation of which is the increase in pulsed pressure. This arterial "hyperpulsability" contributes to a defect in coupling between the heart and the blood vessels which results in an increase in the pulsatile load of the left ventricle and to left ventricular hypertrophy and decreased coronary perfusion. Atherosclerosis seems more of a localised scarring phenomenon of the arterial wall which is exposed to a series of chronic aggressions characterised by deposits of lipids in the intima and whose main complication is thrombosis. Although these two processes may be associated, or interact one with the other, they are clearly different in nature. Therefore, atherosclerosis is a localised disease resulting in a decrease in arterial lumen, quite different from arteriosclerosis which is a diffuse, physiological condition which leads to an increase in the arterial lumen.

  3. Arterial Stiffness and Cardiovascular Therapy

    PubMed Central

    Janić, Miodrag; Lunder, Mojca; Šabovič, Mišo

    2014-01-01

    The world population is aging and the number of old people is continuously increasing. Arterial structure and function change with age, progressively leading to arterial stiffening. Arterial stiffness is best characterized by measurement of pulse wave velocity (PWV), which is its surrogate marker. It has been shown that PWV could improve cardiovascular event prediction in models that included standard risk factors. Consequently, it might therefore enable better identification of populations at high-risk of cardiovascular morbidity and mortality. The present review is focused on a survey of different pharmacological therapeutic options for decreasing arterial stiffness. The influence of several groups of drugs is described: antihypertensive drugs (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers, beta-blockers, diuretics, and nitrates), statins, peroral antidiabetics, advanced glycation end-products (AGE) cross-link breakers, anti-inflammatory drugs, endothelin-A receptor antagonists, and vasopeptidase inhibitors. All of these have shown some effect in decreasing arterial stiffness. Nevertheless, further studies are needed which should address the influence of arterial stiffness diminishment on major adverse cardiovascular and cerebrovascular events (MACCE). PMID:25170513

  4. Specific high-affinity binding of high density lipoproteins to cultured human skin fibroblasts and arterial smooth muscle cells.

    PubMed

    Biesbroeck, R; Oram, J F; Albers, J J; Bierman, E L

    1983-03-01

    Binding of human high density lipoproteins (HDL, d = 1.063-1.21) to cultured human fibroblasts and human arterial smooth muscle cells was studied using HDL subjected to heparin-agarose affinity chromatography to remove apoprotein (apo) E and B. Saturation curves for binding of apo E-free 125I-HDL showed at least two components: low-affinity nonsaturable binding and high-affinity binding that saturated at approximately 20 micrograms HDL protein/ml. Scatchard analysis of high-affinity binding of apo E-free 125I-HDL to normal fibroblasts yielded plots that were significantly linear, indicative of a single class of binding sites. Saturation curves for binding of both 125I-HDL3 (d = 1.125-1.21) and apo E-free 125I-HDL to low density lipoprotein (LDL) receptor-negative fibroblasts also showed high-affinity binding that yielded linear Scatchard plots. On a total protein basis, HDL2 (d = 1.063-1.10), HDL3 and very high density lipoproteins (VHDL, d = 1.21-1.25) competed as effectively as apo E-free HDL for binding of apo E-free 125I-HDL to normal fibroblasts. Also, HDL2, HDL3, and VHDL competed similarly for binding of 125I-HDL3 to LDL receptor-negative fibroblasts. In contrast, LDL was a weak competitor for HDL binding. These results indicate that both human fibroblasts and arterial smooth muscle cells possess specific high affinity HDL binding sites. As indicated by enhanced LDL binding and degradation and increased sterol synthesis, apo E-free HDL3 promoted cholesterol efflux from fibroblasts. These effects also saturated at HDL3 concentrations of 20 micrograms/ml, suggesting that promotion of cholesterol efflux by HDL is mediated by binding to the high-affinity cell surface sites.

  5. An extract from medical leech improve the function of endothelial cells in vitro and attenuates atherosclerosis in ApoE null mice by reducing macrophages in the lesions.

    PubMed

    Wang, Yao; Zhao, Xin; Wang, Yun-Shan; Song, Shu-Liang; Liang, Hao; Ji, Ai-Guo

    2014-12-05

    Medicinal leech has been widely used as a traditional Chinese medicine in cardiovascular diseases. However, its pharmaceutical effect is not fully revealed. The goal of this study was to determine whether a leech extract has the effect of anti-atherosclerosis in ApoE −/− mice and the mechanism of this effect. In vivo experiments: ApoE −/− mice fed on high-cholesterol diet were separated into 5 groups. Control group was administrated with normal water; leech extract of low dose treatment group was given a leech extract of 0.02 g/kg/d; leech extract of medium dose treatment group was given a leech extract of 0.1 g/kg/d; leech extract of high dose treatment group was given a leech extract of 0.5 g/kg/d; simvastatin group was given simvastatin of 10 mg/kg/d. Leech extract significantly reduced atherosclerotic lesions in aortic root compared with control group. And the number of macrophage in or around the atherosclerosis plaque is significantly reduced in the leech extract groups compared with control group. In vitro experiments: human endothelial cell line, EA.hy926, was induced with TNF-α to perform endothelial dysfunction. Control group: EA.hy926 cells with no special treatment; TNF-α group: EA.hy926 cells were induced by 10 ng/ml TNF-α for 6 h; leech extract only group: EA.hy926 cells were treated with 200 mg/ml leech extract only; leech extract and TNF-α group: 200 mg/ml leech extract was applied before TNF-α induction. Protein and mRNA level were detected in each group, leech extract can decrease the expression of intercellular adhesion factor (ICAM-1) and monocyte chemotactic protein (MCP-1) compared with TNF-α group. Furthermore, it showed less adhesion and migration of THP-1 cells to EA.hy926 cells in the adhesion assay and transwell assay. The NF-κB translation to nucleus was blocked by leech extract in the NF-κB translocation assay. Leech extract could obviously attenuate the area of atherosclerosis lesion in ApoE −/− mice. And this

  6. Elevated homocysteine reduces apolipoprotein A-I expression in hyperhomocysteinemic mice and in males with coronary artery disease.

    PubMed

    Mikael, Leonie G; Genest, Jacques; Rozen, Rima

    2006-03-03

    Hyperhomocysteinemia, a risk factor for cardiovascular disease, is caused by nutritional or genetic disturbances in homocysteine metabolism. A polymorphism in methylenetetrahydrofolate reductase (MTHFR) is the most common genetic cause of mild hyperhomocysteinemia. To examine mechanisms by which an elevation in plasma homocysteine leads to vascular disease, we first performed microarray analyses in livers of Mthfr-deficient mice and identified differentially expressed genes that are involved in lipid and cholesterol metabolism. Microarrays and RT-PCR showed decreased mRNA for apolipoprotein A (ApoA)-IV and for ApoA-I and increased mRNA for cholesterol 7alpha hydroxylase (Cyp7A1) in Mthfr(+/-) mice compared with Mthfr(+/+) mice. Western blotting revealed that ApoA-I protein levels in liver and plasma of Mthfr(+/-) mice were 52% and 62% of levels in the respective tissues of Mthfr(+/+) mice. We also performed Western analysis for plasma ApoA-I protein levels in 60 males with coronary artery disease and identified a significant (P<0.01) negative correlation (-0.33) between ApoA-I and plasma homocysteine levels. This cohort also displayed a negative correlation (-0.24, P=0.06) between high-density lipoprotein cholesterol and plasma homocysteine. Treatment of HepG2 cells with supraphysiological levels of 5 mmol/L homocysteine reduced peroxisome proliferator-activated receptor (PPAR) alpha and ApoA-I protein levels and decreased ApoA-I promoter activity. Transfection with a PPARalpha construct upregulated ApoA-I and MTHFR. Our results suggest that hyperhomocysteinemia may increase risk of atherosclerosis by decreasing expression of ApoA-I and increasing expression of CYP7A1.

  7. Enhanced platelet reactivity and thrombosis in Apoe-/- mice exposed to cigarette smoke is attenuated by P2Y12 antagonism.

    PubMed

    Dong, Anping; Caicedo, Jessica; Han, Sung Gu; Mueller, Paul; Saha, Sibu; Smyth, Susan S; Gairola, C Gary

    2010-10-01

    Smoking increases the risk of acute arterial thrombosis, including myocardial infarction, likely due to multi-factorial effects on the vasculature. Heightened platelet reactivity may be among the adverse effects of smoke exposure. To examine the effects of smoke exposure on platelet function in an atherosclerotic environment, Apoe-deficient female mice, maintained on a Western diet, were exposed (4 hrs/d, 5 d/wk) to sidestream cigarette smoke in a whole-body exposure chamber for 12 weeks. A separate group of wild type C57BL/6J mice were also exposed to smoke in an identical fashion. In comparison to control Apoe-/- mice exposed to filtered ambient air, smoke-exposed Apoe-/- mice displayed a 1.8±0.3 fold enhanced ADP-induced fibrinogen binding ex vivo (P<0.001) and had a shorter time to thrombotic occlusion following ferric chloride injury of the carotid artery (median time to thrombosis of 8 vs. 13 min; P=0.015). Administration of the direct-acting P2Y12 antagonist cangrelor blunted ex vivo fibrinogen binding and attenuated thrombosis (median time 20 min) in Apoe-/- mice exposed to sidestream smoke. The effects of smoke exposure required a proatherosclerotic background, as wild-type C57Bl/6J mice exposed to smoke displayed similar fibrinogen binding and thrombotic occlusion times as did control mice. Our results demonstrate that exposure to smoke heightens platelet reactivity and thrombosis in Apoe-/- mice and implicate signaling through platelet P2Y12 receptor as a mediator of the adverse consequence of smoke exposure. These results may partially explain the recent observations that smokers derive greater clinical benefit from the P2Y12 antagonist clopidogrel than do non-smokers. Published by Elsevier Ltd.

  8. eNOS Protects from Atherosclerosis Despite Relevant Superoxide Production by the Enzyme in apoE−/− Mice

    PubMed Central

    Ponnuswamy, Padmapriya; Schröttle, Angelika; Ostermeier, Eva; Grüner, Sabine; Huang, Paul L.; Ertl, Georg; Hoffmann, Ulrich; Nieswandt, Bernhard; Kuhlencordt, Peter J.

    2012-01-01

    Background All three nitric oxide synthase (NOS) isoforms are expressed in atherosclerotic plaques. NOS enzymes in general catalyse NO production. However, under conditions of substrate and cofactor deficiency, the enzyme directly catalyse superoxide formation. Considering this alternative chemistry, the effects of NOS on key events in spontaneous hyperlipidemia driven atherosclerosis have not been investigated yet. Here, we evaluate how endothelial nitric oxide synthase (eNOS) modulates leukocyte/endothelial- (L/E) and platelet/endothelial- (P/E) interactions in atherosclerosis and the production of nitric oxide (NO) and superoxide by the enzyme. Principal Findings Intravital microscopy (IVM) of carotid arteries revealed significantly increased L/E-interactions in apolipoproteinE/eNOS double knockout mice (apoE−/−/eNOS−/−), while P/E-interactions did not differ, compared to apoE−/−. eNOS deficiency increased macrophage infiltration in carotid arteries and vascular cell adhesion molecule-1 (VCAM-1) expression, both in endothelial and smooth muscle cells. Despite the expression of other NOS isoforms (inducible NOS, iNOS and neuronal NOS, nNOS) in plaques, Electron Spin Resonance (ESR) measurements of NO showed significant contribution of eNOS to total circulating and vascular wall NO production. Pharmacological inhibition and genetic deletion of eNOS reduced vascular superoxide production, indicating uncoupling of the enzyme in apoE−/− vessels. Conclusion Overt plaque formation, increased vascular inflammation and L/E- interactions are associated with significant reduction of superoxide production in apoE−/−/eNOS−/− vessels. Therefore, lack of eNOS does not cause an automatic increase in oxidative stress. Uncoupling of eNOS occurs in apoE−/− atherosclerosis but does not negate the enzyme's strong protective effects. PMID:22291917

  9. An effective approach to reduce inflammation and stenosis in carotid artery: polypyrrole nanoparticle-based photothermal therapy

    NASA Astrophysics Data System (ADS)

    Peng, Zhiyou; Qin, Jinbao; Li, Bo; Ye, Kaichuang; Zhang, Yuxin; Yang, Xinrui; Yuan, Fukang; Huang, Lijia; Hu, Junqing; Lu, Xinwu

    2015-04-01

    Photothermal therapy (PTT), as a promising treatment for tumours, has rarely been reported for application in artery restenosis, which is a common complication of endovascular management due to enduring chronic inflammation and abnormal cell proliferation. In our study, biodegradable polypyrrole nanoparticles (PPy-NPs) were synthesized and characterized, including their size distribution, UV-vis-NIR absorbance, molar extinction coefficients, and photothermal properties. We then verified that PPy-NP incubation followed by 915 nm near-infrared (NIR) laser irradiation could effectively ablate inflammatory macrophages in vitro, leading to significant cell apoptosis and cell death. Further, it was found that a combination of local PPy-NP injection with 915 nm NIR laser irradiation could significantly alleviate arterial inflammation by eliminating infiltrating macrophages and further ameliorating artery stenosis in an ApoE-/- mouse model, without showing any obvious toxic side effects. Thus, we propose that PTT based on PPy-NPs as photothermal agents and a 915 nm NIR laser as a power source can serve as a new effective treatment for reducing inflammation and stenosis formation in inflamed arteries after endovascular management.Photothermal therapy (PTT), as a promising treatment for tumours, has rarely been reported for application in artery restenosis, which is a common complication of endovascular management due to enduring chronic inflammation and abnormal cell proliferation. In our study, biodegradable polypyrrole nanoparticles (PPy-NPs) were synthesized and characterized, including their size distribution, UV-vis-NIR absorbance, molar extinction coefficients, and photothermal properties. We then verified that PPy-NP incubation followed by 915 nm near-infrared (NIR) laser irradiation could effectively ablate inflammatory macrophages in vitro, leading to significant cell apoptosis and cell death. Further, it was found that a combination of local PPy-NP injection with

  10. Higher Plasma ApoE Levels are Associated with Low-Normal Thyroid Function: Studies in Diabetic and Nondiabetic Subjects.

    PubMed

    van Tienhoven-Wind, L J N; Dallinga-Thie, G M; Dullaart, R P F

    2016-07-01

    Low-normal thyroid function within the euthyroid range may confer higher plasma triglycerides, but relationships with plasma apolipoprotein (apo) E, which plays an important role in the metabolism of triglyceride-rich apoB-containing lipoproteins, are unknown. We determined relationships of plasma apoE with thyroid stimulating hormone (TSH) and free thyroxine (free T4) in euthyroid subjects with and without Type 2 diabetes mellitus (T2DM). TSH, free T4, lipids, and apoE were measured in fasting plasma from 72 T2DM subjects and 82 nondiabetic subjects. The APOE genotype was also determined. Free T4 was slightly higher in T2DM (p=0.030), but TSH levels were not different vs. nondiabetic subjects. The APOE genotype distribution was not different between the groups. None of the participants had the ε2/ε2 genotype. Plasma triglycerides were higher in T2DM (p=0.037). ApoB and apoE levels were not different between the groups. In all subjects combined, multivariable analysis showed that plasma triglycerides (p=0.039), non-high density lipoprotein (non-HDL) cholesterol (p=0.030), and apoE levels (p=0.002) were each independently and positively associated with TSH after adjustment for age, sex, T2DM and the presence of the APOE ε3 allele. Furthermore, the associations of TSH with apoE remained present after adjustment for either triglycerides, non-HDL cholesterol, or apoB (p=0.005 to 0.023). The presence of T2DM did not modify the relationships of TSH with these (apo) lipoprotein variables (p=0.11 to 0.36). In conclusion, low-normal thyroid function, as indicated by higher TSH levels within the euthyroid range, may influence the metabolism of triglyceride-rich lipoproteins by affecting apoE regulation. © Georg Thieme Verlag KG Stuttgart · New York.

  11. Parallels in Preschoolers&apos; and Adults&apos; Judgments about Ownership Rights and Bodily Rights

    ERIC Educational Resources Information Center

    Van de Vondervoort, Julia W.; Friedman, Ori

    2015-01-01

    Understanding ownership rights is necessary for socially appropriate behavior. We provide evidence that preschoolers&apos; and adults&apos; judgments of ownership rights are related to their judgments of bodily rights. Four-year-olds (n = 70) and adults (n = 89) evaluated the acceptability of harmless actions targeting owned property and body…

  12. Oxidative Stress Impairs Learning and Memory in apoE Knockout Mice

    PubMed Central

    Evola, Marianne; Hall, Allyson; Wall, Trevor; Young, Alice; Grammas, Paula

    2010-01-01

    Cardiovascular risk factors, such as oxidative stress and elevated lipids, are linked to the development of cognitive impairment. A mediator common to both stressors is the apolipoprotein E (apoE). The objectives of this study are to determine the effects of apoE deficiency and diet-induced systemic oxidative stress in mice on vascular expression of inflammatory proteins and on cognitive function. Mice are placed on a diet enriched in homocysteine for fifteen weeks and then assessed for spatial learning using an eight-arm radial maze and for inflammatory protein expression by immunohistochemistry. Our results show that diet-induced oxidative stress does not affect cognitive function in normal mice. In contrast, apoE−/− mice on the homocysteine diet show significantly impaired (p < 0. 001) maze performance. ApoE−/− mice also have high cholesterol levels. There is no expression of inflammatory proteins IL-6 and IL-8 in the vasculature of control mice on normal or homocysteine diet and little in apoE−/− mice on normal diet. In contrast, apoE−/− mice on homocysteine diet show pronounced vascular reactivity to IL-6 and IL-8 antibodies. These data show that systemic oxidative stress correlates with expression of inflammatory proteins in the cerebral vasculature and impaired cognitive function. These results are consistent with the hypothesis that an oxidative-inflammatory cycle in the cerebral vasculature could have deleterious consequences for cognition. PMID:20457176

  13. Mapping of ApoE4 related white matter damage using diffusion MRI

    NASA Astrophysics Data System (ADS)

    Tsao, Sinchai; Gajawelli, Niharika; Hwang, Darryl H.; Kriger, Stephen; Law, Meng; Chui, Helena; Weiner, Michael; Lepore, Natasha

    2014-04-01

    ApoliopoproteinE Ɛ4 (ApoE-Ɛ4) polymorphism is the most well known genetic risk factor for developing Alzheimers Disease. The exact mechanism through which ApoE 4 increases AD risk is not fully known, but may be related to decreased clearance and increased oligomerization of Aβ. By making measurements of white matter integrity via diffusion MR and correlating the metrics in a voxel-based statistical analysis with ApoE-Ɛ4 genotype (whilst controlling for vascular risk factor, gender, cognitive status and age) we are able to identify changes in white matter associated with carrying an ApoE Ɛ4 allele. We found potentially significant regions (Puncorrected < 0:05) near the hippocampus and the posterior cingulum that were independent of voxels that correlated with age or clinical dementia rating (CDR) status suggesting that ApoE may affect cognitive decline via a pathway in dependent of normal aging and acute insults that can be measured by CDR and Framingham Coronary Risk Score (FCRS).

  14. Examining the Relationship between Teachers&apos; Instructional Practices and Students&apos; Mathematics Achievement

    ERIC Educational Resources Information Center

    Firmender, Janine M.; Gavin, M. Katherine; McCoach, D. Betsy

    2014-01-01

    The purpose of this study was to determine whether relationships existed between teachers&apos; implementation of two specific discourse-related instructional practices and students&apos; mathematics achievement in geometry and measurement as part of a research study on the effectiveness of an advanced mathematics curriculum for kindergarten and…

  15. [Effect of Huanglian Jiedu Decoction on Monocyte Development in apoE Gene Knockout Mice].

    PubMed

    Chen, Bing; Kong, Ya-xian; Ll, Yu-mei; Xue, Xin; Zhang, Jian-ping; Zeng, Hui; Hu, Jing- qing; Ma, Ya-luan

    2016-01-01

    To observe monocyte (Mo) development in wild type C57BL/6 mice and apoE gene knockout (apoE(-/-)) mice, and to evaluate the immuno-regulatory effect of Huanglian Jiedu Decoction (HJD) on peripheral Mo development in apoE(-/-) mice. Four, 8, 12, and 16 weeks old female C57BL/6 mice were set up as control groups of different ages, while 4, 8, 12, and 16 weeks old female apoE(-/-) mice were set up as hyperlipidemia groups of different ages. Four-week old female C57BL/6 mice were recruited as a blank group. Four-week old female apoE(-/-) mice were randomly divided into the control group, the Western medicine group, and the Chinese medicine group by paired comparison, 5 in each group. Equivalent clinical dose was administered to mice according to body weight. Mice in the Western medicine group were administered with Atrovastatin at the daily dose of 10 mg/kg by gastrogavage, while those in the Chinese medicine group were administered with HJD at the daily dose of 5 g/kg by gastrogavage. Body weight was detected each week. After 4 weeks blood lipids levels (such as TG, TC, LDL-C, and HDL-C), and the proportions of Mo and Ly6c(hi) were detected. Compared with 4-week-old homogenic mice, the proportion of Mo decreased in 16-week-old C57BL/6 mice (P < 0.05). Levels of TC and TG, and the proportion of Ly6c(hi) subtype increased, but the proportion of Mo de- creased in 8-week-old apoE(-/-) mice (P <0. 05). Levels of TC, TG, and LDL-C increased in 12-week-old apoE(-/-) mice (P < 0.05). Levels of TC, TG, LDL-C, and HDL-C increased in 16-week-old apoE(-/-) mice (P < 0.05, P < 0.01). Compared with 8-week-old homogenic mice, the proportion of Mo decreased in 16-week-old C57BL/6 mice (P < 0.05); levels of TC and LDL-C increased in 12-week-old apoE(-/-) mice (P < 0.05); levels of TC and HDL-C increased in 16-week-old apoE(-/-) mice (P < 0.05, P < 0.01). Compared with C57BL/6 mice of the same age, TC and TG increased, HDL-C decreased (P < 0.01) in 4-and 8-week-old apoE(-/-) mice (P

  16. The effects of fish oil consumption on cardiovascular remodeling in ApoE deficient mice.

    PubMed

    Cleverley, Kelby; Du, Xiaozhou; Premecz, Sheena; Le, Khuong; Zeglinski, Matthew; Nicholson, Tiffany; Goh, Chun Y; Lu, Yan; Anderson, Hope D; Moghadasian, Mohammed H; Jassal, Davinder S

    2013-11-01

    Owing to their spontaneous development of atherosclerosis, apolipoprotein E knockout mice (ApoE(KO)) are one of the best studied animal models for this disease. Little is known about the utility of various omega-3 fatty acid regimens, in particular fish oils, in preventing cardiac disease in ApoE(KO) mice. The purpose of this study was to determine the cardiovascular effects of omega-3 fatty acid supplementation with either safflower oil (control), fish oil, flaxseed oil, or designed oil in ApoE(KO) mice fed a high-fat diet for a total of 16 weeks. In-vivo cardiac function was assessed weekly using murine echocardiography. Blood pressure, plasma lipid levels, and brain natriuretic peptide (BNP) were serially measured. The results show that ApoE(KO) mice fed fish oil demonstrated an increase in left ventricular wall thickness as a result of increased afterload. Despite chronic treatment with fish oil over 16 weeks, blood pressure increased in ApoE(KO) mice by 20% compared with the baseline. Both echocardiographic evidence of left ventricular hypertrophy and biochemical increase in BNP levels confirmed diastolic dysfunction in ApoE(KO) mice fed fish oil. This suggests that high-fat diet supplemented with fish oil may lead to adverse cardiovascular effects in ApoE deficient mice.

  17. ApoE Genotype and Alzheimer's Disease in Adults with Down Syndrome: Meta-Analysis.

    ERIC Educational Resources Information Center

    Prashner, V. P.; Chowdhury, T. A.; Rowe, B. R.; Bain, S. C.

    1997-01-01

    ApoE gene polymorphism was examined in 100 adults with Down syndrome with and without dementia (Alzheimer's disease) and 346 control subjects. Additionally, a meta analysis of studies (total N=480 subjects) was performed. Results indicated a similar incidence of the gene across groups but subjects with the allele tended to an earlier onset of…

  18. Extension&apos;s Role in Developing a Farmers&apos; Market

    ERIC Educational Resources Information Center

    Civittolo, David

    2012-01-01

    Interest in access to local food is increasing. Communities of all types and sizes have volunteers interested in creating farmers&apos; markets. Extension can play an important role in the development of farmers&apos; markets because it is ideally suited to organize and coordinate these volunteer energies. By helping community volunteers focus…

  19. ApoE Genotype and Alzheimer's Disease in Adults with Down Syndrome: Meta-Analysis.

    ERIC Educational Resources Information Center

    Prashner, V. P.; Chowdhury, T. A.; Rowe, B. R.; Bain, S. C.

    1997-01-01

    ApoE gene polymorphism was examined in 100 adults with Down syndrome with and without dementia (Alzheimer's disease) and 346 control subjects. Additionally, a meta analysis of studies (total N=480 subjects) was performed. Results indicated a similar incidence of the gene across groups but subjects with the allele tended to an earlier onset of…

  20. Extension&apos;s Role in Developing a Farmers&apos; Market

    ERIC Educational Resources Information Center

    Civittolo, David

    2012-01-01

    Interest in access to local food is increasing. Communities of all types and sizes have volunteers interested in creating farmers&apos; markets. Extension can play an important role in the development of farmers&apos; markets because it is ideally suited to organize and coordinate these volunteer energies. By helping community volunteers focus…

  1. A molecular pathway of neurodegeneration linking alpha-synuclein to ApoE and Abeta peptides.

    PubMed

    Gallardo, Gilbert; Schlüter, Oliver M; Südhof, Thomas C

    2008-03-01

    Pathogenic aggregates of alpha-synuclein are thought to contribute to the development of Parkinson's disease. Inclusion bodies containing alpha-synuclein are present in Parkinson's disease and other neurodegenerative diseases, including Alzheimer's disease. Moreover, alpha-synuclein mutations are found in cases of familial Parkinson's disease, and transgenic overexpression of alpha-synuclein causes neurodegeneration in mice. The molecular mechanisms involved, however, remain incompletely understood. Here we show that, in transgenic mice, alpha-synuclein induced neurodegeneration involves activation of the ubiquitin/proteasome system, a massive increase in apolipoprotein E (ApoE) levels and accumulation of insoluble mouse Abeta. ApoE was not protective, but was injurious, as deletion of ApoE delayed the neurodegeneration caused by alpha-synuclein and suppressed the accumulation of Abeta. Our data reveal a molecular link between central pathogenic mechanisms implicated in Parkinson's disease and Alzheimer's disease and suggest that intracellular alpha-synuclein is pathogenic, at least in part, by activation of extracellular signaling pathways involving ApoE.

  2. Let&apos;s Burn Them All: A Librarian&apos;s View

    ERIC Educational Resources Information Center

    Werner, Roye

    2014-01-01

    In this rejoinder to "Let&apos;s Burn Them All," a librarian supports the author&apos;s case for eliminating textbooks in the teaching of management and organizational behavior. A move away from textbooks would free libraries from worrying about whether and to what extent to provide expensive textbook access to students, a long-standing…

  3. Relations among Teachers&apos; Emotion Socialization Beliefs and Practices and Preschoolers&apos; Emotional Competence

    ERIC Educational Resources Information Center

    Morris, Carol A. S.; Denham, Susanne A.; Bassett, Hideko H.; Curby, Timothy W.

    2013-01-01

    Research Findings: Utilizing a 3-part model of emotion socialization that included modeling, contingent responding, and teaching, this study examined the associations between 44 teachers&apos; self-reported and observed emotion socialization practices and 326 preschoolers&apos; emotion knowledge and observed emotional behavior. Multilevel analyses…

  4. Let&apos;s Burn Them All: A Librarian&apos;s View

    ERIC Educational Resources Information Center

    Werner, Roye

    2014-01-01

    In this rejoinder to "Let&apos;s Burn Them All," a librarian supports the author&apos;s case for eliminating textbooks in the teaching of management and organizational behavior. A move away from textbooks would free libraries from worrying about whether and to what extent to provide expensive textbook access to students, a long-standing…

  5. Examining the Relationship between Teachers&apos; Instructional Practices and Students&apos; Mathematics Achievement

    ERIC Educational Resources Information Center

    Firmender, Janine M.; Gavin, M. Katherine; McCoach, D. Betsy

    2014-01-01

    The purpose of this study was to determine whether relationships existed between teachers&apos; implementation of two specific discourse-related instructional practices and students&apos; mathematics achievement in geometry and measurement as part of a research study on the effectiveness of an advanced mathematics curriculum for kindergarten and…

  6. Parallels in Preschoolers&apos; and Adults&apos; Judgments about Ownership Rights and Bodily Rights

    ERIC Educational Resources Information Center

    Van de Vondervoort, Julia W.; Friedman, Ori

    2015-01-01

    Understanding ownership rights is necessary for socially appropriate behavior. We provide evidence that preschoolers&apos; and adults&apos; judgments of ownership rights are related to their judgments of bodily rights. Four-year-olds (n = 70) and adults (n = 89) evaluated the acceptability of harmless actions targeting owned property and body…

  7. Maturation of secreted HCV particles by incorporation of secreted ApoE protects from antibodies by enhancing infectivity.

    PubMed

    Bankwitz, Dorothea; Doepke, Mandy; Hueging, Kathrin; Weller, Romy; Bruening, Janina; Behrendt, Patrick; Lee, Ji-Young; Vondran, Florian W R; Manns, Michael P; Bartenschlager, Ralf; Pietschmann, Thomas

    2017-09-01

    Hepatitis C virus (HCV) evades humoral immunity and establishes chronic infections. Virus particles circulate in complex with lipoproteins facilitating antibody escape. Apolipoprotein E (ApoE) is essential for intracellular HCV assembly and for HCV cell entry. We aimed to explore if ApoE released from non-infected cells interacts with and modulates secreted HCV particles. ApoE secreted from non-infected cells was incubated with HCV from primary human hepatocytes or Huh-7.5 cells. Co-immunoprecipitation, viral infectivity and neutralization experiments were conducted. Physiological levels of secreted ApoE (10-60µg/ml) enhanced the infectivity of HCV up to 8-fold across all genotypes, which indirectly decreased virus neutralization by antibodies targeting E1 or E2 up to 10-fold. Infection enhancement was observed for particles produced in primary human hepatocytes and Huh-7.5 cells. Selective depletion of ApoE ablated infection enhancement. Addition of HA-tagged ApoE to HCV particles permitted co-precipitation of HCV virions. Serum ApoE levels ranged between 10-60µg/ml, which is ca 100-fold higher than in Huh-7.5 conditioned cell culture fluids. Serum-derived HCV particles carried much higher amounts of ApoE than cell culture-derived HCV particles. Serum ApoE levels correlated with efficiency of co-precipitation of HCV upon exogenous addition of HA-ApoE. ApoE-dependent infection enhancement was independent of the hypervariable region 1 and SR-B1, but was dependent on heparan sulfate proteoglycans (HSPGs). Physiological quantities of secreted ApoE stimulate HCV infection and increase antibody escape, by incorporating into virus particles and enhancing particle interactions with cellular HSPGs. Thus, secreted particles undergo ApoE-dependent maturation to enhance infectivity and to facilitate evasion from neutralizing antibodies. Lay summary: This study shows that HCV particle infectivity is remodeled by secreted ApoE after particle release from cells. Fluctuation of

  8. Association between arterial stiffness and peripheral artery disease as measured by radial artery tonometry.

    PubMed

    Zahner, Greg J; Gruendl, Magdalena A; Spaulding, Kimberly A; Schaller, Melinda S; Hills, Nancy K; Gasper, Warren J; Grenon, S Marlene

    2017-07-26

    Arterial stiffness and peripheral artery disease (PAD) are both associated with an elevated risk of major adverse cardiac events; however, the association between arterial stiffness and PAD is less well characterized. The goal of this study was to examine the association between parameters of radial artery tonometry, a noninvasive measure of arterial stiffness, and PAD. We conducted a cross-sectional study of 134 vascular surgery outpatients (controls, 33; PAD, 101) using arterial applanation tonometry. Central augmentation index (AIX) normalized to 75 beats/min and peripheral AIX were measured using radial artery pulse wave analysis. Pulse wave velocity was recorded at the carotid and femoral arteries. PAD was defined as symptomatic claudication with an ankle-brachial index of <0.9 or a history of peripheral revascularization. Controls had no history of atherosclerotic vascular disease and an ankle-brachial index ≥0.9. Among the 126 participants with high-quality tonometry data, compared with controls (n = 33), patients with PAD (n = 93) were older, with higher rates of hypertension, hyperlipidemia, diabetes, and smoking (P < .05). Patients with PAD also had greater arterial stiffness as measured by central AIX, peripheral AIX, and pulse wave velocity (P < .05). In a multivariable model, a significantly increased odds of PAD was associated with each 10-unit increase in central AIX (odds ratio, 2.1; 95% confidence interval, 1.1-3.9; P = .03) and peripheral AIX (odds ratio, 1.9; 95% confidence interval, 1.2-3.2; P = .01). In addition, central and peripheral AIX were highly correlated (r120 = 0.76; P < .001). In a cross-sectional analysis, arterial stiffness as measured by the AIX is independently associated with PAD, even when adjusting for several atherosclerotic risk factors. Further prospective data are needed to establish whether radial artery tonometry could be a tool for risk stratification in the PAD population. Copyright © 2017 Society for

  9. Middle Cerebral Artery Calcification

    PubMed Central

    Kao, Hung-Wen; Liou, Michelle; Chung, Hsiao-Wen; Liu, Hua-Shan; Tsai, Ping-Huei; Chiang, Shih-Wei; Chou, Ming-Chung; Peng, Giia-Sheun; Huang, Guo-Shu; Hsu, Hsian-He; Chen, Cheng-Yu

    2015-01-01

    Abstract Calcification of the middle cerebral artery (MCA) is uncommon in the healthy elderly. Whether calcification of the MCA is associated with cerebral ischemic stroke remains undetermined. We intended to investigate the association using Agatston calcium scoring of the MCA. This study retrospectively included 354 subjects with ischemic stroke in the MCA territory and 1518 control subjects who underwent computed tomography (CT) of the brain. We recorded major known risk factors for ischemic stroke, including age, gender, hypertension, diabetes mellitus, smoking, hyperlipidemia, and obesity, along with the MCA calcium burden, measured with the Agatston calcium scoring method. Univariate and modified logistic regression analyses were performed to examine the association between the MCA calcification and ischemic stroke. The univariate analyses showed significant associations of ischemic stroke with age, hypertension, diabetes mellitus, smoking, total MCA Agatston score, and the presence of calcification on both or either side of the MCA. Subjects with the presence of MCA calcification on both or either side of the MCA were 8.46 times (95% confidence interval, 4.93–14.53; P < 0.001) more likely to have a cerebral infarct than subjects without MCA calcification after adjustment for the major known risk factors, including age, hypertension, diabetes mellitus, and smoking. However, a higher degree of MCA calcification reflected by the Agatston score was not associated with higher risk of MCA ischemic stroke after adjustment for the confounding factors and presence of MCA calcification. These results suggest that MCA calcification is associated with ischemic stroke in the MCA territory. Further prospective studies are required to verify the clinical implications of the MCA calcification. PMID:26683969

  10. Pulmonary artery sarcoma.

    PubMed

    Blackmon, Shanda H; Reardon, Michael J

    2010-01-01

    Primary heart tumors are rare, and malignant primary heart tumors are only a small subset of these. Most primary malignant tumors are sarcomas arising from the cells of the structural elements of the heart such as blood vessels, muscle, connective tissue, fat and even bone. Unlike most malignancies, where cell type often dictates treatment choices and prognosis and is used for classification, the histology in primary cardiac sarcoma plays little role in determining therapeutic options or prognosis. We have found that anatomic location within the heart is the major determining factor in clinical presentation, treatment options and prognosis in cardiac sarcoma. Therefore, we accordingly classify primary cardiac sarcomas into right heart sarcomas, left heart sarcomas and pulmonary artery (PA) sarcomas. Since the first autopsy report of a primary PA sarcoma in 1923, there have been fewer than 250 cases reported in the English literature. Most of these reports have been single autopsy or case reports, and patient prognosis has generally been dismal. Since few institutions and even fewer individual physicians acquire much exposure to this disease, the diagnostic and treatment approaches have remained unresolved. Our cardiac sarcoma group working at the Methodist DeBakey Heart & Vascular Center and the MD Anderson Cancer Center has undertaken a systematic study of this disease, and operated on 9 patients using a radical resection with curative intent and multimodality approach. Based on this work, we have suggested a diagnostic strategy, treatment approach and staging system for primary PA sarcoma. A substantial improvement in patient survival over historical controls has also been demonstrated and will be discussed in this review.

  11. A Dietary Treatment Improves Cerebral Blood Flow and Brain Connectivity in Aging apoE4 Mice

    PubMed Central

    Wiesmann, Maximilian; Zerbi, Valerio; Jansen, Diane; Haast, Roy; Lütjohann, Dieter; Broersen, Laus M.; Heerschap, Arend

    2016-01-01

    APOE ε4 (apoE4) polymorphism is the main genetic determinant of sporadic Alzheimer's disease (AD). A dietary approach (Fortasyn) including docosahexaenoic acid, eicosapentaenoic acid, uridine, choline, phospholipids, folic acid, vitamins B12, B6, C, and E, and selenium has been proposed for dietary management of AD. We hypothesize that the diet could inhibit AD-like pathologies in apoE4 mice, specifically cerebrovascular and connectivity impairment. Moreover, we evaluated the diet effect on cerebral blood flow (CBF), functional connectivity (FC), gray/white matter integrity, and postsynaptic density in aging apoE4 mice. At 10–12 months, apoE4 mice did not display prominent pathological differences compared to wild-type (WT) mice. However, 16–18-month-old apoE4 mice revealed reduced CBF and accelerated synaptic loss. The diet increased cortical CBF and amount of synapses and improved white matter integrity and FC in both aging apoE4 and WT mice. We demonstrated that protective mechanisms on vascular and synapse health are enhanced by Fortasyn, independent of apoE genotype. We further showed the efficacy of a multimodal translational approach, including advanced MR neuroimaging, to study dietary intervention on brain structure and function in aging. PMID:27034849

  12. ApoE and S-100 expression and its significance in the brain tissue of rats with focal contusion.

    PubMed

    Wang, Z L; Chai, R F; Yang, W S; Liu, Y; Qin, H; Wu, H; Zhu, X F; Wang, Y X; Dangmurenjiafu, G

    2015-12-29

    This study explored the effect of focal cerebral contusion on the expression of ApoE and S-100, and its significance in determining the time of brain injury. Based on a rat model of cerebral contusion, immunohistochemistry was used to analyze the expressions of S-100 and ApoE at different time points after injury. Thirty minutes following cerebral contusion, ApoE protein expression was significantly increased in cortex neurons (P < 0.01), and S-100 protein expression was significantly (P < 0.001) elevated 2 h after cerebral contusion. Over time, the number of ApoE and S-100 positively expressing cells gradually increased. Three days after injury, ApoE was widely distributed throughout the tissue and the number of ApoE-positive cells and staining intensity reached a peak. ApoE expression decreased after this time point. Five days after cerebral contusion, the number of S-100-positive cells reached a peak level of expression higher than that in the control group. Our data demonstrate that the expression of ApoE and S-100 correlated with the progression of focal cerebral contusion. This suggests that both proteins may serve as effective biomarkers of focal cerebral contusions.

  13. Apolipoprotein E level and cholesterol are associated with reduced synaptic amyloid beta in Alzheimer’s disease and apoE TR mouse cortex

    PubMed Central

    Arold, Stephen; Sullivan, Patrick; Bilousova, Tina; Teng, Edmond; Miller, Carol A.; Poon, Wayne W.; Vinters, Harry V.; Cornwell, Lindsey B.; Saing, Tommy; Cole, Gregory M.

    2012-01-01

    The apolipoprotein E4 allele (APOE4) contributes to Alzheimer’s disease (AD) risk and APOE2 is protective, but the relevant cellular mechanisms are unknown. We have used flow cytometry analysis to measure apolipoprotein E (apoE) and amyloid beta peptide (Aβ) levels in large populations of synaptic terminals from AD and aged cognitively normal controls, and demonstrate that modest but significant increases in soluble apoE levels accompany elevated Aβ in AD cortical synapses and in an APP/PS1 rat model of AD. Dual labeling experiments document co-localization of apoE and Aβ in individual synapses with concentration of Aβ in a small population of apoE-positive synapses in both AD and controls. Consistent with a clearance role, the apoE level was higher in Aβ-positive synapses in control cases. In aged targeted replacement mice expressing human apoE, apoE2/4 synaptic terminals demonstrated the highest level of apoE and the lowest level of Aβ compared to apoE3/3 and apoE4/4 lines. In apoE2/4 terminals, the pattern of immunolabeling for apoE and Aβ closely resembled the pattern in human control cases, and elevated apoE was accompanied by elevated free cholesterol in apoE2/4 synaptic terminals. These results are consistent with a role for APOE in Aβ clearance in AD synapses, and suggest that optimal lipidation of apoE2 compared to E3 and E4 makes an important contribution to Aβ clearance and synaptic function. PMID:22020632

  14. Dominant expression of type III hyperlipoproteinemia. Pathophysiological insights derived from the structural and kinetic characteristics of ApoE-1 (Lys146-->Glu).

    PubMed Central

    Mann, W A; Lohse, P; Gregg, R E; Ronan, R; Hoeg, J M; Zech, L A; Brewer, H B

    1995-01-01

    Type III hyperlipoproteinemia is characterized by delayed chylomicron and VLDL remnant catabolism and is associated with homozygosity for the apoE-2 allele. We have identified a kindred in which heterozygosity for an apoE mutant, apoE-1 (Lys146-->Glu), is dominantly associated with the expression of type III hyperlipoproteinemia. DNA sequence analysis of the mutant apoE gene revealed a single-point mutation that resulted in the substitution of glutamic acid (GAG) for lysine (AAG) at residue 146 in the proposed receptor-binding domain of apoE. The pathophysiological effect of this mutation was investigated in vivo by kinetic studies in the patient and six normal subjects, and in vitro by binding studies of apoE-1 (Lys146-->Glu) to LDL receptors on human fibroblasts and to heparin. The kinetic studies revealed that apoE-1 (Lys146-->Glu) was catabolized significantly slower than apoE-3 in normals (P < 0.005). In the proband, the plasma residence times of both apoEs were substantially longer and the production rate of total apoE was about two times higher than in the control subjects. ApoE-1 (Lys146-->Glu) was defective in interacting with LDL receptors, and its ability to displace LDL in an in vitro assay was reduced to 7.7% compared with apoE-3. The affinity of apoE-1 (Lys146-->Glu) to heparin was also markedly reduced compared with both apoE-2 (Arg158-->Cys) and apoE-3. These abnormal in vitro binding characteristics and the altered in vivo metabolism of apoE-1 (Lys146-->Glu) are proposed to result in the functional dominance of this mutation in the affected kindred. Images PMID:7635945

  15. The safety of brachial artery puncture for arterial blood sampling.

    PubMed

    Okeson, G C; Wulbrecht, P H

    1998-09-01

    This study was designed to determine the incidence of complications in a sample of 6,185 brachial artery punctures for arterial blood gas analysis. The study sample was comprised of adult patients who had arterial blood gas analysis ordered in the course of their clinical evaluations in a multispecialty clinic and hospital affiliated with a university school of medicine. Subjects were entered prospectively at the time the procedure was done. The overall incidence of all complications was 2.0%. Immediate limb pain or parenthesias occurred in 1.1%, while the onset of symptoms was delayed up to 24 h in 0.9%. Hematoma formation occurred in only 0.06%. None of the complications was considered to be of major impact, in that none was associated with limb ischemia or other objective abnormalities. Only one subject required analgesic medication to control pain that ultimately subsided spontaneously without deficit. We believe that brachial artery puncture, when properly performed, is a safe and reliable alternative route for obtaining arterial blood for gas analysis.

  16. Signs and Symptoms of Artery Disease | Coronary Artery Disease | NIH MedlinePlus the Magazine

    MedlinePlus

    ... of this page please turn Javascript on. Feature: Coronary Artery Disease Signs and Symptoms of Artery Disease Past Issues / ... narrows or blocks these arteries—a condition called coronary artery disease (CAD) or coronary heart disease (CHD) occurs. A ...

  17. Hepatic caveolin-1 is enhanced in Cyp27a1/ApoE double knockout mice.

    PubMed

    Zurkinden, Line; Mansour, Yosef T; Rohrbach, Beatrice; Vogt, Bruno; Mistry, Hiten D; Escher, Geneviève

    2016-10-01

    Sterol 27-hydroxylase (CYP27A1) is involved in bile acid synthesis and cholesterol homoeostasis. Cyp27a1((-/-))/Apolipoprotein E((-/-)) double knockout mice (DKO) fed a western diet failed to develop atherosclerosis. Caveolin-1 (CAV-1), the main component of caveolae, is associated with lipid homoeostasis and has regulatory roles in vascular diseases. We hypothesized that liver CAV-1 would contribute to the athero-protective mechanism in DKO mice. Cyp27a1((+/+))/ApoE((-/-)) (ApoE KO), Cyp27a1((+/-))/ApoE((-/-)) (het), and DKO mice were fed a western diet for 2 months. Atherosclerotic plaque and CAV-1 protein were quantified in aortas. Hepatic Cav-1 mRNA was assessed using qPCR, CAV-1 protein by immunohistochemistry and western blotting. Total hepatic and plasma cholesterol was measured using chemiluminescence. Cholesterol efflux was performed in RAW264.7 cells, using mice plasma as acceptor. CAV-1 protein expression in aortas was increased in endothelial cells of DKO mice and negatively correlated with plaque surface (P < 0.05). In the liver, both CAV-1 protein and mRNA expression doubled in DKO, compared to ApoE KO and het mice (P < 0.001 for both) and was negatively correlated with total hepatic cholesterol (P < 0.05). Plasma from DKO, ApoE KO and het mice had the same efflux capacity. In the absence of CYP27A1, CAV-1 overexpression might have an additional athero-protective role by partly overcoming the defect in CYP27A1-mediated cholesterol efflux.

  18. Longitudinal Links between Fathers&apos; and Mothers&apos; Harsh Verbal Discipline and Adolescents&apos; Conduct Problems and Depressive Symptoms

    ERIC Educational Resources Information Center

    Wang, Ming-Te; Kenny, Sarah

    2014-01-01

    This study used cross-lagged modeling to examine reciprocal relations between maternal and paternal harsh verbal discipline and adolescents&apos; conduct problems and depressive symptoms. Data were from a sample of 976 two-parent families and their children (51% males; 54% European American, 40% African American). Mothers&apos; and fathers&apos;…

  19. Living with Letters: An Exploration of Parents&apos;/Caregivers&apos; Perceptions of Shared Learning Activities, Socially Constructed Meaning, and Preschoolers&apos; Literacy Development

    ERIC Educational Resources Information Center

    Janaszak, Jaclyn

    2013-01-01

    The researcher&apos;s purpose in this descriptive case study, drawn from a suburban school population of pre-kindergarten children and their parents/caregivers was: (a) to explore parents&apos;/caregivers&apos; perceptions of the concept of emergent literacy and how their children develop the ability to read and write; (b) to document the ways in…

  20. Longitudinal Links between Fathers&apos; and Mothers&apos; Harsh Verbal Discipline and Adolescents&apos; Conduct Problems and Depressive Symptoms

    ERIC Educational Resources Information Center

    Wang, Ming-Te; Kenny, Sarah

    2014-01-01

    This study used cross-lagged modeling to examine reciprocal relations between maternal and paternal harsh verbal discipline and adolescents&apos; conduct problems and depressive symptoms. Data were from a sample of 976 two-parent families and their children (51% males; 54% European American, 40% African American). Mothers&apos; and fathers&apos;…

  1. Fathers&apos; and Mothers&apos; Home Literacy Involvement and Children&apos;s Cognitive and Social Emotional Development: Implications for Family Literacy Programs

    ERIC Educational Resources Information Center

    Baker, Claire E.

    2013-01-01

    The relations between fathers&apos; and mothers&apos; home literacy involvement at 24 months and children&apos;s cognitive and social emotional development in preschool were examined using a large sample of African American and Caucasian families ("N" = 5190) from the Early Childhood Longitudinal Study-Birth Cohort (ECLS-B). Hierarchical…

  2. Atherosclerotic Oxalosis in Coronary Arteries

    PubMed Central

    Fishbein, Gregory A.; Micheletti, Robert G.; Currier, Judith S.; Singer, Elyse; Fishbein, Michael C.

    2008-01-01

    Summary There are many forms of oxalosis, with deposition of oxalate crystals in various organs, including arteries. In this retrospective study we describe deposition of calcium oxalate crystals within atherosclerotic plaques in coronary arteries of 4 patients, a site of oxalate deposition not previously reported. We suggest the phrase “atherosclerotic oxalosis” for this finding. Background Systemic oxalosis may be hereditary or acquired. In these cases, calcium oxalate deposits have been reported in numerous tissues, including the media of arteries. In any category, calcium oxalate deposition has not been described within atherosclerotic plaques in any arteries. Methods As part of a retrospective clinicopathologic study, 80 hearts were obtained from the National Neurologic AIDS Bank in an effort to study coronary atherosclerosis in patients infected with HIV. The population consisted of 66 HIV-positive and 14 HIV-negative patients with an average age of 47 years; 79% were males. Proximal coronary arteries were serially-sectioned and processed routinely. Sections were studied by H&E staining, and in selected cases, von Kossa stain, and alizarin red S under different conditions, including polarized light, to allow distinction of calcium phosphate from calcium oxalate. Medical histories, autopsy reports, and general autopsy slides were reviewed. Results In 4 patients (3 with AIDS) calcium oxalate crystals were observed within atherosclerotic plaques in the coronary arteries. Similar deposits were seen in the thyroid gland and other organs, but not in the kidneys. None of the patients had chronic renal failure. Conclusion The calcium oxalate crystal deposits observed in the atherosclerotic plaques in coronary arteries of these 4 patients are unique in two ways: 1) these deposits have not previously been described in atherosclerotic plaques, 2) the patients did not demonstrate any of the recognized patterns of oxalosis. We suggest the phrase

  3. Nrf2-dependent gene expression is affected by the proatherogenic apoE4 genotype-studies in targeted gene replacement mice.

    PubMed

    Graeser, Anne-Christin; Boesch-Saadatmandi, Christine; Lippmann, Jana; Wagner, Anika E; Huebbe, Patricia; Storm, Niels; Höppner, Wolfgang; Wiswedel, Ingrid; Gardemann, Andreas; Minihane, Anne M; Döring, Frank; Rimbach, Gerald

    2011-10-01

    An apoE4 genotype is an important risk factor for cardiovascular and other chronic diseases. The higher cardiovascular disease risk of apoE4 carriers as compared to the apoE3 genotype has been mainly attributed to the differences in blood lipids between the two genotype subgroups. Recently, a potential protective role of the transcription factor Nrf2 in cardiovascular disease prevention has been suggested. In this study, we show that Nrf2-dependent gene expression is affected by the apoE genotype. ApoE4 vs. apoE3 mice exhibited lower hepatic Nrf2 nuclear protein levels. Furthermore, mRNA and protein levels of Nrf2 target genes including glutathione-S-transferase, heme oxygenase-1 and NAD(P)H dehydrogenase, quinone 1 were significantly lower in apoE4 as compared to apoE3 mice. Lower hepatic mRNA levels of phase II enzymes, as observed in apoE4 vs. apoE3 mice, were accompanied by higher mRNA levels of phase I enzymes including Cyp26a1 and Cyp3a16. Furthermore, miRNA-144, miRNA-125b, and miRNA-29a involved in Nrf2 signaling, inflammation, and regulation of phase I enzyme gene expression were affected by the apoE genotype. We provide first evidence that Nrf2 is differentially regulated in response to the apoE genotype.

  4. Anomalous superficial ulnar artery based flap

    PubMed Central

    Ramani, C. V.; Kundagulwar, Girish K.; Prabha, Yadav S.; Dushyanth, Jaiswal

    2014-01-01

    Upper limb shows a large number of arterial variations. This case report describes the presence of additional superficial ulnar artery which was used to raise a pedicle flap to cover an arm defect thus avoided using the main vessel of the forearm - radial or ulnar artery. Vascular anomalies occurring in the arm and forearm tend to increase the likelihood of damaging the superficial anomalous arteries during surgery. Superficial ulnar or radial arteries have been described to originate from the upper third of the brachial artery; here we report the origin of the anomalous superficial ulnar artery originating from the brachial artery at the level of elbow with the concomitant presence of normal deep radial and ulnar arteries. PMID:24987217

  5. The central role of arterial retention of cholesterol-rich apolipoprotein-B-containing lipoproteins in the pathogenesis of atherosclerosis: a triumph of simplicity.

    PubMed

    Borén, Jan; Williams, Kevin Jon

    2016-10-01

    Today, it is no longer a hypothesis, but an established fact, that increased plasma concentrations of cholesterol-rich apolipoprotein-B (apoB)-containing lipoproteins are causatively linked to atherosclerotic cardiovascular disease (ASCVD) and that lowering plasma LDL concentrations reduces cardiovascular events in humans. Here, we review evidence behind this assertion, with an emphasis on recent studies supporting the 'response-to-retention' model - namely, that the key initiating event in atherogenesis is the retention, or trapping, of cholesterol-rich apoB-containing lipoproteins within the arterial wall. New clinical trials have shown that ezetimibe and anti-PCSK9 antibodies - both nonstatins - lower ASCVD events, and they do so to the same extent as would be expected from comparable plasma LDL lowering by a statin. These studies demonstrate beyond any doubt the causal role of apoB-containing lipoproteins in atherogenesis. In addition, recent laboratory experimentation and human Mendelian randomization studies have revealed novel information about the critical role of apoB-containing lipoproteins in atherogenesis. New information has also emerged on mechanisms for the accumulation in plasma of harmful cholesterol-rich and triglyceride-rich apoB-containing remnant lipoproteins in states of overnutrition. Like LDL, these harmful cholesterol-rich and triglyceride-rich apoB-containing remnant lipoprotein remnants become retained and modified within the arterial wall, causing atherosclerosis. LDL and other cholesterol-rich, apoB-containing lipoproteins, once they become retained and modified within the arterial wall, cause atherosclerosis. This simple, robust pathophysiologic understanding may finally allow us to eradicate ASCVD, the leading killer in the world.

  6. Surface Roughness Detection of Arteries via Texture Analysis of Ultrasound Images for Early Diagnosis of Atherosclerosis

    PubMed Central

    Niu, Lili; Qian, Ming; Yang, Wei; Meng, Long; Xiao, Yang; Wong, Kelvin K. L.; Abbott, Derek; Liu, Xin; Zheng, Hairong

    2013-01-01

    There is a strong research interest in identifying the surface roughness of the carotid arterial inner wall via texture analysis for early diagnosis of atherosclerosis. The purpose of this study is to assess the efficacy of texture analysis methods for identifying arterial roughness in the early stage of atherosclerosis. Ultrasound images of common carotid arteries of 15 normal mice fed a normal diet and 28 apoE−/− mice fed a high-fat diet were recorded by a high-frequency ultrasound system (Vevo 2100, frequency: 40 MHz). Six different texture feature sets were extracted based on the following methods: first-order statistics, fractal dimension texture analysis, spatial gray level dependence matrix, gray level difference statistics, the neighborhood gray tone difference matrix, and the statistical feature matrix. Statistical analysis indicates that 11 of 19 texture features can be used to distinguish between normal and abnormal groups (p<0.05). When the 11 optimal features were used as inputs to a support vector machine classifier, we achieved over 89% accuracy, 87% sensitivity and 93% specificity. The accuracy, sensitivity and specificity for the k-nearest neighbor classifier were 73%, 75% and 70%, respectively. The results show that it is feasible to identify arterial surface roughness based on texture features extracted from ultrasound images of the carotid arterial wall. This method is shown to be useful for early detection and diagnosis of atherosclerosis. PMID:24146940

  7. APOE gene polymorphisms and diabetic peripheral neuropathy.

    PubMed

    Monastiriotis, Christodoulos; Papanas, Nikolaos; Veletza, Stavroula; Maltezos, Efstratios

    2012-09-08

    Genetic factors may influence the natural course of diabetic peripheral neuropathy and explain some of its variability. The aim of this review was to examine the association between apolipoprotein E (apoE) gene polymorphisms and diabetic peripheral neuropathy. Four relevant studies were identified. The two earlier works provided evidence that the ɛ4 allele is a risk factor for this complication, while the two more recent studies were negative. Important differences in the methodology used and in the populations included are obvious, rendering difficult the comparison between studies. In conclusion, the association between APOE gene polymorphisms and diabetic peripheral neuropathy is still unclear. Available evidence is rather limited and results have so far been contradictory. Future studies should employ more robust methodology, adjusting for potential confounders and for the prevalence of neuropathy in the general population with diabetes.

  8. Atherosclerotic oxalosis in coronary arteries.

    PubMed

    Fishbein, Gregory A; Micheletti, Robert G; Currier, Judith S; Singer, Elyse; Fishbein, Michael C

    2008-01-01

    Systemic oxalosis may be hereditary or acquired. In these cases, calcium oxalate deposits have been reported in numerous tissues, including the media of arteries. In any category, calcium oxalate deposition has not been described within atherosclerotic plaques in any arteries. As part of a retrospective clinicopathologic study, 80 hearts were obtained from the National Neurological AIDS Bank in an effort to study coronary atherosclerosis in patients infected with HIV. The population consisted of 66 HIV-positive and 14 HIV-negative patients with an average age of 47 years; 79% were males. Proximal coronary arteries were serially sectioned and processed routinely. Sections were studied by hematoxylin and eosin staining and, in selected cases, von Kossa stain and alizarin red S under different conditions, including polarized light, to allow distinction of calcium phosphate from calcium oxalate. Medical histories, autopsy reports, and general autopsy slides were reviewed. In four patients (three with AIDS), calcium oxalate crystals were observed within atherosclerotic plaques in the coronary arteries. Similar deposits were seen in the thyroid gland and other organs but not in the kidneys. None of the patients had chronic renal failure. The calcium oxalate crystal deposits observed in the atherosclerotic plaques in the coronary arteries of these four patients are unique in two ways: (a) these deposits have not previously been described in atherosclerotic plaques; (b) the patients did not demonstrate any of the recognized patterns of oxalosis. We suggest the phrase "atherosclerotic oxalosis" to describe this finding.

  9. Engineering of arteries in vitro.

    PubMed

    Huang, Angela H; Niklason, Laura E

    2014-06-01

    This review will focus on two elements that are essential for functional arterial regeneration in vitro: the mechanical environment and the bioreactors used for tissue growth. The importance of the mechanical environment to embryological development, vascular functionality, and vascular graft regeneration will be discussed. Bioreactors generate mechanical stimuli to simulate biomechanical environment of arterial system. This system has been used to reconstruct arterial grafts with appropriate mechanical strength for implantation by controlling the chemical and mechanical environments in which the grafts are grown. Bioreactors are powerful tools to study the effect of mechanical stimuli on extracellular matrix architecture and mechanical properties of engineered vessels. Hence, biomimetic systems enable us to optimize chemo-biomechanical culture conditions to regenerate engineered vessels with physiological properties similar to those of native arteries. In addition, this article reviews various bioreactors designed especially to apply axial loading to engineered arteries. This review will also introduce and examine different approaches and techniques that have been used to engineer biologically based vascular grafts, including collagen-based grafts, fibrin-gel grafts, cell sheet engineering, biodegradable polymers, and decellularization of native vessels.

  10. Arterial calcification: A new perspective?

    PubMed

    Nicoll, R; Henein, M

    2017-02-01

    Arterial calcification is commonly seen in atherosclerosis, chronic kidney disease (CKD) and diabetes and has long been considered a natural progression of atherosclerosis. Yet it is a systemic condition, occurring in a wide and diverse range of disease states and no medical treatment for cardiovascular disease has yet found a way to regress it; on the contrary, lipid-lowering therapy may worsen its progression. Although numerous studies have found associations between calcification and biomarkers, none has yet found a unifying mechanism that explains the calcification found in atherosclerosis, CKD or diabetes and many of the biomarkers are equally associated with atheroma development and cardiovascular events. Furthermore, both presence and absence of coronary artery calcification appear predictive of plaque rupture and cardiovascular events, indicating that the association is not causal. This suggests that we are no further forward in understanding the true nature of arterial calcification or its pathogenesis, other than noting that it is 'multifactorial'. This is because most researchers view arterial calcification as a progressive pathological condition which must be treated. Instead, we hypothesise that calcification develops as an immune response to endothelial injury, such as shear stress or oxidative stress in diabetics, and is consequently part of the body's natural defences. This would explain why it has been found to be protective of plaque rupture and why it is unresponsive to lipid-lowering agents. We propose that instead of attempting to treat arterial calcification, we should instead be attempting to prevent or treat all causes of endothelial injury.

  11. Arterial supply of the thumb: Systemic review.

    PubMed

    Miletin, J; Sukop, A; Baca, V; Kachlik, D

    2017-10-01

    We offer a complete systemic review of the anatomy of arteries of the thumb, including their sources in the first web space. Eleven studies were selected from the PubMed, Medline, Embase, Scopus and Ovid databases. Data about each artery of the thumb were obtained; in particular, the incidence and dominance of each of these arteries were calculated. The ulnopalmar digital artery of the thumb (UPDAT) was found in 99.63%, the radiopalmar digital artery of the thumb (RPDAT) in 99.26%, the ulnodorsal digital artery of the thumb (UDDAT) in 83.39%, and the radiodorsal digital artery of the thumb (RDDAT) in 70.38%. The sources for the thumb arteries are the first palmar metacarpal artery (for UPDAT in 63.15%, for RPDAT in 78.88%, for UDDAT in 56.95% and for RDDAT in 41.48%), the first dorsal metacarpal artery (for UPDAT in 20.54%, for RPDAT 2.53%, for UDDAT in 20.62%, and for RDDAT in 4.81%) and the superficial palmar arch, either complete or incomplete (for UPDAT in 25.57%, for RPDAT in 23.04%, for UDDAT in 0%, and for RDDAT in 5.19%). The dominant source could be identified in 88.2% of cases: the first palmar metacarpal artery (66.2%), the first dorsal metacarpal artery (15.5%) and the superficial palmar arch, complete or incomplete (8.2%). Four arteries usually supply the thumb. Any artery in the first web space can be a source for the thumb arteries. We propose a new classification of the arteries of the hand, dividing them into three systems (superficial palmar, deep palmar and dorsal system), and suggest that the term "princeps pollicis artery" be reconsidered and systemic anatomical terms of the thumb arteries preferred. Clin. Anat. 30:963-973, 2017. ©2017 Wiley-Liss, Inc. © 2017 Wiley Periodicals, Inc.

  12. [Reconstruction of foot arteries after injury in arterial occlusive disease].

    PubMed

    Flis, V; Tomazic, T

    1993-06-01

    At the Maribor Teaching Hospital two elderly with progressive atherosclerotic disease below the knee were treated between 1986-1992 for open fracture of ankle joint and pedal arterial trauma. The only patent atherosclerotic vessel (dorsal artery of the foot) that was disrupted was reconstructed in both cases by interposition of a part of the great and small saphenous vein in one case each. A termino-terminal anastomosis with a long, triangular patch was used, fixed with interrupted sutures. The fractures were stabilized with external fixators. Both extremities were saved.

  13. No Association of ApoE Genotype with Risk of Prostate Cancer: A Nested Case-Control Study.

    PubMed

    Liu, Hui; Shui, Irene M; Platz, Elizabeth A; Mucci, Lorelei A; Giovannucci, Edward L

    2015-10-01

    Previous studies found that low total cholesterol level was associated with a lower risk of high-grade prostate cancer. Apolipoprotein E (ApoE) isoform is associated with total cholesterol level. The aim of this study was to explore associations of ApoE isoforms with prostate cancer risk. We assessed ApoE genotypes and risk of prostate cancer in a prospective case-control study nested among men who provided a blood sample in 1993-95 within the Health Professionals Follow-up Study. We identified 1,169 incident cases of prostate cancer and 1,233 controls in follow-up through 2004. Associations of ApoE isoform and prostate cancer incidence were evaluated by logistic regression models. We found no statistically significant associations of ApoE variants with overall prostate cancer or Gleason sum ≤ 7 (3+4), Gleason sum ≥ 7 (4+3), clinically localized stage, or progression to metastasis or death. There was no evidence of effect modification by circulating total cholesterol or use of cholesterol-lowering drugs prior to diagnosis. ApoE variants were not associated with the risk of prostate cancer or aggressive disease. Our findings suggest that the mechanism of circulating cholesterol level affecting prostate cancer incidence may not rely on ApoE isoforms. ©2015 American Association for Cancer Research.

  14. Coronary revascularization after arterial switch operation.

    PubMed

    Prifti, Edvin; Bonacchi, Massimo; Luisi, Stefano Vincenzo; Vanini, Vittorio

    2002-01-01

    We report two cases presenting bilateral coronary artery obstruction after arterial switch operation. The first patient underwent bilateral internal thoracic artery grafting to the left and right coronary arteries. The other patient, presenting a single coronary ostium, underwent surgical coronary ostial angioplasty in concomitance to proximal arterioplasty of both coronary arteries employing a single "pantaloon" shape autologous pericardial patch. Both patients survived and, at 1 year and 9 months after the coronary revascularization procedures, the coronary angiography demonstrated a good patency of the internal thoracic grafts and excellent ostial plasty results, respectively. A complete literature review of patients undergoing different coronary revascularization procedures after arterial switch operation is reported.

  15. Hyperglycemia and advanced glycosylation end products suppress adipocyte apoE expression: implications for adipocyte triglyceride metabolism.

    PubMed

    Espiritu, Doris Joy; Huang, Zhi Hua; Zhao, Yong; Mazzone, Theodore

    2010-10-01

    Endogenous adipocyte apolipoprotein E (apoE) plays an important role in adipocyte lipoprotein metabolism and lipid flux. A potential role for hyperglycemia in regulating adipocyte apoE expression and triglyceride metabolism was examined. Exposure of adipocytes to high glucose or advanced glycosylation end product-BSA significantly suppressed apoE mRNA and protein levels. This suppression was significantly attenuated by antioxidants or inhibitors of the NF-κB transcription pathway. Hyperglycemia in vivo led to adipose tissue oxidant stress and significant reduction in adipose tissue and adipocyte apoE mRNA level. Incubation with antioxidant in organ culture completely reversed this suppression. Hyperglycemia also reduced adipocyte triglyceride synthesis, and this could be completely reversed by adenoviral-mediated increases in apoE. To more specifically evaluate an in vivo role for adipocyte apoE expression on organismal triglyceride distribution in vivo, WT or apoE knockout (EKO) adipose tissue was transplanted in EKO recipient mice. After 12 wk, WT adipocytes transplanted in EKO mice accumulated more triglyceride compared with transplanted EKO adipocytes. In addition, EKO recipients of WT adipose tissue had reduced hepatic triglyceride content compared with EKO recipients transplanted with EKO adipose tissue. Our results demonstrate that hyperglycemia and advanced glycosylation end products suppress the expression of adipocyte apoE in vitro and in vivo and thereby reduce adipocyte triglyceride synthesis. In vivo results using adipose tissue transplantation suggest that reduction of adipocyte apoE, and subsequent reduction of adipocyte triglyceride accumulation, could influence lipid accumulation in nonadipose tissue.

  16. Superficial ulnar artery perforator flap.

    PubMed

    Schonauer, Fabrizio; Marlino, Sergio; Turrà, Francesco; Graziano, Pasquale; Dell'Aversana Orabona, Giovanni

    2014-09-01

    Superficial ulnar artery is a rare finding but shows significant surgical implications. Its thinness and pliability make this flap an excellent solution for soft tissue reconstruction, especially in the head and neck region. We hereby report a successful free superficial ulnar artery perforator forearm flap transfer for tongue reconstruction. A 64-year-old man presenting with a squamous cell carcinoma of the left tongue underwent a wide resection of the tumor, left radical neck dissection, and reconstruction of the tongue and the left tonsillar pillar with the mentioned flap. No complications were observed postoperatively. The flap survived completely; no recurrence at 6 months of follow-up was detected. Superficial ulnar artery perforator flap has shown to be a safe alternative to other free tissue flaps in specific forearm anatomic conditions.

  17. ACUTE RETINAL ARTERIAL OCCLUSIVE DISORDERS

    PubMed Central

    Hayreh, Sohan Singh

    2011-01-01

    The initial section deals with basic sciences; among the various topics briefly discussed are the anatomical features of ophthalmic, central retinal and cilioretinal arteries which may play a role in acute retinal arterial ischemic disorders. Crucial information required in the management of central retinal artery occlusion (CRAO) is the length of time the retina can survive following that. An experimental study shows that CRAO for 97 minutes produces no detectable permanent retinal damage but there is a progressive ischemic damage thereafter, and by 4 hours the retina has suffered irreversible damage. In the clinical section, I discuss at length various controversies on acute retinal arterial ischemic disorders. Classification of acute retinal arterial ischemic disorders These are of 4 types: CRAO, branch retinal artery occlusion (BRAO), cotton wools spots and amaurosis fugax. Both CRAO and BRAO further comprise multiple clinical entities. Contrary to the universal belief, pathogenetically, clinically and for management, CRAO is not one clinical entity but 4 distinct clinical entities – non-arteritic CRAO, non-arteritic CRAO with cilioretinal artery sparing, arteritic CRAO associated with giant cell arteritis (GCA) and transient non-arteritic CRAO. Similarly, BRAO comprises permanent BRAO, transient BRAO and cilioretinal artery occlusion (CLRAO), and the latter further consists of 3 distinct clinical entities - non-arteritic CLRAO alone, non-arteritic CLRAO associated with central retinal vein occlusion and arteritic CLRAO associated with GCA. Understanding these classifications is essential to comprehend fully various aspects of these disorders. Central retinal artery occlusion The pathogeneses, clinical features and management of the various types of CRAO are discussed in detail. Contrary to the prevalent belief, spontaneous improvement in both visual acuity and visual fields does occur, mainly during the first 7 days. The incidence of spontaneous visual

  18. "It&apos;s All Shiny and There&apos;s No Pollution": "Barbapapa&apos;s Ark," Environmental Influences

    ERIC Educational Resources Information Center

    Lowe, Virginia

    2013-01-01

    The environmental picture book "Barbapapa&apos;s Ark" was published in 1974. I was keeping a parent-observer record of my two children at the time. The book had a strong influence on them from ages three to six, moving them to query pollution and hunting, in book and environment, and as adults, becoming committed activists for the…

  19. "It&apos;s All Shiny and There&apos;s No Pollution": "Barbapapa&apos;s Ark," Environmental Influences

    ERIC Educational Resources Information Center

    Lowe, Virginia

    2013-01-01

    The environmental picture book "Barbapapa&apos;s Ark" was published in 1974. I was keeping a parent-observer record of my two children at the time. The book had a strong influence on them from ages three to six, moving them to query pollution and hunting, in book and environment, and as adults, becoming committed activists for the…

  20. First jejunal artery, an alternative graft for right hepatic artery reconstruction.

    PubMed

    Aryal, Bibek; Komokata, Teruo; Kadono, Jun; Motodaka, Hiroyuki; Ueno, Tetsuya; Furoi, Akira; Imoto, Yutaka

    2015-04-08

    Common bile duct cancer invading right hepatic artery is sometimes diagnosed intraoperatively. Excision and safe reconstruction of the artery with suitable graft is essential. Arterial reconstruction with autologous saphenous vein graft is the preferred method practiced routinely. However the right hepatic artery reconstruction has also been carried out with several other vessels like gastroduodenal artery, right gastroepiploic artery or the splenic artery. We report a case of 63-year-old man presenting with history of progressive jaundice, pruritus and impaired appetite. Following various imaging modalities including computed tomography, endoscopic retrograde cholangiopancreatography, magnetic resonance cholangiopancreatography, intraductal ultrasound extrahepatic bile duct cancer was diagnosed; however, none of those detected vessel invasion. Intraoperatively, right hepatic artery invasion was revealed. Right hepatic artery was resected and reconstructed with a graft harvested from the first jejunal artery (JA). Postoperative outcome was satisfactory with a long-term graft patency. First JA can be a reliable graft option for right hepatic artery reconstruction.

  1. Effect of plasma lipids and APOE genotype on cognitive decline.

    PubMed

    Yasuno, Fumihiko; Asada, Takashi

    2013-03-01

    A central tenet of brain aging is that "what is good for the heart is good for the brain." We examined the combined effect of plasma lipids and APOE genotype on cognitive function in elderly individuals. Plasma concentrations of high-density lipoprotein (HDL), low-density lipoprotein, triglyceride, total cholesterol, and apolipoprotein E (apoE) were evaluated in 622 community-dwelling individuals aged 65 years and older. We investigated the associations between plasma lipids and cognitive function in APOE4 carrier (E4+) and APOE4 noncarrier (E4-) groups using 3-year longitudinal data. At baseline and 3 years later, cognitive scores were correlated with plasma apoE levels in both E4- and E4+, and HDL level in E4-. Our findings suggest that an interaction between apoE and HDL is facilitated by APOE4, and is possibly linked with an enhancement of neuroplasticity and with resultant protective effects on cognitive function in later life. Preservation of higher plasma apoE and HDL from early life is proposed as a possible strategy for maintaining cognitive function in later life, especially for APOE4-positive individuals.

  2. Lung inflammation and genotoxicity following pulmonary exposure to nanoparticles in ApoE-/- mice

    PubMed Central

    Jacobsen, Nicklas Raun; Møller, Peter; Jensen, Keld Alstrup; Vogel, Ulla; Ladefoged, Ole; Loft, Steffen; Wallin, Håkan

    2009-01-01

    Background The toxic and inflammatory potential of 5 different types of nanoparticles were studied in a sensitive model for pulmonary effects in apolipoprotein E knockout mice (ApoE-/-). We studied the effects instillation or inhalation Printex 90 of carbon black (CB) and compared CB instillation in ApoE-/- and C57 mice. Three and 24 h after pulmonary exposure, inflammation was assessed by mRNA levels of cytokines in lung tissue, cell composition, genotoxicity, protein and lactate dehydrogenase activity in broncho-alveolar lavage (BAL) fluid. Results Firstly, we found that intratracheal instillation of CB caused far more pulmonary toxicity in ApoE-/- mice than in C57 mice. Secondly, we showed that instillation of CB was more toxic than inhalation of a presumed similar dose with respect to inflammation in the lungs of ApoE-/- mice. Thirdly, we compared effects of instillation in ApoE-/- mice of three carbonaceous particles; CB, fullerenes C60 (C60) and single walled carbon nanotubes (SWCNT) as well as gold particles and quantum dots (QDs). Characterization of the instillation media revealed that all particles were delivered as agglomerates and aggregates. Significant increases in Il-6, Mip-2 and Mcp-1 mRNA were detected in lung tissue, 3 h and 24 h following instillation of SWCNT, CB and QDs. DNA damage in BAL cells, the fraction of neutrophils in BAL cells and protein in BAL fluid increased statistically significantly. Gold and C60 particles caused much weaker inflammatory responses. Conclusion Our data suggest that ApoE-/- model is sensitive for evaluating particle induced inflammation. Overall QDs had greatest effects followed by CB and SWCNT with C60 and gold being least inflammatory and DNA-damaging. However the gold was used at a much lower mass dose than the other particles. The strong effects of QDs were likely due to Cd release. The surface area of the instilled dose correlated well the inflammatory response for low toxicity particles. PMID:19138394

  3. Triglyceride-rich lipoprotein metabolism in women: roles of apoC-II and apoC-III.

    PubMed

    Ooi, Esther M; Chan, Dick C; Hodson, Leanne; Adiels, Martin; Boren, Jan; Karpe, Fredrik; Fielding, Barbara A; Watts, Gerald F; Barrett, P Hugh R

    2016-08-01

    Experimental data suggest that apolipoprotein (apo) C-II and C-III regulate triglyceride-rich lipoprotein (TRL) metabolism, but there are limited studies in humans. We investigated the metabolic associations of TRLs with apoC-II and apoC-III concentrations and kinetics in women. The kinetics of plasma apoC-II, apoC-III and very low-density lipoprotein (VLDL) apoB-100 and triglycerides were measured in the postabsorptive state using stable isotopic techniques and compartmental modelling in 60 women with wide-ranging body mass index (19·5-32·9 kg/m(2) ). Plasma apoC-II and apoC-III concentrations were positively associated with the concentrations of plasma triglycerides, VLDL1 - and VLDL2 -apoB-100 and triglyceride (all P < 0·05). ApoC-II production rate (PR) was positively associated with VLDL1 -apoB-100 concentration, VLDL1 triglyceride concentration and VLDL1 triglyceride PR, while apoC-II fractional catabolic rate (FCR) was positively associated with VLDL1 triglyceride FCR (all P < 0·05). No significant associations were observed between apoC-II and VLDL2 apoB-100 or triglyceride kinetics. ApoC-III PR, but not FCR, was positively associated with VLDL1 triglyceride, and VLDL2 -apoB-100 and triglyceride concentrations (all P < 0·05). No significant associations were observed between apoC-III and VLDL-apoB-100 and triglyceride kinetics. In multivariable analysis, including homoeostasis model assessment score, menopausal status and obesity, apoC-II concentration was significantly associated with plasma triglyceride, VLDL1 -apoB-100 and VLDL1 triglyceride concentrations and PR. Using the same multivariable analysis, apoC-III was significantly associated with plasma triglyceride and VLDL1 - and VLDL2 -apoB-100 and triglyceride concentrations and FCR. In women, plasma apoC-II and apoC-III concentrations are regulated by their respective PR and are significant, independent determinants of the kinetics and plasma concentrations of TRLs. © 2016 Stichting

  4. Arterial Pressure Monitoring in Mice

    PubMed Central

    Zhao, Xin; Ho, David; Gao, Shumin; Hong, Chull; Vatner, Dorothy E.; Vatner, Stephen F.

    2011-01-01

    The use of mice for the evaluation and study of cardiovascular pathophysiology is growing rapidly, primarily due to the relative ease for developing genetically engineered mouse models. Arterial pressure monitoring is central to the evaluation of the phenotypic changes associated with cardiovascular pathology and interventions in these transgenic and knockout models. There are four major techniques for measuring arterial pressure in the mouse: tail cuff system, implanted fluid filled catheters, Millar catheters and implanted telemetry systems. Here we provide protocols for their use and discuss the advantages and limitations for each of these techniques . PMID:21686061

  5. Genome-wide screen for modulation of hepatic apolipoprotein A-I (ApoA-I) secretion.

    PubMed

    Miles, Rebecca R; Perry, William; Haas, Joseph V; Mosior, Marian K; N'Cho, Mathias; Wang, Jian W J; Yu, Peng; Calley, John; Yue, Yong; Carter, Quincy; Han, Bomie; Foxworthy, Patricia; Kowala, Mark C; Ryan, Timothy P; Solenberg, Patricia J; Michael, Laura F

    2013-03-01

    Control of plasma cholesterol levels is a major therapeutic strategy for management of coronary artery disease (CAD). Although reducing LDL cholesterol (LDL-c) levels decreases morbidity and mortality, this therapeutic intervention only translates into a 25-40% reduction in cardiovascular events. Epidemiological studies have shown that a high LDL-c level is not the only risk factor for CAD; low HDL cholesterol (HDL-c) is an independent risk factor for CAD. Apolipoprotein A-I (ApoA-I) is the major protein component of HDL-c that mediates reverse cholesterol transport from tissues to the liver for excretion. Therefore, increasing ApoA-I levels is an attractive strategy for HDL-c elevation. Using genome-wide siRNA screening, targets that regulate hepatocyte ApoA-I secretion were identified through transfection of 21,789 siRNAs into hepatocytes whereby cell supernatants were assayed for ApoA-I. Approximately 800 genes were identified and triaged using a convergence of information, including genetic associations with HDL-c levels, tissue-specific gene expression, druggability assessments, and pathway analysis. Fifty-nine genes were selected for reconfirmation; 40 genes were confirmed. Here we describe the siRNA screening strategy, assay implementation and validation, data triaging, and example genes of interest. The genes of interest include known and novel genes encoding secreted enzymes, proteases, G-protein-coupled receptors, metabolic enzymes, ion transporters, and proteins of unknown function. Repression of farnesyltransferase (FNTA) by siRNA and the enzyme inhibitor manumycin A caused elevation of ApoA-I secretion from hepatocytes and from transgenic mice expressing hApoA-I and cholesterol ester transfer protein transgenes. In total, this work underscores the power of functional genetic assessment to identify new therapeutic targets.

  6. Conventional and Advanced Lipid Parameters in Premature Coronary Artery Disease Patients in India

    PubMed Central

    Agarwal, Sarita; Daga, Mridul Kumar

    2015-01-01

    Background Coronary artery disease (CAD) is the leading cause of death worldwide and has assumed alarming proportions in India with gradual increase in its incidence and prevalence over the last decade. India is in the middle of epidemic of coronary artery disease which is leading cause of hospital admissions, morbidity and mortality. In the Indian population, there is higher tendency to develop CAD at a younger age, which cannot be explained on the basis of conventional lipid parameters. Aim The purpose of this study is to find advanced lipid parameters which correlate better with premature CAD, as compared to the conventional lipid parameters. Materials and Methods Thirty middle aged individuals suffering from premature CAD and 30 age and gender matched healthy individuals without any history of clinical evidence suggestive of CAD were studied. Fasting venous blood samples of all the subjects under study were collected after an overnight fasting and conventional lipid parameters and advanced lipid parameters (i.e. oxidized LDL, Lp (a), ApoA-1, small dense LDL, ApoB) were estimated. Correlation of conventional and advanced lipid parameters with premature CAD and among each other was calculated using Pearson correlation coefficient. Results In our study the values of ox-LDL, sdLDL, Lp (a) and ApoB, total cholesterol, TG, LDL-C were significantly higher while HDL-C and Apo A1 and were significantly lower in cases than in controls. Advanced lipid parameters have higher correlation with premature CAD as compared to conventional lipid parameters. Ox-LDL show the highest correlation coefficient (r=+0.89) among these parameters followed by Lp (a) (r=+0.86) and ApoB (r=+0.79). Conclusion Advanced lipid parameters (i.e. oxidized LDL, Lp (a), ApoA-1, small dense LDL, ApoB) are better discriminator of premature CAD as compared to conventional lipid parameters (total cholesterol, triglycerides, low density lipoprotein and high density lipoprotein). Oxidised LDL, small dense

  7. Dietary potassium regulates vascular calcification and arterial stiffness.

    PubMed

    Sun, Yong; Byon, Chang Hyun; Yang, Youfeng; Bradley, Wayne E; Dell'Italia, Louis J; Sanders, Paul W; Agarwal, Anupam; Wu, Hui; Chen, Yabing

    2017-10-05

    Vascular calcification is a risk factor that predicts adverse cardiovascular complications of several diseases including atherosclerosis. Reduced dietary potassium intake has been linked to cardiovascular diseases such as hypertension and incidental stroke, although the underlying molecular mechanisms remain largely unknown. Using the ApoE-deficient mouse model, we demonstrated for the first time to our knowledge that reduced dietary potassium (0.3%) promoted atherosclerotic vascular calcification and increased aortic stiffness, compared with normal (0.7%) potassium-fed mice. In contrast, increased dietary potassium (2.1%) attenuated vascular calcification and aortic stiffness. Mechanistically, reduction in the potassium concentration to the lower limit of the physiological range increased intracellular calcium, which activated a cAMP response element-binding protein (CREB) signal that subsequently enhanced autophagy and promoted vascular smooth muscle cell (VSMC) calcification. Inhibition of calcium signals and knockdown of either CREB or ATG7, an autophagy regulator, attenuated VSMC calcification induced by low potassium. Consistently, elevated autophagy and CREB signaling were demonstrated in the calcified arteries from low potassium diet-fed mice as well as aortic arteries exposed to low potassium ex vivo. These studies established a potentially novel causative role of dietary potassium intake in regulating atherosclerotic vascular calcification and stiffness, and uncovered mechanisms that offer opportunities to develop therapeutic strategies to control vascular disease.

  8. Transplantation of periaortic adipose tissue from angiotensin receptor blocker-treated mice markedly ameliorates atherosclerosis development in apoE-/- mice.

    PubMed

    Irie, Daisuke; Kawahito, Hiroyuki; Wakana, Noriyuki; Kato, Taku; Kishida, Sou; Kikai, Masakazu; Ogata, Takehiro; Ikeda, Koji; Ueyama, Tomomi; Matoba, Satoaki; Yamada, Hiroyuki

    2015-03-01

    Perivascular adipose tissue is implicated in vasoreactivity; however, its effect on atherosclerosis remains undefined. We examined the effect of a high-cholesterol diet (HCD) on phenotypic alterations of the thoracic periaortic adipose tissue (tPAT) in apoE-deficient (apoE(-/-)) mice. Gene expression of the components of the renin angiotensin system and that of macrophage markers were significantly higher in apoE(-/-) mice fed an HCD than in those fed a chow diet (CD). These changes were absent both in angiotensin II (AngII) receptor blocker (ARB)-treated apoE(-/-) mice and in Ang II type 1 (AT1) receptor-deficient apoE(-/-) (Agtr1(-/-)/apoE(-/-)) mice. To evaluate their effect on atherosclerosis, we transplanted tPAT into apoE(-/-) mice alongside the distal abdominal aorta. Transplanted tPAT was harvested from apoE(-/-) and Agtr1(-/-)/apoE(-/-) mice fed a CD (tPAT-CD/apoE(-/-), tPAT-CD/Agtr1(-/-)/apoE(-/-)), HCD (tPAT-HCD/apoE(-/-), tPAT-HCD/Agtr1(-/-)/apoE(-/-)), or HCD in combination with ARB treatment (tPAT-HCD/ARB/apoE(-/-)). Four weeks after transplantation, a significantly increased oil red O-positive area was observed in the aorta of tPAT-HCD/apoE(-/-) mice than in tPAT-CD/apoE(-/-) mice. Such a change was absent in tPAT-HCD/ARB/apoE(-/-) and tPAT-HCD/Agtr1(-/-)/apoE(-/-) mice. Our findings demonstrated that AT1 receptor plays a crucial role in HCD-induced phenotypic alterations of tPAT, modulation of which could exert beneficial effects on atherosclerosis. © The Author(s) 2014.

  9. Association of serum lipids and coronary artery disease with polymorphisms in the apolipoprotein AI-CIII-AIV gene cluster.

    PubMed

    Rai, Himanshu; Sinha, Nakul; Finn, James; Agrawal, Suraksha; Mastana, Sarabjit

    2016-12-31

    Genetic variants are considered as one of the main determinants of the concentration of serum lipids and coronary artery disease (CAD). Polymorphisms in the Apolipoprotein (Apo) AI-CIII-AIV gene cluster has been known to affect the concentrations of various lipid sub-fractions and the risk of CAD. The present study assessed associations between polymorphisms of the Apo AI-CIII-AIV gene cluster, [ApoA-I,-75G > A, (rs1799837); ApoC-III 3238C > G, (SstI), (rs5128) and ApoA-IV, Thr347Ser(347A > T), (rs675)] with serum lipids and their contributions to CAD in North Indian population. We recruited age, sex matched, 200 CAD patients and 200 healthy controls and tested them for fasting levels of serum lipids. We genotyped selected polymorphisms using polymerase chain reaction-restriction fragment length polymorphism. There were no statistically significant association of selected polymorphisms (or their combinations) with CAD even after employing additive, dominant and recessive models. However there was significant association of selected polymorphisms with various lipid traits amongst the control cohort (p < 0.05). Mean levels of high density lipoprotein cholesterol and triglycerides were found to be significantly higher among controls carrying at least one mutant allele at ApoA1-75G > A (p = 0.019) and ApoCIII SstI (p < 0.001) polymorphism respectively. Our study observed that the selected polymorphisms in the ApoAI-CIII-AIV gene cluster although significantly affect various lipid traits but this affect does not seem to translate into association with CAD, at least among North Indian population.

  10. Association of serum lipids and coronary artery disease with polymorphisms in the apolipoprotein AI-CIII-AIV gene cluster

    PubMed Central

    Rai, Himanshu; Sinha, Nakul; Finn, James; Agrawal, Suraksha; Mastana, Sarabjit

    2016-01-01

    Abstract Genetic variants are considered as one of the main determinants of the concentration of serum lipids and coronary artery disease (CAD). Polymorphisms in the Apolipoprotein (Apo) AI-CIII-AIV gene cluster has been known to affect the concentrations of various lipid sub-fractions and the risk of CAD. The present study assessed associations between polymorphisms of the Apo AI-CIII-AIV gene cluster, [ApoA-I,-75G > A, (rs1799837); ApoC-III 3238C > G, (SstI), (rs5128) and ApoA-IV, Thr347Ser(347A > T), (rs675)] with serum lipids and their contributions to CAD in North Indian population. We recruited age, sex matched, 200 CAD patients and 200 healthy controls and tested them for fasting levels of serum lipids. We genotyped selected polymorphisms using polymerase chain reaction-restriction fragment length polymorphism. There were no statistically significant association of selected polymorphisms (or their combinations) with CAD even after employing additive, dominant and recessive models. However there was significant association of selected polymorphisms with various lipid traits amongst the control cohort (p < 0.05). Mean levels of high density lipoprotein cholesterol and triglycerides were found to be significantly higher among controls carrying at least one mutant allele at ApoA1-75G > A (p = 0.019) and ApoCIII SstI (p < 0.001) polymorphism respectively. Our study observed that the selected polymorphisms in the ApoAI-CIII-AIV gene cluster although significantly affect various lipid traits but this affect does not seem to translate into association with CAD, at least among North Indian population. PMID:28261635

  11. Treatment of peripheral arterial disease via percutaneous brachial artery access.

    PubMed

    Franz, Randall W; Tanga, Christopher F; Herrmann, Joseph W

    2017-08-01

    This review was conducted to evaluate the types of endovascular procedures that can be performed via brachial artery access, evaluate the access success rate, and determine the incidence of technical complications. A retrospective 10-year record review at a tertiary facility from January 1, 2005, through June 30, 2015, was completed. Patients who underwent attempted brachial artery access were eligible for review. Outcomes intended to be evaluated included ability to access the vessel, reach an identified lesion, and perform an indicated procedure, while describing the incidence and type of complications that occurred to clarify the utility and safety of brachial artery access. The review included 265 access cases in 179 patients. The access success rate was 98.9%. Intervention was performed in 223 cases (84.2%). Angioplasty was the most common intervention (59%, [154 cases]), with stents, atherectomy, coiling, and percutaneous thrombectomy having also been performed. Complications included hematoma (2.3%) and pseudoaneurysm (1.5%). Complications requiring intervention occurred in 1.9% of procedures. Interventions were performed on all major vessels as distal as the dorsalis pedis. Sheath sizes ranged from 4F to 7F. Intervention was performed on bilateral lower extremities in 38 cases (14.5%). A femoral bypass graft was present in 141 patients (53%) as the main indication for brachial artery access. Brachial access is a reliable and effective option for treatment of peripheral vascular disease and should be considered when femoral access is difficult or contraindicated and when a bypass graft is present in the femoral region. In addition, bilateral lesions may be approached easily through one brachial artery access site, making this approach advantageous when bilateral lesions are expected. The complication rate is similar to femoral access and can be minimized with ultrasound-guided access distally over the humerus, micropuncture access, and a dedicated

  12. Decoding of lipoprotein – receptor interactions; Properties of ligand binding modules governing interactions with ApoE

    PubMed Central

    Guttman, Miklos; Prieto, J. Helena; Croy, Johnny E.; Komives, Elizabeth A.

    2010-01-01

    Clusters of complement-type ligand binding repeats in the LDL receptor family are thought to mediate the interactions between these receptors and their various ligands. Apolipoprotein E, a key ligand for cholesterol homeostasis, has been shown to interact with LDLR, LRP and VLDLR, through these clusters. LDLR and VLDLR each contain a single ligand-binding repeat cluster, whereas LRP contains three large clusters of ligand binding repeats, each with ligand binding functions. We show that within sLRP3, the three-repeat subcluster CR16-18 recapitulated ligand binding to the isolated receptor binding portion of ApoE (residues 130-149). Binding experiments with LA3-5 of LDLR and CR16-18 showed that a conserved W25/D30 pair appears critical for high affinity binding to ApoE(130-149). The triple repeat LA3-5 showed the expected interaction with ApoE(1-191)•DMPC, but surprisingly CR16-18 did not interact with this form of ApoE. To understand these differences in ApoE binding affinity, we introduced mutations of conserved residues from LA5 into CR18, and produced a CR16-18 variant capable of binding ApoE(1-191)•DMPC. This change cannot fully be accounted for by the interaction with the proposed ApoE receptor binding region, therefore we speculate that LA5 is recognizing a distinct epitope on ApoE that may only exists in the lipid bound form. The combination of avidity effects with this distinct recognition process likely governs the ApoE-LDL receptor interaction. PMID:20030366

  13. Bronchial Artery Aneurysm with Associated Bronchial Artery to Pulmonary Artery Fistula: Treatment by Embolization

    PubMed Central

    Hsieh, Caleb G; Le, Thomas; Fogelfeld, Keren; Kamangar, Nader

    2017-01-01

    Bronchial artery aneurysm (BAA) is a rare vascular phenomenon. This review highlights a case of a BAA that was complicated by the presence of a bronchial artery to pulmonary artery (BA-PA) fistula, consequently presenting a unique challenge to management. BAAs have a strongly reported risk of rupture resulting in life-threatening hemoptysis. Embolization has thus become routine for the management such severe cases. The management of incidentally found anomalies is less obvious, but prophylactic embolization is a generally accepted practice. In this report, we review some of the risks and benefits associated with BAA embolization with specific consideration of the challenges in cases of co-existing BA-PA fistula. PMID:28217405

  14. Angioplasty and stent placement - carotid artery

    MedlinePlus

    ... in your carotid artery. Moving x-ray pictures (fluoroscopy) are used to see the artery and guide ... 18403765 . Kinlay S, Bhatt DL. Treatment of noncoronary obstructive ... versus surgery for asymptomatic carotid stenosis. N Engl J Med . ...

  15. Types of Coronary Artery Bypass Grafting

    MedlinePlus

    ... from the NHLBI on Twitter. Types of Coronary Artery Bypass Grafting There are several types of coronary ... for you based on your needs. Traditional Coronary Artery Bypass Grafting Traditional CABG is used when at ...

  16. Flows In Model Human Femoral Arteries

    NASA Technical Reports Server (NTRS)

    Back, Lloyd H.; Kwack, Eug Y.; Crawford, Donald W.

    1990-01-01

    Flow is visualized with dye traces, and pressure measurements made. Report describes experimental study of flow in models of human femoral artery. Conducted to examine effect of slight curvature of artery on flow paths and distribution of pressure.

  17. Histological structure affects recellularization of decellularized arteries.

    PubMed

    Negishi, Jun; Hashimoto, Yoshihide; Yamashita, Akitatsu; Kimura, Tsuyoshi; Kishida, Akio; Funamoto, Seiichi

    2017-01-01

    Decellularized arteries were prepared to evaluate the in vivo recellularization of biological material after implantation. Porcine aortas and radial arteries were decellularized using high-hydrostatic pressure to form materials with histologically-different structures. Successful removal of cells from decellularized arteries was evaluated by hematoxylin-eosin staining and measurement of residual DNA. Cell remnants were eliminated completely from the decellularized arteries, and histological structures were preserved. Cells adhered to all decellularized artery samples, but infiltration of cells was observed only from the adventitial side of the decellularized radial artery. Rats were implanted subcutaneously with a decellularized aorta or radial artery to evaluate in vivo performance. Decellularized aortic tissue prevented cell infiltration better than that of the decellularized radial artery, suggesting that the elastin lamina in decellularized tissues prevents cell infiltration and suppresses recellularization. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Could Peripheral Arterial Disease Be Your Problem?

    MedlinePlus

    ... exercise and yoga classes and has returned to teaching. Fast Facts Peripheral arterial disease (P.A.D.) occurs when a fatty material called plaque (pronounced plak) builds up on the inside walls of the arteries that carry blood from ...

  19. Trigeminal neuralgia caused by a trigeminocerebellar artery.

    PubMed

    Amagasaki, Kenichi; Abe, Shoko; Watanabe, Saiko; Naemura, Kazuaki; Nakaguchi, Hiroshi

    2014-10-01

    This 31-year-old woman presented with typical right trigeminal neuralgia caused by a trigeminocerebellar artery, manifesting as pain uncontrollable with medical treatment. Preoperative neuroimaging studies demonstrated that the offending artery had almost encircled the right trigeminal nerve. This finding was confirmed intraoperatively, and decompression was completed. The neuralgia resolved after the surgery; the patient had slight transient hypesthesia, which fully resolved within the 1st month after surgery. The neuroimaging and intraoperative findings showed that the offending artery directly branched from the upper part of the basilar artery and, after encircling and supplying tiny branches to the nerve root, maintained its diameter and coursed toward the rostral direction of the cerebellum, which indicated that the artery supplied both the trigeminal nerve and the cerebellum. The offending artery was identified as the trigeminocerebellar artery. This case of trigeminal neuralgia caused by a trigeminocerebellar artery indicates that this variant is important for a better understanding of the vasculature of the trigeminal nerve root.

  20. Peripheral Arterial Disease Can Be a Killer

    MedlinePlus

    ... Issue Past Issues Special Section Peripheral Arterial Disease Can Be a Killer Past Issues / Summer 2008 Table ... the arteries to narrow or become blocked, which can reduce or block blood flow. P.A.D. ...

  1. Flip Your Students&apos; Learning

    ERIC Educational Resources Information Center

    Sams, Aaron; Bergmann, Jonathan

    2013-01-01

    Flipped learning is not about how to use videos in lessons. It&apos;s about how to best use in-class time with students. That insight is causing educators in classrooms from kindergarten to college to reevaluate how they teach. Flipped learning helps teachers move away from direct instruction as their primary teaching tool toward a more…

  2. Gutenberg&apos;s Effects on Universities

    ERIC Educational Resources Information Center

    Moodie, Gavin

    2014-01-01

    This article considers the effects on universities of Gutenberg&apos;s invention of printing. It considers four major effects: the gradual displacement of Latin as the language of scholarship with vernacular languages, the expansion and eventual opening of libraries, major changes to curriculum, and major changes to pedagogy including lectures.…

  3. Quirks of Stirling&apos;s Approximation

    ERIC Educational Resources Information Center

    Macrae, Roderick M.; Allgeier, Benjamin M.

    2013-01-01

    Stirling&apos;s approximation to ln "n"! is typically introduced to physical chemistry students as a step in the derivation of the statistical expression for the entropy. However, naive application of this approximation leads to incorrect conclusions. In this article, the problem is first illustrated using a familiar "toy…

  4. Students&apos; Images of Mathematics

    ERIC Educational Resources Information Center

    Martin, Lee; Gourley-Delaney, Pamela

    2014-01-01

    Students&apos; judgments about "what counts" as mathematics in and out of school have important consequences for problem solving and transfer, yet our understanding of the source and nature of these judgments remains incomplete. Thirty-five sixth grade students participated in a study focused on what activities students judge as…

  5. MFA Writers&apos; Relationships with Writing

    ERIC Educational Resources Information Center

    Olthouse, Jill M.

    2013-01-01

    Through a qualitative research design, I explored how eight talented masters in fine arts (MFA) writers related to their craft. The phenomenon "relationship with writing" includes writers&apos; goals, values, identity, and emotions as these relate to writing. I found that that these MFA writers experience compatibilities and conflicts…

  6. Dewey or Don&apos;t We?

    ERIC Educational Resources Information Center

    Pendergrass, Devona J.

    2013-01-01

    "Dewey or don&apos;t we?" is the question that hundreds, if not thousands, of school librarians across the country are currently asking themselves. Do they throw out what is old but trusted for new organizational systems, or do they continue using the Dewey Decimal Classification (DDC) system and make changes and adjustments to the…

  7. What&apos;s in a Symbol?

    ERIC Educational Resources Information Center

    Leadstone, Stuart

    2013-01-01

    This "Science Note" explores the new adaptation of Newton&apos;s Second Law of Motion, "F = ma." In older physics and applied mathematics textbooks this expression appears as "P = mf." The author examines why "f" is now favored over "a" and why practitioners write "P = mf" rather than…

  8. Dewey or Don&apos;t We?

    ERIC Educational Resources Information Center

    Pendergrass, Devona J.

    2013-01-01

    "Dewey or don&apos;t we?" is the question that hundreds, if not thousands, of school librarians across the country are currently asking themselves. Do they throw out what is old but trusted for new organizational systems, or do they continue using the Dewey Decimal Classification (DDC) system and make changes and adjustments to the…

  9. My Brother&apos;s Keeper

    ERIC Educational Resources Information Center

    Obama, Barack

    2014-01-01

    In a White House address, the president announced an initiative to reclaim young boys and men of color. The "My Brother&apos;s Keeper" initiative partners with businesses, foundations, and nonprofits to address disparities in education, justice, and employment. President Obama was introduced by Christian, one of a group of students from…

  10. Text Complexity: Primary Teachers&apos; Views

    ERIC Educational Resources Information Center

    Fitzgerald, Jill; Hiebert, Elfrieda H.; Bowen, Kimberly; Relyea-Kim, E. Jackie; Kung, Melody; Elmore, Jeff

    2015-01-01

    The research question was, "What text characteristics do primary teachers think are most important for early grades text complexity?" Teachers from across the United States accomplished a two-part task. First, to stimulate teachers&apos; thinking about important text characteristics, primary teachers completed an online paired-text…

  11. Exploring Teachers&apos; Practices of Responding

    ERIC Educational Resources Information Center

    Milewski, Amanda

    2012-01-01

    In the two decades since the introduction of the Professional Standards for Teaching Mathematics (NCTM, 1991) describing effective mathematics instruction, researchers have found U.S. teachers still lack the ability to foster productive mathematical discourse. Three instructional practices are key to teachers&apos; ability to support rich…

  12. Students&apos; Perceptions of Plagiarism

    ERIC Educational Resources Information Center

    Fish, Reva; Hura, Gerri

    2013-01-01

    While plagiarism by college students is a serious problem that must be addressed, students generally overestimate the frequency of plagiarism at their schools and blame students they do not know for the majority of incidents. This study looked at students&apos; estimations of the frequency of plagiarism at a large urban college and explored how…

  13. Inquiry on Teachers&apos; Emotion

    ERIC Educational Resources Information Center

    Schutz, Paul A.

    2014-01-01

    Teaching, like other caring professions, is emotional. These emotions tend to emerge as teachers&apos; goals, standards, and beliefs transact with other classroom stakeholders during everyday school activities. As such, for teachers, the classroom context involves both the extreme happiness and joy from a lesson that goes as planned to the intense…

  14. Students&apos; Ratings of Teacher Practices

    ERIC Educational Resources Information Center

    Stevens, T.; Harris, G.; Liu, X.; Aguirre-Munoz, Z.

    2013-01-01

    In this paper, we explore a novel approach for assessing the impact of a professional development programme on classroom practice of in-service middle school mathematics teachers. The particular focus of this study is the assessment of the impact on teachers&apos; employment of strategies used in the classroom to foster the mathematical habits of…

  15. My Brother&apos;s Keeper

    ERIC Educational Resources Information Center

    Obama, Barack

    2014-01-01

    In a White House address, the president announced an initiative to reclaim young boys and men of color. The "My Brother&apos;s Keeper" initiative partners with businesses, foundations, and nonprofits to address disparities in education, justice, and employment. President Obama was introduced by Christian, one of a group of students from…

  16. Text Complexity: Primary Teachers&apos; Views

    ERIC Educational Resources Information Center

    Fitzgerald, Jill; Hiebert, Elfrieda H.; Bowen, Kimberly; Relyea-Kim, E. Jackie; Kung, Melody; Elmore, Jeff

    2015-01-01

    The research question was, "What text characteristics do primary teachers think are most important for early grades text complexity?" Teachers from across the United States accomplished a two-part task. First, to stimulate teachers&apos; thinking about important text characteristics, primary teachers completed an online paired-text…

  17. America&apos;s Descent into Madness

    ERIC Educational Resources Information Center

    Giroux, Henry A.

    2014-01-01

    This article describes America&apos;s descent into madness under the regime of neoliberalism that has emerged in the United States since the late 1970s. In part, this is due to the emergence of a public pedagogy produced by the corporate-owned media that now saturates Americans with a market-driven value system that undermines those formative…

  18. Inquiry on Teachers&apos; Emotion

    ERIC Educational Resources Information Center

    Schutz, Paul A.

    2014-01-01

    Teaching, like other caring professions, is emotional. These emotions tend to emerge as teachers&apos; goals, standards, and beliefs transact with other classroom stakeholders during everyday school activities. As such, for teachers, the classroom context involves both the extreme happiness and joy from a lesson that goes as planned to the intense…

  19. Students&apos; Images of Mathematics

    ERIC Educational Resources Information Center

    Martin, Lee; Gourley-Delaney, Pamela

    2014-01-01

    Students&apos; judgments about "what counts" as mathematics in and out of school have important consequences for problem solving and transfer, yet our understanding of the source and nature of these judgments remains incomplete. Thirty-five sixth grade students participated in a study focused on what activities students judge as…

  20. America&apos;s Descent into Madness

    ERIC Educational Resources Information Center

    Giroux, Henry A.

    2014-01-01

    This article describes America&apos;s descent into madness under the regime of neoliberalism that has emerged in the United States since the late 1970s. In part, this is due to the emergence of a public pedagogy produced by the corporate-owned media that now saturates Americans with a market-driven value system that undermines those formative…

  1. "Math for America" Isn&apos;t

    ERIC Educational Resources Information Center

    Wolfmeyer, Mark

    2014-01-01

    Aspects of the Math for America organization&apos;s actions, aims and affiliations are analyzed for their effects on urban schools and society at large. These aspects are argued as evidence to consider MfA as an agent working against democratic practice and in favor of furthering profit and its resultant inequitable resource distribution. The…

  2. Gutenberg&apos;s Effects on Universities

    ERIC Educational Resources Information Center

    Moodie, Gavin

    2014-01-01

    This article considers the effects on universities of Gutenberg&apos;s invention of printing. It considers four major effects: the gradual displacement of Latin as the language of scholarship with vernacular languages, the expansion and eventual opening of libraries, major changes to curriculum, and major changes to pedagogy including lectures.…

  3. What&apos;s in a Symbol?

    ERIC Educational Resources Information Center

    Leadstone, Stuart

    2013-01-01

    This "Science Note" explores the new adaptation of Newton&apos;s Second Law of Motion, "F = ma." In older physics and applied mathematics textbooks this expression appears as "P = mf." The author examines why "f" is now favored over "a" and why practitioners write "P = mf" rather than…

  4. Quirks of Stirling&apos;s Approximation

    ERIC Educational Resources Information Center

    Macrae, Roderick M.; Allgeier, Benjamin M.

    2013-01-01

    Stirling&apos;s approximation to ln "n"! is typically introduced to physical chemistry students as a step in the derivation of the statistical expression for the entropy. However, naive application of this approximation leads to incorrect conclusions. In this article, the problem is first illustrated using a familiar "toy…

  5. "Math for America" Isn&apos;t

    ERIC Educational Resources Information Center

    Wolfmeyer, Mark

    2014-01-01

    Aspects of the Math for America organization&apos;s actions, aims and affiliations are analyzed for their effects on urban schools and society at large. These aspects are argued as evidence to consider MfA as an agent working against democratic practice and in favor of furthering profit and its resultant inequitable resource distribution. The…

  6. Relationship of lipid and lipoprotein ratios with coronary severity in patients with new on-set coronary artery disease complicated with type 2 diabetics

    PubMed Central

    Du, Ying; Chen, Juan; Chen, Man-Hua; Yang, Sheng-Hua; Li, Sha; Guo, Yuan-Lin; Zhu, Cheng-Gang; Xu, Rui-Xia; Dong, Qian; Li, Jian-Jun

    2016-01-01

    Background Diabetes mellitus (DM) is associated with coronary artery disease (CAD) progression. Although previous studies have demonstrated the association of lipid and lipoprotein ratios with CAD, no data are currently available concerning the relationship between lipid and lipoprotein ratios and the severity of new on-set CAD in diabetics. Therefore, the aim of the present study was to investigate the usefulness of lipid and lipoprotein ratios in predicting the severity of CAD in patients with type 2 DM (T2DM). Methods A total of 380 consecutive T2DM patients with new on-set CAD were enrolled in the present study. Then, they were classified into the three groups according to Gensini score (GS) tertiles. The relationship between lipid and lipoprotein ratios currently used and the GS was investigated. Results Positive correlations of natural log-transformed GS (lnGS) with apolipoprotein B to apoA-I ratio (apoB/apoA-I), non-high-density lipoprotein cholesterol to apoA-I ratio (non-HDL-C/apoA-I), and low-density lipoprotein cholesterol to apoA-I ratio (LDL-C/apoA-I) were found (r = 0.18, 0.13, 0.12, respectively, all P < 0.05). Multivariate logistic analysis indicated apoB/apoA-I as the strongest predictor for high GS (OR = 5.67, 95% CI: 1.45–23.92, P = 0.003). Area under receivers operating characteristic curve of apoB/apoA-I was 0.63 (95% CI: 0.60–0.66, P = 0.001) for predicting high GS. The optimal cutoff value of apoB/apoA-I to predict high GS was 0.72 with the sensitivity of 61.2% and the specificity of 62.1%. Conclusions Lipid and lipoprotein ratios might be useful for predicting the severity of new on-set CAD in T2DM patients, and the apoB/apoA-I appeared as the most significant predictor in this population. PMID:27781059

  7. Robust association of the APOE epsilon4 allele with premature myocardial infarction especially in patients without hypercholesterolaemia: the Aachen study.

    PubMed

    Schmitz, F; Mevissen, V; Krantz, C; Kimmel, M; Erdmann, J; Hoffmann, R; Zerres, K; Ortlepp, J R

    2007-02-01

    Genetic influence on the manifestation of coronary artery disease (CAD) and myocardial infarction (MI) has been shown previously. From many candidate genes the APOE (apolipoprotein E) with the major alleles epsilon2/epsilon3/epsilon4 is in the focus of interest. In 1817 patients admitted for their first left heart catheterization at a premature age (males < 55 and females < 65) the association of APOE alleles with MI was analysed. Genotyping was done by 5' exonuclease assay (TaqMan). RESULTS APOE was significantly associated with hypercholesterolaemia (epsilon4 72% vs. epsilon3 66% vs. epsilon2 51%; P < 0.0001), and premature MI (epsilon4 57% vs. epsilon3 50% vs. epsilon2 41%; P < 0.0001; hazard ratio 1.41, 95%CI 1.14-1.75). In patients without hypercholesterolaemia, the APOE allele epsilon4 was highly predictive for the presence of premature MI (epsilon4 55% vs. epsilon3 45% vs. epsilon2 28%; P < 0.0001; hazard ratio 1.75, 95%CI 1.19-2.57). The APOEepsilon4 allele shows a robust association with premature MI independent of hypercholesterolaemia.

  8. Effects of ApoE4 and maternal history of dementia on hippocampal atrophy

    PubMed Central

    Andrawis, John P.; Hwang, Kristy S.; Green, Amity E.; Kotlerman, Jenny; Elashoff, David; Morra, Jonathan H.; Cummings, Jeffrey L.; Toga, Arthur W.; Thompson, Paul M.; Apostolova, Liana G.

    2010-01-01

    We applied an automated hippocampal segmentation technique based on adaptive boosting (AdaBoost) to the 1.5T MRI baseline and 1-year follow-up data of 243 subjects with mild cognitive impairment (MCI), 96 with Alzheimer's disease (AD) and 145 normal controls (NC) scanned as part of the Alzheimer's Disease Neuroimaging Initiative (ADNI). MCI subjects with positive maternal history of dementia had smaller hippocampal volumes at baseline and at follow-up, and greater 12-month atrophy rates than subjects with negative maternal history. 3D maps and volumetric multiple regression analyses demonstrated a significant effect of positive maternal history of dementia on hippocampal atrophy in MCI and AD after controlling for age, ApoE4 genotype and paternal history of dementia, resp. ApoE4 showed an independent effect on hippocampal atrophy in MCI and AD and in the pooled sample. PMID:20833446

  9. Arterial grafts: clinical classification and pharmacological management

    PubMed Central

    2013-01-01

    In comparison with standard saphenous vein grafts, use of the internal mammary artery (IMA) as a coronary artery bypass graft has achieved superior long-term results. This is related to the differences in the biological characteristics between the venous and arterial grafts. However, even arterial grafts are not uniform in their biological characteristics. The variation in the perioperative behavior of the grafts and in their long-term patency may be related to different characteristics. These factors should be taken into account in the use of arterial grafts, some of which are subjected to more active pharmacological intervention during and after the operation to obtain satisfactory results. To better understand the biological behavior of the grafts, their common features and their differences, a clinical classification may be useful for a practicing surgeon. Based on experimental studies of their vasoreactivity combined with anatomical, physiological and embryological considerations, we have proposed a functional classification for arterial grafts that may be useful clinically. Our classification suggests that there are three types of arterial grafts: Type I—somatic arteries; Type II—splanchnic arteries; and Type III—limb arteries. Type I arteries have enhanced endothelial function and release more nitric oxide and other relaxing factors. Type II arteries, such as the gastro-epiploic artery, and Type III arteries, such as the radial artery (RA), have higher pharmacological reactivity to vasoconstrictors. This classification explains why the IMA has the best long-term patency. Because Type II and III arteries are prone to spasms due to higher contractility, they require more active pharmacological interventions. Furthermore, the harvesting technique of the conduits, including the saphenous vein and IMA, are described and discussed in this article. Prevention of spasms using two cocktails of medications (verapamil + nitroglycerin and nicardipine

  10. Arterial Patterns of the Face in Perissodactyla.

    PubMed

    Kowalczyk, Karolina; Frąckowiak, Hieronim

    2017-09-01

    Considerable consistency in the arterial pattern of the head has been observed in species of Artiodactyla, but few studies have examined the order Perissodactyla. Here, we describe arteries supplying the intermandibular, mental, masseteric, buccal, labial, and nasal regions in eight perissodactylans, including representing of all families comprising this order. Observations were made on a total of 45 preparations of head arteries, obtained by injection of arteries with acetone-dissolved stained vinyl superchloride or stained latex LBS3060. In the Equidae species alone it was found that the facial artery descends from the linguofacial trunk. In tapirs and rhinos the facial artery branches off directly from the main arteries of the head. In tapirs alone it was found that the inferior alveolar artery gives off the buccal and sublingual arteries, and then extends into the mental artery. In the rhino a specific feature of the arterial pattern of the head was the exit of the occipital artery from the superficial temporal artery. In all equines studied, the transverse facial artery gave off a larger blood vessel to the masseter muscle and ran along the facial crest, while in tapirs and rhinos the transverse facial artery fanned out branches in the masseteric fossa. The variations observed can be considered in future studies on the origin of Perissodactyla. In this context, we note that the most similar patterns of exit and course of the facial, mental, transverse facial and infraorbital arteries exist in tapirs and rhinos (Ceratomorpha suborder), at least among the perissodactylans studied here. Anat Rec, 300:1529-1534, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  11. Surgical management of extensive pulmonary artery sarcoma.

    PubMed

    Shehatha, Jaffar; Saxena, Pankaj; Clarke, Belinda; Dunning, John; Konstantinov, Igor E

    2009-04-01

    Primary pulmonary artery sarcoma is a rare tumor that can be misdiagnosed as acute or chronic pulmonary thromboembolic disease. This article reports a patient with a preoperative diagnosis of pulmonary embolism who was found to have an extensive pulmonary artery tumor. Surgical resection of the primary pulmonary artery sarcoma and reconstruction of the central pulmonary arteries, followed by adjuvant chemoradiotherapy, provided significant improvement in his clinical symptoms.

  12. Artery Tertiary Lymphoid Organs: Powerhouses of Atherosclerosis Immunity

    PubMed Central

    Yin, Changjun; Mohanta, Sarajo Kumar; Srikakulapu, Prasad; Weber, Christian; Habenicht, Andreas J. R.

    2016-01-01

    Artery tertiary lymphoid organs (ATLOs) are atherosclerosis-associated lymphoid aggregates with varying degrees of complexity ranging from small T/B-cell clusters to well-structured lymph node-like though unencapsulated lymphoid tissues. ATLOs arise in the connective tissue that surrounds diseased arteries, i.e., the adventitia. ATLOs have been identified in aged atherosclerosis-prone hyperlipidemic apolipoprotein E-deficient (ApoE−/−) mice: they are organized into distinct immune cell compartments, including separate T-cell areas, activated B-cell follicles, and plasma cell niches. Analyses of ATLO immune cell subsets indicate antigen-specific T- and B-cell immune reactions within the atherosclerotic arterial wall adventitia. Moreover, ATLOs harbor innate immune cells, including a large component of inflammatory macrophages, B-1 cells, and an aberrant set of antigen-presenting cells. There is marked neoangiogenesis, irregular lymphangiogenesis, neoformation of high endothelial venules, and de novo synthesis of lymph node-like conduits. Molecular mechanisms of ATLO formation remain to be identified though media vascular smooth muscle cells may adopt features of lymphoid tissue organizer-like cells by expressing lymphorganogenic chemokines, i.e., CXCL13 and CCL21. Although these data are consistent with the view that ATLOs participate in primary T- and B-cell responses against elusive atherosclerosis-specific autoantigens, their specific protective or disease-promoting roles remain to be identified. In this review, we discuss what is currently known about ATLOs and their potential impact on atherosclerosis and make attempts to define challenges ahead. PMID:27777573

  13. Insulin Resistance Promotes Early Atherosclerosis via Increased Proinflammatory Proteins and Oxidative Stress in Fructose-Fed ApoE-KO Mice

    PubMed Central

    Cannizzo, Beatriz; Luján, Agustín; Estrella, Natalia; Lembo, Carina; Cruzado, Montserrat; Castro, Claudia

    2012-01-01

    High fructose intake induces an insulin resistance state associated with metabolic syndrome (MS). The effect of vascular inflammation in this model is not completely addressed. The aim of this study was to evaluate vascular remodeling, inflammatory and oxidative stress markers, and atheroma development in high-fructose diet-induced insulin resistance of ApoE-deficient mice (ApoE-KO). Mice were fed with either a normal chow or a 10% w/v fructose (HF) in drinking water over a period of 8 weeks. Thereafter, plasma metabolic parameters, vascular remodeling, atheroma lesion size, inflammatory markers, and NAD(P)H oxidase activity in the arteries were determined. HF diet induced a marked increase in plasma glucose, insulin, and triglycerides in ApoE-KO mice, provoked vascular remodeling, enhanced expression of vascular cell-adhesion molecule-1 (VCAM-1) and matrix metalloprotease 9 (MMP-9) and enlarged atherosclerotic lesion in aortic and carotid arteries. NAD(P)H oxidase activity was enhanced by fructose intake, and this effect was attenuated by tempol, a superoxide dismutase mimetic, and losartan, an Angiotensin II receptor antagonist. Our study results show that high-fructose-induced insulin resistance promotes a proinflammatory and prooxidant state which accelerates atherosclerotic plaque formation in ApoE-KO mice. PMID:22474431

  14. ApoM/HDL-C and apoM/apoA-I ratios are indicators of diabetic nephropathy in healthy controls and type 2 diabetes mellitus.

    PubMed

    Zhang, Puhong; Gao, Jialin; Pu, Chun; Feng, Gang; Wang, Lizhuo; Huang, Lizhu; Zhang, Yao

    2017-03-01

    Apolipoprotein M (apoM) concentrations were decreased in type 2 diabetes mellitus (T2DM). ApoM was selectively expressed in renal tubular epithelial cells. We investigated the changes in plasma apoM concentrations in diabetic nephropathy (DN) patients and the potential of apoM as a biomarker of DN. A total of 96 DN patients and 100 age- and sex-matched diabetic non-nephropathy (non-DN) patients and 110 healthy controls were included. All T2DM patients were divided into 3 groups according to urinary albumin excretion: normoalbuminuria (n=100), microalbuminuria (n=50) and macroalbuminuria (n=46). Plasma apoM concentrations were measured by enzyme-linked immunosorbent assay. DN Patients had higher plasma apoM concentrations than those in non-DN patients (22.23±11.69 vs. 18.96±7.85ng/μl, P<0.05). In addition, microalbuminuria group showed higher plasma apoM concentrations than those in normoalbuminuria group (22.67±11.40 vs. 18.96±7.85ng/μl, P<0.05). The areas under curve (AUC) of apoM using a receiver-operating characteristic (ROC) curve analysis showed that plasma apoM concentrations were not indicators for identification of DN from healthy people (AUC=0.478, P=0.585) and from T2DM (AUC=0.563, P=0.125). DN patients had higher ratios of apoM/HDL-C and apoM/apoA1 than those in healthy controls and in non-DN patients. ApoM/HDL-C and apoM/apoA1 ratios could be used as indicators for identification of DN from healthy people (AUC=0.597, P=0.016; AUC=0.665, P=0.000, respectively) and from T2DM (AUC=0.580, P=0.050; AUC=0.601, P=0.015, respectively). ApoM/HDL-C and apoM/apoA1 ratios could be used as indicators for identification of DN from healthy people and from T2DM patients. Copyright © 2017. Published by Elsevier B.V.

  15. Arterial switch operation for transposition of the great arteries with coronary arteries from a single aortic sinus.

    PubMed

    Sung, Si Chan; Chang, Yun Hee; Lee, Hyoung Doo; Kim, Siho; Woo, Jong Soo; Lee, Young Seok

    2005-08-01

    The reimplantation of the coronary arteries from a single aortic sinus (single sinus coronary artery) in an arterial switch operation remains a technically challenging procedure. The technique of coronary transfer in this situation should be individualized depending on coronary ostial anatomy. We reviewed our techniques of coronary reimplantation with early and midterm results. Among 103 patients who underwent arterial switch operations from March 1994 to June 2004, 16 (15.5%) had single sinus coronary artery (median age, 9 days; mean body weight, 3.5 kg). Fourteen patients (14/16, 87.5%) had coronary arteries from right facing sinus (sinus 2). Of these 14 patients, 11 had separate ostia including intramural course of the left coronary artery (n = 9) and 3 had single ostium. Two patients (2/16, 12.5%) had coronary arteries from left facing sinus (sinus 1) with single ostium. Aortic arch obstruction was associated in 5 patients. All 5 single sinus coronary arteries with single ostium were reimplanted with the trap-door technique. Of the 11 patients with separate ostia, 8 underwent coronary transfer with the aortocoronary flap technique and 3 with the double-button technique. Two of the 3 patients who underwent the double-button technique required left coronary artery bypass using left subclavian artery free graft as the salvaging procedure. There was one early death (1/16, 6.3%), which occurred during our earlier experience, in a patient who had arch anomaly and intramural left coronary artery. There was no late death. All but one patient had good ventricular function. All single sinus coronary artery with single ostium can be transferred with the trap-door technique with excellent results. The aortocoronary flap technique in those with separate ostia with or without intramural left coronary artery may be a good option. However, reimplantation of the intramural left coronary artery using separate coronary buttons should be performed with great care.

  16. Epidemiology of the arterial stiffness.

    PubMed

    Breithaupt-Grögler, K; Belz, G G

    1999-06-01

    Aortic stiffening is as much an important risk factor in cardiovascular morbidity and mortality, as it serves as reliable surrogate marker for clinical endpoints like myocardial and cerebrovascular incidents. Elevated aortic stiffness induces high systolic blood pressure, augmented pulse pressure with increased ventricular afterload, reduced subendocardial blood flow and augmented pulsatile stress in the peripheral arteries. Factors with relevant impact on the epidemiology of arterial stiffness are widely spread. 3 major groups of parameters influencing the stiffness of the aorta and the large arteries have been studied and described up to now: (i) physiological properties like age, gender, body height, pressure, hormonal state, genetic factors; (ii) environmental factors like nutrition (fish-, salt-, garlic consumption), smoking, performance of sports and aerobic capacity; (iii) diseases like hypertension, hypercholesterolemia, diabetes, coronary heart disease, cerebrovascular disease, renal failure, Marfan-syndrome, growth hormone deficiency. Close association between several of these factors impedes analyzing them independently from each other. Age and blood pressure were found to be the most prominent predictors of arterial stiffness in normal as well as in disease populations. Physiological and environmental factors can modulate these effects of aging, diseases generally seem to amplify them.

  17. Photonic sensing of arterial distension

    PubMed Central

    Ruh, Dominic; Subramanian, Sivaraman; Sherman, Stanislav; Ruhhammer, Johannes; Theodor, Michael; Dirk, Lebrecht; Foerster, Katharina; Heilmann, Claudia; Beyersdorf, Friedhelm; Zappe, Hans; Seifert, Andreas

    2016-01-01

    Most cardiovascular diseases, such as arteriosclerosis and hypertension, are directly linked to pathological changes in hemodynamics, i.e. the complex coupling of blood pressure, blood flow and arterial distension. To improve the current understanding of cardiovascular diseases and pave the way for novel cardiovascular diagnostics, innovative tools are required that measure pressure, flow, and distension waveforms with yet unattained spatiotemporal resolution. In this context, miniaturized implantable solutions for continuously measuring these parameters over the long-term are of particular interest. We present here an implantable photonic sensor system capable of sensing arterial wall movements of a few hundred microns in vivo with sub-micron resolution, a precision in the micrometer range and a temporal resolution of 10 kHz. The photonic measurement principle is based on transmission photoplethysmography with stretchable optoelectronic sensors applied directly to large systemic arteries. The presented photonic sensor system expands the toolbox of cardiovascular measurement techniques and makes these key vital parameters continuously accessible over the long-term. In the near term, this new approach offers a tool for clinical research, and as a perspective, a continuous long-term monitoring system that enables novel diagnostic methods in arteriosclerosis and hypertension research that follow the trend in quantifying cardiovascular diseases by measuring arterial stiffness and more generally analyzing pulse contours. PMID:27699095

  18. Peripheral arterial disease in women.

    PubMed

    Aronow, Wilbert S

    2009-12-20

    Peripheral arterial disease (PAD) is chronic arterial occlusive disease of the lower extremities caused by atherosclerosis whose prevalence increases with age. Only one-half of women with PAD are symptomatic. Symptomatic and asymptomatic women with PAD are at increased risk for all-cause mortality, cardiovascular mortality, and mortality from coronary artery disease. Modifiable risk factors that predispose women to PAD include active cigarette smoking, passive smoking, diabetes mellitus, hypertension, dyslipidemia, increased plasma homocysteine levels and hypothyroidism. With regard to management, women who smoke should be encouraged to quit and referred to a smoking cessation program. Hypertension, diabetes mellitus, dyslipidemia, and hypothyroidism require treatment. Statins reduce the incidence of intermittent claudication and improve exercise duration until the onset of intermittent claudication in women with PAD and hypercholesterolemia. Anti-platelet drugs such as aspirin or especially clopidogrel, angiotensin-converting enzyme inhibitors and statins should be given to all women with PAD. Beta blockers are recommended if coronary artery disease is present. Exercise rehabilitation programs and cilostazol increase exercise time until intermittent claudication develops. Chelation therapy should be avoided as it is ineffective. Indications for lower extremity percutaneous transluminal angioplasty or bypass surgery in women are (1) incapacitating claudication interfering with work or lifestyle; and (2) limb salvage in women with limb-threatening ischemia as manifested by rest pain, non-healing ulcers, and/or infection or gangrene. Future research includes investigation of mechanisms underlying why women have a higher risk of graft failure and major amputation.

  19. Capsaicin and arterial hypertensive crisis.

    PubMed

    Patanè, Salvatore; Marte, Filippo; La Rosa, Felice Carmelo; La Rocca, Roberto

    2010-10-08

    Chili peppers are rich in capsaicin. The potent vasodilator calcitonin gene-related peptide (CGRP) is stored in a population of C-fiber afferents that are sensitive to capsaicin. CGRP and peptides released from cardiac C fibers have a beneficial effect in myocardial ischemia and reperfusion. It has been reported that capsaicin pretreatment can deplete cardiac C-fiber peptide stores. Furthermore, it has also been reported that capsaicin-treated pigs have significantly increased mean arterial blood pressure compared with controls, and that the decrease in CGRP synthesis and release contributes to the elevated blood pressure. A case has also been reported of an arterial hypertensive crisis in a patient with a large ingestion of peppers and chili peppers the day before. We present a case of an arterial hypertensive crisis in a 19-year-old Italian man with an abundant ingestion of peppers and of chili peppers the preceding day. This case describes an unusual pattern of arterial hypertensive crisis due to capsaicin.

  20. Bilateral internal thoracic artery grafting

    PubMed Central

    2013-01-01

    The effectiveness of the left internal mammary artery graft to the anterior descending coronary artery as a surgical strategy has been shown to improve the survival rate and decrease the risk of adverse cardiac events in patients undergoing coronary bypass surgery. These clinical benefits appear to be related to the superior short and long-term patency rates of the internal thoracic artery graft. Although the advantages of using of both internal thoracic arteries (ITA) for bypass grafting have taken longer to prove, recent results from multiple data sets now support these findings. The major advantage of bilateral ITA grafting appears to be improved survival rate, while the disadvantages of complex ITA grafting include the increased complexity of operation, and an increased risk of wound complications. While these short-term disadvantages have been mitigated in contemporary surgical practice, they have not eliminated. Bilateral ITA grafting should be considered the procedure of choice for patients undergoing coronary bypass surgery that have a predicted survival rate of longer than ten years. PMID:23977627

  1. Compliant transducer measures artery profile

    NASA Technical Reports Server (NTRS)

    Feldstein, C.; Culler, V. H.; Crawford, D. W.; Spears, J. R.

    1981-01-01

    Instrument consisting of compliant fingers with attached semiconductor pickups measures inside contours of narrow vessels. Instrument, originally designed to monitor human arteries, is drawn through vessel to allow finges to follow contours. Lead wires transmit electrical signals to external processing equipment.

  2. Pulmonary Artery Sarcoma - Multimodality Imaging.

    PubMed

    Jeong, Nari; Seol, Sang-Hoon; Kim, Il Hwan; Kim, Ji Yeon

    2016-01-01

    Pulmonary artery sarcoma (PAS) is a rare and fatal disease. PAS can often be misdiagnosed as pulmonary thromboembolism. Moreover, the correct diagnosis is frequently delayed due to nonspecific signs and symptoms. The prognosis of patients with PAS is poor. We report a case of a woman with a primary PAS who was initially diagnosed with pulmonary thromboembolism.

  3. Pulmonary Artery Sarcoma - Multimodality Imaging

    PubMed Central

    Jeong, Nari; Seol, Sang-Hoon; Kim, Il Hwan; Kim, Ji Yeon

    2016-01-01

    Pulmonary artery sarcoma (PAS) is a rare and fatal disease. PAS can often be misdiagnosed as pulmonary thromboembolism. Moreover, the correct diagnosis is frequently delayed due to nonspecific signs and symptoms. The prognosis of patients with PAS is poor. We report a case of a woman with a primary PAS who was initially diagnosed with pulmonary thromboembolism. PMID:27833785

  4. Engineering of arteries in vitro

    PubMed Central

    Huang, Angela H.; Niklason, Laura E.

    2014-01-01

    This review will focus on two elements that are essential for functional arterial regeneration in vitro: the mechanical environment and the bioreactors used for tissue growth. The importance of the mechanical environment to embryological development, vascular functionality, and vascular graft regeneration will be discussed. Bioreactors generate mechanical stimuli to simulate the biomechanical environment of the arterial system. This system has been used to reconstruct arterial grafts with appropriate mechanical strength for implantation by controlling the chemical and mechanical environments in which the grafts are grown. Bioreactors are powerful tools to study the effect of mechanical stimuli on extracellular matrix (ECM) architecture and the mechanical properties of engineered vessels. Hence biomimetic systems enable us to optimize chemo-biomechanical culture conditions to regenerate engineered vessels with physiological properties similar to those of native arterial vessels. In addition, this review will introduce and examine various approaches and techniques that have been used to engineer biologically-based vascular grafts, including collagen-based grafts, fibrin-gel grafts, cell sheet engineering, biodegradable polymers, and decellularization of native vessels. PMID:24399290

  5. Small artery remodelling in diabetes.

    PubMed

    Rosei, Enrico Agabiti; Rizzoni, Damiano

    2010-05-01

    The aim of this article is to briefly review available data regarding changes in the structure of microvessels observed in patients with diabetes mellitus, and possible correction by effective treatment. The development of structural changes in the systemic vasculature is the end result of established hypertension. In essential hypertension, small arteries of smooth muscle cells are restructured around a smaller lumen and there is no net growth of the vascular wall, although in some secondary forms of hypertension, a hypertrophic remodelling may be detected. Moreover, in non-insulin-dependent diabetes mellitus a hypertrophic remodelling of subcutaneous small arteries is present. Indices of small resistance artery structure, such as the tunica media to internal lumen ratio, may have a strong prognostic significance in hypertensive and diabetic patients, over and above all other known cardiovascular risk factors. Therefore, regression of vascular alterations is an appealing goal of antihypertensive treatment. Different antihypertensive drugs seem to have different effect on vascular structure. In diabetic hypertensive patients, a significant regression of structural alterations of small resistance arteries with drugs blocking the renin-angiotensin system (angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers) was demonstrated. Alterations in the microcirculation represent a common pathological finding, and microangiopathy is one of the most important mechanisms involved in the development of organ damage as well as of clinical events in patients with diabetes mellitus. Renin-angiotensin system blockade seems to be effective in preventing/regressing alterations in microvascular structure.

  6. Small artery remodelling in diabetes

    PubMed Central

    Rosei, Enrico Agabiti; Rizzoni, Damiano

    2010-01-01

    Abstract The aim of this article is to briefly review available data regarding changes in the structure of microvessels observed in patients with diabetes mellitus, and possible correction by effective treatment. The development of structural changes in the systemic vasculature is the end result of established hypertension. In essential hypertension, small arteries of smooth muscle cells are restructured around a smaller lumen and there is no net growth of the vascular wall, although in some secondary forms of hypertension, a hypertrophic remodelling may be detected. Moreover, in non-insulin-dependent diabetes mellitus a hypertrophic remodelling of subcutaneous small arteries is present. Indices of small resistance artery structure, such as the tunica media to internal lumen ratio, may have a strong prognostic significance in hypertensive and diabetic patients, over and above all other known cardiovascular risk factors. Therefore, regression of vascular alterations is an appealing goal of antihypertensive treatment. Different antihypertensive drugs seem to have different effect on vascular structure. In diabetic hypertensive patients, a significant regression of structural alterations of small resistance arteries with drugs blocking the renin–angiotensin system (angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers) was demonstrated. Alterations in the microcirculation represent a common pathological finding, and microangiopathy is one of the most important mechanisms involved in the development of organ damage as well as of clinical events in patients with diabetes mellitus. Renin–angiotensin system blockade seems to be effective in preventing/regressing alterations in microvascular structure. PMID:20646125

  7. Leucine supplementation via drinking water reduces atherosclerotic lesions in apoE null mice

    PubMed Central

    Zhao, Yang; Dai, Xiao-yan; Zhou, Zhou; Zhao, Ge-xin; Wang, Xian; Xu, Ming-jiang

    2016-01-01

    Aim: Recent evidence suggests that the essential amino acid leucine may be involved in systemic cholesterol metabolism. In this study, we investigated the effects of leucine supplementation on the development of atherosclerosis in apoE null mice. Methods: ApoE null mice were fed with chow supplemented with leucine (1.5% w/v) in drinking water for 8 week. Aortic atherosclerotic lesions were examined using Oil Red O staining. Plasma lipoprotein-cholesterol levels were measured with fast protein liquid chromatography. Hepatic gene expression was detected using real-time PCR and Western blot analyses. Results: Leucine supplementation resulted in 57.6% reduction of aortic atherosclerotic lesion area in apoE null mice, accompanied by 41.2% decrease of serum LDL-C levels and 40.2% increase of serum HDL-C levels. The body weight, food intake and blood glucose level were not affected by leucine supplementation. Furthermore, leucine supplementation increased the expression of Abcg5 and Abcg8 (that were involved in hepatic cholesterol efflux) by 1.28- and 0.86-fold, respectively, and significantly increased their protein levels. Leucine supplementation also increased the expression of Srebf1, Scd1 and Pgc1b (that were involved in hepatic triglyceride metabolism) by 3.73-, 1.35- and 1.71-fold, respectively. Consequently, leucine supplementation resulted in 51.77% reduction of liver cholesterol content and 2.2-fold increase of liver triglyceride content. Additionally, leucine supplementation did not affect the serum levels of IL-6, IFN-γ, TNF-α, IL-10 and IL-12, but markedly decreased the serum level of MCP-1. Conclusion: Leucine supplementation effectively attenuates atherosclerosis in apoE null mice by improving the plasma lipid profile and reducing systemic inflammation. PMID:26687933

  8. Cerebral amyloid angiopathy in a 95+ cohort: complement activation and apolipoprotein E (ApoE) genotype.

    PubMed

    Tanskanen, M; Lindsberg, P J; Tienari, P J; Polvikoski, T; Sulkava, R; Verkkoniemi, A; Rastas, S; Paetau, A; Kiuru-Enari, S

    2005-12-01

    There is growing evidence that in Alzheimer's disease (AD) amyloid beta-protein (Abeta) triggers a chronic inflammatory reaction in cerebral amyloid plaques, including complement proteins. Abeta also accumulates cerebrovascularly in age- and AD-associated cerebral amyloid angiopathy (CAA). We investigated complement proteins in CAA in a population-based series using histological and immunohistochemical staining methods. The 74 subjects, aged 95 years or more, had undergone clinical neurological examination and apolipoprotein E (ApoE) genotyping. The brains had been studied for AD post-mortem, allowing us to relate the histopathological findings to clinical and genetic conditions. CAA with congophilic amyloid was found in 36/74 individuals (48.6%). The vascular amyloid deposits immunoreacted with antibodies to Abeta and complements 3d (C3d) and 9 (C9). The positivity in complement stains increased with growing severity of CAA (P = 0.001). The presence of CAA associated with ApoE epsilon4 (P = 0.0005) and overrepresentation of epsilon4 among those with moderate or severe vs. mild CAA (P = 0.03) was demonstrated. The presence of CAA associated with dementia (P = 0.01), which was contributed by both epsilon4+ (P = 0.02) and epsilon4- (P = 0.06) subjects. Our study shows that complement proteins are deposited in the affected vessels in Abeta-associated CAA. They may solely represent the cerebral Abeta- burden associated to inflammatory stimuli, or signal a contribution in the clearance of cerebral Abeta, thereby contributing to the events associated with evolution of clinical dementia. Our results demonstrate a strong association between CAA and ApoE epsilon4 as well as dementia and suggest that the contribution of CAA to dementia is largely independent of ApoE epsilon4.

  9. Gene sequences regulating the production of apoE and cerebral palsy of variable severity.

    PubMed

    Lien, Espen; Andersen, Guro L; Bao, Yongde; Gordish-Dressman, Heather; Skranes, Jon; Blackman, James A; Vik, Torstein

    2014-09-01

    The apoE protein is the most important lipid transporter in the brain and has also been shown to have several regulatory functions in the central nervous system. The production of apoE is regulated by a number of genes and increases under certain conditions such as cerebral injury in adults. Our aim was to study whether variations in genes regulating the expression of the APOE gene were associated with severity of cerebral palsy (CP). Children enrolled in the Cerebral Palsy Register of Norway (CPRN) were invited to participate in this cross-sectional study; 281 of the invited 703 children (40%) returned swabs with buccal cells collected by parents. Six genetic variations thought to affect the production of apoE were genotyped and correlated with clinical data recorded in the CPRN. Compared with children carrying the GG allele, children with genotype GT or TT in a specific genetic variation (rs59007384 located in the nearby TOMM40 gene) had excess risk for worse fine motor function (Odds ratio (OR): 1.82; 95% Confidence interval (CI): 1.10-2.99; p = 0.019) and epilepsy (OR: 2.32; CI: 1.17-4.61; p = 0.016). There was no association between severity of CP and any of the other five genetic variations analyzed. Our findings suggest that genetic variations in one of the sequences regulating the expression of APOE, may be associated with worse clinical outcome in children with cerebral palsy. Copyright © 2014 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  10. Removal of copper from Octopus vulgaris haemocyanin. Preparation of the half-apo and apo derivatives.

    PubMed Central

    Beltramini, M; Ricchelli, F; Piazzesi, A; Barel, A; Salvato, B

    1984-01-01

    The two copper ions bound in the active site of Octopus vulgaris haemocyanin can be removed by cyanide. The two metal ions react with the ligand sequentially. In this paper the preparation of Octopus half-apo-haemocyanin, containing at the active site a single copper ion, is described. Moreover, the conditions to obtain Octopus apo-haemocyanin, containing less than 3% of copper still bound, are given. PMID:6477505

  11. Removal of copper from Octopus vulgaris haemocyanin. Preparation of the half-apo and apo derivatives.

    PubMed

    Beltramini, M; Ricchelli, F; Piazzesi, A; Barel, A; Salvato, B

    1984-08-01

    The two copper ions bound in the active site of Octopus vulgaris haemocyanin can be removed by cyanide. The two metal ions react with the ligand sequentially. In this paper the preparation of Octopus half-apo-haemocyanin, containing at the active site a single copper ion, is described. Moreover, the conditions to obtain Octopus apo-haemocyanin, containing less than 3% of copper still bound, are given.

  12. Leucine supplementation via drinking water reduces atherosclerotic lesions in apoE null mice.

    PubMed

    Zhao, Yang; Dai, Xiao-yan; Zhou, Zhou; Zhao, Ge-xin; Wang, Xian; Xu, Ming-jiang

    2016-02-01

    Recent evidence suggests that the essential amino acid leucine may be involved in systemic cholesterol metabolism. In this study, we investigated the effects of leucine supplementation on the development of atherosclerosis in apoE null mice. ApoE null mice were fed with chow supplemented with leucine (1.5% w/v) in drinking water for 8 week. Aortic atherosclerotic lesions were examined using Oil Red O staining. Plasma lipoprotein-cholesterol levels were measured with fast protein liquid chromatography. Hepatic gene expression was detected using real-time PCR and Western blot analyses. Leucine supplementation resulted in 57.6% reduction of aortic atherosclerotic lesion area in apoE null mice, accompanied by 41.2% decrease of serum LDL-C levels and 40.2% increase of serum HDL-C levels. The body weight, food intake and blood glucose level were not affected by leucine supplementation. Furthermore, leucine supplementation increased the expression of Abcg5 and Abcg8 (that were involved in hepatic cholesterol efflux) by 1.28- and 0.86-fold, respectively, and significantly increased their protein levels. Leucine supplementation also increased the expression of Srebf1, Scd1 and Pgc1b (that were involved in hepatic triglyceride metabolism) by 3.73-, 1.35- and 1.71-fold, respectively. Consequently, leucine supplementation resulted in 51.77% reduction of liver cholesterol content and 2.2-fold increase of liver triglyceride content. Additionally, leucine supplementation did not affect the serum levels of IL-6, IFN-γ, TNF-α, IL-10 and IL-12, but markedly decreased the serum level of MCP-1. Leucine supplementation effectively attenuates atherosclerosis in apoE null mice by improving the plasma lipid profile and reducing systemic inflammation.

  13. Caspase-3 Deletion Promotes Necrosis in Atherosclerotic Plaques of ApoE Knockout Mice

    PubMed Central

    Schrijvers, Dorien M.; Hermans, Marthe; Van Hoof, Viviane O.; De Meyer, Guido R. Y.

    2016-01-01

    Apoptosis of macrophages and vascular smooth muscle cells (VSMCs) in advanced atherosclerotic plaques contributes to plaque progression and instability. Caspase-3, a key executioner protease in the apoptotic pathway, has been identified in human and mouse atherosclerotic plaques but its role in atherogenesis is not fully explored. We therefore investigated the impact of caspase-3 deletion on atherosclerosis by crossbreeding caspase-3 knockout (Casp3−/−) mice with apolipoprotein E knockout (ApoE−/−) mice. Bone marrow-derived macrophages and VSMCs isolated from Casp3−/−ApoE−/− mice were resistant to apoptosis but showed increased susceptibility to necrosis. However, caspase-3 deficiency did not sensitize cells to undergo RIP1-dependent necroptosis. To study the effect on atherosclerotic plaque development, Casp3+/+ApoE−/− and Casp3−/−ApoE−/− mice were fed a western-type diet for 16 weeks. Though total plasma cholesterol, triglycerides, and LDL cholesterol levels were not altered, both the plaque size and percentage necrosis were significantly increased in the aortic root of Casp3−/−ApoE−/− mice as compared to Casp3+/+ApoE−/− mice. Macrophage content was significantly decreased in plaques of Casp3−/−ApoE−/− mice as compared to controls, while collagen content and VSMC content were not changed. To conclude, deletion of caspase-3 promotes plaque growth and plaque necrosis in ApoE−/− mice, indicating that this antiapoptotic strategy is unfavorable to improve atherosclerotic plaque stability. PMID:27847551

  14. Lipoprotein(a) Promotes Smooth Muscle Cell Proliferation and Dedifferentiation in Atherosclerotic Lesions of Human Apo(a) Transgenic Rabbits

    PubMed Central

    Ichikawa, Tomonaga; Unoki, Hiroyuki; Sun, Huijun; Shimoyamada, Hiroaki; Marcovina, Santica; Shikama, Hisataka; Watanabe, Teruo; Fan, Jianglin

    2002-01-01

    Elevated plasma lipoprotein(a) [Lp(a)] levels constitute an independent risk factor for the development of atherosclerosis. However, the mechanism underlying Lp(a) atherogenicity is unclear. Recently, we demonstrated that Lp(a) may potentially be proatherogenic in transgenic rabbits expressing human apolipoprotein(a) [apo(a)]. In this study, we further investigated atherosclerotic lesions of transgenic rabbits by morphometry and immunohistochemistry. On a cholesterol diet, human apo(a) transgenic rabbits had more extensive atherosclerotic lesions of the aorta, carotid artery, iliac artery, and coronary artery than did nontransgenic littermate rabbits as defined by increased intimal lesion area. Enhanced lesion development in transgenic rabbits was characterized by increased accumulation of smooth muscle cells, that was often associated with the Lp(a) deposition. To explore the possibility that Lp(a) may be involved in the smooth-muscle cell phenotypic modulation, we stained the lesions using a panel of monoclonal antibodies against smooth-muscle myosin heavy-chain isoforms (SM1, SM2, and SMemb) and basic transcriptional element binding protein-2 (BTEB2). We found that a large number of smooth muscle cells located in the apo(a)-containing areas of transgenic rabbits were positive for SMemb and BTEB2, suggesting that these smooth muscle cells were either immature or in the state of activation. In addition, transgenic rabbits showed delayed fibrinolytic activity accompanied by increased plasma plasminogen activator inhibitor-1. We conclude that Lp(a) may enhance the lesion development by mediating smooth muscle cell proliferation and dedifferentiation possibly because of impaired fibrinolytic activity. PMID:11786416

  15. Interrogating Meanings of Work in Children&apos;s Literature

    ERIC Educational Resources Information Center

    Wieland, Stacey M. B.; Bauer, Janell C.

    2015-01-01

    In this article, Wieland and Bauer discuss a teaching activity that helps students understand how meanings of work (MOW) are socially constructed through commonplace texts: children&apos;s books. The activity helps students consider how children&apos;s books shape future workers&apos; understandings of what work is, what kinds of work are most…

  16. The Not-so-Random Drunkard&apos;s Walk

    ERIC Educational Resources Information Center

    Ehrhardt, George

    2013-01-01

    This dataset contains the results of a quasi-experiment, testing Karl Pearson&apos;s "drunkard&apos;s walk" analogy for an abstract random walk. Inspired by the alternate hypothesis that drunkards stumble to the side of their dominant hand, it includes data on intoxicated test subjects walking a 10&apos; line. Variables include: the…

  17. Towards a Sociocultural Understanding of Children&apos;s Voice

    ERIC Educational Resources Information Center

    Maybin, Janet

    2013-01-01

    While "voice" is frequently invoked in discussions of pupils&apos; agency and empowerment, less attention has been paid to the dialogic dynamics of children&apos;s voices and the sociocultural features shaping their emergence. Drawing on linguistic ethnographic research involving recent recordings of 10- and 11-year-old children&apos;s…

  18. Towards a Sociocultural Understanding of Children&apos;s Voice

    ERIC Educational Resources Information Center

    Maybin, Janet

    2013-01-01

    While "voice" is frequently invoked in discussions of pupils&apos; agency and empowerment, less attention has been paid to the dialogic dynamics of children&apos;s voices and the sociocultural features shaping their emergence. Drawing on linguistic ethnographic research involving recent recordings of 10- and 11-year-old children&apos;s…

  19. Revitalizing Ernst Mach&apos;s Popular Scientific Lectures

    ERIC Educational Resources Information Center

    Euler, Manfred

    2007-01-01

    Compared to Ernst Mach&apos;s influence on the conceptual development of physics, his efforts to popularize science and his reflections on science literacy are known to a much lesser degree. The approach and the impact of Mach&apos;s popular scientific lectures are discussed in view of today&apos;s problems of understanding science. The key issues…

  20. Asperger&apos;s in the Holmes Family

    ERIC Educational Resources Information Center

    Altschuler, Eric L.

    2013-01-01

    I show that Mycroft Holmes (Sherlock Holmes&apos; brother) is a formally described case of Asperger&apos;s syndrome a half century before Asperger&apos;s description of the syndrome. Further, given the genetic similarity and links between the brothers stated by Sherlock, this also cinches the same diagnosis for Sherlock.