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Sample records for advanced human atherosclerotic

  1. Increased size and cellularity of advanced atherosclerotic lesions in mice with endothelial overexpression of the human TRPC3 channel

    PubMed Central

    Smedlund, Kathryn B.; Birnbaumer, Lutz; Vazquez, Guillermo

    2015-01-01

    In previous in vitro studies, we showed that Transient Receptor Potential Canonical 3 (TRPC3), a calcium-permeable, nonselective cation channel endowed with high constitutive function, is an obligatory component of the inflammatory signaling that controls expression of the vascular cell adhesion molecule-1 (VCAM-1) and monocyte adhesion to coronary artery endothelial cells. Also, TRPC3 expression in these cells was found to be up-regulated by proatherogenic factors, which enhanced inflammation and VCAM-1 expression. However, it remained to be determined whether these in vitro findings were of relevance to atherosclerotic lesion development in vivo. To answer this important question in the present work, we generated mice with endothelial-specific overexpression of human TRPC3 in an Apoe knockout background (TgEST3ApoeKO) and examined lesions in the aortic sinus following 10 and 16 wk on a high-fat diet. No significant differences were found in size or complexity of early stage lesions (10 wk). However, advanced plaques (16 wk) from TgEST3ApoeKO mice exhibited a significant increase in size and macrophage content compared with nontransgenic littermate controls. Remarkably, this change was correlated with increased VCAM-1 and phospho-IkBα immunoreactivity along the endothelial lining of lesions from transgenic animals compared with controls. These findings validate the in vivo relevance of previous in vitro findings and represent, to our knowledge, the first in vivo evidence for a proatherogenic role of endothelial TRPC3. PMID:25870279

  2. Isolation of calcifiable vesicles from human atherosclerotic aortas.

    PubMed

    Hsu, H H; Camacho, N P

    1999-04-01

    Advanced mineralization can cause brittleness of aortic walls with decreased elasticity thereby causing the wall to rupture. Although the precise mechanisms of dystrophic calcification remain unknown, morphological evidence reveals the presence of mineral-associated vesicles in the lesions and defective bioprosthetic valves. In an attempt to demonstrate the calcifiability of the vesicles, small segments of human atherosclerotic aortas with calcified lesions were removed at autopsy and then digested in a crude collagenase solution to release vesicles. A differential centrifugation was then used to isolate calcifiable vesicles, which was precipitated at 300,000 x g for 20 min. An exposure of the vesicles to a calcifying medium containing physiologic levels of Ca2+, Pi, and 1 mM ATP caused Ca deposition in a vesicle protein-concentration dependent manner. The calcifiability of the vesicles was further demonstrated by electron microscopy. Fourier transform spectroscopic analysis of the deposited mineral revealed the presence of a hydroxyapatite phase, closely resembling the native form of mineral in atherosclerotic plaques. In addition, calcifiable vesicles were enriched in ATP-hydrolyzing enzymes including Mg2+ or Ca2+-ATPase and NTP pyrophosphohydrolase that may be involved in normal and pathological calcification. Triton X-100 at 0.01% abolished 80% of both ATPase activity and ATP-initiated calcification. A comparison of vesicles isolated from non-atherosclerotic and atherosclerotic aortas indicated that atherosclerotic vesicles tended to have higher calcifiability. These observations suggest that the calcifiable vesicles play a part in dystrophic calcification of aortas in atherosclerosis. PMID:10217364

  3. Human urotensin II promotes hypertension and atherosclerotic cardiovascular diseases.

    PubMed

    Watanabe, Takuya; Arita, Shigeko; Shiraishi, Yuji; Suguro, Toshiaki; Sakai, Tetsuo; Hongo, Shigeki; Miyazaki, Akira

    2009-01-01

    Human urotensin II (U-II), the most potent vasoconstrictor undecapeptide identified to date, and its receptor (UT) are involved in the pathogenesis of systemic and pulmonary hypertension. Here, we review recent advances in our understanding of the pathophysiology of U-II with particular reference to its role in atherosclerotic cardiovascular diseases. Single-nucleotide polymorphisms of U-II gene (S89N) are associated with onset of essential hypertension, type II diabetes mellitus, and insulin resistance in the Asian population. Plasma U-II levels are elevated in patients with vascular endothelial dysfunction-related diseases such as essential hypertension, diabetes mellitus, atherosclerosis, ischemic heart disease, and heart failure. Chronic infusion of U-II enhances atherosclerotic lesions in the aorta in apolipoprotein E-knockout mice. In human atherosclerotic plaques from the aorta and coronary and carotid arteries, U-II is expressed at high levels in endothelial cells (ECs) and lymphocytes, whereas UT is expressed at high levels in vascular smooth muscle cells (VSMCs), ECs, monocytes, and macrophages. U-II stimulates vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 expression in human ECs as chemoattractant for monocytes, and accelerates foam cell formation by up-regulation of acyl-coenzyme A:cholesterol acyltransferase-1 in human monocyte-derived macrophages. U-II produces reactive oxygen species (ROS) via nicotinamide adenine dinucleotide phosphate oxidase activation in human VSMCs, and stimulates VSMC proliferation with synergistic effects when combined with ROS, oxidized LDL, and serotonin. Clinical studies demonstrated increased plasma U-II levels in accordance with the severity of carotid atherosclerosis in patients with essential hypertension and that of coronary artery lesions in patients with ischemic heart disease. Here, we summarize the key roles of U-II in progression of hypertension and atherosclerotic cardiovascular diseases

  4. Quantification of Various Inflammatory Cells in Advanced Atherosclerotic Plaques

    PubMed Central

    Paul, Christina Mary Priya; Kuruvilla, Sarah

    2016-01-01

    Introduction Atherosclerosis, the pathological basis of coronary artery disease is being extensively studied as understanding of the complex processes involved in the formation and progression that can provide an insight into prevention and treatment of the same. This is an autopsy study to identify and quantify various inflammatory cells in advanced atherosclerotic plaques. Aim This study aims at identifying and categorizing the various inflammatory cells present in advanced atherosclerotic plaques, noting their distribution in the plaque, quantifying them using histomorphometry and comparing them across plaques of different AHA types. Materials and Methods Post-mortem angiogram was performed on 3 heart specimens obtained at autopsy of random Road Traffic Accident (RTA) cases which revealed evidence of coronary artery disease. End-arterectomy was done and the arteries with atherosclerotic plaques were cut into serial sections and made into tissue blocks. Sections from these blocks were stained with H & E stain and the plaques were classified based on AHA classification. 50 advanced atherosclerotic plaques of AHA Type IV and V were chosen for this study and were screened for inflammatory cells, first with H & E stain and then with different immunohistochemical stains for T-lymphocytes, B-lymphocytes and neutrophils. The T-lymphocytes thus identified was further sub-typed into CD4+ and CD8+ cells again using IHC markers and the percentage area of each was measured using histomorphometry. Then, these values were compared between AHA Type IV and AHA Type V lesions. Results It was found that the inflammatory cells found in advanced atherosclerotic plaques were predominantly T-lymphocytes as evidenced by their CD3 positivity and they were found to be distributed mainly around the shoulder region and fibrous cap of the plaque. When categorized further, it was found that CD8+ T-cells were always more than CD4+ T-cells in advanced lesions. Meloperoxidase stain for

  5. Grating interferometry-based phase microtomography of atherosclerotic human arteries

    NASA Astrophysics Data System (ADS)

    Buscema, Marzia; Holme, Margaret N.; Deyhle, Hans; Schulz, Georg; Schmitz, Rüdiger; Thalmann, Peter; Hieber, Simone E.; Chicherova, Natalia; Cattin, Philippe C.; Beckmann, Felix; Herzen, Julia; Weitkamp, Timm; Saxer, Till; Müller, Bert

    2014-09-01

    Cardiovascular diseases are the number one cause of death and morbidity in the world. Understanding disease development in terms of lumen morphology and tissue composition of constricted arteries is essential to improve treatment and patient outcome. X-ray tomography provides non-destructive three-dimensional data with micrometer-resolution. However, a common problem is simultaneous visualization of soft and hard tissue-containing specimens, such as atherosclerotic human coronary arteries. Unlike absorption based techniques, where X-ray absorption strongly depends on atomic number and tissue density, phase contrast methods such as grating interferometry have significant advantages as the phase shift is only a linear function of the atomic number. We demonstrate that grating interferometry-based phase tomography is a powerful method to three-dimensionally visualize a variety of anatomical features in atherosclerotic human coronary arteries, including plaque, muscle, fat, and connective tissue. Three formalin-fixed, human coronary arteries were measured using advanced laboratory μCT. While this technique gives information about plaque morphology, it is impossible to extract the lumen morphology. Therefore, selected regions were measured using grating based phase tomography, sinograms were treated with a wavelet-Fourier filter to remove ring artifacts, and reconstructed data were processed to allow extraction of vessel lumen morphology. Phase tomography data in combination with conventional laboratory μCT data of the same specimen shows potential, through use of a joint histogram, to identify more tissue types than either technique alone. Such phase tomography data was also rigidly registered to subsequently decalcified arteries that were histologically sectioned, although the quality of registration was insufficient for joint histogram analysis.

  6. Differential expression of bone matrix regulatory proteins in human atherosclerotic plaques.

    PubMed

    Dhore, C R; Cleutjens, J P; Lutgens, E; Cleutjens, K B; Geusens, P P; Kitslaar, P J; Tordoir, J H; Spronk, H M; Vermeer, C; Daemen, M J

    2001-12-01

    In the present study, we examined the expression of regulators of bone formation and osteoclastogenesis in human atherosclerosis because accumulating evidence suggests that atherosclerotic calcification shares features with bone calcification. The most striking finding of this study was the constitutive immunoreactivity of matrix Gla protein, osteocalcin, and bone sialoprotein in nondiseased aortas and the absence of bone morphogenetic protein (BMP)-2, BMP-4, osteopontin, and osteonectin in nondiseased aortas and early atherosclerotic lesions. When atherosclerotic plaques demonstrated calcification or bone formation, BMP-2, BMP-4, osteopontin, and osteonectin were upregulated. Interestingly, this upregulation was associated with a sustained immunoreactivity of matrix Gla protein, osteocalcin, and bone sialoprotein. The 2 modulators of osteoclastogenesis (osteoprotegerin [OPG] and its ligand, OPGL) were present in the nondiseased vessel wall and in early atherosclerotic lesions. In advanced calcified lesions, OPG was present in bone structures, whereas OPGL was only present in the extracellular matrix surrounding calcium deposits. The observed expression patterns suggest a tight regulation of the expression of bone matrix regulatory proteins during human atherogenesis. The expression pattern of both OPG and OPGL during atherogenesis might suggest a regulatory role of these proteins not only in osteoclastogenesis but also in atherosclerotic calcification. PMID:11742876

  7. Sialyltransferase activity in normal and atherosclerotic human aorta intima.

    PubMed

    Gracheva, E V; Samovilova, N N; Golovanova, N K; Il'inskaya, O P; Tararak, E M; Prokazova, N V

    2001-04-01

    Sialyltransferase activity has been determined in Golgi membrane fractions isolated from atherosclerotic and normal intima of human aorta by measuring the transfer of N-acetylneuraminic acid (NeuAc) from CMP-NeuAc to asialofetuin. The asialofetuin-sialyltransferase activity was found to be twofold higher in the atherosclerotic intima than in the normal intima. The mean value of the apparent Michaelis constant (Km) for the sialylating enzyme in both tissues did not differ and was 57 microM. In contrast, the maximal velocity (Vmax) was 2-fold higher for the atherosclerotic intima than for the normal intima. These results suggest that expression of asialofetuin-sialyltransferases of the aortal intima may be increased in atherosclerosis. PMID:11403646

  8. Human atherosclerosis. II. Immunocytochemical analysis of the cellular composition of human atherosclerotic lesions.

    PubMed Central

    Gown, A. M.; Tsukada, T.; Ross, R.

    1986-01-01

    The authors have performed immunocytochemical investigations of the distribution of various cell types in human atherosclerotic plaques using monoclonal antibodies specific to smooth muscle cells (CGA7 [Gown et al, J Cell Biol 1985, 100:807-813] and HHF35 [Tsukada et al, Am J Pathol (In press)] ); lymphocytes (T200 antigen); endothelial cells (Factor VIII and the Ulex europeus agglutinin); and macrophages, the latter with a new macrophage-specific antibody HAM56. All studies were performed on methanol-Carnoy's-fixed, paraffin-embedded tissues. In areas of grossly normal aorta, significant numbers of macrophages were noted within areas of diffuse intimal thickening. The cellular composition of the following three types of raised lesions were analyzed: fibro-fatty lesions, which, despite their gross appearance, consistent with fibrous plaques, were composed almost exclusively of macrophages and lymphocytes and almost devoid of smooth muscle cells; fibrous plaques, which were predominantly composed of smooth muscle cells displaying considerable morphologic heterogeneity and an admixture of blood-borne cells; advanced plaques, which were characterized by complex layers of smooth muscle cells and macrophages with considerable variation from region to region. Also noted were foci of medial and even intimal vascularization subjacent to the more advanced plaques. These studies demonstrate the application of monoclonal antibody technology to the study of the cellular composition of human atherosclerotic lesions. Images Figure 1 Figure 2 p195-a Figure 3 Figure 4 Figure 5 Figure 6 p201-a Figure 7 Figure 8 PMID:3777135

  9. Myeloperoxidase, a catalyst for lipoprotein oxidation, is expressed in human atherosclerotic lesions.

    PubMed Central

    Daugherty, A; Dunn, J L; Rateri, D L; Heinecke, J W

    1994-01-01

    Oxidatively modified lipoproteins have been implicated in atherogenesis, but the mechanisms that promote oxidation in vivo have not been identified. Myeloperoxidase, a heme protein secreted by activated macrophages, generates reactive intermediates that oxidize lipoproteins in vitro. To explore the potential role of myeloperoxidase in the development of atherosclerosis, we determined whether the enzyme was present in surgically excised human vascular tissue. In detergent extracts of atherosclerotic arteries subjected to Western blotting, a rabbit polyclonal antibody monospecific for myeloperoxidase detected a 56-kD protein, the predicted molecular mass of the heavy subunit. Both the immunoreactive protein and authentic myeloperoxidase bound to a lectin-affinity column; after elution with methyl mannoside their apparent molecular masses were indistinguishable by nondenaturing size-exclusion chromatography. Peroxidase activity in detergent extracts of atherosclerotic lesions likewise bound to a lectin column and eluted with methyl mannoside. Moreover, eluted peroxidase generated the cytotoxic oxidant hypochlorous acid (HOCl), indicating that enzymatically active myeloperoxidase was present in lesions. Patterns of immunostaining of arterial tissue with antihuman myeloperoxidase antibodies were similar to those produced by an antimacrophage antibody, and were especially prominent in the shoulder region of transitional lesions. Intense foci of myeloperoxidase immunostaining also appeared adjacent to cholesterol clefts in lipid-rich regions of advanced atherosclerotic lesions. These findings identify myeloperoxidase as a component of human vascular lesions. Because this heme protein can generate reactive species that damage lipids and proteins, myeloperoxidase may contribute to atherogenesis by catalyzing oxidative reactions in the vascular wall. Images PMID:8040285

  10. Expression of lipoprotein lipase mRNA and secretion in macrophages isolated from human atherosclerotic aorta.

    PubMed

    Mattsson, L; Johansson, H; Ottosson, M; Bondjers, G; Wiklund, O

    1993-10-01

    The expression of lipoprotein lipase (LPL) mRNA and the LPL activity were studied in macrophages (CD14 positive) from human atherosclerotic tissue. Macrophages were isolated after collagenase digestion by immunomagnetic isolation. About 90% of the cells were foam cells with oil red O positive lipid droplets. To analyze the mRNA expression, PCR with specific primers for LPL was used. Arterial macrophages were analyzed directly after isolation and the data showed low expression of LPL mRNA when compared with monocyte-derived macrophages. To induce the expression of LPL mRNA in macrophages, PMA was used. When incubating arterial macrophages with PMA for 24 h we could not detect any increase in LPL mRNA levels. Similarly, the cells secreted very small amounts of LPL even after PMA stimulation. In conclusion, these studies show a very low expression of LPL mRNA in the CD14-positive macrophage-derived foam cells isolated from human atherosclerotic tissue. These data suggest that the CD14-positive cells are a subpopulation of foam cells that express low levels of lipoprotein lipase, and the lipid content could be a major factor for downregulation of LPL. However, the cells were isolated from advanced atherosclerotic lesions, and these findings may not reflect the situation in early fatty streaks. PMID:8408628

  11. Detection of nanobacteria-like particles in human atherosclerotic plaques.

    PubMed

    Puskás, L G; Tiszlavicz, L; Rázga, Zs; Torday, L L; Krenács, T; Papp, J Gy

    2005-01-01

    Recent and historical evidence is consistent with the view that atherosclerosis is an infectious disease or microbial toxicosis impacted by genetics and behavior. Because small bacterial-like particles, also known as nanobacteria have been detected in kidney stones, kidney and liver cyst fluids, and can form a calcium apatite coat we posited that this agent is present in calcified human atherosclerotic plaques. Carotid and aortic atherosclerotic plaques and blood samples collected at autopsy were examined for nanobacteria-like structures by light microscopy (hematoxylin-eosin and a calcium-specific von Kossa staining), immuno-gold labeling for transmission electron microscopy (TEM) for specific nanobacterial antigens, and propagation from homogenized, filtered specimens in culture medium. Nanobacterial antigens were identified in situ by immuno-TEM in 9 of 14 plaque specimens, but none of the normal carotid or aortic tissue (5 specimens). Nanobacteria-like particles were propagated from 26 of 42 sclerotic aorta and carotid samples and were confirmed by dot immunoblot, light microscopy and TEM. [3H]L-aspartic acid was incorporated into high molecular weight compounds of demineralized particles. PCR amplification of 16S rDNA sequences from the particles was unsuccessful by traditional protocols. Identification of nanobacteria-like particles at the lesion supports, but does not by itself prove the hypothesis that these agents contribute to the pathogenesis of atherosclerosis, especially vascular calcifications. PMID:16196199

  12. Colocalization of iron and ceroid in human atherosclerotic lesions.

    PubMed

    Lee, F Y; Lee, T S; Pan, C C; Huang, A L; Chau, L Y

    1998-06-01

    The presence of ceroid, a complex of protein associated with oxidized lipids, is commonly observed in human atherosclerotic lesions. When the human aortic walls were examined by Perls' staining, it was found that the iron deposits were evident in aortas with atherosclerosis. The extent of iron deposition was associated with the severity of the lesion. Furthermore, the iron deposits appeared to be colocalized with ceroids either extracellularly or intracellularly in foam cell-like macrophages or smooth muscle cells. Electron microscopy and X-ray microanalysis revealed that some of the extracellular iron aggregates were present within the ceroids. Likewise, some of the subcellular iron aggregates were found to be located near the lipid droplets or within the ceroids of foam cells. Collectively, these observations support the theory that the lipid oxidation occurring in lipid-laden cells of aortic lesions is facilitated by iron-overload in these cells. PMID:9690911

  13. Alternation of histone and DNA methylation in human atherosclerotic carotid plaques.

    PubMed

    Greißel, A; Culmes, M; Napieralski, R; Wagner, E; Gebhard, H; Schmitt, M; Zimmermann, A; Eckstein, H-H; Zernecke, A; Pelisek, J

    2015-08-01

    Little is known about epigenetics and its possible role in atherosclerosis. We here analysed histone and DNA methylation and the expression of corresponding methyltransferases in early and advanced human atherosclerotic carotid lesions in comparison to healthy carotid arteries. Western Blotting was performed on carotid plaques from our biobank with early (n=60) or advanced (n=60) stages of atherosclerosis and healthy carotid arteries (n=12) to analyse di-methylation patterns of histone H3 at positions K4, K9 and K27. In atherosclerotic lesions, di-methylation of H3K4 was unaltered and that of H3K9 and H3K27 significantly decreased compared to control arteries. Immunohistochemistry revealed an increased appearance of di-methylated H3K4 in smooth muscle cells (SMCs), a decreased expression of di-methylated H3K9 in SMCs and inflammatory cells, and reduced di-methylated H3K27 in inflammatory cells in advanced versus early atherosclerosis. Expression of corresponding histone methyltransferases MLL2 and G9a was increased in advanced versus early atherosclerosis. Genomic DNA hypomethylation, as determined by PCR for methylated LINE1 and SAT-alpha, was observed in early and advanced plaques compared to control arteries and in cell-free serum of patients with high-grade carotid stenosis compared to healthy volunteers. In contrast, no differences in DNA methylation were observed in blood cells. Expression of DNA-methyltransferase DNMT1 was reduced in atherosclerotic plaques versus controls, DNMT3A was undetectable, and DNMT3B not altered. DNA-demethylase TET1 was increased in atherosclerosisc plaques. The extent of histone and DNA methylation and expression of some corresponding methyltransferases are significantly altered in atherosclerosis, suggesting a possible contribution of epigenetics in disease development. PMID:25993995

  14. Laser ablation of human atherosclerotic plaque without adjacent tissue injury

    NASA Technical Reports Server (NTRS)

    Grundfest, W. S.; Litvack, F.; Forrester, J. S.; Goldenberg, T.; Swan, H. J. C.

    1985-01-01

    Seventy samples of human cadaver atherosclerotic aorta were irradiated in vitro using a 308 nm xenon chloride excimer laser. Energy per pulse, pulse duration and frequency were varied. For comparison, 60 segments were also irradiated with an argon ion and an Nd:YAG laser operated in the continuous mode. Tissue was fixed in formalin, sectioned and examined microscopically. The Nd:YAG and argon ion-irradiated tissue exhibited a central crater with irregular edges and concentric zones of thermal and blast injury. In contrast, the excimer laser-irradiated tissue had narrow deep incisions with minimal or no thermal injury. These preliminary experiments indicate that the excimer laser vaporizes tissue in a manner different from that of the continuous wave Nd:YAG or argon ion laser. The sharp incision margins and minimal damage to adjacent normal tissue suggest that the excimer laser is more desirable for general surgical and intravascular uses than are the conventionally used medical lasers.

  15. 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.

  16. Local effects of human PCSK9 on the atherosclerotic lesion.

    PubMed

    Giunzioni, Ilaria; Tavori, Hagai; Covarrubias, Roman; Major, Amy S; Ding, Lei; Zhang, Youmin; DeVay, Rachel M; Hong, Liang; Fan, Daping; Predazzi, Irene M; Rashid, Shirya; Linton, MacRae F; Fazio, Sergio

    2016-01-01

    Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes atherosclerosis by increasing low-density lipoprotein (LDL) cholesterol levels through degradation of hepatic LDL receptor (LDLR). Studies have described the systemic effects of PCSK9 on atherosclerosis, but whether PCSK9 has local and direct effects on the plaque is unknown. To study the local effect of human PCSK9 (hPCSK9) on atherosclerotic lesion composition, independently of changes in serum cholesterol levels, we generated chimeric mice expressing hPCSK9 exclusively from macrophages, using marrow from hPCSK9 transgenic (hPCSK9tg) mice transplanted into apoE(-/-) and LDLR(-/-) mice, which were then placed on a high-fat diet (HFD) for 8 weeks. We further characterized the effect of hPCSK9 expression on the inflammatory responses in the spleen and by mouse peritoneal macrophages (MPM) in vitro. We found that MPMs from transgenic mice express both murine (m) Pcsk9 and hPCSK9 and that the latter reduces macrophage LDLR and LRP1 surface levels. We detected hPCSK9 in the serum of mice transplanted with hPCSK9tg marrow, but did not influence lipid levels or atherosclerotic lesion size. However, marrow-derived PCSK9 progressively accumulated in lesions of apoE(-/-) recipient mice, while increasing the infiltration of Ly6C(hi) inflammatory monocytes by 32% compared with controls. Expression of hPCSK9 also increased CD11b- and Ly6C(hi) -positive cell numbers in spleens of apoE(-/-) mice. In vitro, expression of hPCSK9 in LPS-stimulated macrophages increased mRNA levels of the pro-inflammatory markers Tnf and Il1b (40% and 45%, respectively) and suppressed those of the anti-inflammatory markers Il10 and Arg1 (30% and 44%, respectively). All PCSK9 effects were LDLR-dependent, as PCSK9 protein was not detected in lesions of LDLR(-/-) recipient mice and did not affect macrophage or splenocyte inflammation. In conclusion, PCSK9 directly increases atherosclerotic lesion inflammation in an LDLR-dependent but

  17. CANCER BIOMARKERS IN HUMAN ATHEROSCLEROTIC LESIONS: DETECTION OF DNA ADDUCTS

    EPA Science Inventory

    Since somatic mutations are suspected to contribute to the pathogenesis not only of cancer but also of atherosclerotic plaques, we measured DNA adducts in the smooth muscle layer of atherosclerotic lesions in abnormal aorta specimens taken at surgery from seven patients. NA adduc...

  18. Development of Advanced Atherosclerotic Plaque by Injection of Inflammatory Proteins in a Rabbit Iliac Artery Model

    PubMed Central

    Kim, Jung-Sun; Lee, Seul-Gee; Oh, Jaewon; Park, Se-Il; Hong, Sung-Yu; Kim, Sehoon; Lee, Sang-Hak; Ko, Young-Guk; Choi, Donghoon; Hong, Myeong-Ki; Jang, Yangsoo

    2016-01-01

    Purpose Appropriate animal models of atherosclerotic plaque are crucial to investigating the pathophysiology of atherosclerosis, as well as for the evaluation of the efficacy and safety of vascular devices. We aimed to develop a novel animal model that would be suitable for the study of advanced atherosclerotic lesions in vivo. Materials and Methods Atherosclerotic plaque was induced in 24 iliac arteries from 12 rabbits by combining a high cholesterol diet, endothelial denudation, and injection into the vessel wall with either saline (n=5), olive oil (n=6), or inflammatory proteins [n=13, high-mobility group protein B1 (HMGB1) n=8 and tumor necrosis factor (TNF)-α n=5] using a Cricket™ Micro-infusion catheter. Optical coherence tomography (OCT) was performed to detect plaque characteristics after 4 weeks, and all tissues were harvested for histological evaluation. Results Advanced plaque was more frequently observed in the group injected with inflammatory proteins. Macrophage infiltration was present to a higher degree in the HMGB1 and TNF-α groups, compared to the oil or saline group (82.1±5.1% and 94.6±2.2% compared to 49.6±14.0% and 46.5±9.6%, p-value<0.001), using RAM11 antibody staining. On OCT, lipid rich plaques were more frequently detected in the inflammatory protein group [saline group: 2/5 (40%), oil group: 3/5 (50%), HMGB1 group: 6/8 (75%), and TNF-α group: 5/5 (100%)]. Conclusion These data indicate that this rabbit model of atherosclerotic lesion formation via direct injection of pro-inflammatory proteins into the vessel wall is useful for in vivo studies investigating atherosclerosis. PMID:27401639

  19. Morphometric analysis of atherosclerotic plaques in human carotid arteries.

    PubMed

    Shishkina, V S; Kashirina, S V; Sirotkin, V N; Il'inskaya, O P; Tararak, E M

    2012-03-01

    Morphometric analysis of 35 biopsy specimens from patients with stable (n=10) and unstable (n=25) atherosclerotic lesions was carried out. The structure of the plaques and their connective tissue caps was studied by various methods of histological sections staining. A new morphometric approach to quantitative evaluation of atherosclerotic lesions instability is suggested. It consists in calculation of the morphological "rigidity" coefficient, due to which the plaque is characterized more accurately. The proportion of areas of the "rigid" (connective tissue and calcium salt deposition areas) to "soft" (atheronecrotic nuclei, microvessels, clots and hemorrhages) structures of the plaque is evaluated. Plaque instability (liability of a to rupture) is associated with changes in the extracellular matrix components in the cap: accumulation of collagen and reduction of elastic fiber content reducing vessel elasticity and making its locally more rigid. PMID:22803155

  20. 12- and 15-lipoxygenases in human carotid atherosclerotic lesions: Associations with cerebrovascular symptoms

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Lipoxygenase (ALOX) enzymes are implicated in both pro- and anti-atherogenic processes. The aim of this study was to investigate mRNA expression of 12- and 15-lipoxygenases (ALOX12, ALOX12B, ALOX15, ALOX15B) and the atypical ALOXE3 in human carotid atherosclerotic lesions, in relation to cerebrovasc...

  1. A Proteomic Focus on the Alterations Occurring at the Human Atherosclerotic Coronary Intima*

    PubMed Central

    de la Cuesta, Fernando; Alvarez-Llamas, Gloria; Maroto, Aroa S.; Donado, Alicia; Zubiri, Irene; Posada, Maria; Padial, Luis R.; Pinto, Angel G.; Barderas, Maria G.; Vivanco, Fernando

    2011-01-01

    Coronary atherosclerosis still represents the major cause of mortality in western societies. Initiation of atherosclerosis occurs within the intima, where major histological and molecular changes are produced during pathogenesis. So far, proteomic analysis of the atherome plaque has been mainly tackled by the analysis of the entire tissue, which may be a challenging approach because of the great complexity of this sample in terms of layers and cell type composition. Based on this, we aimed to study the intimal proteome from the human atherosclerotic coronary artery. For this purpose, we analyzed the intimal layer from human atherosclerotic coronaries, which were isolated by laser microdissection, and compared with those from preatherosclerotic coronary and radial arteries, using a two-dimensional Differential-In-Gel-Electrophoresis (DIGE) approach. Results have pointed out 13 proteins to be altered (seven up-regulated and six down-regulated), which are implicated in the migrative capacity of vascular smooth muscle cells, extracellular matrix composition, coagulation, apoptosis, heat shock response, and intraplaque hemorrhage deposition. Among these, three proteins (annexin 4, myosin regulatory light 2, smooth muscle isoform, and ferritin light chain) constitute novel atherosclerotic coronary intima proteins, because they were not previously identified at this human coronary layer. For this reason, these novel proteins were validated by immunohistochemistry, together with hemoglobin and vimentin, in an independent cohort of arteries. PMID:21248247

  2. Ex vivo differential phase contrast and magnetic resonance imaging for characterization of human carotid atherosclerotic plaques.

    PubMed

    Meletta, Romana; Borel, Nicole; Stolzmann, Paul; Astolfo, Alberto; Klohs, Jan; Stampanoni, Marco; Rudin, Markus; Schibli, Roger; Krämer, Stefanie D; Herde, Adrienne Müller

    2015-10-01

    Non-invasive detection of specific atherosclerotic plaque components related to vulnerability is of high clinical relevance to prevent cerebrovascular events. The feasibility of magnetic resonance imaging (MRI) for characterization of plaque components was already demonstrated. We aimed to evaluate the potential of ex vivo differential phase contrast X-ray tomography (DPC) to accurately characterize human carotid plaque components in comparison to high field multicontrast MRI and histopathology. Two human plaque segments, obtained from carotid endarterectomy, classified according to criteria of the American Heart Association as stable and unstable plaque, were examined by ex vivo DPC tomography and multicontrast MRI (T1-, T2-, and proton density-weighted imaging, magnetization transfer contrast, diffusion-weighted imaging). To identify specific plaque components, the plaques were subsequently sectioned and stained for fibrous and cellular components, smooth muscle cells, hemosiderin, and fibrin. Histological data were then matched with DPC and MR images to define signal criteria for atherosclerotic plaque components. Characteristic structures, such as the lipid and necrotic core covered by a fibrous cap, calcification and hemosiderin deposits were delineated by histology and found with excellent sensitivity, resolution and accuracy in both imaging modalities. DPC tomography was superior to MRI regarding resolution and soft tissue contrast. Ex vivo DPC tomography allowed accurate identification of structures and components of atherosclerotic plaques at different lesion stages, in good correlation with histopathological findings. PMID:26179860

  3. [Comparative transcriptome analysis of human aorta atherosclerotic lesions and peripheral blood leukocytes from essential hypertension patients].

    PubMed

    Timofeeva, A V; Goriunova, L E; Khaspekov, G L; Il'inskaia, O P; Sirotkin, V N; Andreeva, E R; Tararak, E M; Bulkina, O S; Buza, V V; Britareva, V V; Karpov, Iu A; Bibilashvili, R Sh

    2009-01-01

    One of the major cardiovascular risk factor which predisposes to and accelerates atherosclerosis is arterial hypertension (AH). To determine the molecular basis of the crosslink between AH and atherosclerosis for the development of new treatment strategies large-scale transcriptome analysis of the cells implicated in atherogenesis is needed. We used cDNA microarray technique for simultaneous analysis of gene expression in human abdominal aorta normal sites and atherosclerotic lesions of different histological types, as well as in peripheral blood leukocytes from patients with essential hypertension (EH) and donors. The microarray data were verified by quantitative RT-PCR (reverse transcription coupled with polymerase chain reaction) and immunohistochemical analysis. Differential expression of 40 genes has been found, among which twenty two genes demonstrated up-regulation and 18 genes demonstrated down-regulation in atherosclerotic aorta compared with normal vessel. New gene-candidates, implicated in atherogenesis, have been identified - FPRL2, CD37, CD53, RGS1, LCP1, SPI1, CTSA, EPAS1, FHL1, GEM, RHOB, SPARCL1, ITGA8, PLN, and COL14A1. These genes participate in cell migration and adhesion, phenotypic changes of smooth muscle cells, immune and inflammatory reactions, oxidative processes and extracellular matrix remodeling. We have found increased expression levels of CD53, SPI1, FPRL2, SPP1, CTSD, ACP5, LCP1, CTSA and LIPA genes in peripheral blood leukocytes from EH patients and in atherosclerotic lesions of human aorta. The majority of these genes significantly (p<0.005) positively (r>0.5) correlated with AH stage as well as with histological grading of atherosclerotic lesions. PMID:19772500

  4. Platelet-derived growth factor gene expression in human atherosclerotic plaques and normal artery wall.

    PubMed Central

    Barrett, T B; Benditt, E P

    1988-01-01

    We previously demonstrated that the B chain of platelet-derived growth factor (PDGF-B) is transcribed in human atherosclerotic plaques, indicating that production of growth factors within plaques could occur during atherogenesis. However, since atherosclerotic plaques are composed of several cell types and three of these--macrophages, endothelial cells, and smooth muscle cells--can express the PDGF genes, the cell type responsible for PDGF gene expression was not clear. In the present study we explore further the expression of PDGF-A and -B and identify transcriptionally active cell types. We assayed PDGF-A and -B mRNA levels in dissected fractions of carotid atherosclerotic plaques and normal artery and then sequentially rehybridized these blots with three cDNA probes that recognize cell type-specific markers: fms for macrophages, von Willebrand factor for endothelial cells, and smooth muscle alpha-actin for smooth muscle cells. In plaques, PDGF-A expression correlated with smooth muscle actin; PDGF-B expression correlated strongly with fms. PDGF-A expression correlated with smooth muscle actin. In normal vessel wall, PDGF-A expression was high in the media and again correlated with smooth muscle actin, whereas PDGF-B expression was high in the adventitia. Since transcripts from both PDGF genes are found in normal artery where cell turnover is very low, we suggest that PDGF gene expression does not necessarily function to produce smooth muscle cell proliferation. We propose that these genes may have an important nonmitogenic, maintenance function in normal arterial tissue and in the atherosclerotic plaque. Images PMID:3282240

  5. Simulation of human atherosclerotic femoral plaque tissue: the influence of plaque material model on numerical results

    PubMed Central

    2015-01-01

    Background Due to the limited number of experimental studies that mechanically characterise human atherosclerotic plaque tissue from the femoral arteries, a recent trend has emerged in current literature whereby one set of material data based on aortic plaque tissue is employed to numerically represent diseased femoral artery tissue. This study aims to generate novel vessel-appropriate material models for femoral plaque tissue and assess the influence of using material models based on experimental data generated from aortic plaque testing to represent diseased femoral arterial tissue. Methods Novel material models based on experimental data generated from testing of atherosclerotic femoral artery tissue are developed and a computational analysis of the revascularisation of a quarter model idealised diseased femoral artery from a 90% diameter stenosis to a 10% diameter stenosis is performed using these novel material models. The simulation is also performed using material models based on experimental data obtained from aortic plaque testing in order to examine the effect of employing vessel appropriate material models versus those currently employed in literature to represent femoral plaque tissue. Results Simulations that employ material models based on atherosclerotic aortic tissue exhibit much higher maximum principal stresses within the plaque than simulations that employ material models based on atherosclerotic femoral tissue. Specifically, employing a material model based on calcified aortic tissue, instead of one based on heavily calcified femoral tissue, to represent diseased femoral arterial vessels results in a 487 fold increase in maximum principal stress within the plaque at a depth of 0.8 mm from the lumen. Conclusions Large differences are induced on numerical results as a consequence of employing material models based on aortic plaque, in place of material models based on femoral plaque, to represent a diseased femoral vessel. Due to these large

  6. Increased Platelet Reactivity Is Associated with Circulating Platelet-Monocyte Complexes and Macrophages in Human Atherosclerotic Plaques

    PubMed Central

    Vrijenhoek, Joyce E. P.; van Holten, Thijs C.; Elsenberg, Ellen H. A. M.; Mak-Nienhuis, Elske M.; de Borst, Gert Jan; Jukema, J. Wouter; Pijls, Nico H. J.; Waltenberger, Johannes; van Zonneveld, Anton Jan; Moll, Frans L.; McClellan, Elizabeth; Stubbs, Andrew; Pasterkamp, Gerard; Hoefer, Imo; de Groot, Philip G.; Roest, Mark

    2014-01-01

    Objective Platelet reactivity, platelet binding to monocytes and monocyte infiltration play a detrimental role in atherosclerotic plaque progression. We investigated whether platelet reactivity was associated with levels of circulating platelet-monocyte complexes (PMCs) and macrophages in human atherosclerotic carotid plaques. Methods Platelet reactivity was determined by measuring platelet P-selectin expression after platelet stimulation with increasing concentrations of adenosine diphosphate (ADP), in two independent cohorts: the Circulating Cells cohort (n = 244) and the Athero-Express cohort (n = 91). Levels of PMCs were assessed by flow cytometry in blood samples of patients who were scheduled for percutaneous coronary intervention (Circulating Cells cohort). Monocyte infiltration was semi-quantitatively determined by histological examination of atherosclerotic carotid plaques collected during carotid endarterectomy (Athero-Express cohort). Results We found increased platelet reactivity in patients with high PMCs as compared to patients with low PMCs (median (interquartile range): 4153 (1585–11267) area under the curve (AUC) vs. 9633 (3580–21565) AUC, P<0.001). Also, we observed increased platelet reactivity in patients with high macrophage levels in atherosclerotic plaques as compared to patients with low macrophage levels in atherosclerotic plaques (mean±SD; 8969±3485 AUC vs. 7020±3442 AUC, P = 0.02). All associations remained significant after adjustment for age, sex and use of drugs against platelet activation. Conclusion Platelet reactivity towards ADP is associated with levels of PMCs and macrophages in human atherosclerotic carotid plaques. PMID:25122139

  7. Recombinant Human Elastase Alters the Compliance of Atherosclerotic Tibial Arteries After Ex Vivo Angioplasty

    PubMed Central

    Bingham, Karen; Moss, Emma; Gottlieb, Daniel P.; Wong, Marco D.; Bland, Kimberly S.; Franano, F. Nicholas

    2016-01-01

    Purpose: This study was designed to determine whether vonapanitase (formerly PRT-201), a recombinant human elastase, treatment can fragment the protein elastin in elastic fibers and cause dilation of atherosclerotic human peripheral arteries subjected to ex vivo balloon angioplasty. Materials and Methods: Seven patients undergoing lower limb amputation for peripheral artery disease or who died and donated their bodies to science donated 11 tibial arteries (5 anterior, 6 posterior) for this study. All arteries were atherosclerotic by visual inspection. The arteries underwent ex vivo balloon angioplasty and thereafter were cut into rings and studied on wire myographs where the rings were stretched and tension was recorded. After treatment with vonapanitase 2 mg/mL or vehicle control, myography was repeated and the rings were then subject to elastin content measurement using a desmosine radioimmunoassay and elastic fiber visualization by histology. The wire myography data were used to derive compliance, stress-strain, and incremental elastic modulus curves. Results: Vonapanitase treatment reduced elastin (desmosine) content by 60% and decreased elastic fiber histologic staining. Vonapanitase-treated rings experienced less tension at any level of stretch and as a result had shifts in the compliance and stress-strain curves relative to vehicle-treated rings. Vonapanitase treatment did not alter the incremental elastic modulus curve. Conclusions: Vonapanitase treatment of atherosclerotic human peripheral arteries after ex vivo balloon angioplasty fragmented elastin in elastic fibers, decreased tension in the rings at any level of stretch, and altered the compliance and stress-strain curves in a manner predicting arterial dilation in vivo. Based on this result, local treatment of balloon angioplasty sites may increase blood vessel diameter and thereby improve the success of balloon angioplasty in peripheral artery disease. PMID:26745001

  8. A Human Ex Vivo Atherosclerotic Plaque Model to Study Lesion Biology

    PubMed Central

    Akhavanpoor, Mohammadreza; Zhao, Li; Wangler, Susanne; Hakimi, Maani; Doesch, Andreas; Dengler, Thomas J.; Katus, Hugo A.; Gleissner, Christian A.

    2014-01-01

    Atherosclerosis is a chronic inflammatory disease of the vasculature. There are various methods to study the inflammatory compound in atherosclerotic lesions. Mouse models are an important tool to investigate inflammatory processes in atherogenesis, but these models suffer from the phenotypic and functional differences between the murine and human immune system. In vitro cell experiments are used to specifically evaluate cell type-dependent changes caused by a substance of interest, but culture-dependent variations and the inability to analyze the influence of specific molecules in the context of the inflammatory compound in atherosclerotic lesions limit the impact of the results. In addition, measuring levels of a molecule of interest in human blood helps to further investigate its clinical relevance, but this represents systemic and not local inflammation. Therefore, we here describe a plaque culture model to study human atherosclerotic lesion biology ex vivo. In short, fresh plaques are obtained from patients undergoing endarterectomy or coronary artery bypass grafting and stored in RPMI medium on ice until usage. The specimens are cut into small pieces followed by random distribution into a 48-well plate, containing RPMI medium in addition to a substance of interest such as cytokines or chemokines alone or in combination for defined periods of time. After incubation, the plaque pieces can be shock frozen for mRNA isolation, embedded in Paraffin or OCT for immunohistochemistry staining or smashed and lysed for western blotting. Furthermore, cells may be isolated from the plaque for flow cytometry analysis. In addition, supernatants can be collected for protein measurement by ELISA. In conclusion, the presented ex vivo model opens the possibility to further study inflammatory lesional biology, which may result in identification of novel disease mechanisms and therapeutic targets. PMID:24836700

  9. A human ex vivo atherosclerotic plaque model to study lesion biology.

    PubMed

    Erbel, Christian; Okuyucu, Deniz; Akhavanpoor, Mohammadreza; Zhao, Li; Wangler, Susanne; Hakimi, Maani; Doesch, Andreas; Dengler, Thomas J; Katus, Hugo A; Gleissner, Christian A

    2014-01-01

    Atherosclerosis is a chronic inflammatory disease of the vasculature. There are various methods to study the inflammatory compound in atherosclerotic lesions. Mouse models are an important tool to investigate inflammatory processes in atherogenesis, but these models suffer from the phenotypic and functional differences between the murine and human immune system. In vitro cell experiments are used to specifically evaluate cell type-dependent changes caused by a substance of interest, but culture-dependent variations and the inability to analyze the influence of specific molecules in the context of the inflammatory compound in atherosclerotic lesions limit the impact of the results. In addition, measuring levels of a molecule of interest in human blood helps to further investigate its clinical relevance, but this represents systemic and not local inflammation. Therefore, we here describe a plaque culture model to study human atherosclerotic lesion biology ex vivo. In short, fresh plaques are obtained from patients undergoing endarterectomy or coronary artery bypass grafting and stored in RPMI medium on ice until usage. The specimens are cut into small pieces followed by random distribution into a 48-well plate, containing RPMI medium in addition to a substance of interest such as cytokines or chemokines alone or in combination for defined periods of time. After incubation, the plaque pieces can be shock frozen for mRNA isolation, embedded in Paraffin or OCT for immunohistochemistry staining or smashed and lysed for western blotting. Furthermore, cells may be isolated from the plaque for flow cytometry analysis. In addition, supernatants can be collected for protein measurement by ELISA. In conclusion, the presented ex vivo model opens the possibility to further study inflammatory lesional biology, which may result in identification of novel disease mechanisms and therapeutic targets. PMID:24836700

  10. Phage Display Identification of CD100 in Human Atherosclerotic Plaque Macrophages and Foam Cells

    PubMed Central

    Luque, Maria Carolina Aquino; Gutierrez, Paulo Sampaio; Debbas, Victor; Martins, Waleska Kerllen; Puech-Leao, Pedro; Porto, Georgia; Coelho, Verônica; Boumsell, Laurence; Kalil, Jorge; Stolf, Beatriz

    2013-01-01

    Atherosclerosis is a complex disease in which vessels develop plaques comprising dysfunctional endothelium, monocyte derived lipid laden foam cells and activated lymphocytes. Considering that humans and animal models of the disease develop quite distinct plaques, we used human plaques to search for proteins that could be used as markers of human atheromas. Phage display peptide libraries were probed to fresh human carotid plaques, and a bound phage homologous to plexin B1, a high affinity receptor for CD100, was identified. CD100 is a member of the semaphorin family expressed by most hematopoietic cells and particularly by activated T cells. CD100 expression was analyzed in human plaques and normal samples. CD100 mRNA and protein were analyzed in cultured monocytes, macrophages and foam cells. The effects of CD100 in oxLDL-induced foam cell formation and in CD36 mRNA abundance were evaluated. Human atherosclerotic plaques showed strong labeling of CD100/SEMA4D. CD100 expression was further demonstrated in peripheral blood monocytes and in in vitro differentiated macrophages and foam cells, with diminished CD100 transcript along the differentiation of these cells. Incubation of macrophages with CD100 led to a reduction in oxLDL-induced foam cell formation probably through a decrease of CD36 expression, suggesting for the first time an atheroprotective role for CD100 in the human disease. Given its differential expression in the numerous foam cells and macrophages of the plaques and its capacity to decrease oxLDL engulfment by macrophages we propose that CD100 may have a role in atherosclerotic plaque development, and may possibly be employed in targeted treatments of these atheromas. PMID:24098722

  11. Association between Human Plasma Chondroitin Sulfate Isomers and Carotid Atherosclerotic Plaques.

    PubMed

    Zinellu, Elisabetta; Lepedda, Antonio Junior; Cigliano, Antonio; Pisanu, Salvatore; Zinellu, Angelo; Carru, Ciriaco; Bacciu, Pietro Paolo; Piredda, Franco; Guarino, Anna; Spirito, Rita; Formato, Marilena

    2012-01-01

    Several studies have evidenced variations in plasma glycosaminoglycans content in physiological and pathological conditions. In normal human plasma GAGs are present mainly as undersulfated chondroitin sulfate (CS). The aim of the present study was to evaluate possible correlations between plasma CS level/structure and the presence/typology of carotid atherosclerotic lesion. Plasma CS was purified from 46 control subjects and 47 patients undergoing carotid endarterectomy showing either a soft or a hard plaque. The concentration and structural characteristics of plasma CS were assessed by capillary electrophoresis of constituent unsaturated fluorophore-labeled disaccharides. Results showed that the concentration of total CS isomers was increased by 21.4% (P < 0.01) in plasma of patients, due to a significant increase of undersulfated CS. Consequently, in patients the plasma CS charge density was significantly reduced with respect to that of controls. After sorting for plaque typology, we found that patients with soft plaques and those with hard ones differently contribute to the observed changes. In plasma from patients with soft plaques, the increase in CS content was not associated with modifications of its sulfation pattern. On the contrary, the presence of hard plaques was associated with CS sulfation pattern modifications in presence of quite normal total CS isomers levels. These results suggest that the plasma CS content and structure could be related to the presence and the typology of atherosclerotic plaque and could provide a useful diagnostic tool, as well as information on the molecular mechanisms responsible for plaque instability. PMID:22216412

  12. Cells carrying C5b-9 complement complexes in human atherosclerotic wall.

    PubMed

    Rus, H G; Niculescu, F; Poruţiu, D; Ghiurca, V; Vlaicu, R

    1989-03-01

    Fibrous plaques and intimal thickenings of 5 femoral and 5 iliac human arteries obtained at surgery were processed for indirect and double-labeling immunoelectron microscopy using an affinity purified rabbit IgG anti-C5b-9 neoantigen and the EBM 11 monoclonal antibody anti-human macrophages. The C5b-9 complexes were localized in intact cells, disintegrated cells and cell debris enmeshed in the connective tissue matrix. Some of the cell debris bearing C5b-9 deposits was found to be of macrophage origin. Endocyted or exocyted pieces of membrane with pore-forming C5b-9 complexes were also identified. Damage of cells by complement in atherosclerotic lesions may contribute to atherogenesis. PMID:2714850

  13. Immunoelectron-microscopic localization of S-protein/vitronectin in human atherosclerotic wall.

    PubMed

    Niculescu, F; Rus, H G; Poruţiu, D; Ghiurca, V; Vlaicu, R

    1989-08-01

    S-protein/vitronectin is a multifunctional glycoprotein interacting with both complement activation and coagulation pathways. Its presence was investigated in 5 femoral and 5 iliac atherosclerotic human arteries, obtained at surgery, by immunoelectron microscopy using an affinity purified rabbit IgG specific for human S-protein/vitronectin. The immunoelectron dense specific deposits were found in both intimal thickenings and fibrous plaques in association with elastic fibers, collagen bundles and cell debris in the vicinity of elastin. Cell debris embedded in the collagen matrix were S-protein/vitronectin negative. S-protein/vitronectin was also absent on intact cells, lipid droplets and cholesterol clefts. All cell debris, however, was positive for C5b-9 deposits suggesting that complement activation had occurred at these sites with or without S-protein/vitronectin interaction. S-protein/vitronectin may play a role in the arterial wall defence by restricting the extent of complement activation. PMID:2476993

  14. Human macrophage scavenger receptors: primary structure, expression, and localization in atherosclerotic lesions.

    PubMed Central

    Matsumoto, A; Naito, M; Itakura, H; Ikemoto, S; Asaoka, H; Hayakawa, I; Kanamori, H; Aburatani, H; Takaku, F; Suzuki, H

    1990-01-01

    Two types of cDNAs for human macrophage scavenger receptors were cloned from a cDNA library derived from the phorbol ester-treated human monocytic cell line THP-1. The type I and type II human scavenger receptors encoded by these cDNAs are homologous (73% and 71% amino acid identity) to their previously characterized bovine counterparts and consist of six domains: cytoplasmic (I), membrane-spanning (II), spacer (III), alpha-helical coiled-coil (IV), collagen-like (V), and a type-specific C-terminal (VI). The receptor gene is located on human chromosome 8. The human receptors expressed in CHO-K1 cells mediated endocytosis of modified low density lipoproteins. Two mRNAs, 4.0 and 3.2 kilobases, have been detected in human liver, placenta, and brain. Immunohistochemical studies using an anti-peptide antibody which recognizes human scavenger receptors indicated the presence of the scavenger receptors in the macrophages of lipid-rich atherosclerotic lesions, suggesting the involvement of scavenger receptors in atherogenesis. Images PMID:2251254

  15. Localized adhesion of monocytes to human atherosclerotic plaques demonstrated in vitro: implications for atherogenesis.

    PubMed Central

    Poston, R. N.; Johnson-Tidey, R. R.

    1996-01-01

    Blood-derived macrophages in the arterial intima are a characteristic feature of active atherosclerotic plaques. Adherent monocytes on the luminal surface and increased adhesion molecules on the endothelium have suggested that specific molecular mechanisms are involved in monocyte/macrophage traffic into the arterial wall. Adhesion of human monocytes and related cell lines was therefore studied in vitro to histological sections of human plaques. At 37 degrees C, these cells bound selectively to the plaques. Binding to the endothelium occurred and was also present extensively in the diseased intima. Inhibition studies showed that the endothelial and general intimal binding had largely similar molecular properties. Strong inhibition was produced by antibodies to the monocyte-specific adhesion molecule CD14, to beta2 integrins, and to ICAM-1. Likewise, a peptide containing the Arg-Gly-Asp sequence was strongly inhibitory, suggesting that binding of leukocyte integrins to arterial extracellular matrix was synergistic with cell-cell interactions. A P-selectin antibody was exceptional in giving selective inhibition of endothelial adhesion, which correlates with the specific endothelial localization of this adhesion molecule. These results show that monocytes adhere to atherosclerotic plaques through the focal activation of multiple arterial wall adhesion molecules, confirming the adhesion hypothesis. A positive feedback theory for the pathogenesis of atherosclerosis can be suggested, based on the ability of macrophages in the wall to activate the endothelium, induce adhesion molecules, and facilitate additional monocyte entry. The adhesion assay provides a means for the identification of adhesion inhibitors with therapeutic potential. Images Figure 2 PMID:8686764

  16. Ticagrelor promotes atherosclerotic plaque stability in a mouse model of advanced atherosclerosis

    PubMed Central

    Preusch, Michael R; Rusnak, Jonas; Staudacher, Kathrin; Mogler, Carolin; Uhlmann, Lorenz; Sievers, Philipp; Bea, Florian; Katus, Hugo A; Blessing, Erwin; Staudacher, Ingo

    2016-01-01

    Objective There is increasing evidence supporting the role of platelets in atherosclerotic vascular disease. The G-protein-coupled receptor P2Y12 is a central mediator of platelet activation and aggregation but has also been linked to platelet-independent vascular disease. Ticagrelor is an oral P2Y12 antagonist that is used as a standard treatment in patients after acute myocardial infarction. However, the effects of ticagrelor on advanced atherosclerosis have not been investigated. Materials and methods Twenty-week-old apolipoprotein-E-deficient mice received standard chow or standard chow supplemented with 0.15% ticagrelor (approximately 270 mg/kg/day) for 25 weeks. The lesion area was evaluated in the aortic sinus by Movat’s pentachrome staining and lesion composition, thickness of the fibrous cap, and size of the necrotic core evaluated by morphometry. RAW 264.7 macrophages were serum starved and treated with ticagrelor in vitro for the detection and quantification of apoptosis. In addition, oxLDL uptake in RAW 264.7 macrophages was evaluated. Results A trend toward the reduction of total lesion size was detected. However, data did not reach the levels of significance (control, n=11, 565,881 μm2 [interquartile range {IQR} 454,778–603,925 μm2] versus ticagrelor, n=13, 462,595 μm2 [IQR 379,740–546,037 μm2]; P=0.1). A significant reduction in the relative area of the necrotic core (control, n=11, 0.46 [IQR 0.4–0.51] versus ticagrelor, n=13, 0.34 [IQR 0.31–0.39]; P=0.008), and a significant increase in fibrous caps thickness (control, n=11, 3.7 μm [IQR 3.4–4.2 μm] versus ticagrelor, n=13, 4.7 [IQR 4.3–5.5 μm], P=0.04) were seen in ticagrelor-treated mice. In vitro studies demonstrated a reduction in apoptotic RAW 264.7 macrophages (control 0.07±0.03 versus ticagrelor 0.03±0.03; P=0.0002) when incubated with ticagrelor. Uptake of oxLDL in RAW 264.7 was significantly reduced when treated with ticagrelor (control 9.2 [IQR 5.3–12.9] versus

  17. Matrix metalloproteinase-2 of human carotid atherosclerotic plaques promotes platelet activation. Correlation with ischaemic events.

    PubMed

    Lenti, Massimo; Falcinelli, Emanuela; Pompili, Marcella; de Rango, Paola; Conti, Valentina; Guglielmini, Giuseppe; Momi, Stefania; Corazzi, Teresa; Giordano, Giuseppe; Gresele, Paolo

    2014-06-01

    Purified active matrix metalloproteinase-2 (MMP-2) is able to promote platelet aggregation. We aimed to assess the role of MMP-2 expressed in atherosclerotic plaques in the platelet-activating potential of human carotid plaques and its correlation with ischaemic events. Carotid plaques from 81 patients undergoing endarterectomy were tested for pro-MMP-2 and TIMP-2 content by zymography and ELISA. Plaque extracts were incubated with gel-filtered platelets from healthy volunteers for 2 minutes before the addition of a subthreshold concentration of thrombin receptor activating peptide-6 (TRAP-6) and aggregation was assessed. Moreover, platelet deposition on plaque extracts immobilised on plastic coverslips under high shear-rate flow conditions was measured. Forty-three plaque extracts (53%) potentiated platelet aggregation (+233 ± 26.8%), an effect prevented by three different specific MMP-2 inhibitors (inhibitor II, TIMP-2, moAb anti-MMP-2). The pro-MMP-2/TIMP-2 ratio of plaques potentiating platelet aggregation was significantly higher than that of plaques not potentiating it (3.67 ± 1.21 vs 1.01 ± 0.43, p<0.05). Moreover, the platelet aggregation-potentiating effect, the active-MMP-2 content and the active MMP-2/pro-MMP-2 ratio of plaque extracts were significantly higher in plaques from patients who developed a subsequent major cardiovascular event. In conclusion, atherosclerotic plaques exert a prothrombotic effect by potentiating platelet activation due to their content of MMP-2; an elevated MMP-2 activity in plaques is associated with a higher rate of subsequent ischaemic cerebrovascular events. PMID:24499865

  18. Cellular composition of atherosclerotic and uninvolved human aortic subendothelial intima. Light-microscopic study of dissociated aortic cells.

    PubMed Central

    Orekhov, A. N.; Karpova, I. I.; Tertov, V. V.; Rudchenko, S. A.; Andreeva, E. R.; Krushinsky, A. V.; Smirnov, V. N.

    1984-01-01

    Alcoholic-alkaline dissociation was used in the study of cellular composition of human aorta. Cells were isolated from an uninvolved intima and intima with different types of atherosclerotic lesions: fatty infiltration, fatty streak, and atherosclerotic plaque. In the isolated suspension we evaluated the ratio of four previously described morphologic forms of cells: stellate, elongated, elongated with side processes, and flat cells of irregular shape. It was demonstrated that the quota of stellate cells in an atherosclerotic lesion considerably exceeds that of the normal intima. For elongated cells the opposite is true. The other two cell forms are represented in the uninvolved and atherosclerotic intima in approximately equal proportions. Alteration of the ratio of different morphologic forms occurs because of the fact that the number of cells belonging to different morphologic forms increases disproportionately in the lesion zone. Specifically, the number of stellate cells is increased much more substantially, compared with elongated cells. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:6711678

  19. Human miR-221/222 in Physiological and Atherosclerotic Vascular Remodeling

    PubMed Central

    Chistiakov, Dmitry A.; Sobenin, Igor A.; Orekhov, Alexander N.; Bobryshev, Yuri V.

    2015-01-01

    A cluster of miR-221/222 is a key player in vascular biology through exhibiting its effects on vascular smooth muscle cells (VSMCs) and endothelial cells (ECs). These miRNAs contribute to vascular remodeling, an adaptive process involving phenotypic and behavioral changes in vascular cells in response to vascular injury. In proliferative vascular diseases such as atherosclerosis, pathological vascular remodeling plays a prominent role. The miR-221/222 cluster controls development and differentiation of ECs but inhibits their proangiogenic activation, proliferation, and migration. miR-221/222 are primarily implicated in maintaining endothelial integrity and supporting quiescent EC phenotype. Vascular expression of miR-221/222 is upregulated in initial atherogenic stages causing inhibition of angiogenic recruitment of ECs and increasing endothelial dysfunction and EC apoptosis. In contrast, these miRNAs stimulate VSMCs and switching from the VSMC “contractile” phenotype to the “synthetic” phenotype associated with induction of proliferation and motility. In atherosclerotic vessels, miR-221/222 drive neointima formation. Both miRNAs contribute to atherogenic calcification of VSMCs. In advanced plaques, chronic inflammation downregulates miR-221/222 expression in ECs that in turn could activate intralesion neoangiogenesis. In addition, both miRNAs could contribute to cardiovascular pathology through their effects on fat and glucose metabolism in nonvascular tissues such as adipose tissue, liver, and skeletal muscles. PMID:26221589

  20. Human miR-221/222 in Physiological and Atherosclerotic Vascular Remodeling.

    PubMed

    Chistiakov, Dmitry A; Sobenin, Igor A; Orekhov, Alexander N; Bobryshev, Yuri V

    2015-01-01

    A cluster of miR-221/222 is a key player in vascular biology through exhibiting its effects on vascular smooth muscle cells (VSMCs) and endothelial cells (ECs). These miRNAs contribute to vascular remodeling, an adaptive process involving phenotypic and behavioral changes in vascular cells in response to vascular injury. In proliferative vascular diseases such as atherosclerosis, pathological vascular remodeling plays a prominent role. The miR-221/222 cluster controls development and differentiation of ECs but inhibits their proangiogenic activation, proliferation, and migration. miR-221/222 are primarily implicated in maintaining endothelial integrity and supporting quiescent EC phenotype. Vascular expression of miR-221/222 is upregulated in initial atherogenic stages causing inhibition of angiogenic recruitment of ECs and increasing endothelial dysfunction and EC apoptosis. In contrast, these miRNAs stimulate VSMCs and switching from the VSMC "contractile" phenotype to the "synthetic" phenotype associated with induction of proliferation and motility. In atherosclerotic vessels, miR-221/222 drive neointima formation. Both miRNAs contribute to atherogenic calcification of VSMCs. In advanced plaques, chronic inflammation downregulates miR-221/222 expression in ECs that in turn could activate intralesion neoangiogenesis. In addition, both miRNAs could contribute to cardiovascular pathology through their effects on fat and glucose metabolism in nonvascular tissues such as adipose tissue, liver, and skeletal muscles. PMID:26221589

  1. Atorvastatin modulates the profile of proteins released by human atherosclerotic plaques.

    PubMed

    Durán, M Carmen; Martín-Ventura, Jose L; Mohammed, Shabaz; Barderas, María G; Blanco-Colio, Luis M; Mas, Sebastián; Moral, Verónica; Ortega, Luis; Tuñón, Jose; Jensen, Ole N; Vivanco, Fernando; Egido, Jesús

    2007-05-01

    The mechanisms by which hydroxymethylglutaryl CoenzymeA reductase inhibitors (statins) reduce atherosclerotic cardiovascular morbidity and mortality remain poorly understood. Statins have been shown to modulate the levels of different inflammatory proteins both in carotid atherosclerotic plaques and in the blood of patients with atherosclerosis. In this work, we hypothesize that statins could also modulate the levels of the proteins secreted by cultured atherosclerotic plaques. Thus, the secretomes obtained from complicated atherosclerotic plaques incubated in the presence/absence of atorvastatin (10 micromol/l, 24 h) were analysed and compared by two-dimensional electrophoresis, considering the fibrous adjacent areas as controls. In total, 54 proteins (83 protein isoforms) were identified by Mass Spectrometry (MS): 24 proteins were increased and 20 proteins decreased in atheroma plaque supernatants compared to controls. Some of these proteins, like Cathepsin D, could play a significant role in plaque instability, becoming a potential target for therapeutical treatment. Interestingly, 66% of the proteins differentially released by atherosclerotic plaques reverted to control values after administration of atorvastatin, among them, Cathepsin D. Moreover, plaques obtained from patients who received atorvastatin treatment prior to carotid endarterectomy showed decreased Cathepsin D expression relative to plaques from non-treated patients. In conclusion, this proteomic approach has shown that statins are able to modulate the secretome of atherosclerotic plaques, and new therapeutical targets for statins have been characterised. PMID:17336287

  2. Direct association between diet and the stability of human atherosclerotic plaque.

    PubMed

    Gonçalves, Isabel; Andersson Georgiadou, Elisavet; Mattsson, Sören; Skog, Göran; Pedro, Luís; Fernandes E Fernandes, José; Dias, Nuno; Engström, Gunnar; Nilsson, Jan; Stenström, Kristina

    2015-01-01

    Mediterranean diet has been suggested to explain why coronary heart disease mortality is lower in southern than northern Europe. Dietary habits can be revealed by isotope ratio mass spectrometry (IRMS) measurement of carbon (δ(13)C) and nitrogen (δ(15)N) in biological tissues. To study if diet is associated with human plaque stability, atherosclerotic plaques from carotid endarterectomy on 56 patients (21 Portuguese and 35 Swedish) were analysed by IRMS and histology. Plaque components affecting rupture risk were measured. Swedish plaques had more apoptosis, lipids and larger cores, as well as fewer proliferating cells and SMC than the Portuguese, conferring the Swedish a more rupture-prone phenotype. Portuguese plaques contained higher δ(13)C and δ(15)N than the Swedish, indicating that Portuguese plaques were more often derived from marine food. Plaque δ(13)C correlated with SMC and proliferating cells, and inversely with lipids, core size, apoptosis. Plaque δ(15)N correlated with SMC and inversely with lipids, core size and apoptosis. This is the first observational study showing that diet is reflected in plaque components associated with its vulnerability. The Portuguese plaques composition is consistent with an increased marine food intake and those plaques are more stable than those from Swedish patients. Marine-derived food is associated with plaque stability. PMID:26490319

  3. Direct association between diet and the stability of human atherosclerotic plaque

    PubMed Central

    Gonçalves, Isabel; Andersson Georgiadou, Elisavet; Mattsson, Sören; Skog, Göran; Pedro, Luís; Fernandes e Fernandes, José; Dias, Nuno; Engström, Gunnar; Nilsson, Jan; Stenström, Kristina

    2015-01-01

    Mediterranean diet has been suggested to explain why coronary heart disease mortality is lower in southern than northern Europe. Dietary habits can be revealed by isotope ratio mass spectrometry (IRMS) measurement of carbon (δ13C) and nitrogen (δ15N) in biological tissues. To study if diet is associated with human plaque stability, atherosclerotic plaques from carotid endarterectomy on 56 patients (21 Portuguese and 35 Swedish) were analysed by IRMS and histology. Plaque components affecting rupture risk were measured. Swedish plaques had more apoptosis, lipids and larger cores, as well as fewer proliferating cells and SMC than the Portuguese, conferring the Swedish a more rupture-prone phenotype. Portuguese plaques contained higher δ13C and δ15N than the Swedish, indicating that Portuguese plaques were more often derived from marine food. Plaque δ13C correlated with SMC and proliferating cells, and inversely with lipids, core size, apoptosis. Plaque δ15N correlated with SMC and inversely with lipids, core size and apoptosis. This is the first observational study showing that diet is reflected in plaque components associated with its vulnerability. The Portuguese plaques composition is consistent with an increased marine food intake and those plaques are more stable than those from Swedish patients. Marine-derived food is associated with plaque stability. PMID:26490319

  4. Circulating and platelet-derived microparticles in human blood enhance thrombosis on atherosclerotic plaques.

    PubMed

    Suades, Rosa; Padró, Teresa; Vilahur, Gemma; Badimon, Lina

    2012-12-01

    Plaque rupture followed by thrombosis is the underlying cause of the majority of acute coronary syndromes. Circulating microparticles (cMPs), membrane blebs released into blood by activated cells, have been associated to vascular diseases. Specifically, high levels of platelet-derived microparticles (pMPs) have been found in patients with coronary disease. However, it is unknown whether microparticles have a contributing role to the development of damaged vessel wall-induced arterial thrombi. The aim of this proof of concept study was to investigate whether an increased number of cMPs and pMPs could functionally contribute to blood thrombogenicity on areas of arterial damage. Microparticles were isolated from blood of healthy volunteers and were characterised by flow cytometry. Effects of microparticles on platelet deposition were assessed under controlled flow conditions exposing damaged arterial wall in the Badimon perfusion chamber and collagen type-I in the flat perfusion chamber to human blood. Platelet deposition on damaged arteries was significantly increased in cMP- and pMP-enriched bloods (p<0.05). pMPs also induced increase in platelet (p<0.05) and fibrin (p<0.05) deposition on human atherosclerotic arteries and in platelet adhesion to purified collagen surfaces. pMP-enriched blood induced a dose-dependent shortening of epinephrine/collagen closure time evaluated by PFA-100 (p<0.001), increased low-dose ADP-induced platelet aggregation by LTA (p<0.05), and decreased clotting time by thromboelastography (p<0.01). In conclusion, an increased content of cMPs and pMPs, even in normal blood conditions, enhance platelet deposition and thrombus formation. This study shows for the first time that, beyond biomarkers of cell activation, blood microparticles have functional effects on cardiovascular atherothrombotic disease. PMID:23138460

  5. A uni-extension study on the ultimate material strength and extreme extensibility of atherosclerotic tissue in human carotid plaques

    PubMed Central

    Teng, Zhongzhao; Feng, Jiaxuan; Zhang, Yongxue; Sutcliffe, Michael P.F.; Huang, Yuan; Brown, Adam J.; Jing, Zaiping; Lu, Qingsheng; Gillard, Jonathan H.

    2015-01-01

    Atherosclerotic plaque rupture occurs when mechanical loading exceeds its material strength. Mechanical analysis has been shown to be complementary to the morphology and composition for assessing vulnerability. However, strength and stretch thresholds for mechanics-based assessment are currently lacking. This study aims to quantify the ultimate material strength and extreme extensibility of atherosclerotic components from human carotid plaques. Tissue strips of fibrous cap, media, lipid core and intraplaque hemorrhage/thrombus were obtained from 21 carotid endarterectomy samples of symptomatic patients. Uni-extension test with tissue strips was performed until they broke or slid. The Cauchy stress and stretch ratio at the peak loading of strips broken about 2 mm away from the clamp were used to characterize their ultimate strength and extensibility. Results obtained indicated that ultimate strength of fibrous cap and media were 158.3 [72.1, 259.3] kPa (Median [Inter quartile range]) and 247.6 [169.0, 419.9] kPa, respectively; those of lipid and intraplaque hemorrhage/thrombus were 68.8 [48.5, 86.6] kPa and 83.0 [52.1, 124.9] kPa, respectively. The extensibility of each tissue type were: fibrous cap – 1.18 [1.10, 1.27]; media – 1.21 [1.17, 1.32]; lipid – 1.25 [1.11, 1.30] and intraplaque hemorrhage/thrombus – 1.20 [1.17, 1.44]. Overall, the strength of fibrous cap and media were comparable and so were lipid and intraplaque hemorrhage/thrombus. Both fibrous cap and media were significantly stronger than either lipid or intraplaque hemorrhage/thrombus. All atherosclerotic components had similar extensibility. Moreover, fibrous cap strength in the proximal region (closer to the heart) was lower than that of the distal. These results are helpful in understanding the material behavior of atherosclerotic plaques. PMID:26472304

  6. Platelet-derived growth factor mRNA detection in human atherosclerotic plaques by in situ hybridization.

    PubMed Central

    Wilcox, J N; Smith, K M; Williams, L T; Schwartz, S M; Gordon, D

    1988-01-01

    Platelet-derived growth factor (PDGF) mRNA, and mRNA for its receptor, have been localized to specific cell types within the human atherosclerotic plaque, using in situ hybridization. The predominant cell types found to express PDGF A and B chain mRNA are mesenchymal-appearing intimal cells and endothelial cells, respectively, with little or no expression detected in macrophages. The distribution of PDGF receptor mRNA containing cells was also examined and found to be localized predominantly in the plaque intima. Images PMID:2843568

  7. Expression of cartilage-specific markers in calcified and non-calcified atherosclerotic lesions.

    PubMed

    Aigner, Thomas; Neureiter, Daniel; Câmpean, Valentina; Soder, Stephan; Amann, Kerstin

    2008-01-01

    Recently, molecular mechanisms resembling endochondral ossification were suggested to be important for atherosclerotic vessel calcification. The aim of this study was to investigate in a series of human atherosclerotic (non-diabetic) lesions of the crural arteries the distribution and expression of classical marker genes of the endochondral ossification pathway. Immunostaining for marker proteins S-100 protein and collagen types II and X were performed on atherosclerotic lesions of different grades (according to Stary). Quantitative real-time PCR for human COL1A1, COL2A1, COL10A1, SOX9, and BMP-2 was applied on RNA isolated from atherosclerotic arteries. In most samples, no expression of collagen type II and S-100 protein was found. Exceptionally, S-100 protein and type II collagen expression was observed very focally within advanced atherosclerotic plaques. Type X collagen was not detected in any of the lesions investigated. Overall, in our study we found no evidence that chondrogenic differentiation pathways are generally active in atherosclerotic plaque formation. In particular type X collagen, one important molecule in cartilage calcification, was not expressed in any of the investigated specimens. Occasionally, however, chondrocytic differentiation markers occur within atherosclerotic lesions. This most likely represents a metaplastic event associated, but not causative for atherosclerotic vessel degeneration and calcification. PMID:17335825

  8. Discrimination of human coronary artery atherosclerotic lipid-rich lesions by time-resolved laser-induced fluorescence spectroscopy.

    PubMed

    Marcu, L; Fishbein, M C; Maarek, J M; Grundfest, W S

    2001-07-01

    Lesion composition plays a significant role in atherosclerotic lesion instability and rupture. Current clinical techniques cannot fully characterize lesion composition or accurately identify unstable lesions. This study investigates the use of time-resolved fluorescence spectroscopy for unstable atherosclerotic lesion diagnosis. The fluorescence of human coronary artery samples was induced with nitrogen laser and detected in the 360- to 510-nm wavelength range. The samples were sorted into 7 groups according to the AHA classification: normal wall and types I, II(a) (fatty streaks), III (preatheroma), IV (atheroma), V(a) (fibrous), and V(b) (calcified) lesions. Spectral intensities and time-dependent parameters [average lifetime tau(f); decay constants: tau(1) (fast-term), tau(2) (slow-term), A(1) (fast-term amplitude contribution)] derived from the time-resolved spectra of coronary samples were used for tissue characterization. We determined that a few intensity values at longer wavelengths (>430 nm) and time-dependent parameters at peak emission region (390 nm) discriminate between all types of arterial samples except between normal wall and type I lesions. The lipid-rich lesions (more unstable) can be discriminated from fibrous lesions (more stable) on the basis of time-dependent parameters (lifetime and fast-term decay). We inferred that features of lipid fluorescence are reflected on lipid-rich lesion emission. Our results demonstrate that analysis of the time-resolved spectra may be used to enhance the discrimination between different grades of atherosclerotic lesions and provide a means of discrimination between lipid-rich and fibrous lesions. PMID:11451759

  9. Is Cadmium Exposure Associated with the Burden, Vulnerability and Rupture of Human Atherosclerotic Plaques?

    PubMed Central

    Sallsten, Gerd; Lundh, Thomas; Barregard, Lars

    2015-01-01

    The general population is exposed to cadmium from food and smoking. Cadmium is a widely spread toxic pollutant that seems to be associated with cardiovascular diseases, although little is known if it contributes to the occurrence of atherosclerotic plaques and the process whereby plaques become vulnerable and are prone to rupture. We tested the hypotheses that cadmium exposure is associated not only with an increased subclinical burden of atherosclerotic plaques in different vascular territories and early signs of plaque vulnerability, but also with cadmium content and plaque-rupture in the clinical phase of the disease. Ultrasound technique was used to measure plaque prevalence and echogenicity in the carotid and femoral arteries in a population sample of women (n = 599) in whom blood cadmium was measured. In addition cadmium was measured in snap-frozen endarterectomies and whole blood obtained from patients who were referred to surgery because of symptomatic carotid plaques (n = 37). Sixteen endarterectomies were divided into three parts corresponding to different flow conditions and plaque vulnerability. In the population sample blood cadmium was associated with the number of vascular territories with plaques (p = 0.003 after adjustment for potential confounders). The cadmium concentrations in symptomatic plaques were 50-fold higher in plaque tissue than in blood. Cadmium levels in blood and plaque correlated, also after adjustment for smoking and other cardiovascular risk factors (p<0.001). Compared with the other parts of the plaque, the cadmium content was double as high in the part where plaque rupture usually occurs. In conclusion, the results show that cadmium exposure is associated with the burden of subclinical atherosclerosis in middle-aged women with different degrees of glucose tolerance, and that the content of cadmium in symptomatic plaques in patients is related to that in blood, but much higher, and preferentially located in the part of plaque

  10. Mechanical, biological and structural characterization of human atherosclerotic femoral plaque tissue.

    PubMed

    Cunnane, E M; Mulvihill, J J E; Barrett, H E; Healy, D A; Kavanagh, E G; Walsh, S R; Walsh, M T

    2015-01-01

    The failure of endovascular treatments of peripheral arterial disease represents a critical clinical issue. Specialized data are required to tailor such procedures to account for the mechanical response of the diseased femoral arterial tissue to medical device deployment. The purpose of this study is to characterize the mechanical response of atherosclerotic femoral arterial tissue to large deformation, the conditions typical of angioplasty and stenting, and also to determine the mechanically induced failure properties and to relate this behaviour to biological content and structural composition using uniaxial testing, Fourier transform infrared spectroscopy and scanning electron microscopy. Mechanical and biological characterization of 20 plaque samples obtained from femoral endarterectomy identified three distinct classifications. "Lightly calcified" samples display linear mechanical responses and fail at relatively high stretch. "Moderately calcified" samples undergo an increase in stiffness and ultimate strength coupled with a decrease in ductility. Structural characterization reveals calcified nodules within this group that may be acting to reinforce the tissue matrix, thus increasing the stiffness and ultimate strength. "Heavily calcified" samples account for the majority of samples tested and exhibit significantly reduced ultimate strength and ductility compared to the preceding groups. Structural characterization of this group reveals large areas of calcified tissue dominating the failure cross-sections of the samples. The frequency and structural dominance of these features solely within this group offers an explanation as to the reduced ultimate strength and ductility and highlights the need for modern peripheral endovascular devices to account for this behaviour during novel medical device design. PMID:25242646

  11. Morphometric and hemodynamic analysis of atherosclerotic progression in human carotid artery bifurcations.

    PubMed

    Huang, Xu; Yin, Xiaoping; Xu, Yingjin; Jia, Xinwei; Li, Jianhui; Niu, Pei; Shen, Wenzeng; Kassab, Ghassan S; Tan, Wenchang; Huo, Yunlong

    2016-03-01

    Although atherosclerosis has been widely investigated at carotid artery bifurcation, there is a lack of morphometric and hemodynamic data at different stages of the disease. The purpose of this study was to determine the lesion difference in patients with carotid artery disease compared with healthy control subjects. The three-dimensional (3D) geometry of carotid artery bifurcation was reconstructed from computed tomography angiography (CTA) images of Chinese control subjects (n = 30) and patients with carotid artery disease (n = 30). We defined two novel vector angles (i.e., angles 1 and 2) that were tangential to the reconstructed contour of the 3D vessel. The best-fit diameter was computed along the internal carotid artery (ICA) center line. Hemodynamic analysis was performed at various bifurcations. Patients with stenotic vessels have larger angles 1 and 2 (151 ± 11° and 42 ± 20°) and smaller diameters of the external carotid artery (ECA) (4.6 ± 0.85 mm) compared with control subjects (144 ± 13° and 36 ± 16°, 5.2 ± 0.57 mm) although there is no significant difference in the common carotid artery (CCA) (7.1 ± 1.2 vs. 7.5 ± 1.0 mm, P = 0.18). In particular, all patients with carotid artery disease have a stenosis at the proximal ICA (including both sinus and carina regions), while 20% of patients have stenosis at the middle ICA and 20% have stenosis expansion to the entire cervical ICA. Morphometric and hemodynamic analyses suggest that atherosclerotic plaques initiate at both sinus and carina regions of ICA and progress downstream. PMID:26747497

  12. Imaging Atherosclerotic Plaque Calcification: Translating Biology.

    PubMed

    Bailey, Grant; Meadows, Judith; Morrison, Alan R

    2016-08-01

    Calcification of atherosclerotic lesions was long thought to be an age - related, passive process, but increasingly data has revealed that atherosclerotic calcification is a more active process, involving complex signaling pathways and bone-like genetic programs. Initially, imaging of atherosclerotic calcification was limited to gross assessment of calcium burden, which is associated with total atherosclerotic burden and risk of cardiovascular mortality and of all cause mortality. More recently, sophisticated molecular imaging studies of the various processes involved in calcification have begun to elucidate information about plaque calcium composition and consequent vulnerability to rupture, leading to hard cardiovascular events like myocardial infarction. As such, there has been renewed interest in imaging calcification to advance risk assessment accuracy in an evolving era of precision medicine. Here we summarize recent advances in our understanding of the biologic process of atherosclerotic calcification as well as some of the molecular imaging tools used to assess it. PMID:27339750

  13. Regional differences in the distribution of the proteoglycans biglycan and decorin in the extracellular matrix of atherosclerotic and restenotic human coronary arteries.

    PubMed Central

    Riessen, R.; Isner, J. M.; Blessing, E.; Loushin, C.; Nikol, S.; Wight, T. N.

    1994-01-01

    Proteoglycans are important constituents of blood vessels and accumulate in various forms of vascular disease. Little is known concerning the proteoglycan composition of restenotic lesions formed after angioplasty and whether the proteoglycan composition of these lesions differs from that of primary atherosclerosis. Accordingly, we sought to characterize the distribution of two proteoglycans, biglycan and decorin, in primary atherosclerotic and restenotic lesions of human coronary arteries. Restenosis (n = 37) and primary (n = 11) lesions obtained from 48 patients by directional atherectomy of human coronary arteries were stained with antibodies against biglycan and decorin. To further characterize the extracellular matrix of restenotic tissues, we studied the co-distribution of these proteoglycans with collagen types I, III, and IV. The loose fibroproliferative tissue seen predominantly in restenosis lesions consistently stained positively for biglycan in patterns of deposition ranging from disseminated to homogeneous. The density and intensity of biglycan staining was correlated with the density of collagen type I and III fiber networks, both of which were observed to interweave among the loose fibroproliferative tissue. The compact connective tissue of primary atherosclerotic plaque was characterized by strong biglycan staining which co-localized with intense collagen type I and III staining. Only basement membrane-like structures rich in collagen type IV demonstrated negative biglycan staining. In contrast, loose fibroproliferative tissue exhibited no significant staining for decorin. Strong immunostaining for decorin, however, was found in primary atherosclerotic plaque. There are thus regional differences in the distribution of extracellular matrix proteoglycans of restenotic and primary human atherosclerotic lesions; these observations suggest that differences established for the biological roles of biglycan and decorin in other organ systems may extend as

  14. Anti-atherosclerotic activity of platycodin D derived from roots of Platycodon grandiflorum in human endothelial cells.

    PubMed

    Wu, Jingtao; Yang, Guiwen; Zhu, Wenxing; Wen, Wujun; Zhang, Fumiao; Yuan, Jinduo; An, Liguo

    2012-01-01

    This study examined the effects of platycodin D (PD), a triterpene saponin from the the root of Platycodon grandiflorum A.DC on human umbilical vein endothelial cells (HUVECs) in vitro, which were pre-treated with PD (0.01, 0.15, 0.25 mg/mL), respectively, and treated with 50 mg/L oxidized low-density lipoprotein (oxLDL). The levels of nitric oxide (NO) and malonaldehyde (MAD) in the culture medium, vascular cell adhesion molecule-1 (VCAM-1) and intercellular cell adhesion molecule-1 (ICAM-1) mRNA expression in endothelium cells and the adhesion of monocytes to endothelial cells were measured. The results showed that PD increased NO concentration and decreased MDA level induced by oxLDL in the medium of endothelial cells. Moreover, PD significantly inhibited the oxLDL-induced increase in monocyte adhesion to endothelial cells as well as decreasing mRNA expression levels of VCAM-1 and ICAM-1 on these cells. Based on these results, it is suggested that PD is a promising anti-atherosclerotic activity, which is at least in part the result of its increasing NO concentration, reducing the oxLDL-induced cell adhesion molecule expression in endothelial cells and the endothelial adhesion to monocytes. PMID:22863916

  15. Advances in human genetics

    SciTech Connect

    Harris, H.; Hirschhorn, K.

    1993-01-01

    This book has five chapters covering peroxisomal diseases, X-linked immunodeficiencies, genetic mutations affecting human lipoproteins and their receptors and enzymes, genetic aspects of cancer, and Gaucher disease. The chapter on peroxisomes covers their discovery, structure, functions, disorders, etc. The chapter on X-linked immunodeficiencies discusses such diseases as agammaglobulinemia, severe combined immunodeficiency, Wiskott-Aldrich syndrome, animal models, linkage analysis, etc. Apolipoprotein formation, synthesis, gene regulation, proteins, etc. are the main focus of chapter 3. The chapter on cancer covers such topics as oncogene mapping and the molecular characterization of some recessive oncogenes. Gaucher disease is covered from its diagnosis, classification, and prevention, to its organ system involvement and molecular biology.

  16. Characterising human atherosclerotic carotid plaque tissue composition and morphology using combined spectroscopic and imaging modalities

    PubMed Central

    2015-01-01

    Calcification is a marked pathological component in carotid artery plaque. Studies have suggested that calcification may induce regions of high stress concentrations therefore increasing the potential for rupture. However, the mechanical behaviour of the plaque under the influence of calcification is not fully understood. A method of accurately characterising the calcification coupled with the associated mechanical plaque properties is needed to better understand the impact of calcification on the mechanical behaviour of the plaque during minimally invasive treatments. This study proposes a comparison of biochemical and structural characterisation methods of the calcification in carotid plaque specimens to identify plaque mechanical behaviour. Biochemical analysis, by Fourier Transform Infrared (FTIR) spectroscopy, was used to identify the key components, including calcification, in each plaque sample. However, FTIR has a finite penetration depth which may limit the accuracy of the calcification measurement. Therefore, this FTIR analysis was coupled with the identification of the calcification inclusions located internally in the plaque specimen using micro x-ray computed tomography (μX-CT) which measures the calcification volume fraction (CVF) to total tissue content. The tissue characterisation processes were then applied to the mechanical material plaque properties acquired from experimental circumferential loading of human carotid plaque specimen for comparison of the methods. FTIR characterised the degree of plaque progression by identifying the functional groups associated with lipid, collagen and calcification in each specimen. This identified a negative relationship between stiffness and 'lipid to collagen' and 'calcification to collagen' ratios. However, μX-CT results suggest that CVF measurements relate to overall mechanical stiffness, while peak circumferential strength values may be dependent on specific calcification geometries. This study

  17. The impact of scaled boundary conditions on wall shear stress computations in atherosclerotic human coronary bifurcations.

    PubMed

    Schrauwen, Jelle T C; Schwarz, Janina C V; Wentzel, Jolanda J; van der Steen, Antonius F W; Siebes, Maria; Gijsen, Frank J H

    2016-05-15

    The aim of this study was to determine if reliable patient-specific wall shear stress (WSS) can be computed when diameter-based scaling laws are used to impose the boundary conditions for computational fluid dynamics. This study focused on mildly diseased human coronary bifurcations since they are predilection sites for atherosclerosis. Eight patients scheduled for percutaneous coronary intervention were imaged with angiography. The velocity proximal and distal of a bifurcation was acquired with intravascular Doppler measurements. These measurements were used for inflow and outflow boundary conditions for the first set of WSS computations. For the second set of computations, absolute inflow and outflow ratios were derived from geometry-based scaling laws based on angiography data. Normalized WSS maps per segment were obtained by dividing the absolute WSS by the mean WSS value. Absolute and normalized WSS maps from the measured-approach and the scaled-approach were compared. A reasonable agreement was found between the measured and scaled inflows, with a median difference of 0.08 ml/s [-0.01; 0.20]. The measured and the scaled outflow ratios showed a good agreement: 1.5 percentage points [-19.0; 4.5]. Absolute WSS maps were sensitive to the inflow and outflow variations, and relatively large differences between the two approaches were observed. For normalized WSS maps, the results for the two approaches were equivalent. This study showed that normalized WSS can be obtained from angiography data alone by applying diameter-based scaling laws to define the boundary conditions. Caution should be taken when absolute WSS is assessed from computations using scaled boundary conditions. PMID:26945083

  18. Laser probe ablation of normal and atherosclerotic human aorta in vitro: a first thermographic and histologic analysis.

    PubMed

    Welch, A J; Bradley, A B; Torres, J H; Motamedi, M; Ghidoni, J J; Pearce, J A; Hussein, H; O'Rourke, R A

    1987-12-01

    The metal-tipped optical fiber or "laser probe" has been extensively studied in animal preparations in vivo and in human clinical trials of revascularization. The aim of this study was to evaluate the thermal characteristics of laser probe tissue ablation and to contrast the vascular tissue response to exposure to the laser probe and bare optical fiber. A 2 mm laser probe was heated with up to 4 W of argon-ion laser irradiation and applied to six postmortem strips of human nonatherosclerotic aorta as well as to five atherosclerotic aortic specimens. Surface temperature maps of the laser probe and of the vascular tissue in air were obtained via 8 to 12 micron thermographic imaging. Laser probe temperature was additionally monitored via thermocouples. Two strips each of normal and diseased aorta were irradiated directly with the bare optical fiber. Thus a total of 43 laser probe application sites and 19 bare fiberoptic laser irradiation sites on a total of 15 aortic strips were analyzed both thermographically and histologically. Based on measured temperature rises and histologic findings, the following observations were made: (1) The laser probe heats initially at its tip and attains a uniform surface temperature distribution within 5 sec. The steady-state temperature attained by the probe is inversely related to the thermal conductivity of the surrounding media. In all media studied, probe temperature increases linearly with applied laser energy. (2) Tissue ablation starts at temperatures greater than 100 degrees C, and ablation temperatures typically exceed 180 degrees C. Adventitial temperatures during laser probe application may reach 70 degrees C. Tissue ablation is enhanced both by greater laser energy deposition in the probe and by higher force at which the probe is applied to tissue. (3) Ablation of fibrofatty atheromata is more extensive than of nonatherosclerotic aortic tissue. This may be due to the lower thermal conductivity of atheromatous tissue. (4) In

  19. Expression of IL-17A in human atherosclerotic lesions is associated with increased inflammation and plaque vulnerability.

    PubMed

    Erbel, Christian; Dengler, Thomas J; Wangler, Susanne; Lasitschka, Felix; Bea, Florian; Wambsganss, Nadine; Hakimi, Maani; Böckler, Dittmar; Katus, Hugo A; Gleissner, Christian A

    2011-01-01

    A chronic (auto)immune response is the critical mechanism in atherosclerosis. Interleukin-17A is a pivotal effector cytokine, which modulates immune cell trafficking and initiates inflammation in (auto)immune and infectious diseases. However, expression of IL-17A in the context of human atherosclerosis has hardly been explored. Carotid artery plaques were collected from 79 patients undergoing endarterectomy. Patients were grouped according to their symptomatic status (TIA, stroke), plaque morphology and medication. Quantitative RT-PCR was used to analyze tissue inflammation and immunohistochemistry to assess cellular source of IL-17A expression and lesion morphology. Carotid plaques from patients with ischemic symptoms were characterized by a highly activated inflammatory milieu including accumulation of T cells (p = 0.04) and expression of IL-6 and VCAM1 (p = 0.02, 0.01). Expression of IL-17A and its positive regulators IL-21 and IL-23 was present in atherosclerotic lesions, significantly upregulated in atheromas of symptomatic patients (p = 0.005, 0.004, 0.03), and expression of IL-17A and IL-21 showed a strong correlation (p = 0.002, r = 0.52). The cellular sources of lesional IL-17A expression are T cells, macrophages, B cells and plasma cells. Vulnerable/ruptured (complicated) plaques were significantly associated with IL-17A expression levels (p = 0.003). In addition, IL-17A showed a marked negative correlation with the potent anti-inflammatory/atheroprotective cytokine IL-10 (p = 0.0006, r = -0.46). Furthermore, treatment with a HMG-CoA reductase inhibitor or acetylsalicylic acid showed reduced levels of IL-21, IL-23 and VCAM1 (all p < 0.05), but did not influence IL-17A. The association of IL-17A with ischemic symptoms and vulnerable plaque characteristics suggests that the pro-inflammatory cytokine IL-17A may contribute to atherosclerosis und plaque instability. PMID:21116822

  20. Noninvasive imaging modalities to visualize atherosclerotic plaques

    PubMed Central

    2016-01-01

    Atherosclerotic cardiovascular disease is becoming a major cause of death in the world due to global epidemic of diabetes and obesity. For the prevention of atherosclerotic cardiovascular disease, it is necessary to detect high-risk atherosclerotic plaques prior to events. Recent technological advances enable to visualize atherosclerotic plaques noninvasively. This ability of noninvasive imaging helps to refine cardiovascular risk assessment in various individuals, select optimal therapeutic strategy and evaluate the efficacy of medical therapies. In this review, we discuss the role of the currently available imaging modalities including computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography. Advantages and disadvantages of each noninvasive imaging modality will be also summarized. PMID:27500092

  1. Noninvasive imaging modalities to visualize atherosclerotic plaques.

    PubMed

    Shishikura, Daisuke

    2016-08-01

    Atherosclerotic cardiovascular disease is becoming a major cause of death in the world due to global epidemic of diabetes and obesity. For the prevention of atherosclerotic cardiovascular disease, it is necessary to detect high-risk atherosclerotic plaques prior to events. Recent technological advances enable to visualize atherosclerotic plaques noninvasively. This ability of noninvasive imaging helps to refine cardiovascular risk assessment in various individuals, select optimal therapeutic strategy and evaluate the efficacy of medical therapies. In this review, we discuss the role of the currently available imaging modalities including computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography. Advantages and disadvantages of each noninvasive imaging modality will be also summarized. PMID:27500092

  2. Propionibacterium acnes Recovered from Atherosclerotic Human Carotid Arteries Undergoes Biofilm Dispersion and Releases Lipolytic and Proteolytic Enzymes in Response to Norepinephrine Challenge In Vitro.

    PubMed

    Lanter, Bernard B; Davies, David G

    2015-10-01

    In the present study, human atherosclerotic carotid arteries were examined following endarterectomy for the presence of the Gram-positive bacterium Propionibacterium acnes and its potential association with biofilm structures within the arterial wall. The P. acnes 16S rRNA gene was detectable in 4 of 15 carotid artery samples, and viable P. acnes was one among 10 different bacterial species recoverable in culture. Fluorescence in situ hybridization analysis of 5 additional atherosclerotic carotid arteries demonstrated biofilm bacteria within all samples, with P. acnes detectable in 4 samples. We also demonstrated that laboratory-grown cultures of P. acnes biofilms were susceptible to induction of a biofilm dispersion response when challenged with physiologically relevant levels of norepinephrine in the presence of iron-bound transferrin or with free iron. The production and release of lipolytic and proteolytic extracellular enzymes by P. acnes were shown to increase in iron-induced dispersed biofilms, and these dispersion-induced P. acnes VP1 biofilms showed increased expression of mRNAs for the triacylglycerol lipases PPA2105 and PPA1796 and the hyaluronate lyase PPA380 compared to that in untreated biofilms. These results demonstrate that P. acnes can infect the carotid arteries of humans with atherosclerosis as a component of multispecies biofilms and that dispersion is inducible for this organism, at least in vitro, with physiologically relevant levels of norepinephrine resulting in the production and release of degradative enzymes. PMID:26216428

  3. Propionibacterium acnes Recovered from Atherosclerotic Human Carotid Arteries Undergoes Biofilm Dispersion and Releases Lipolytic and Proteolytic Enzymes in Response to Norepinephrine Challenge In Vitro

    PubMed Central

    Lanter, Bernard B.

    2015-01-01

    In the present study, human atherosclerotic carotid arteries were examined following endarterectomy for the presence of the Gram-positive bacterium Propionibacterium acnes and its potential association with biofilm structures within the arterial wall. The P. acnes 16S rRNA gene was detectable in 4 of 15 carotid artery samples, and viable P. acnes was one among 10 different bacterial species recoverable in culture. Fluorescence in situ hybridization analysis of 5 additional atherosclerotic carotid arteries demonstrated biofilm bacteria within all samples, with P. acnes detectable in 4 samples. We also demonstrated that laboratory-grown cultures of P. acnes biofilms were susceptible to induction of a biofilm dispersion response when challenged with physiologically relevant levels of norepinephrine in the presence of iron-bound transferrin or with free iron. The production and release of lipolytic and proteolytic extracellular enzymes by P. acnes were shown to increase in iron-induced dispersed biofilms, and these dispersion-induced P. acnes VP1 biofilms showed increased expression of mRNAs for the triacylglycerol lipases PPA2105 and PPA1796 and the hyaluronate lyase PPA380 compared to that in untreated biofilms. These results demonstrate that P. acnes can infect the carotid arteries of humans with atherosclerosis as a component of multispecies biofilms and that dispersion is inducible for this organism, at least in vitro, with physiologically relevant levels of norepinephrine resulting in the production and release of degradative enzymes. PMID:26216428

  4. Active macrophage-associated TGF-beta co-localizes with type I procollagen gene expression in atherosclerotic human pulmonary arteries.

    PubMed Central

    Bahadori, L.; Milder, J.; Gold, L.; Botney, M.

    1995-01-01

    Vascular remodeling in adult atherosclerotic pulmonary arteries is characterized by discrete areas of neointimal smooth muscle cell extracellular matrix gene expression in close proximity to non-foamy macrophages, suggesting regulation by local macrophage-associated factors. The purpose of these studies was to begin addressing the role of putative macrophage-associated factors such as transforming growth factor-beta (TGF-beta), by determining the spatial relationship between TGF-beta and neointimal matrix gene expression in human atherosclerotic pulmonary arteries. For example, the participation of TGF-beta in vascular remodeling could be inferred by its colocalization with non-foamy macrophages in areas of active matrix synthesis. In situ hybridization and immunohistochemistry demonstrated focal neointimal procollagen gene expression in close association with non-foamy but not foamy macrophages. Immunohistochemistry with isoform-specific anti-TGF-beta antibodies demonstrated all three isoforms of TGF-beta associated with non-foamy macrophages, but foamy macrophages were not immunoreactive. Neointimal and medial smooth muscle cells stained lightly. In contrast, intense TGF-beta immunoreactivity was also associated with medial smooth muscle cells in normal nonremodeling vessels. Immunohistochemistry with antibodies specific for latent TGF-beta was similar to immunohistochemistry for mature TGF-beta in both remodeling and nonremodeling vessels. Finally, using an antibody specific for active TGF-beta 1, immunoreactivity was only seen in non-foamy neointimal macrophages but not in foamy macrophages or medial smooth muscle cells from hypertensive or normal vessels. These observations suggest non-foamy macrophages may participate in modulating matrix gene expression in atherosclerotic remodeling via a TGF-beta-dependent mechanism. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:7747808

  5. The influence of constitutive law choice used to characterise atherosclerotic tissue material properties on computing stress values in human carotid plaques.

    PubMed

    Teng, Zhongzhao; Yuan, Jianmin; Feng, Jiaxuan; Zhang, Yongxue; Brown, Adam J; Wang, Shuo; Lu, Qingsheng; Gillard, Jonathan H

    2015-11-01

    Calculating high stress concentration within carotid atherosclerotic plaques has been shown to be complementary to anatomical features in assessing vulnerability. Reliability of stress calculation may depend on the constitutive laws/strain energy density functions (SEDFs) used to characterize tissue material properties. Different SEDFs, including neo-Hookean, one-/two-term Ogden, Yeoh, 5-parameter Mooney-Rivlin, Demiray and modified Mooney-Rivlin, have been used to describe atherosclerotic tissue behavior. However, the capacity of SEDFs to fit experimental data and the difference in the stress calculation remains unexplored. In this study, seven SEDFs were used to fit the stress-stretch data points of media, fibrous cap, lipid and intraplaque hemorrhage/thrombus obtained from 21 human carotid plaques. Semi-analytic solution, 2D structure-only and 3D fully coupled fluid-structure interaction (FSI) analyses were used to quantify stress using different SEDFs and the related material stability examined. Results show that, except for neo-Hookean, all other six SEDFs fitted the experimental points well, with vessel stress distribution in the circumferential and radial directions being similar. 2D structural-only analysis was successful for all seven SEDFs, but 3D FSI were only possible with neo-Hookean, Demiray and modified Mooney-Rivlin models. Stresses calculated using Demiray and modified Mooney-Rivlin models were nearly identical. Further analyses indicated that the energy contours of one-/two-term Ogden and 5-parameter Mooney-Rivlin models were not strictly convex and the material stability indictors under homogeneous deformations were not always positive. In conclusion, considering the capacity in characterizing material properties and stabilities, Demiray and modified Mooney-Rivlin SEDF appear practical choices for mechanical analyses to predict the critical mechanical conditions within carotid atherosclerotic plaques. PMID:26472305

  6. The influence of constitutive law choice used to characterise atherosclerotic tissue material properties on computing stress values in human carotid plaques

    PubMed Central

    Teng, Zhongzhao; Yuan, Jianmin; Feng, Jiaxuan; Zhang, Yongxue; Brown, Adam J.; Wang, Shuo; Lu, Qingsheng; Gillard, Jonathan H.

    2015-01-01

    Calculating high stress concentration within carotid atherosclerotic plaques has been shown to be complementary to anatomical features in assessing vulnerability. Reliability of stress calculation may depend on the constitutive laws/strain energy density functions (SEDFs) used to characterize tissue material properties. Different SEDFs, including neo-Hookean, one-/two-term Ogden, Yeoh, 5-parameter Mooney–Rivlin, Demiray and modified Mooney–Rivlin, have been used to describe atherosclerotic tissue behavior. However, the capacity of SEDFs to fit experimental data and the difference in the stress calculation remains unexplored. In this study, seven SEDFs were used to fit the stress–stretch data points of media, fibrous cap, lipid and intraplaque hemorrhage/thrombus obtained from 21 human carotid plaques. Semi-analytic solution, 2D structure-only and 3D fully coupled fluid-structure interaction (FSI) analyses were used to quantify stress using different SEDFs and the related material stability examined. Results show that, except for neo-Hookean, all other six SEDFs fitted the experimental points well, with vessel stress distribution in the circumferential and radial directions being similar. 2D structural-only analysis was successful for all seven SEDFs, but 3D FSI were only possible with neo-Hookean, Demiray and modified Mooney–Rivlin models. Stresses calculated using Demiray and modified Mooney–Rivlin models were nearly identical. Further analyses indicated that the energy contours of one-/two-term Ogden and 5-parameter Mooney–Rivlin models were not strictly convex and the material stability indictors under homogeneous deformations were not always positive. In conclusion, considering the capacity in characterizing material properties and stabilities, Demiray and modified Mooney–Rivlin SEDF appear practical choices for mechanical analyses to predict the critical mechanical conditions within carotid atherosclerotic plaques. PMID:26472305

  7. ACAT inhibition reduces the progression of pre-existing, advanced atherosclerotic mouse lesions without plaque or systemic toxicity

    PubMed Central

    Rong, James X.; Blachford, Courtney; Feig, Jonathan E.; Bander, Ilda; Mayne, Jeffrey; Kusunoki, Jun; Miller, Christine; Davis, Matthew; Wilson, Martha; Dehn, Shirley; Thorp, Edward; Tabas, Ira; Taubman, Mark B.; Rudel, Lawrence L.; Fisher, Edward A.

    2013-01-01

    Objective Acyl-CoA:cholesterol acyltransferase (ACAT) converts cholesterol to cholesteryl esters in plaque foam cells. Complete deficiency of macrophage ACAT has been shown to increase atherosclerosis in hypercholesterolemic mice due to cytotoxicity from free cholesterol accumulation, while we previously showed that partial ACAT inhibition by Fujirebio compound F1394 decreased early atherosclerosis development. In this report, we tested F1394 effects on pre-established, advanced lesions of apoE-/- mice. Methods & Results ApoE-/- mice on Western diet for 14 weeks developed advanced plaques, and were either sacrificed (“Baseline”), or continued on Western diet without or with F1394 and sacrificed after 14 more weeks. F1394 was not associated with systemic toxicity. Compared to the baseline group, lesion size progressed in both groups; however, F1394 significantly retarded plaque progression, and reduced plaque macrophage, free and esterified cholesterol, and tissue factor contents compared to the untreated group. Apoptosis of plaque cells was not increased, consistent with the decrease in lesional free cholesterol, plaque necrosis was not increased, and efferocytosis (phagocytic clearance of apoptotic cells) was not impaired. The effects of F1394 were independent of changes in plasma cholesterol levels. Conclusions Partial ACAT inhibition by F1394 lowered plaque cholesterol content and had other antiatherogenic effects in advanced lesions in apoE-/- mice without overt systemic or plaque toxicity, suggesting the continued potential of ACAT inhibition for the clinical treatment of atherosclerosis in spite of recent trial data. PMID:23139293

  8. Urine Proteome Analysis Reflects Atherosclerotic Disease in an ApoE−/− Mouse Model and Allows the Discovery of New Candidate Biomarkers in Mouse and Human Atherosclerosis*

    PubMed Central

    von zur Muhlen, Constantin; Schiffer, Eric; Sackmann, Christine; Zürbig, Petra; Neudorfer, Irene; Zirlik, Andreas; Htun, Nay; Iphöfer, Alexander; Jänsch, Lothar; Mischak, Harald; Bode, Christoph; Chen, Yung C.; Peter, Karlheinz

    2012-01-01

    Noninvasive diagnosis of atherosclerosis via single biomarkers has been attempted but remains elusive. However, a previous polymarker or pattern approach of urine polypeptides in humans reflected coronary artery disease with high accuracy. The aim of the current study is to use urine proteomics in ApoE−/− mice to discover proteins with pathophysiological roles in atherogenesis and to identify urinary polypeptide patterns reflecting early stages of atherosclerosis. Urine of ApoE−/− mice either on high fat diet (HFD) or chow diet was collected over 12 weeks; urine of wild type mice on HFD was used to exclude diet-related proteome changes. Capillary electrophoresis coupled to mass spectrometry (CE-MS) of samples identified 16 polypeptides specific for ApoE−/− mice on HFD. In a blinded test set, these polypeptides allowed identification of atherosclerosis at a sensitivity of 90% and specificity of 100%, as well as monitoring of disease progression. Sequencing of the discovered polypeptides identified fragments of α1-antitrypsin, epidermal growth factor (EGF), kidney androgen-regulated protein, and collagen. Using immunohistochemistry, α1-antitrypsin, EGF, and collagen type I were shown to be highly expressed in atherosclerotic plaques of ApoE−/− mice on HFD. Urinary excretion levels of collagen and α1-antitrypsin fragments also significantly correlated with intraplaque collagen and α1-antitrypsin content, mirroring plaque protein expression in the urine proteome. To provide further confirmation that the newly identified proteins are relevant in humans, the presence of collagen type I, α1-antitrypsin, and EGF was also confirmed in human atherosclerotic disease. Urine proteome analysis in mice exemplifies the potential of a novel multimarker approach for the noninvasive detection of atherosclerosis and monitoring of disease progression. Furthermore, this approach represents a novel discovery tool for the identification of proteins relevant in murine

  9. Urine proteome analysis reflects atherosclerotic disease in an ApoE-/- mouse model and allows the discovery of new candidate biomarkers in mouse and human atherosclerosis.

    PubMed

    von zur Muhlen, Constantin; Schiffer, Eric; Sackmann, Christine; Zürbig, Petra; Neudorfer, Irene; Zirlik, Andreas; Htun, Nay; Iphöfer, Alexander; Jänsch, Lothar; Mischak, Harald; Bode, Christoph; Chen, Yung C; Peter, Karlheinz

    2012-07-01

    Noninvasive diagnosis of atherosclerosis via single biomarkers has been attempted but remains elusive. However, a previous polymarker or pattern approach of urine polypeptides in humans reflected coronary artery disease with high accuracy. The aim of the current study is to use urine proteomics in ApoE(-/-) mice to discover proteins with pathophysiological roles in atherogenesis and to identify urinary polypeptide patterns reflecting early stages of atherosclerosis. Urine of ApoE(-/-) mice either on high fat diet (HFD) or chow diet was collected over 12 weeks; urine of wild type mice on HFD was used to exclude diet-related proteome changes. Capillary electrophoresis coupled to mass spectrometry (CE-MS) of samples identified 16 polypeptides specific for ApoE(-/-) mice on HFD. In a blinded test set, these polypeptides allowed identification of atherosclerosis at a sensitivity of 90% and specificity of 100%, as well as monitoring of disease progression. Sequencing of the discovered polypeptides identified fragments of α(1)-antitrypsin, epidermal growth factor (EGF), kidney androgen-regulated protein, and collagen. Using immunohistochemistry, α(1)-antitrypsin, EGF, and collagen type I were shown to be highly expressed in atherosclerotic plaques of ApoE(-/-) mice on HFD. Urinary excretion levels of collagen and α(1)-antitrypsin fragments also significantly correlated with intraplaque collagen and α(1)-antitrypsin content, mirroring plaque protein expression in the urine proteome. To provide further confirmation that the newly identified proteins are relevant in humans, the presence of collagen type I, α(1)-antitrypsin, and EGF was also confirmed in human atherosclerotic disease. Urine proteome analysis in mice exemplifies the potential of a novel multimarker approach for the noninvasive detection of atherosclerosis and monitoring of disease progression. Furthermore, this approach represents a novel discovery tool for the identification of proteins relevant in

  10. Cooperative interactions between RB and p53 regulate cell proliferation, cell senescence, and apoptosis in human vascular smooth muscle cells from atherosclerotic plaques.

    PubMed

    Bennett, M R; Macdonald, K; Chan, S W; Boyle, J J; Weissberg, P L

    1998-04-01

    Compared with vascular smooth muscle cells (VSMCs) from normal vessels, VSMCs from human atherosclerotic plaques proliferate more slowly, undergo earlier senescence, and demonstrate higher levels of apoptosis in culture. The tumor suppressor genes p105RB (retinoblastoma, acting through the E2F transcription factor family) and p53 regulate cell proliferation, cell senescence, and apoptosis in many cell types. We have therefore determined whether these stable growth properties of plaque VSMCs reflect altered activity of RB and/or p53. VSMCs were derived from coronary atherectomies or from normal coronary arteries from transplant recipients. Compared with normal VSMCs, plaque VSMCs showed a higher ratio of the active (hypophosphorylated) to the inactive (phosphorylated) form of RB and a lower level of E2F transcriptional activity. Cells were stably transfected with retrovirus constructs that inhibited RB or p53 alone or in combination. Suppression of RB alone increased rates of cell proliferation and apoptosis and inhibited cell senescence in normal VSMCs. Suppression of p53 and RB together had similar effects but, additionally, resulted in immortalization of normal VSMC cultures. In contrast, inhibition of RB binding to E2F or ectopic expression of E2F-1 in plaque VSMCs induced massive apoptosis, which required suppression of p53 to rescue cells. Suppression of RB and p53 together increased cell proliferation and delayed senescence but failed to immortalize plaque VSMCs. Inhibition of p53 alone had minimal effects on plaque VSMCs but increased the lifespan of normal VSMCs. We conclude that human plaque VSMCs have slower rates of cell proliferation and earlier senescence than do cells from normal vessels because of a defect in phosphorylation of RB. Furthermore, both disruption of RB/E2F and inhibition of p53 are required for plaque VSMCs to proliferate without apoptosis. This observation may explain the relatively low level of cell proliferation and high level of

  11. A method to compensate for the underestimation of collagen with polarized picrosirius red imaging in human artery atherosclerotic plaques

    NASA Astrophysics Data System (ADS)

    Greiner, C. A.; Grainger, S. J.; Su, J. L.; Madden, S. P.; Muller, J. E.

    2016-04-01

    Although picrosirius red (PSR) is known to be in quantifying collagen under polarized light (PL), commonly used linearly PL can result in an underestimation of collagen, as some of the fibers may appear dark if aligned with the transmission axis of the polarizers. To address this, a sample may be imaged with circularly polarized light at the expense of higher background intensity. However, the quality and alignment of the microscope illumination optics, polarizers and waveplates can still produce imaging variability with circular polarization. A simpler technique was tested that minimized variability and background intensity with linear polarization by acquiring images at multiple angles of histology slide rotation to create a composite co-registered image, permitting the optimal semi-quantitative visualization of collagen. Linear polarization imaging was performed on PSR stained artery sections. By rotating the slide at 60° intervals while maintaining illumination, polarization and exposure parameters, 6 images were acquired for each section. A composite image was created from the 6 co-registered images, and comprised of the maximum pixel intensity at each point. Images from any of the 6 rotation positions consistently showed variation in PSR signal. A composite image compensates for this variability, without loss of spatial resolution. Additionally, grayscale analysis showed an increased intensity range of 15 - 50% with a linearly polarized composite image over a circularly polarized image after background correction, indicating better SNR. This proposed technique will be applied in the development of a near infrared spectroscopy algorithm to detect vulnerable atherosclerotic plaques in vivo.

  12. Introduction. Teaching Advanced Placement Human Geography.

    ERIC Educational Resources Information Center

    Murphy, Alexander B.

    2000-01-01

    Introduces this special issue of "Journal of Geography" focusing on the teaching of Advanced Placement (AP) human geography. States that essays were developed by members of the AP Human Geography Development Committee focusing on areas in the human geography course outline which are included in the appendix. (CMK)

  13. Differential expression of oxidation-specific epitopes and apolipoprotein(a) in progressing and ruptured human coronary and carotid atherosclerotic lesions.

    PubMed

    van Dijk, Rogier A; Kolodgie, Frank; Ravandi, Amir; Leibundgut, Gregor; Hu, Patrick P; Prasad, Anand; Mahmud, Ehtisham; Dennis, Edward; Curtiss, Linda K; Witztum, Joseph L; Wasserman, Bruce A; Otsuka, Fumiyuki; Virmani, Renu; Tsimikas, Sotirios

    2012-12-01

    The relationships between oxidation-specific epitopes (OSE) and lipoprotein (a) [Lp(a)] and progressive atherosclerosis and plaque rupture have not been determined. Coronary artery sections from sudden death victims and carotid endarterectomy specimens were immunostained for apoB-100, oxidized phospholipids (OxPL), apo(a), malondialdehyde-lysine (MDA), and MDA-related epitopes detected by antibody IK17 and macrophage markers. The presence of OxPL captured in carotid and saphenous vein graft distal protection devices was determined with LC-MS/MS. In coronary arteries, OSE and apo(a) were absent in normal coronary arteries and minimally present in early lesions. As lesions progressed, apoB and MDA epitopes did not increase, whereas macrophage, apo(a), OxPL, and IK17 epitopes increased proportionally, but they differed according to plaque type and plaque components. Apo(a) epitopes were present throughout early and late lesions, especially in macrophages and the necrotic core. IK17 and OxPL epitopes were strongest in late lesions in macrophage-rich areas, lipid pools, and the necrotic core, and they were most specifically associated with unstable and ruptured plaques. Specific OxPL were present in distal protection devices. Human atherosclerotic lesions manifest a differential expression of OSEs and apo(a) as they progress, rupture, and become clinically symptomatic. These findings provide a rationale for targeting OSE for biotheranostic applications in humans. PMID:22969153

  14. Genomic profiling of acquired resistance to apoptosis in cells derived from human atherosclerotic lesions: potential role of STATs, cyclinD1, BAD, and Bcl-XL.

    PubMed

    Gagarin, Dmitry; Yang, Zhaoqing; Butler, Jason; Wimmer, Monika; Du, Baoheng; Cahan, Patrick; McCaffrey, Timothy A

    2005-09-01

    Current theories suggest that atherosclerosis, plaque rupture, stroke, and restenosis after angioplasty may involve defective apoptotic mechanisms in vascular cells. Prior work has demonstrated that cells from human atherosclerotic lesions, and cells from the aorta of aged rats, exhibit functional resistance to apoptosis induced by TGF-beta and glucocorticoids. The present studies demonstrate that human lesion-derived cells (LDC) are also resistant to apoptosis induced by fas ligation compared to cells derived from the adjacent media, and that in vitro expansion of LDC causes acquired resistance to apoptosis. Microarray profiling of fas-resistant versus sensitive cells identified a set of genes including STATs, caspase 1, cyclin D1, Bcl-xL, VDAC2, and BAD. The STAT proteins have been implicated in resistance to apoptosis, potentially via their ability to modulate caspase 1 (ICE), Bcl-xL, and cyclin D1 expression. Western blot analysis of sensitive and resistant LDC clonal lines confirmed increases in cyclin D1, STAT6, Bcl-xL, and BAD, with decreased expression of caspase 1. Thus, transcript profiling has identified a potential pathway of apoptotic regulation in subsets of lesion cells. The resistant phenotype may contribute to plaque stability and excessive vascular repair, while sensitive cells may be involved in plaque rupture and infarction. The data suggests both genetic interventions and novel small-molecule inhibitors that may be effective modulators of apoptosis in atherosclerosis, angina, and in-stent restenosis. PMID:16005468

  15. Mechanism of atherosclerotic calcification.

    PubMed

    Shioi, A; Mori, K; Jono, S; Wakikawa, T; Hiura, Y; Koyama, H; Okuno, Y; Nishizawa, Y; Morii, H

    2000-01-01

    Calcification is almost invariably associated with atherosclerotic plaque lesions. Recent data suggest that plaque calcification is an active, regulated process similar to osteogenesis. In order to clarify the mechanism of plaque calcification, we developed an in vitro model of vascular calcification by utilizing bovine vascular smooth muscle cells (BVSMCs). This model is useful in that diffuse and massive calcification can be induced within 2 weeks and thereby biochemical analyses of vascular calcification can be performed. We have analyzed several aspects of vascular calcification by using this model and demonstrated as follows: 1) in vitro calcification of BVSMCs is regulated by calciotropic hormones and BVSMCs are equipped with a unique autocrine and/or paracrine system regulating calcium metabolism. 2) Sodium-dependent phosphate cotransport plays a crucial role in BVSMC calcification as well as in mineralization of skeletal tissues. 3) BVSMCs acquire osteoblastic phenotype under certain conditions. Finally, we discuss the roles of macrophages in the development of atherosclerotic calcification. Interferon-gamma (IFN-gamma) induces gene expression of 25-hydrovitamin D-1 alpha-hydroxylase (1 alpha OHase) and its activity in macrophages. Since 1 alpha OHase can locally convert 25-hydroxyvitamin D into 1 alpha, 25-dihydroxyvitamin D (1,25(OH)2D), an active metabolite of vitamin D, it is suggested that local production of 1,25(OH)2D by macrophages may promote atherosclerotic calcification. Moreover, macrophages may be involved in the phenotypic changes of vascular smooth muscle cells (VSMCs) to acquire calcifying capacity. Therefore, the phenotypic changes of VSMCs in atherosclerotic plaque may contribute to the development of atherosclerotic calcification. PMID:10769407

  16. The lipid-rich core region of human atherosclerotic fibrous plaques. Prevalence of small lipid droplets and vesicles by electron microscopy.

    PubMed Central

    Guyton, J. R.; Klemp, K. F.

    1989-01-01

    Abundant extracellular lipid deposits are associated with cell necrosis and tissue weakening in the core region of human atherosclerotic fibrous plaques. The ultrastructural morphology of the core region, previously undefined because of lipid extraction artifacts, was studied with the aid of new osmium-thiocarbohydrazide-osmium and osmium-tannic acid-paraphenylenediamine sequences for tissue processing. Small droplets of neutral lipid (30 to 400 nm profile diameter) and lipid vesicles with aqueous centers accounted for more than 90% of the area occupied by lipid-rich structures in the core region. No foam cells were present. Cholesterol crystals, lipid droplets of a size similar to those in foam cells (0.4 to 6 mu), and larger neutral lipid deposits (greater than 6 mu) together occupied less than 10% of the total area of lipid structures. Abundant lipid vesicles were associated with the nearby presence of cholesterol crystals, whereas small lipid droplets were predominant in areas without crystals. Many droplets had surface defects in the form of pits and vesicular blebs. These morphologic findings are explained most concisely by postulating direct accumulation of extracellular lipid from interstitial lipoproteins as a major process in core region formation. Moreover, a dynamic state of ongoing physical/metabolic transformation of extracellular lipid deposits is suggested. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 7 Figure 8 Figure 9 PMID:2646938

  17. Inhibitory effects of oleoylethanolamide (OEA) on H2O2-induced human umbilical vein endothelial cell (HUVEC) injury and apolipoprotein E knockout (ApoE-/-) atherosclerotic mice

    PubMed Central

    Ma, Li; Guo, Xiaobing; Chen, Wei

    2015-01-01

    Atherosclerosis (AS) is initiated by vascular endothelial cell injury, which is induced by lipid and protein oxidation. Oleoylethanolamide (OEA), a dietary fat-derived lipid, has shown atheroprotective effect. In vitro studies demonstrated that OEA showed cytoprotective effects on H2O2-induced primary cultured human umbilical vein endothelial cell (HUVEC) injury model. Further investigation of the cytoprotective effects of OEA demonstrated that OEA exerted its function by scavenging for reactive oxygen species, as well as increasing anti-oxidative enzymes, reducing lipid peroxidation, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive cells and apoptosis-related proteins expression. The in vivo study using an ApoE-/- mouse model fed with high-fat diet for 8 weeks showed that OEA (10 mg/kg/day, i.g.) administration reduced blood lipid levels, prevented endothelial cell damage and inhibited early AS plaque formation. In conclusion, our results suggested that OEA exerted a pharmacological effect on ameliorating atherosclerotic plaque formation through the inhibition of oxidative stress-induced endothelial cell injury and therefore OEA can be a potential candidate drug for anti-atherosclerosis. PMID:26261506

  18. Inhibitory effects of oleoylethanolamide (OEA) on H₂O₂-induced human umbilical vein endothelial cell (HUVEC) injury and apolipoprotein E knockout (ApoE-/-) atherosclerotic mice.

    PubMed

    Ma, Li; Guo, Xiaobing; Chen, Wei

    2015-01-01

    Atherosclerosis (AS) is initiated by vascular endothelial cell injury, which is induced by lipid and protein oxidation. Oleoylethanolamide (OEA), a dietary fat-derived lipid, has shown atheroprotective effect. In vitro studies demonstrated that OEA showed cytoprotective effects on H2O2-induced primary cultured human umbilical vein endothelial cell (HUVEC) injury model. Further investigation of the cytoprotective effects of OEA demonstrated that OEA exerted its function by scavenging for reactive oxygen species, as well as increasing anti-oxidative enzymes, reducing lipid peroxidation, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive cells and apoptosis-related proteins expression. The in vivo study using an ApoE-/- mouse model fed with high-fat diet for 8 weeks showed that OEA (10 mg/kg/day, i.g.) administration reduced blood lipid levels, prevented endothelial cell damage and inhibited early AS plaque formation. In conclusion, our results suggested that OEA exerted a pharmacological effect on ameliorating atherosclerotic plaque formation through the inhibition of oxidative stress-induced endothelial cell injury and therefore OEA can be a potential candidate drug for anti-atherosclerosis. PMID:26261506

  19. Whither Humanities and Advanced Technologies?

    ERIC Educational Resources Information Center

    Jones, Paul

    1997-01-01

    Discusses humanities projects that can be facilitated by communications technology: multiple language representations, providing cross-platform multilingual font sets and distributed multilingual enabling technologies; high-quality images and tools for archival image annotation, search, and retrieval; three-dimensional representations to provide…

  20. Inhibiting macrophage proliferation suppresses atherosclerotic plaque inflammation

    PubMed Central

    Tang, Jun; Lobatto, Mark E.; Hassing, Laurien; van der Staay, Susanne; van Rijs, Sarian M.; Calcagno, Claudia; Braza, Mounia S.; Baxter, Samantha; Fay, Francois; Sanchez-Gaytan, Brenda L.; Duivenvoorden, Raphaël; Sager, Hendrik B.; Astudillo, Yaritzy M.; Leong, Wei; Ramachandran, Sarayu; Storm, Gert; Pérez-Medina, Carlos; Reiner, Thomas; Cormode, David P.; Strijkers, Gustav J.; Stroes, Erik S. G.; Swirski, Filip K.; Nahrendorf, Matthias; Fisher, Edward A.; Fayad, Zahi A.; Mulder, Willem J. M.

    2015-01-01

    Inflammation drives atherosclerotic plaque progression and rupture, and is a compelling therapeutic target. Consequently, attenuating inflammation by reducing local macrophage accumulation is an appealing approach. This can potentially be accomplished by either blocking blood monocyte recruitment to the plaque or increasing macrophage apoptosis and emigration. Because macrophage proliferation was recently shown to dominate macrophage accumulation in advanced plaques, locally inhibiting macrophage proliferation may reduce plaque inflammation and produce long-term therapeutic benefits. To test this hypothesis, we used nanoparticle-based delivery of simvastatin to inhibit plaque macrophage proliferation in apolipoprotein E–deficient mice (Apoe−/−) with advanced atherosclerotic plaques. This resulted in the rapid reduction of plaque inflammation and favorable phenotype remodeling. We then combined this short-term nanoparticle intervention with an 8-week oral statin treatment, and this regimen rapidly reduced and continuously suppressed plaque inflammation. Our results demonstrate that pharmacologically inhibiting local macrophage proliferation can effectively treat inflammation in atherosclerosis. PMID:26295063

  1. Advances in gene technology: Human genetic disorders

    SciTech Connect

    Scott, W.A.; Ahmad, F.; Black, S.; Schultz, J.; Whelan, W.J.

    1984-01-01

    This book discusses the papers presented at the conference on the subject of ''advances in Gene technology: Human genetic disorders''. Molecular biology of various carcinomas and inheritance of metabolic diseases is discussed and technology advancement in diagnosis of hereditary diseases is described. Some of the titles discussed are-Immunoglobulin genes translocation and diagnosis; hemophilia; oncogenes; oncogenic transformations; experimental data on mice, hamsters, birds carcinomas and sarcomas.

  2. Human factors challenges for advanced process control

    SciTech Connect

    Stubler, W.F.; O`Hara, J..M.

    1996-08-01

    New human-system interface technologies provide opportunities for improving operator and plant performance. However, if these technologies are not properly implemented, they may introduce new challenges to performance and safety. This paper reports the results from a survey of human factors considerations that arise in the implementation of advanced human-system interface technologies in process control and other complex systems. General trends were identified for several areas based on a review of technical literature and a combination of interviews and site visits with process control organizations. Human factors considerations are discussed for two of these areas, automation and controls.

  3. Technological advances for studying human behavior

    NASA Technical Reports Server (NTRS)

    Roske-Hofstrand, Renate J.

    1990-01-01

    Technological advances for studying human behavior are noted in viewgraph form. It is asserted that performance-aiding systems are proliferating without a fundamental understanding of how they would interact with the humans who must control them. Two views of automation research, the hardware view and the human-centered view, are listed. Other viewgraphs give information on vital elements for human-centered research, a continuum of the research process, available technologies, new technologies for persistent problems, a sample research infrastructure, the need for metrics, and examples of data-link technology.

  4. Advances in human reproductive ecology.

    PubMed

    Ellison, P T

    1994-01-01

    Human reproductive ecology pertains to reproduction biology and changes due to environmental influences. The research literature relies on clinical, epidemiological, and demographic analysis. The emphasis is on normal, nonpathological states and a broad range of ecological conditions. This review focused on the importance of age and energetic stress from ecological conditions rather than dieting or self-directed exercise in changing female fecundity. The literature on male reproductive ecology is still small but growing. J.W. Wood provided a comprehensive overview of the field. Natural fertility, as defined by Henry, is the lack of parity-specific fertility limitation. There is evidence that fertility can vary widely in natural fertility populations. There are consistent age patterns among different natural fertility populations. Doring found that there was higher frequency of anovulatory and luteal insufficiency in cycles during perimenarche and perimenopausal periods. Infertility studies have shown declines in pregnancy rates in women over the age of 30 years. Ovum donation evaluations have found both uterine age and ovarian and oocyte age to be related to the probability of a successful pregnancy. Basal follicle stimulating hormone and the endometrial thickness are important predictors of ovarian capacity and related to age and declining fecundity. Much of the literature on fecundity is derived from women with impaired reproductive physiology. In Lipson and Ellison's study of healthy women, average follicular and average luteal estradiol values declined with increasing subject age. Low follicular levels were correlated with smaller follicular size, low oocyte fertilizability, reduced endometrial thickness, and low pregnancy rates. Comparisons across populations have shown that populations experience declines in luteal function with age, but levels of luteal functions varied widely. Chronic conditions which slow growth and delay reproductive maturation may impact

  5. [The relationship between Chlamydia pneumoniae and atherosclerotic lesions of the aorta].

    PubMed

    Gloria Breceda, F; Meaney Mendiolea, E; Valero Elizondo, G; Vela Huerta, A

    1997-01-01

    Although atherogenic main factors have been extensively studied, there are others whose real importance has not been well defined. There are some pathologic and immunologic evidences relating several infectious agents with the genesis or development of coronary atherosclerosis. Recently, a link has been established between Chlamydia pneumoniae and atherogenesis, due to immunological evidence of infection in human atherosclerotic lesions. We studied 16 aortic specimens obtained from necropsies performed in subjects who died with coronary heart disease. The infection of Ch. pneumoniae was determined by means of an immunofluorescent technique using a specific monoclonal murine antibody. A positive reaction was found in advanced non-ulcerated fibrolipid lesions in just 2 patients (13%), according with several other observations. It is not known the true relationship between the chlamydia infection and atherogenesis, neither if the infection starts or aggravates the atherosclerotic process or if it is an independent phenomenon. PMID:9221706

  6. Population in Advanced Placement Human Geography.

    ERIC Educational Resources Information Center

    Sharma, Martha B.

    2000-01-01

    Addresses the population section of the Advanced Placement course outline for human geography, focusing on four themes: (1) geographical analysis of population; (2) population distribution and composition; (3) population growth and decline over time and space; and (4) population movement. Identifies strategies for instructional activities.…

  7. Modern Agriculture in Advanced Placement Human Geography.

    ERIC Educational Resources Information Center

    Lanegran, David A.

    2000-01-01

    Discusses the four sections of the Advanced Placement (AP) human geography course focusing on agriculture: (1) development and diffusion of agriculture; (2) major agricultural production regions; (3) rural land use and change; and (4) impacts of modern agricultural change. Includes references and a resource list. (CMK)

  8. Percutaneous endovascular management of atherosclerotic axillary artery stenosis: Report of 2 cases and review of literature

    PubMed Central

    Vijayvergiya, Rajesh; Yadav, Mukesh; Grover, Anil

    2011-01-01

    With recent advancement in percutaneous endovascular management, most atherosclerotic peripheral arterial diseases are amenable for intervention. However, there is limited published literature about atherosclerotic axillary artery involvement and its endovascular management. We report two cases of atherosclerotic axillary artery stenosis, which were successfully managed with stent angioplasty using self expanding nitinol stents. The associated coronary artery disease was treated by percutaneous angioplasty and stenting. The long term follow-up revealed patent axillary stents in both cases. PMID:21666817

  9. [Atherosclerotic renal artery stenosis].

    PubMed

    Sauguet, A; Honton, B

    2014-12-01

    Atherosclerotic renal artery stenosis can cause ischaemic nephropathy and arterial hypertension. Renal artery stenosis (RAS) continues to be a problem for clinicians, with no clear consensus on how to investigate and assess the clinical significance of stenotic lesions and manage the findings. RAS caused by fibromuscular dysplasia is probably commoner than previously appreciated, should be actively looked for in younger hypertensive patients and can be managed successfully with angioplasty. Atheromatous RAS is associated with increased incidence of cardiovascular events and increased cardiovascular mortality, and is likely to be seen with increasing frequency. Many patients with RAS may be managed effectively with medical therapy for several years without endovascular stenting, as demonstrated by randomized, prospective trials including the cardiovascular outcomes in Renal Atherosclerotic Lesions (CORAL) trial, the Angioplasty and Stenting for Renal Artery Lesions (ASTRAL) trial. These trials share the limitation of excluding subsets of patients with high-risk clinical presentations, including episodic pulmonary edema and rapidly progressing renal failure and hypertension. Blood pressure control and medication adjustment may become more difficult with declining renal function and may prevent the use of angiotensin receptor blocker and angiotensin-converting enzyme inhibitors. The objective of this review is to evaluate the current management of RAS for cardiologists in the context of recent randomized clinical trials. There is now interest in looking more closely at patient selection for intervention, with focus on intervening only in patients with the highest-risk presentations such as flash pulmonary edema, rapidly declining renal function and severe resistant hypertension. PMID:25450992

  10. Wall shear stress as a stimulus for carotid atherosclerotic plaque progression: An MRI-based CFD pilot study

    NASA Astrophysics Data System (ADS)

    Canton, Gador; Chiu, Bernard; Hatsukami, Tom; Kerwin, William; Yuan, Chun

    2010-11-01

    The aim of this study was to explore the hypothesis that intra-plaque hemorrhage, a feature associated with adverse outcomes and atherosclerotic plaque progression and destabilization, is more likely to occur in plaques with elevated levels of wall shear stress (WSS). We used multi-sequence in-vivo magnetic resonance imaging (MRI) to characterize ten human carotid atherosclerotic plaques and an MRI-based computational fluid dynamics (CFD) model to solve the equations governing the blood flow. Hemorrhage was detected within the necrotic core (intra-plaque hemorrhage) in five of these ten cases. WSS data were extracted from the results of the CFD simulations to compare patterns between the cases with and without hemorrhage. We computed the mean value of the WSS (for each time point of the cardiac cycle) at the region where a necrotic core was detected. The results from this pilot study indicate a possible link between the presence of hemorrhage within a lipid-rich necrotic core in human carotid atherosclerotic plaques and elevated levels of shear stress force acting on the luminal surface. Thus, elevated wall shear stress may be used as a high risk feature in advanced carotid atherosclerotic plaques.

  11. Microsatellite mutation of type II transforming growth factor-beta receptor is rare in atherosclerotic plaques.

    PubMed

    Clark, K J; Cary, N R; Grace, A A; Metcalfe, J C

    2001-04-01

    A somatic mutation within a microsatellite polyA tract in the coding region of the type II transforming growth factor (TGF)-beta receptor gene was reported to occur in human atherosclerotic and restenotic lesions. This mutation occurs frequently in colorectal cancer with the replication error repair phenotype and results in loss of sensitivity to the growth inhibitory effects of TGF-beta in cells from the tumors. The mutation was proposed to account for the clonal expansion of vascular smooth muscle cells observed in atherosclerotic plaques, through loss of the growth inhibitory effect of TGF-beta. The frequency of the mutation and the extent of clonal expansion of the mutated cells have major implications for the mechanism of atherogenesis and therapeutic strategies. We analyzed a set of 22 coronary arterial and 9 aortic samples containing early to advanced atherosclerotic lesions for the mutation in the type II TGF-beta receptor polyA tract. Only 1 coronary arterial sample from an advanced lesion showed detectable amounts of the mutation, present at a low level (8% of the DNA sample). The data imply that the mutation occurs only at low frequency and is not a major mechanistic contributor to the development of atherosclerosis. PMID:11304472

  12. Advances in Computationally Modeling Human Oral Bioavailability

    PubMed Central

    Wang, Junmei; Hou, Tingjun

    2015-01-01

    Although significant progress has been made in experimental high throughput screening (HTS) of ADME (absorption, distribution, metabolism, excretion) and pharmacokinetic properties, the ADME and Toxicity (ADME-Tox) in silico modeling is still indispensable in drug discovery as it can guide us to wisely select drug candidates prior to expensive ADME screenings and clinical trials. Compared to other ADME-Tox properties, human oral bioavailability (HOBA) is particularly important but extremely difficult to predict. In this paper, the advances in human oral bioavailability modeling will be reviewed. Moreover, our deep insight on how to construct more accurate and reliable HOBA QSAR and classification models will also discussed. PMID:25582307

  13. Advances in computationally modeling human oral bioavailability.

    PubMed

    Wang, Junmei; Hou, Tingjun

    2015-06-23

    Although significant progress has been made in experimental high throughput screening (HTS) of ADME (absorption, distribution, metabolism, excretion) and pharmacokinetic properties, the ADME and Toxicity (ADME-Tox) in silico modeling is still indispensable in drug discovery as it can guide us to wisely select drug candidates prior to expensive ADME screenings and clinical trials. Compared to other ADME-Tox properties, human oral bioavailability (HOBA) is particularly important but extremely difficult to predict. In this paper, the advances in human oral bioavailability modeling will be reviewed. Moreover, our deep insight on how to construct more accurate and reliable HOBA QSAR and classification models will also discussed. PMID:25582307

  14. The Advancement of Humans in Space

    NASA Technical Reports Server (NTRS)

    Graves, John A.

    2014-01-01

    The advancement of humans into space and potentially beyond started slow but has greatly increased in speed over the past 2 generations. NASA has been at the forefront of this development and coontinues to lead the way into space exploration. This presentation provides a brief historical overview of NASA's space exploration efforts and touches on the abilityof each new generation to greatly expand our presence in space.

  15. Pathophysiology of Atherosclerotic Plaque Development.

    PubMed

    Rognoni, Andrea; Cavallino, Chiara; Veia, Alessia; Bacchini, Sara; Rosso, Roberta; Facchini, Manuela; Secco, Gioel G; Lupi, Alessandro; Nardi, Federico; Rametta, Francesco; Bongo, Angelo S

    2015-01-01

    Cardiovascular diseases and in particular coronary atherosclerotic disease are the leading cause of mortality and morbidity in the industrialized countries. Coronary atherosclerosis has been recognized for over a century and it was the subject of various studies. Pathophysiological studies have unravelled the interactions of molecular and cellular elements involved in atherogenesis; during the last decades the basic research has focused on the study of the instability of atherosclerotic plaque. Plaque rupture and resulting intracoronary thrombosis are thought to account for most acute coronary syndromes including ST - segment elevation myocardial infarction and non ST - segment elevation myocardial infarction. This is a brief review of the pathophysiology of atherosclerotic plaque development. PMID:25544119

  16. Application of IR and NIR fiber optic imaging in thermographic and spectroscopic diagnosis of atherosclerotic vulnerable plaques: preliminary experience

    NASA Astrophysics Data System (ADS)

    Naghavi, Morteza; Khan, Tania; Gu, Bujin; Soller, Babs R.; Melling, Peter; Asif, Mohammed; Gul, Khawar; Madjid, Mohammad; Casscells, S. W.; Willerson, James T.

    2000-12-01

    Despite major advances in cardiovascular science and technology during the past three decades, approximately half of all myocardial infarctions and sudden deaths occur unexpectedly. It is widely accepted that coronary atherosclerotic plaques and thrombotic complications resulting from their rupture or erosion are the underlying causes of this major health problem. The majority of these vulnerable plaques exhibit active inflammation, a large necrotic lipid core, a thin fibrous cap, and confer a stenosis of less than 70%. These lesions are not detectable by stress testing or coronary angiography. Our group is exploring the possibility of a functional classification based on physiological variables such as plaque temperature, pH, oxygen consumption, lactate production etc. We have shown that heat accurately locates the inflamed plaques. We also demonstrated human atherosclerotic plaques are heterogeneous with regard to pH and hot plaques and are more likely to be acidic. To develop a nonsurgical method for locating the inflamed plaques, we are developing both IR fiber optic imaging and NIR spectroscopic systems in our laboratory to detect hot and acidic plaque in atherosclerotic arterial walls. Our findings introduce the possibility of an isolated/combined IR and NIR fiber optic catheter that can bring new insight into functional assessment of atherosclerotic plaque and thereby detection of active and inflamed lesions responsible for heart attacks and strokes.

  17. Advances in Human B Cell Phenotypic Profiling

    PubMed Central

    Kaminski, Denise A.; Wei, Chungwen; Qian, Yu; Rosenberg, Alexander F.; Sanz, Ignacio

    2012-01-01

    To advance our understanding and treatment of disease, research immunologists have been called-upon to place more centralized emphasis on impactful human studies. Such endeavors will inevitably require large-scale study execution and data management regulation (“Big Biology”), necessitating standardized and reliable metrics of immune status and function. A well-known example setting this large-scale effort in-motion is identifying correlations between eventual disease outcome and T lymphocyte phenotype in large HIV-patient cohorts using multiparameter flow cytometry. However, infection, immunodeficiency, and autoimmunity are also characterized by correlative and functional contributions of B lymphocytes, which to-date have received much less attention in the human Big Biology enterprise. Here, we review progress in human B cell phenotyping, analysis, and bioinformatics tools that constitute valuable resources for the B cell research community to effectively join in this effort. PMID:23087687

  18. Advancing a vaccine to prevent human schistosomiasis.

    PubMed

    Merrifield, Maureen; Hotez, Peter J; Beaumier, Coreen M; Gillespie, Portia; Strych, Ulrich; Hayward, Tara; Bottazzi, Maria Elena

    2016-06-01

    Several candidate human schistosomiasis vaccines are in different stages of preclinical and clinical development. The major targets are Schistosoma haematobium (urogenitial schistosomiasis) and Schistosoma mansoni (intestinal schistosomiasis) that account for 99% of the world's 252 million cases, with 90% of these cases in Africa. Two recombinant S. mansoni vaccines - Sm-TSP-2 and Sm-14 are in Phase 1 trials, while Smp80 (calpain) is undergoing testing in non-human primates. Sh28GST, also known as Bilhvax is in advanced clinical development for S. haematobium infection. The possibility remains that some of these vaccines may cross-react to target both schistosome species. These vaccines were selected on the basis of their protective immunity in preclinical challenge models, through human immune-epidemiological studies or both. They are being advanced through a combination of academic research institutions, non-profit vaccine product development partnerships, biotechnology companies, and developing country vaccine manufacturers. In addition, new schistosome candidate vaccines are being identified through bioinformatics, OMICs approaches, and moderate throughput screening, although the full potential of reverse vaccinology for schistosomiasis has not yet been realized. The target product profiles of these vaccines vary but many focus on vaccinating children, in some cases following mass treatment with praziquantel, also known as vaccine-linked chemotherapy. Several regulatory pathways have been proposed, some of which rely on World Health Organization prequalification. PMID:27036511

  19. [Advance directives, a tool to humanize care].

    PubMed

    Olmari-Ebbing, M; Zumbach, C N; Forest, M I; Rapin, C H

    2000-07-01

    The relationship between the patient and a medical care giver is complex specially as it implies to the human, juridical and practical points of view. It depends on legal and deontological considerations, but also on professional habits. Today, we are confronted to a fundamental modification of this relationship. Professional guidelines exist, but are rarely applied and rarely taught in universities. However, patients are eager to move from a paternalistic relationship to a true partnership, more harmonious and more respectful of individual values ("value based medicine"). Advance directives give us an opportunity to improve our practices and to provide care consistent with the needs and wishes of each patient. PMID:10967645

  20. Plaque and arterial vulnerability investigation in a three-layer atherosclerotic human coronary artery using computational fluid-structure interaction method

    NASA Astrophysics Data System (ADS)

    Karimi, Alireza; Navidbakhsh, Mahdi; Razaghi, Reza

    2014-08-01

    Coronary artery disease is the common form of cardiovascular diseases and known to be the main reason of deaths in the world. Fluid-Structure Interaction (FSI) simulations can be employed to assess the interactions of artery/plaque and blood to provide a more precise anticipation for rupture of arterial tissue layers and plaque tissues inside an atherosclerotic artery. To date, the arterial tissue in computational FSI simulations has been considered as a one-layer structure. However, a single layer assumption might have deeply bounded the results and, consequently, more computational simulation is needed by considering the arterial tissue as a three-layer structure. In this study, a three-dimensional computational FSI model of an atherosclerotic artery with a three-layer structure and different plaque types was established to perform a more accurate arterial wall/plaque tissue vulnerability assessment. The hyperelastic material coefficients of arterial layers were calculated and implemented in the computational model. The fully coupled fluid and structure models were solved using the explicit dynamics finite element code LS-DYNA. The results revealed the significant role of plaque types in the normal and shear stresses induced within the arterial tissue layers. The highest von Mises and shear stresses were observed on the stiffest calcified plaque with 3.59 and 3.27 MPa, while the lowest von Mises and shear stresses were seen on the hypocellular plaque with 1.15 and 0.63 MPa, respectively. Regardless of plaque types, the media and adventitia layers were played protective roles by displaying less stress on their wall, whilst the intima layer was at a high risk of rupture. The findings of this study have implications not only for determining the most vulnerable arterial layer/plaque tissue inside an atherosclerotic coronary artery but also for balloon-angioplasty, stenting, and bypass surgeries.

  1. Atherosclerotic Renal Artery Stenosis and Hypertension: Pragmatism, Pitfalls, and Perspectives.

    PubMed

    Bavishi, Chirag; de Leeuw, Peter W; Messerli, Franz H

    2016-06-01

    For many years and even decades, a diagnostic work-up to look for a secondary form of hypertension, particularly of renovascular origin, has been a central tenet in medicine. Atherosclerotic renal artery stenosis is considered the most common cause of renovascular hypertension. However, advances in understanding the complex pathophysiology of this condition and the recently documented futility of renal revascularization bring into question whether atherosclerotic renal artery stenosis truly causes "renovascular hypertension." From a clinical point of view, a clear distinction should be made between hypertension associated with atherosclerotic renal artery stenosis and hypertension caused by renal artery stenosis-induced activation of the renin-angiotensin-aldosterone system. Most patients with atherosclerotic renal artery stenosis do not have a form of hypertension that is remediable or improved by angioplasty; to expose them to the cost, inconvenience, and risk of a diagnostic work-up add up to little more than a wild goose chase. However, with very few exceptions, medical therapy with antihypertensives and statins remains the cornerstone for the management of patients with atherosclerotic renal artery stenosis and hypertension. PMID:26522797

  2. Hyperspectral imaging of atherosclerotic plaques in vitro

    NASA Astrophysics Data System (ADS)

    Larsen, Eivind L. P.; Randeberg, Lise L.; Olstad, Elisabeth; Haugen, Olav A.; Aksnes, Astrid; Svaasand, Lars O.

    2011-02-01

    Vulnerable plaques constitute a risk for serious heart problems, and are difficult to identify using existing methods. Hyperspectral imaging combines spectral- and spatial information, providing new possibilities for precise optical characterization of atherosclerotic lesions. Hyperspectral data were collected from excised aorta samples (n = 11) using both white-light and ultraviolet illumination. Single lesions (n = 42) were chosen for further investigation, and classified according to histological findings. The corresponding hyperspectral images were characterized using statistical image analysis tools (minimum noise fraction, K-means clustering, principal component analysis) and evaluation of reflectance/fluorescence spectra. Image analysis combined with histology revealed the complexity and heterogeneity of aortic plaques. Plaque features such as lipids and calcifications could be identified from the hyperspectral images. Most of the advanced lesions had a central region surrounded by an outer rim or shoulder-region of the plaque, which is considered a weak spot in vulnerable lesions. These features could be identified in both the white-light and fluorescence data. Hyperspectral imaging was shown to be a promising tool for detection and characterization of advanced atherosclerotic plaques in vitro. Hyperspectral imaging provides more diagnostic information about the heterogeneity of the lesions than conventional single point spectroscopic measurements.

  3. Laboratory Diagnosis of Human Rabies: Recent Advances

    PubMed Central

    Mani, Reeta Subramaniam; Madhusudana, Shampur Narayan

    2013-01-01

    Rabies, an acute progressive, fatal encephalomyelitis, transmitted most commonly through the bite of a rabid animal, is responsible for an estimated 61,000 human deaths worldwide. The true disease burden and public health impact due to rabies remain underestimated due to lack of sensitive laboratory diagnostic methods. Rapid diagnosis of rabies can help initiate prompt infection control and public health measures, obviate the need for unnecessary treatment/medical tests, and assist in timely administration of pre- or postexposure prophylactic vaccination to family members and medical staff. Antemortem diagnosis of human rabies provides an impetus for clinicians to attempt experimental therapeutic approaches in some patients, especially after the reported survival of a few cases of human rabies. Traditional methods for antemortem and postmortem rabies diagnosis have several limitations. Recent advances in technology have led to the improvement or development of several diagnostic assays which include methods for rabies viral antigen and antibody detection and assays for viral nucleic acid detection and identification of specific biomarkers. These assays which complement traditional methods have the potential to revolutionize rabies diagnosis in future. PMID:24348170

  4. Recent advances in human viruses imaging studies.

    PubMed

    Florian, Paula Ecaterina; Rouillé, Yves; Ruta, Simona; Nichita, Norica; Roseanu, Anca

    2016-06-01

    Microscopy techniques are often exploited by virologists to investigate molecular details of critical steps in viruses' life cycles such as host cell recognition and entry, genome replication, intracellular trafficking, and release of mature virions. Fluorescence microscopy is the most attractive tool employed to detect intracellular localizations of various stages of the viral infection and monitor the pathogen-host interactions associated with them. Super-resolution microscopy techniques have overcome the technical limitations of conventional microscopy and offered new exciting insights into the formation and trafficking of human viruses. In addition, the development of state-of-the art electron microscopy techniques has become particularly important in studying virus morphogenesis by revealing ground-braking ultrastructural details of this process. This review provides recent advances in human viruses imaging in both, in vitro cell culture systems and in vivo, in the animal models recently developed. The newly available imaging technologies bring a major contribution to our understanding of virus pathogenesis and will become an important tool in early diagnosis of viral infection and the development of novel therapeutics to combat the disease. PMID:27059598

  5. Subject-Specific Fully-Coupled and One-Way Fluid-Structure Interaction Models for Modeling of Carotid Atherosclerotic Plaques in Humans

    PubMed Central

    Tao, Xiaojuan; Gao, Peiyi; Jing, Lina; Lin, Yan; Sui, Binbin

    2015-01-01

    Background Hemodynamics play an important role in the development and progression of carotid atherosclerosis, and may be important in the assessment of plaque vulnerability. The aim of this study was to develop a system to assess the hemodynamics of carotid atherosclerotic plaques using subject-specific fluid-structure interaction (FSI) models based on magnetic resonance imaging (MRI). Material/Methods Models of carotid bifurcations (n=86 with plaques from 52 patients, n=14 normal carotids from 12 participants) were obtained at the Department of Radiology, Beijing Tian Tan Hospital between 2010 and 2013. The maximum von Mises stress, minimum pressure, and flow velocity values were assessed at the most stenotic site in patients, or at the carotid bifurcations in healthy volunteers. Results of one-way FSI were compared with fully-coupled FSI for the plaques of 19 randomly selected models. Results The maximum von Mises stress and the minimum pressure and velocity were significantly increased in the stenosis group compared with controls based on one-way FSI (all P<0.05). The maximum von Mises stress and the minimum pressure were significantly higher and the velocity was significantly lower based on fully coupled FSI compared with on-way FSI (all P<0.05). Although there were differences in numerical values, both methods were equivalent. The maximum von Mises stress of vulnerable plaques was significantly higher than stable plaques (P<0.001). The maximum von Mises stress of the group with fibrous cap defect was significantly higher than the group without fibrous cap defect (P=0.001). Conclusions The hemodynamics of atherosclerotic plaques can be assessed noninvasively using subject-specific models of FSI based on MRI. PMID:26510514

  6. Cyclooxygenase-2 is widely expressed in atherosclerotic lesions affecting native and transplanted human coronary arteries and colocalizes with inducible nitric oxide synthase and nitrotyrosine particularly in macrophages.

    PubMed

    Baker, C S; Hall, R J; Evans, T J; Pomerance, A; Maclouf, J; Creminon, C; Yacoub, M H; Polak, J M

    1999-03-01

    Inflammation appears to have a major role in the development of atherosclerotic lesions affecting native and transplanted coronary arteries. The subsequent risk of plaque rupture and acute ischemic events correlates with the degree of inflammation and may be modified by aspirin, an anti-inflammatory cyclooxygenase inhibitor. Cyclooxygenase-2 (Cox-2) and inducible nitric oxide synthase (iNOS) are involved in the inflammatory response via the rapid and exaggerated production of prostanoids and nitric oxide, both of which may have proatherosclerotic effects. These effects may be mediated by the formation of peroxynitrite in the case of nitric oxide and involve "cross talk" between the two enzyme systems. This study aimed to investigate native and transplant atherosclerosis for the presence and distribution of Cox-2 and iNOS. Immunocytochemical studies were performed on atherosclerotic lesions from patients with native (n=12) and transplant (n=5) coronary disease by using antibodies to Cox-2, iNOS, and nitrotyrosine (an indicator of peroxynitrite production). Control tissue was obtained from unused donor hearts and at the time of autopsy. Cox-2 and iNOS colocalized predominantly in macrophages/foam cells in both types of atherosclerosis. Cox-2 expression was also detected in medial smooth muscle cells and endothelial cells, including those of the vasa vasorum. Nitrotyrosine was found in the same distribution as that of iNOS and was colocalized with Cox-2 in macrophages. Cox-2 and iNOS are coexpressed in native and transplant atherosclerosis, possibly allowing for interaction between the enzymes and suggesting an alternative mechanism for the benefits of aspirin via inhibition of Cox-2 activity. PMID:10073969

  7. Atherosclerotic Renovascular Disease.

    PubMed

    Spitalewitz, Samuel; Reiser, Ira W.

    1996-04-01

    hydronephrosis. Both kidneys were noted to be echogenic. Assays for antinuclear antibodies and antineutrophilic cytoplasmic antibodies were negative, and the patient's serum complement levels were normal. For several days after his admission, his serum creatinine gradually rose to 10.7 mg/dl, and hemodialysis was initiated for uremic encephalopathy. Because of the high index of suspicion for renal artery stenosis as the case of both his hypertension and renal failure, a renal angiogram was performed. It revealed a 90% occlusion of the right renal artery with ostial involvement and a 70% occlusion of the left renal artery; both kidneys had poor distal renal vasculature and there was marked atherosclerotic disease of the aorta. After being hemodialyzed for 3 treatments, his renal function began to improve spontaneously. His serum creatinine returned to 3.4 mg/dl, and a subsequent 24-hour urine demonstrated a creatinine clearance of 20 ml/min and an excretion of 1.2 g of protein. Following his discharge from the hospital, his renal function remained unchanged for 3 years, and his blood pressure was easily controlled on monotherapy with a long-acting calcium channel blocker. He recently died from pneumonia. PMID:11862267

  8. Plaque Rupture and Thrombosis: the Value of the Atherosclerotic Rabbit Model in Defining the Mechanism.

    PubMed

    Abela, Oliver G; Ahsan, Chowdhury H; Alreefi, Fadi; Salehi, Negar; Baig, Imran; Janoudi, Abed; Abela, George S

    2016-06-01

    Persistent inflammation and mechanical injury associated with cholesterol crystal accretion within atherosclerotic plaques typically precedes plaque disruption (rupture and/or erosion) and thrombosis-often the terminal events of atherosclerotic cardiovascular disease. To elucidate the mechanisms of these events, the atherosclerotic rabbit model provides a unique and powerful tool that facilitates studies of atherogenesis starting with plaque buildup to eventual disruption. Examination of human coronary arteries obtained from patients who died with myocardial infarction demonstrates evidence of cholesterol crystals perforating the plaque cap and intimal surface of the arterial wall that can lead to rupture. These observations were made possible by omitting ethanol, an avid lipid solvent, from the tissue processing steps. Importantly, the atherosclerotic rabbit model exhibits a similar pathology of cholesterol crystals perforating the intimal surface as seen in ruptured human plaques. Local and systemic inflammatory responses in the model are also similar to those observed in humans. The strong parallel between the rabbit and human pathology validates the atherosclerotic rabbit model as a predictor of human pathophysiology of atherosclerosis. Thus, the atherosclerotic rabbit model can be used with confidence to evaluate diagnostic imaging and efficacy of novel anti-atherosclerotic therapy. PMID:27091328

  9. Detection of High-Risk Atherosclerotic Plaque

    PubMed Central

    Fleg, Jerome L.; Stone, Gregg W.; Fayad, Zahi A.; Granada, Juan F.; Hatsukami, Thomas S.; Kolodgie, Frank D.; Ohayon, Jacques; Pettigrew, Roderic; Sabatine, Marc S.; Tearney, Guillermo; Waxman, Sergio; Domanski, Michael J.; Srinivas, Pothur R.; Narula, Jagat

    2013-01-01

    The leading cause of major morbidity and mortality in most countries around the world is atherosclerotic cardiovascular disease, most commonly caused by thrombotic occlusion of a high-risk coronary plaque resulting in myocardial infarction or cardiac death, or embolization from a high-risk carotid plaque resulting in stroke. The lesions prone to result in such clinical events are termed vulnerable or high-risk plaques, and their identification may lead to the development of pharmacological and mechanical intervention strategies to prevent such events. Autopsy studies from patients dying of acute myocardial infarction or sudden death have shown that such events typically arise from specific types of atherosclerotic plaques, most commonly the thin-cap fibroatheroma. However, the search in human beings for vulnerable plaques before their becoming symptomatic has been elusive. Recently, the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study demonstrated that coronary plaques that are likely to cause future cardiac events, regardless of angiographic severity, are characterized by large plaque burden and small lumen area and/or are thin-cap fibroatheromas verified by radiofrequency intravascular ultrasound imaging. This study opened the door to identifying additional invasive and noninvasive imaging modalities that may improve detection of high-risk atherosclerotic lesions and patients. Beyond classic risk factors, novel biomarkers and genetic profiling may identify those patients in whom noninvasive imaging for vulnerable plaque screening, followed by invasive imaging for risk confirmation is warranted, and in whom future pharmacological and/or device-based focal or regional therapies may be applied to improve long-term prognosis. PMID:22974808

  10. Advancing swine models for human health and diseases.

    PubMed

    Walters, Eric M; Prather, Randall S

    2013-01-01

    Swine models are relatively new kids on the block for modeling human health and diseases when compared to rodents and dogs. Because of the similarity to humans in size, physiology, and genetics, the pig has made significant strides in advancing the understanding of the human condition, and is thus an excellent choice for an animal model. Recent technological advances to genetic engineering of the swine genome enhance the utility of swine as models of human genetic diseases. PMID:23829105

  11. Mediterranean diet polyphenols reduce inflammatory angiogenesis through MMP-9 and COX-2 inhibition in human vascular endothelial cells: a potentially protective mechanism in atherosclerotic vascular disease and cancer.

    PubMed

    Scoditti, Egeria; Calabriso, Nadia; Massaro, Marika; Pellegrino, Mariangela; Storelli, Carlo; Martines, Giuseppe; De Caterina, Raffaele; Carluccio, Maria Annunziata

    2012-11-15

    Diets with high content of antioxidant polyphenols are associated with low prevalence of cardiovascular diseases and cancer. Inflammatory angiogenesis is a key pathogenic process both in cancer and atherosclerosis, and is tightly regulated by the proinflammatory enzyme cyclooxygenase (COX)-2 and the matrix degrading enzymes matrix metalloproteinases (MMPs). We studied the effects of antioxidant polyphenols from virgin olive oil (oleuropein and hydroxytyrosol) and red wine (resveratrol and quercetin) on endothelial cell angiogenic response in vitro, and explored underlying mechanisms. Cultured endothelial cells were pre-incubated with 0.1-50 μmol/L polyphenols before stimulation with phorbol myristate acetate (PMA). All tested polyphenols reduced endothelial cell tube formation on matrigel and migration in wound healing assays. The reduced angiogenesis was associated with the inhibition of PMA-induced COX-2 protein expression and prostanoid production, as well as MMP-9 protein release and gelatinolytic activity. These effects were accompanied by a significant reduction in the stimulated intracellular reactive oxygen species levels and in the activation of the redox-sensitive transcription factor nuclear factor (NF)-κB. Our findings reveal that olive oil and red wine polyphenols reduce inflammatory angiogenesis in cultured endothelial cells, through MMP-9 and COX-2 inhibition, supporting a potential protective role for dietary polyphenols in atherosclerotic vascular disease and cancer. PMID:22595400

  12. Morpheus: Advancing Technologies for Human Exploration

    NASA Technical Reports Server (NTRS)

    Olansen, Jon B.; Munday, Stephen R.; Mitchell, Jennifer D.; Baine, Michael

    2012-01-01

    NASA's Morpheus Project has developed and tested a prototype planetary lander capable of vertical takeoff and landing. Designed to serve as a vertical testbed (VTB) for advanced spacecraft technologies, the vehicle provides a platform for bringing technologies from the laboratory into an integrated flight system at relatively low cost. This allows individual technologies to mature into capabilities that can be incorporated into human exploration missions. The Morpheus vehicle is propelled by a LOX/Methane engine and sized to carry a payload of 1100 lb to the lunar surface. In addition to VTB vehicles, the Project s major elements include ground support systems and an operations facility. Initial testing will demonstrate technologies used to perform autonomous hazard avoidance and precision landing on a lunar or other planetary surface. The Morpheus vehicle successfully performed a set of integrated vehicle test flights including hot-fire and tethered hover tests, leading up to un-tethered free-flights. The initial phase of this development and testing campaign is being conducted on-site at the Johnson Space Center (JSC), with the first fully integrated vehicle firing its engine less than one year after project initiation. Designed, developed, manufactured and operated in-house by engineers at JSC, the Morpheus Project represents an unprecedented departure from recent NASA programs that traditionally require longer, more expensive development lifecycles and testing at remote, dedicated testing facilities. Morpheus testing includes three major types of integrated tests. A hot-fire (HF) is a static vehicle test of the LOX/Methane propulsion system. Tether tests (TT) have the vehicle suspended above the ground using a crane, which allows testing of the propulsion and integrated Guidance, Navigation, and Control (GN&C) in hovering flight without the risk of a vehicle departure or crash. Morpheus free-flights (FF) test the complete Morpheus system without the additional

  13. Advancing Humanities Studies at Community, Technical, and Junior Colleges.

    ERIC Educational Resources Information Center

    Eisenberg, Diane U.; And Others

    The American Association of Community and Junior Colleges' (AACJC's) two-year Advancing the Humanities Project (AHP) has assisted selected community colleges in promoting the humanities on their campuses. Parts I and II of this report on the AHP present statements by Dale Parnell and Judith Jeffrey Howard about the AACJC's humanities initiatives…

  14. Human factors survey of advanced instrumentation and controls

    SciTech Connect

    Carter, R.J.

    1989-01-01

    A survey oriented towards identifying the human factors issues in regard to the use of advanced instrumentation and controls (I C) in the nuclear industry was conducted. A number of United States (US) and Canadian nuclear vendors and utilities were participants in the survey. Human factors items, subsumed under the categories of computer-generated displays (CGD), controls, organizational support, training, and related topics, were discussed. The survey found the industry to be concerned about the human factors issues related to the implementation of advanced I C. Fifteen potential human factors problems were identified. They include: the need for an advanced I C guideline equivalent to NUREG-0700; a role change in the control room from operator to supervisor; information overload; adequacy of existing training technology for advanced I C; and operator acceptance and trust. 11 refs., 1 tab.

  15. Advancing Usability Evaluation through Human Reliability Analysis

    SciTech Connect

    Ronald L. Boring; David I. Gertman

    2005-07-01

    This paper introduces a novel augmentation to the current heuristic usability evaluation methodology. The SPAR-H human reliability analysis method was developed for categorizing human performance in nuclear power plants. Despite the specialized use of SPAR-H for safety critical scenarios, the method also holds promise for use in commercial off-the-shelf software usability evaluations. The SPAR-H method shares task analysis underpinnings with human-computer interaction, and it can be easily adapted to incorporate usability heuristics as performance shaping factors. By assigning probabilistic modifiers to heuristics, it is possible to arrive at the usability error probability (UEP). This UEP is not a literal probability of error but nonetheless provides a quantitative basis to heuristic evaluation. When combined with a consequence matrix for usability errors, this method affords ready prioritization of usability issues.

  16. Leukoaraiosis Is a Chronic Atherosclerotic Disease

    PubMed Central

    Ben-Assayag, Einor; Mijajlovic, Milija; Shenhar-Tsarfaty, Shani; Bova, Irena; Shopin, Ludmila; Bornstein, Natan M.

    2012-01-01

    Background and Purpose. White matter changes (WMCs), or leukoaraiosis (LA), are associated with increased age, hypertension, diabetes mellitus, and history of stroke. Although several lines of evidence suggest a role of atherosclerosis in atherothrombotic vascular events, their involvement in LA remains to be determined. Our study examines this association in ischemic stroke patients. Methods. One hundred and seventy consecutive ischemic stroke or transient ischemic attack (TIA) patients were included. All patients underwent brain computed tomography (CT) with assessment of the extension and severity of WMCs, carotid arteries duplex scan with measurements of intima-media thickness (IMT) and plaques. Results. Seventy-two patients (42.4%) were found to have white matter lesions, of whom 28.8% had advanced LA. Mean IMT was significantly higher in patients with LA and with advanced LA (P = 0.002, P = 0.003, resp.). In addition, LA and LA severity were associated with existence of carotid plaque (P = 0.007, P = 0.004, resp.). In multivariate logistic regression analysis, including all vascular risk factors, LA was found to be associated with age and IMT. Conclusion. This study reinforces the tight association between LA and carotid atherosclerosis in ischemic stroke patients. We conclude that a chronic atherosclerotic disease underlies the pathophysiology of leukoaraiosis and its progression. PMID:22675271

  17. Human factors aspects of advanced instrumentation in the nuclear industry

    SciTech Connect

    Carter, R.J.

    1989-01-01

    An important consideration in regards to the use of advanced instrumentation in the nuclear industry is the interface between the instrumentation system and the human. A survey, oriented towards identifying the human factors aspects of digital instrumentation, was conducted at a number of United States (US) and Canadian nuclear vendors and utilities. Human factors issues, subsumed under the categories of computer-generated displays, controls, organizational support, training, and related topics were identified. 20 refs., 2 tabs.

  18. IL-17A influences essential functions of the monocyte/macrophage lineage and is involved in advanced murine and human atherosclerosis.

    PubMed

    Erbel, Christian; Akhavanpoor, Mohammadreza; Okuyucu, Deniz; Wangler, Susanne; Dietz, Alex; Zhao, Li; Stellos, Konstantinos; Little, Kristina M; Lasitschka, Felix; Doesch, Andreas; Hakimi, Maani; Dengler, Thomas J; Giese, Thomas; Blessing, Erwin; Katus, Hugo A; Gleissner, Christian A

    2014-11-01

    Atherosclerosis is a chronic inflammatory disease. Lesion progression is primarily mediated by cells of the monocyte/macrophage lineage. IL-17A is a proinflammatory cytokine, which modulates immune cell trafficking and is involved inflammation in (auto)immune and infectious diseases. But the role of IL-17A still remains controversial. In the current study, we investigated effects of IL-17A on advanced murine and human atherosclerosis, the common disease phenotype in clinical care. The 26-wk-old apolipoprotein E-deficient mice were fed a standard chow diet and treated either with IL-17A mAb (n = 15) or irrelevant Ig (n = 10) for 16 wk. Furthermore, essential mechanisms of IL-17A in atherogenesis were studied in vitro. Inhibition of IL-17A markedly prevented atherosclerotic lesion progression (p = 0.001) by reducing inflammatory burden and cellular infiltration (p = 0.01) and improved lesion stability (p = 0.01). In vitro experiments showed that IL-17A plays a role in chemoattractance, monocyte adhesion, and sensitization of APCs toward pathogen-derived TLR4 ligands. Also, IL-17A induced a unique transcriptome pattern in monocyte-derived macrophages distinct from known macrophage types. Stimulation of human carotid plaque tissue ex vivo with IL-17A induced a proinflammatory milieu and upregulation of molecules expressed by the IL-17A-induced macrophage subtype. In this study, we show that functional blockade of IL-17A prevents atherosclerotic lesion progression and induces plaque stabilization in advanced lesions in apolipoprotein E-deficient mice. The underlying mechanisms involve reduced inflammation and distinct effects of IL-17A on monocyte/macrophage lineage. In addition, translational experiments underline the relevance for the human system. PMID:25261478

  19. IL-17A Influences Essential Functions of the Monocyte/Macrophage Lineage and Is Involved in Advanced Murine and Human Atherosclerosis

    PubMed Central

    Akhavanpoor, Mohammadreza; Okuyucu, Deniz; Wangler, Susanne; Dietz, Alex; Zhao, Li; Stellos, Konstantinos; Little, Kristina M.; Lasitschka, Felix; Doesch, Andreas; Hakimi, Maani; Dengler, Thomas J.; Giese, Thomas; Blessing, Erwin; Katus, Hugo A.; Gleissner, Christian A.

    2014-01-01

    Atherosclerosis is a chronic inflammatory disease. Lesion progression is primarily mediated by cells of the monocyte/macrophage lineage. IL-17A is a proinflammatory cytokine, which modulates immune cell trafficking and is involved inflammation in (auto)immune and infectious diseases. But the role of IL-17A still remains controversial. In the current study, we investigated effects of IL-17A on advanced murine and human atherosclerosis, the common disease phenotype in clinical care. The 26-wk-old apolipoprotein E–deficient mice were fed a standard chow diet and treated either with IL-17A mAb (n = 15) or irrelevant Ig (n = 10) for 16 wk. Furthermore, essential mechanisms of IL-17A in atherogenesis were studied in vitro. Inhibition of IL-17A markedly prevented atherosclerotic lesion progression (p = 0.001) by reducing inflammatory burden and cellular infiltration (p = 0.01) and improved lesion stability (p = 0.01). In vitro experiments showed that IL-17A plays a role in chemoattractance, monocyte adhesion, and sensitization of APCs toward pathogen-derived TLR4 ligands. Also, IL-17A induced a unique transcriptome pattern in monocyte-derived macrophages distinct from known macrophage types. Stimulation of human carotid plaque tissue ex vivo with IL-17A induced a proinflammatory milieu and upregulation of molecules expressed by the IL-17A–induced macrophage subtype. In this study, we show that functional blockade of IL-17A prevents atherosclerotic lesion progression and induces plaque stabilization in advanced lesions in apolipoprotein E–deficient mice. The underlying mechanisms involve reduced inflammation and distinct effects of IL-17A on monocyte/macrophage lineage. In addition, translational experiments underline the relevance for the human system. PMID:25261478

  20. Advanced Solid State Lighting for Human Evaluation Project

    NASA Technical Reports Server (NTRS)

    Zeitlin, Nancy; Holbert, Eirik

    2015-01-01

    Lighting intensity and color have a significant impact on human circadian rhythms. Advanced solid state lighting was developed for the Advanced Exploration System (AES) Deep Space Habitat(DSH) concept demonstrator. The latest generation of assemblies using the latest commercially available LED lights were designed for use in the Bigelow Aerospace Environmental Control and Life Support System (ECLSS) simulator and the University of Hawaii's Hawaii Space Exploration Analog and Simulation (Hi-SEAS) habitat. Agreements with both these organizations will allow the government to receive feedback on the lights and lighting algorithms from long term human interaction.

  1. Primary Stenting of Intracranial Atherosclerotic Stenoses

    SciTech Connect

    Straube, T. Stingele, Robert; Jansen, Olav

    2005-04-15

    Purpose: To determine the feasibility and safety of stenting intracranial atherosclerotic stenoses.Methods: In 12 patients the results of primary intracranial stenting were evaluated retrospectively. Patient ages ranged from 49 to 79 years (mean 64 years). Six patients presented with stenoses in the anterior circulation, and six had stenosis in the posterior circulation. One patient presented with extra- and intracranial tandem stenosis of the left internal carotid artery. Three patients presented with acute basilar thrombosis, caused by high-grade basilar stenoses.Results: Intracranial stenoses were successfully stented in 11 of 12 patients. In one patient the stent could not be advanced over the carotid siphon to reach the stenosis of the ophthalmic internal carotid artery. Follow-up digital subtraction angiographic studies were obtained in two patients who had presented with new neurologic signs or symptoms. In both cases the angiogram did not show any relevant stenotic endothelial hyperplasia. In one patient, after local thrombolysis the stenosis turned out to be so narrow that balloon angioplasty had to be performed before stent deployment. All three patients treated for stenosis-related basilar thrombosis died due to brainstem infarction that had ensued before the intervention.Conclusions: Prophylactic primary stenting of intracranial stenoses of the anterior or posterior cerebral circulation can be performed with a low complication rate; technical problems such as stent flexibility must still be solved. Local thrombolysis followed by stenting in stenosis-related thrombotic occlusion is technically possible.

  2. Coexpression of type I and type II human macrophage scavenger receptors in macrophages of various organs and foam cells in atherosclerotic lesions.

    PubMed Central

    Naito, M.; Suzuki, H.; Mori, T.; Matsumoto, A.; Kodama, T.; Takahashi, K.

    1992-01-01

    Macrophage scavenger receptors are trimeric membrane glycoproteins implicated in the pathologic deposition of cholesterol in arterial walls during atherogenesis. Two types of cDNAs for functional human receptors have been cloned, but their physiologic roles remain obscure. To study the expression of these receptors, the authors generated antibodies against scavenger receptor type-specific synthetic peptide. Immunohistochemical examination using these antibodies and other anti-human receptor antibodies shows that type I and type II receptor proteins can be detected in foam cells in various stages of atherosclerosis, most evidently in fatty streaks. Co-expression of the two types of receptor protein was also detected in macrophages of various organs. Both types of the protein were detected on the surface and the membrane of endosomes in macrophages. These results indicate that both type I and type II scavenger receptors are expressed and functionally active in physiologic and pathologic conditions. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:1519666

  3. Mucosal Administration of Collagen V Ameliorates the Atherosclerotic Plaque Burden by Inducing Interleukin 35-dependent Tolerance.

    PubMed

    Park, Arick C; Huang, Guorui; Jankowska-Gan, Ewa; Massoudi, Dawiyat; Kernien, John F; Vignali, Dario A; Sullivan, Jeremy A; Wilkes, David S; Burlingham, William J; Greenspan, Daniel S

    2016-02-12

    We have shown previously that collagen V (col(V)) autoimmunity is a consistent feature of atherosclerosis in human coronary artery disease and in the Apoe(-/-) mouse model. We have also shown sensitization of Apoe(-/-) mice with col(V) to markedly increase the atherosclerotic burden, providing evidence of a causative role for col(V) autoimmunity in atherosclerotic pathogenesis. Here we sought to determine whether induction of immune tolerance to col(V) might ameliorate atherosclerosis, providing further evidence for a causal role for col(V) autoimmunity in atherogenesis and providing insights into the potential for immunomodulatory therapeutic interventions. Mucosal inoculation successfully induced immune tolerance to col(V) with an accompanying reduction in plaque burden in Ldlr(-/-) mice on a high-cholesterol diet. The results therefore demonstrate that inoculation with col(V) can successfully ameliorate the atherosclerotic burden, suggesting novel approaches for therapeutic interventions. Surprisingly, tolerance and reduced atherosclerotic burden were both dependent on the recently described IL-35 and not on IL-10, the immunosuppressive cytokine usually studied in the context of induced tolerance and amelioration of atherosclerotic symptoms. In addition to the above, using recombinant protein fragments, we were able to localize two epitopes of the α1(V) chain involved in col(V) autoimmunity in atherosclerotic Ldlr(-/-) mice, suggesting future courses of experimentation for the characterization of such epitopes. PMID:26721885

  4. Human life support for advanced space exploration.

    PubMed

    Schwartzkopf, S H

    1997-01-01

    The requirements for a human life support system for long-duration space missions are reviewed. The system design of a controlled ecological life support system is briefly described, followed by a more detailed account of the study of the conceptual design of a Lunar Based CELSS. The latter is to provide a safe, reliable, recycling lunar base life support system based on a hybrid physicochemical/biological representative technology. The most important conclusion reached by this study is that implementation of a completely recycling CELSS approach for a lunar base is not only feasible, but eminently practical. On a cumulative launch mass basis, a 4-person Lunar Base CELSS would pay for itself in approximately 2.6 years relative to a physicochemical air/water recycling system with resupply of food from the Earth. For crew sizes of 30 and 100, the breakeven point would come even sooner, after 2.1 and 1.7 years, respectively, due to the increased mass savings that can be realized with the larger plant growth units. Two other conclusions are particularly important with regard to the orientation of future research and technology development. First, the mass estimates of the Lunar Base CELSS indicate that a primary design objective in implementing this kind of system must be to minimized the mass and power requirement of the food production plant growth units, which greatly surpass those of the other air and water recycling systems. Consequently, substantial research must be directed at identifying ways to produce food more efficiently. On the other hand, detailed studies to identify the best technology options for the other subsystems should not be expected to produce dramatic reductions in either mass or power requirement of a Lunar Base CELSS. The most crucial evaluation criterion must, therefore, be the capability for functional integration of these technologies into the ultimate design of the system. Secondly, this study illustrates that existing or near

  5. Human life support for advanced space exploration

    NASA Technical Reports Server (NTRS)

    Schwartzkopf, S. H.

    1997-01-01

    The requirements for a human life support system for long-duration space missions are reviewed. The system design of a controlled ecological life support system is briefly described, followed by a more detailed account of the study of the conceptual design of a Lunar Based CELSS. The latter is to provide a safe, reliable, recycling lunar base life support system based on a hybrid physicochemical/biological representative technology. The most important conclusion reached by this study is that implementation of a completely recycling CELSS approach for a lunar base is not only feasible, but eminently practical. On a cumulative launch mass basis, a 4-person Lunar Base CELSS would pay for itself in approximately 2.6 years relative to a physicochemical air/water recycling system with resupply of food from the Earth. For crew sizes of 30 and 100, the breakeven point would come even sooner, after 2.1 and 1.7 years, respectively, due to the increased mass savings that can be realized with the larger plant growth units. Two other conclusions are particularly important with regard to the orientation of future research and technology development. First, the mass estimates of the Lunar Base CELSS indicate that a primary design objective in implementing this kind of system must be to minimized the mass and power requirement of the food production plant growth units, which greatly surpass those of the other air and water recycling systems. Consequently, substantial research must be directed at identifying ways to produce food more efficiently. On the other hand, detailed studies to identify the best technology options for the other subsystems should not be expected to produce dramatic reductions in either mass or power requirement of a Lunar Base CELSS. The most crucial evaluation criterion must, therefore, be the capability for functional integration of these technologies into the ultimate design of the system. Secondly, this study illustrates that existing or near

  6. Industrialization and Economic Development in Advanced Placement Human Geography.

    ERIC Educational Resources Information Center

    Bailey, Adrian J.

    2000-01-01

    Focuses on the industrialization and economic development section of the Advanced Placement (AP) human geography course, addressing four specific aspects: (1) the character of industrialization; (2) spatial aspects of the rise of industrial economies; (3) contemporary global patterns of industrialization and resource extraction; and (4) impacts of…

  7. Cities and Urban Land Use in Advanced Placement Human Geography.

    ERIC Educational Resources Information Center

    Ford, Larry R.

    2000-01-01

    Discusses the cities and urban land use section of the Advanced Placement (AP) human geography course, focusing on the: (1) definitions of urbanism; (2) origin and evolution of cities; (3) functional character of contemporary cities; (4) built environment and social space; and (5) responses to urban growth. (CMK)

  8. Advanced Placement Human Geography: The First Five Years

    ERIC Educational Resources Information Center

    Gray, Paul T., Jr.; Hidlebrant, Barbara S.; Strauss, Tim R.

    2006-01-01

    Advanced Placement Human Geography (APHG) has grown steadily from 3,272 tests at the first test administration in 2001 to 14,139 tests in 2005. This paper examines the dynamics of growth throughout the United States through numbers of students and numbers of high schools involved in the program. APHG is discussed relative to the establishment of…

  9. Imagining STEM Higher Education Futures: Advancing Human Well-Being

    ERIC Educational Resources Information Center

    Walker, Melanie

    2015-01-01

    The paper explores a conceptual approach to the question of what it means to provide a university education that addresses equity, and encourages the formation of STEM graduates oriented to public-good values and with commitments to making professional contributions to society which will advance human well-being. It considers and rejects…

  10. High speed intravascular photoacoustic imaging of atherosclerotic arteries (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Piao, Zhonglie; Ma, Teng; Qu, Yueqiao; Li, Jiawen; Yu, Mingyue; He, Youmin; Shung, K. Kirk; Zhou, Qifa; Kim, Chang-Seok; Chen, Zhongping

    2016-02-01

    Cardiovascular disease is the leading cause of death in the industrialized nations. Accurate quantification of both the morphology and composition of lipid-rich vulnerable atherosclerotic plaque are essential for early detection and optimal treatment in clinics. In previous works, intravascular photoacoustic (IVPA) imaging for detection of lipid-rich plaque within coronary artery walls has been demonstrated in ex vivo, but the imaging speed is still limited. In order to increase the imaging speed, a high repetition rate laser is needed. In this work, we present a high speed integrated IVPA/US imaging system with a 500 Hz optical parametric oscillator laser at 1725 nm. A miniature catheter with 1.0 mm outer diameter was designed with a 200 μm multimode fiber and an ultrasound transducer with 45 MHz center frequency. The fiber was polished at 38 degree and enclosed in a glass capillary for total internal reflection. An optical/electrical rotary junction and pull-back mechanism was applied for rotating and linearly scanning the catheter to obtain three-dimensional imaging. Atherosclerotic rabbit abdominal aorta was imaged as two frame/second at 1725 nm. Furthermore, by wide tuning range of the laser wavelength from 1680 nm to 1770 nm, spectroscopic photoacoustic analysis of lipid-mimicking phantom and an human atherosclerotic artery was performed ex vivo. The results demonstrated that the developed IVPA/US imaging system is capable for high speed intravascular imaging for plaque detection.

  11. LOX-1 in atherosclerotic disease.

    PubMed

    Sawamura, Tatsuya; Wakabayashi, Ichiro; Okamura, Tomonori

    2015-02-01

    Oxidized low-density lipoprotein (LDL) exhibits various biological activities and accumulates in atheromas. LOX-1 (lectin-like oxidized LDL receptor) is the receptor that mediates oxidized LDL activity in vascular endothelial cells. Activation of LOX-1 results in oxidized LDL-induced endothelial dysfunction and hyperlipidemia-induced vascular lipid deposition. We hypothesized that LOX-1 is a candidate risk factor beyond LDL cholesterol (LDLC) and developed a novel assay to quantify LOX-1 ligand containing apoB (LAB). In men from the United States, serum LAB showed a significant positive association with carotid intima-media thickness, independent of LDLC. LAB and the LOX index (obtained by multiplying LAB by sLOX-1) were significantly associated with the incidence of coronary artery disease and ischemic stroke after adjusting for confounding factors, including non-HDL cholesterol. sLOX-1 is thought to be a better biomarker for early diagnosis of acute coronary syndrome than traditional biomarkers, including troponin T. LAB was associated with various atherosclerotic risk factors such as smoking, obesity, diabetes, diastolic hypertension, hypertriglyceridemia, and metabolic syndrome. Measurement of the soluble form of LOX-1 (sLOX-1) and LAB seems to be useful for evaluating the state and risk of atherosclerosis and atherosclerosis-related diseases. Further prospective studies using large populations and randomized clinical trials on sLOX-1, LAB, and the LOX index are needed. PMID:25463747

  12. Advanced Video Analysis Needs for Human Performance Evaluation

    NASA Technical Reports Server (NTRS)

    Campbell, Paul D.

    1994-01-01

    Evaluators of human task performance in space missions make use of video as a primary source of data. Extraction of relevant human performance information from video is often a labor-intensive process requiring a large amount of time on the part of the evaluator. Based on the experiences of several human performance evaluators, needs were defined for advanced tools which could aid in the analysis of video data from space missions. Such tools should increase the efficiency with which useful information is retrieved from large quantities of raw video. They should also provide the evaluator with new analytical functions which are not present in currently used methods. Video analysis tools based on the needs defined by this study would also have uses in U.S. industry and education. Evaluation of human performance from video data can be a valuable technique in many industrial and institutional settings where humans are involved in operational systems and processes.

  13. Advanced automated glass cockpit certification: Being wary of human factors

    NASA Technical Reports Server (NTRS)

    Amalberti, Rene; Wilbaux, Florence

    1994-01-01

    This paper presents some facets of the French experience with human factors in the process of certification of advanced automated cockpits. Three types of difficulties are described: first, the difficulties concerning the hotly debated concept of human error and its non-linear relationship to risk of accident; a typology of errors to be taken into account in the certification process is put forward to respond to this issue. Next, the difficulties connected to the basically gradual and evolving nature of pilot expertise on a given type of aircraft, which contrasts with the immediate and definitive style of certifying systems. The last difficulties to be considered are those related to the goals of certification itself on these new aircraft and the status of findings from human factor analyses (in particular, what should be done with disappointing results, how much can the changes induced by human factors investigation economically affect aircraft design, how many errors do we need to accumulate before we revise the system, what should be remedied when human factor problems are discovered at the certification stage: the machine? pilot training? the rules? or everything?). The growth of advanced-automated glass cockpits has forced the international aeronautical community to pay more attention to human factors during the design phase, the certification phase and pilot training. The recent creation of a human factor desk at the DGAC-SFACT (Official French services) is a direct consequence of this. The paper is divided into three parts. Part one debates human error and its relationship with system design and accident risk. Part two describes difficulties connected to the basically gradual and evolving nature of pilot expertise on a given type of aircraft, which contrasts with the immediate and definitive style of certifying systems. Part three focuses on concrete outcomes of human factors for certification purposes.

  14. Atherosclerotic Vessel Changes in Sarcoidosis.

    PubMed

    Tuleta, I; Pingel, S; Biener, L; Pizarro, C; Hammerstingl, C; Öztürk, C; Schahab, N; Grohé, C; Nickenig, G; Schaefer, C; Skowasch, D

    2016-01-01

    Sarcoidosis is a systemic granulomatous disease. Atherosclerosis is a chronic inflammatory vessel disease. The aim of our present study was to investigate whether sarcoidosis could be associated with increased risk of atherosclerotic vessel changes. Angiological analysis and blood tests were performed in 71 sarcoidosis patients and 12 matched controls in this prospective cross-sectional study. Specifically, angiological measurements comprised ankle brachial index (ABI), central pulse wave velocity (cPWV), pulse wave index (PWI), and duplex sonography of central and peripheral arteries. Sarcoidosis activity markers (angiotensin converting enzyme, soluble interleukin-2 receptor) and cardiovascular risk parameters such as cholesterol, lipoprotein(a), C-reactive protein, interleukin 6, fibrinogen, d-dimer, and blood count were analyzed in blood. We found no relevant differences in ABI, cPWV, and plaque burden between the sarcoidosis and control groups (1.10 ± 0.02 vs. 1.10 ± 0.02, 6.7 ± 0.5 vs. 6.1 ± 1.2, 53.7 % vs. 54.5 %, respectively). However, PWI was significantly higher in sarcoidosis patients (146.2 ± 6.8) compared with controls (104.9 ± 8.8), irrespectively of the activity of sarcoidosis and immunosuppressive medication. Except for increased lipoprotein(a) and d-dimer in sarcoidosis, the remaining cardiovascular markers were similar in both groups. We conclude that sarcoidosis is associated with increased pulse wave index, which may indicate an early stage of atherosclerosis. PMID:26820732

  15. Multiscale investigation of USPIO nanoparticles in atherosclerotic plaques and their catabolism and storage in vivo.

    PubMed

    Maraloiu, Valentin-Adrian; Appaix, Florence; Broisat, Alexis; Le Guellec, Dominique; Teodorescu, Valentin Serban; Ghezzi, Catherine; van der Sanden, Boudewijn; Blanchin, Marie-Genevieve

    2016-01-01

    The storage and catabolism of Ultrasmall SuperParamagnetic Iron Oxide (USPIO) nanoparticles were analyzed through a multiscale approach combining Two Photon Laser Scanning Microscopy (TPLSM) and High-Resolution Transmission Electron Microscopy (HRTEM) at different times after intravenous injection in an atherosclerotic ApoE(-/-) mouse model. The atherosclerotic plaque features and the USPIO heterogeneous biodistribution were revealed down from organ's scale to subcellular level. The biotransformation of the nanoparticle iron oxide (maghemite) core into ferritin, the non-toxic form of iron storage, was demonstrated for the first time ex vivo in atherosclerotic plaques as well as in spleen, the iron storage organ. These results rely on an innovative spatial and structural investigation of USPIO's catabolism in cellular phagolysosomes. This study showed that these nanoparticles were stored as non-toxic iron compounds: maghemite oxide or ferritin, which is promising for MRI detection of atherosclerotic plaques in clinics using these USPIOs. From the Clinical Editor: Advance in nanotechnology has brought new contrast agents for clinical imaging. In this article, the authors investigated the use and biotransformation of Ultrasmall Super-paramagnetic Iron Oxide (USPIO) nanoparticles for analysis of atherosclerotic plagues in Two Photon Laser Scanning Microscopy (TPLSM) and High-Resolution Transmission Electron Microscopy (HRTEM). The biophysical data generated from this study could enable the possible use of these nanoparticles for the benefits of clinical patients. PMID:26370708

  16. Advanced haptic sensor for measuring human skin conditions

    NASA Astrophysics Data System (ADS)

    Tsuchimi, Daisuke; Okuyama, Takeshi; Tanaka, Mami

    2009-12-01

    This paper is concerned with the development of a tactile sensor using PVDF (Polyvinylidene Fluoride) film as a sensory receptor of the sensor to evaluate softness, smoothness, and stickiness of human skin. Tactile sense is the most important sense in the sensation receptor of the human body along with eyesight, and we can examine skin condition quickly using these sense. But, its subjectivity and ambiguity make it difficult to quantify skin conditions. Therefore, development of measurement device which can evaluate skin conditions easily and objectively is demanded by dermatologists, cosmetic industries, and so on. In this paper, an advanced haptic sensor system that can measure multiple information of skin condition in various parts of human body is developed. The applications of the sensor system to evaluate softness, smoothness, and stickiness of skin are investigated through two experiments.

  17. Advanced haptic sensor for measuring human skin conditions

    NASA Astrophysics Data System (ADS)

    Tsuchimi, Daisuke; Okuyama, Takeshi; Tanaka, Mami

    2010-01-01

    This paper is concerned with the development of a tactile sensor using PVDF (Polyvinylidene Fluoride) film as a sensory receptor of the sensor to evaluate softness, smoothness, and stickiness of human skin. Tactile sense is the most important sense in the sensation receptor of the human body along with eyesight, and we can examine skin condition quickly using these sense. But, its subjectivity and ambiguity make it difficult to quantify skin conditions. Therefore, development of measurement device which can evaluate skin conditions easily and objectively is demanded by dermatologists, cosmetic industries, and so on. In this paper, an advanced haptic sensor system that can measure multiple information of skin condition in various parts of human body is developed. The applications of the sensor system to evaluate softness, smoothness, and stickiness of skin are investigated through two experiments.

  18. Wall thickening pattern in atherosclerotic basilar artery stenosis.

    PubMed

    Zhu, Xianjin; Liu, Lei; He, Xinxin; Zhang, Xuebin; Hu, Libin; Du, Bin; Wang, Wu; Jiang, Weijian; Liu, Zunjing

    2016-02-01

    Our aim was to investigate wall thickening (WT) pattern of atherosclerotic basilar artery stenosis with three-dimensional volumetric isotropic turbo spin echo acquisition (3D VISTA), and the relationship with clinical characteristics. Twenty consecutive patients with atherosclerotic basilar artery stenosis were prospectively enrolled. All cross-sectional slices on VISTA images of basilar arteries were assessed, and classified as eccentric or concentric WT. Clinical characteristics and degree of stenosis were compared between the patients with different wall WT pattern. Wall abnormalities were identified in 568 cross-sectional slices in basilar arteries of 20 patients including eccentric WT in 497 (87.5 %) slices, and concentric WT in 71 (12.5 %) slices. In 11 of 20 patients, all the cross-sectional slices (293 slices) showed eccentric WT. In 9 of 20 patients, the cross-sectional slices (275 slices) showed both eccentric WT (204 slices, 74.2 %) and concentric WT (71 slices, 25.8 %). No lesion showed only concentric WT. At the slices of maximum luminal narrowing sites, only one patient showed concentric WT. Symptomatic stenosis was more common in the patients with mixed WT (eccentric and concentric), compared to patients with only eccentric WT (100 vs 54.5 %, p = 0.038). Atherosclerotic basilar artery stenosis could show both eccentric and concentric WT based on each slice analysis. Concentric WT was found in near half of the patients, but tended to locate in minimal slices. No lesion was entirely concentric. Lesions with mixed WT (concentric and eccentric) might represent advanced atherosclerosis with high risk of ischemic event. PMID:26520844

  19. A Cryptochrome 2 mutation yields advanced sleep phase in humans.

    PubMed

    Hirano, Arisa; Shi, Guangsen; Jones, Christopher R; Lipzen, Anna; Pennacchio, Len A; Xu, Ying; Hallows, William C; McMahon, Thomas; Yamazaki, Maya; Ptáček, Louis J; Fu, Ying-Hui

    2016-01-01

    Familial Advanced Sleep Phase (FASP) is a heritable human sleep phenotype characterized by very early sleep and wake times. We identified a missense mutation in the human Cryptochrome 2 (CRY2) gene that co-segregates with FASP in one family. The mutation leads to replacement of an alanine residue at position 260 with a threonine (A260T). In mice, the CRY2 mutation causes a shortened circadian period and reduced phase-shift to early-night light pulse associated with phase-advanced behavioral rhythms in the light-dark cycle. The A260T mutation is located in the phosphate loop of the flavin adenine dinucleotide (FAD) binding domain of CRY2. The mutation alters the conformation of CRY2, increasing its accessibility and affinity for FBXL3 (an E3 ubiquitin ligase), thus promoting its degradation. These results demonstrate that CRY2 stability controlled by FBXL3 plays a key role in the regulation of human sleep wake behavior. PMID:27529127

  20. Advances in Culture and Manipulation of Human Pluripotent Stem Cells

    PubMed Central

    Qian, X.; Villa-Diaz, L.G.; Krebsbach, P.H.

    2013-01-01

    Recent advances in the understanding of pluripotent stem cell biology and emerging technologies to reprogram somatic cells to a stem cell–like state are helping bring stem cell therapies for a range of human disorders closer to clinical reality. Human pluripotent stem cells (hPSCs) have become a promising resource for regenerative medicine and research into early development because these cells are able to self-renew indefinitely and are capable of differentiation into specialized cell types of all 3 germ layers and trophoectoderm. Human PSCs include embryonic stem cells (hESCs) derived from the inner cell mass of blastocyst-stage embryos and induced pluripotent stem cells (hiPSCs) generated via the reprogramming of somatic cells by the overexpression of key transcription factors. The application of hiPSCs and the finding that somatic cells can be directly reprogrammed into different cell types will likely have a significant impact on regenerative medicine. However, a major limitation for successful therapeutic application of hPSCs and their derivatives is the potential xenogeneic contamination and instability of current culture conditions. This review summarizes recent advances in hPSC culture and methods to induce controlled lineage differentiation through regulation of cell-signaling pathways and manipulation of gene expression as well as new trends in direct reprogramming of somatic cells. PMID:23934156

  1. Specific imaging of atherosclerotic plaque lipids with two-wavelength intravascular photoacoustics

    PubMed Central

    Wu, Min; Jansen, Krista; van der Steen, Antonius F. W.; van Soest, Gijs

    2015-01-01

    The lipid content in plaques is an important marker for identifying atherosclerotic lesions and disease states. Intravascular photoacoustic (IVPA) imaging can be used to visualize lipids in the artery. In this study, we further investigated lipid detection in the 1.7-µm spectral range. By exploiting the relative difference between the IVPA signal strengths at 1718 and 1734 nm, we could successfully detect and differentiate between the plaque lipids and peri-adventitial fat in human coronary arteries ex vivo. Our study demonstrates that IVPA imaging can positively identify atherosclerotic plaques using only two wavelengths, which could enable rapid data acquisition in vivo. PMID:26417500

  2. Genesis and growth of extracellular-vesicle-derived microcalcification in atherosclerotic plaques

    NASA Astrophysics Data System (ADS)

    Hutcheson, Joshua D.; Goettsch, Claudia; Bertazzo, Sergio; Maldonado, Natalia; Ruiz, Jessica L.; Goh, Wilson; Yabusaki, Katsumi; Faits, Tyler; Bouten, Carlijn; Franck, Gregory; Quillard, Thibaut; Libby, Peter; Aikawa, Masanori; Weinbaum, Sheldon; Aikawa, Elena

    2016-03-01

    Clinical evidence links arterial calcification and cardiovascular risk. Finite-element modelling of the stress distribution within atherosclerotic plaques has suggested that subcellular microcalcifications in the fibrous cap may promote material failure of the plaque, but that large calcifications can stabilize it. Yet the physicochemical mechanisms underlying such mineral formation and growth in atheromata remain unknown. Here, by using three-dimensional collagen hydrogels that mimic structural features of the atherosclerotic fibrous cap, and high-resolution microscopic and spectroscopic analyses of both the hydrogels and of calcified human plaques, we demonstrate that calcific mineral formation and maturation results from a series of events involving the aggregation of calcifying extracellular vesicles, and the formation of microcalcifications and ultimately large calcification areas. We also show that calcification morphology and the plaque’s collagen content--two determinants of atherosclerotic plaque stability--are interlinked.

  3. Genesis and growth of extracellular vesicle-derived microcalcification in atherosclerotic plaques

    PubMed Central

    Hutcheson, Joshua D.; Goettsch, Claudia; Bertazzo, Sergio; Maldonado, Natalia; Ruiz, Jessica L.; Goh, Wilson; Yabusaki, Katsumi; Faits, Tyler; Bouten, Carlijn; Franck, Gregory; Quillard, Thibaut; Libby, Peter; Aikawa, Masanori; Weinbaum, Sheldon; Aikawa, Elena

    2015-01-01

    Clinical evidence links arterial calcification and cardiovascular risk. Finite-element modelling of the stress distribution within atherosclerotic plaques has suggested that subcellular microcalcifications in the fibrous cap may promote material failure of the plaque, but that large calcifications can stabilize it. Yet the physicochemical mechanisms underlying such mineral formation and growth in atheromata remain unknown. Here, by using three-dimensional collagen hydrogels that mimic structural features of the atherosclerotic fibrous cap, and high-resolution microscopic and spectroscopic analyses of both the hydrogels and of calcified human plaques, we demonstrate that calcific mineral formation and maturation results from a series of events involving the aggregation of calcifying extracellular vesicles, and the formation of microcalcifications and ultimately large calcification zones. We also show that calcification morphology and the plaque’s collagen content – two determinants of atherosclerotic plaque stability - are interlinked. PMID:26752654

  4. Genesis and growth of extracellular-vesicle-derived microcalcification in atherosclerotic plaques.

    PubMed

    Hutcheson, Joshua D; Goettsch, Claudia; Bertazzo, Sergio; Maldonado, Natalia; Ruiz, Jessica L; Goh, Wilson; Yabusaki, Katsumi; Faits, Tyler; Bouten, Carlijn; Franck, Gregory; Quillard, Thibaut; Libby, Peter; Aikawa, Masanori; Weinbaum, Sheldon; Aikawa, Elena

    2016-03-01

    Clinical evidence links arterial calcification and cardiovascular risk. Finite-element modelling of the stress distribution within atherosclerotic plaques has suggested that subcellular microcalcifications in the fibrous cap may promote material failure of the plaque, but that large calcifications can stabilize it. Yet the physicochemical mechanisms underlying such mineral formation and growth in atheromata remain unknown. Here, by using three-dimensional collagen hydrogels that mimic structural features of the atherosclerotic fibrous cap, and high-resolution microscopic and spectroscopic analyses of both the hydrogels and of calcified human plaques, we demonstrate that calcific mineral formation and maturation results from a series of events involving the aggregation of calcifying extracellular vesicles, and the formation of microcalcifications and ultimately large calcification areas. We also show that calcification morphology and the plaque's collagen content-two determinants of atherosclerotic plaque stability-are interlinked. PMID:26752654

  5. Recent advances in research on climate and human conflict

    NASA Astrophysics Data System (ADS)

    Hsiang, S. M.

    2014-12-01

    A rapidly growing body of empirical, quantitative research examines whether rates of human conflict can be systematically altered by climatic changes. We discuss recent advances in this field, including Bayesian meta-analyses of the effect of temperature and rainfall on current and future large-scale conflicts, the impact of climate variables on gang violence and suicides in Mexico, and probabilistic projections of personal violence and property crime in the United States under RCP scenarios. Criticisms of this research field will also be explained and addressed.

  6. Laser recanalization of occluded atherosclerotic arteries in vivo and in vitro.

    PubMed

    Abela, G S; Normann, S J; Cohen, D M; Franzini, D; Feldman, R L; Crea, F; Fenech, A; Pepine, C J; Conti, C R

    1985-02-01

    Controlled laser irradiation was used to recanalize atherosclerotic stenoses in vivo and in vitro. In 15 rabbits with atherosclerotic arteries a catheter was positioned in the distal aorta for angiographic examination and as a guide for a small silica optical fiber. Both Nd-YAG and argon lasers were used for recanalization with varying power and duration. As determined by angiographic studies the severity of iliofemoral stenoses in eight 15 arteries decreased from 78 +/- 18% to 32 +/- 11% (mean +/- SD). In one additional artery the stenosis improved from 45% to 25%, but this was associated with perforation. The other six arteries were perforated (two after fiber manipulation, four after laser discharge) without obvious improvement in severity of stenosis. No angiographic loss of distal circulation was noted. To better define tissue- laser interactions in the live-rabbits, lasing of 15 totally occluded atherosclerotic rabbit arterial segments in vitro was done while the optical fiber was advanced or fixed. When the fiber was fixed, serial sections showed that the new lumen was flame shaped. The width and depth of the lumen increased with increasing laser energy. When the fiber was advanced, histologic examination showed a smooth cylindrical vascular channel with limited lateral tissue damage. This study demonstrated that lasers can recanalize atherosclerotic stenoses in a live animal preparation; however, arterial perforation remains a problem. PMID:3965181

  7. Lipidome of Atherosclerotic Plaques from Hypercholesterolemic Rabbits

    PubMed Central

    Bojic, Lazar A.; McLaren, David G.; Shah, Vinit; Previs, Stephen F.; Johns, Douglas G.; Castro-Perez, Jose M.

    2014-01-01

    The cellular, macromolecular and neutral lipid composition of the atherosclerotic plaque has been extensively characterized. However, a comprehensive lipidomic analysis of the major lipid classes within atherosclerotic lesions has not been reported. The objective of this study was to produce a detailed framework of the lipids that comprise the atherosclerotic lesion of a widely used pre-clinical model of plaque progression. Male New Zealand White rabbits were administered regular chow supplemented with 0.5% cholesterol (HC) for 12 weeks to induce hypercholesterolemia and atherosclerosis. Our lipidomic analyses of plaques isolated from rabbits fed the HC diet, using ultra-performance liquid chromatography (UPLC) and high-resolution mass spectrometry, detected most of the major lipid classes including: Cholesteryl esters, triacylglycerols, phosphatidylcholines, sphingomyelins, diacylglycerols, fatty acids, phosphatidylserines, lysophosphatidylcholines, ceramides, phosphatidylglycerols, phosphatidylinositols and phosphatidylethanolamines. Given that cholesteryl esters, triacylglycerols and phosphatidylcholines comprise greater than 75% of total plasma lipids, we directed particular attention towards the qualitative and quantitative assessment of the fatty acid composition of these lipids. We additionally found that sphingomyelins were relatively abundant lipid class within lesions, and compared the abundance of sphingomyelins to their precursor phosphatidylcholines. The studies presented here are the first approach to a comprehensive characterization of the atherosclerotic plaque lipidome. PMID:25517033

  8. NASA's Advanced Life Support Systems Human-Rated Test Facility

    NASA Technical Reports Server (NTRS)

    Henninger, D. L.; Tri, T. O.; Packham, N. J.

    1996-01-01

    Future NASA missions to explore the solar system will be long-duration missions, requiring human life support systems which must operate with very high reliability over long periods of time. Such systems must be highly regenerative, requiring minimum resupply, to enable the crews to be largely self-sufficient. These regenerative life support systems will use a combination of higher plants, microorganisms, and physicochemical processes to recycle air and water, produce food, and process wastes. A key step in the development of these systems is establishment of a human-rated test facility specifically tailored to evaluation of closed, regenerative life supports systems--one in which long-duration, large-scale testing involving human test crews can be performed. Construction of such a facility, the Advanced Life Support Program's (ALS) Human-Rated Test Facility (HRTF), has begun at NASA's Johnson Space Center, and definition of systems and development of initial outfitting concepts for the facility are underway. This paper will provide an overview of the HRTF project plan, an explanation of baseline configurations, and descriptive illustrations of facility outfitting concepts.

  9. Does human cognition allow Human Factors (HF) certification of advanced aircrew systems?

    NASA Technical Reports Server (NTRS)

    Macleod, Iain S.; Taylor, Robert M.

    1994-01-01

    This paper has examined the requirements of HF specification and certification within advanced or complex aircrew systems. It suggests reasons for current inadequacies in the use of HF in the design process, giving some examples in support, and suggesting an avenue towards the improvement of the HF certification process. The importance of human cognition to the operation and performance of advanced aircrew systems has been stressed. Many of the shortfalls of advanced aircrew systems must be attributed to over automated designs that show little consideration on either the mental limits or the cognitive capabilities of the human system component. Traditional approaches to system design and HF certification are set within an over physicalistic foundation. Also, traditionally it was assumed that physicalistic system functions could be attributed to either the human or the machine on a one to one basis. Moreover, any problems associated with the parallel needs, or promoting human understanding alongside system operation and direction, were generally equated in reality by the natural flexibility and adaptability of human skills. The consideration of the human component of a complex system is seen as being primarily based on manifestations of human behavior to the almost total exclusion of any appreciation of unobservable human mental and cognitive processes. The argument of this paper is that the considered functionality of any complex human-machine system must contain functions that are purely human and purely cognitive. Human-machine system reliability ultimately depends on human reliability and dependability and, therefore, on the form and frequency of cognitive processes that have to be conducted to support system performance. The greater the demand placed by an advanced aircraft system on the human component's basic knowledge processes or cognition, rather than on skill, the more insiduous the effects the human may have on that system. This paper discusses one

  10. CO2 vascular anastomosis of atherosclerotic and calcified arteries

    NASA Astrophysics Data System (ADS)

    White, John V.; Leefmans, Eric; Stewart, Gwendolyn J.; Katz, Mira L.; Comerota, Anthony J.

    1990-06-01

    The technique for CO2 laser fusion vascular anastomosis in normal vessels has been well established. Normal arterial wall has a predictable thermal response to the incident laser energy, with rapid heating and cooling of collagen within the arterial wall. Since atherosclerosis involves subendothelial cellular proliferation, lipid and calcium deposition, it may modify the thermal responsiveness of the arterial wall. To this study, CO2 laser fusion anastomoses were attempted in rabbits with non-calcific atherosclerosis and humans with calcific atherosclerosis. All anastomoses were successfully completed without alteration in technique despite the presence of plaque at the site of laser fusion. Histology of rabbit vessels revealed the classic laser fusion cap within the adventitia and persistent atherosclerotic plaque at the flow surface. Duplex imaging of patients post-operatively demonstrated long term anastomotic patency in 2 of 3 fistulae. These results suggest that neither non-calcified or calcified atherosclerosis significantly alters the arterial wall thermal responsiveness to CO2 laser energy or inhibits creation of laser fusion anastomoses. Therefore, this technique may be applicable to the treatment of patients with atherosclerotic occlusive disease.

  11. Consciousness in humans and non-human animals: recent advances and future directions

    PubMed Central

    Boly, Melanie; Seth, Anil K.; Wilke, Melanie; Ingmundson, Paul; Baars, Bernard; Laureys, Steven; Edelman, David B.; Tsuchiya, Naotsugu

    2013-01-01

    This joint article reflects the authors' personal views regarding noteworthy advances in the neuroscience of consciousness in the last 10 years, and suggests what we feel may be promising future directions. It is based on a small conference at the Samoset Resort in Rockport, Maine, USA, in July of 2012, organized by the Mind Science Foundation of San Antonio, Texas. Here, we summarize recent advances in our understanding of subjectivity in humans and other animals, including empirical, applied, technical, and conceptual insights. These include the evidence for the importance of fronto-parietal connectivity and of “top-down” processes, both of which enable information to travel across distant cortical areas effectively, as well as numerous dissociations between consciousness and cognitive functions, such as attention, in humans. In addition, we describe the development of mental imagery paradigms, which made it possible to identify covert awareness in non-responsive subjects. Non-human animal consciousness research has also witnessed substantial advances on the specific role of cortical areas and higher order thalamus for consciousness, thanks to important technological enhancements. In addition, much progress has been made in the understanding of non-vertebrate cognition relevant to possible conscious states. Finally, major advances have been made in theories of consciousness, and also in their comparison with the available evidence. Along with reviewing these findings, each author suggests future avenues for research in their field of investigation. PMID:24198791

  12. Percutaneous arterial gene transfer in a rabbit model. Efficiency in normal and balloon-dilated atherosclerotic arteries.

    PubMed Central

    Leclerc, G; Gal, D; Takeshita, S; Nikol, S; Weir, L; Isner, J M

    1992-01-01

    The possibility of using an exclusively percutaneous strategy to deliver foreign DNA to normal and balloon-dilated atherosclerotic arteries was studied by analysis of transfection efficiency in a rabbit model. A total of 22 external iliac arteries from 22 rabbits (10 normal and 12 atherosclerotic) were transfected with a solution of luciferase expression vector plasmid and liposome, using a dual balloon-catheter system. Analysis of the transfected segments revealed luciferase activity in 10 of the 22 arteries (4/10 normal vs 6/12 balloon-injured atherosclerotic, P = NS); no activity could be detected in the contralateral limb arterial segments used as controls. Luciferase activity levels in successfully transfected segments measured 4.10 +/- 1.19 (m +/- SEM) Turner light units (TLU), with 3.03 +/- 1.16 TLU found in normals vs 4.81 +/- 1.87 TLU in balloon-injured atherosclerotic arteries (P = NS). In situ hybridization of successfully transfected atherosclerotic sections showed expression of the luciferase gene mRNA from rare cells (less than 1/1,000) limited to the neointimal lesion. Thus, expression of new genetic material may be achieved in both normal and balloon-dilated atherosclerotic arteries following an exclusively percutaneous approach. The low efficiency of the current delivery strategy, however, represents a potential limitation that must be improved if this strategy is to be applied as a therapeutic approach to human vascular disease. Images PMID:1387886

  13. Developing Advanced Human Support Technologies for Planetary Exploration Missions

    NASA Technical Reports Server (NTRS)

    Berdich, Debra P.; Campbell, Paul D.; Jernigan, J. Mark

    2004-01-01

    The United States Vision for Space Exploration calls for sending robots and humans to explore the Earth's moon, the planet Mars, and beyond. The National Aeronautics and Space Administration (NASA) is developing a set of design reference missions that will provide further detail to these plans. Lunar missions are expected to provide a stepping stone, through operational research and evaluation, in developing the knowledge base necessary to send crews on long duration missions to Mars and other distant destinations. The NASA Exploration Systems Directorate (ExSD), in its program of bioastronautics research, manages the development of technologies that maintain human life, health, and performance in space. Using a system engineering process and risk management methods, ExSD's Human Support Systems (HSS) Program selects and performs research and technology development in several critical areas and transfers the results of its efforts to NASA exploration mission/systems development programs in the form of developed technologies and new knowledge about the capabilities and constraints of systems required to support human existence beyond Low Earth Orbit. HSS efforts include the areas of advanced environmental monitoring and control, extravehicular activity, food technologies, life support systems, space human factors engineering, and systems integration of all these elements. The HSS Program provides a structured set of deliverable products to meet the needs of exploration programs. These products reduce the gaps that exist in our knowledge of and capabilities for human support for long duration, remote space missions. They also reduce the performance gap between the efficiency of current space systems and the greater efficiency that must be achieved to make human planetary exploration missions economically and logistically feasible. In conducting this research and technology development program, it is necessary for HSS technologists and program managers to develop a

  14. Recent advances in managing human papillomavirus-positive oropharyngeal tumors

    PubMed Central

    Riccio, Stefano; Colombo, Sarah; Pompilio, Madia; Formillo, Paolo

    2010-01-01

    Human papillomavirus (HPV) is detected in a subset of patients with head and neck squamous cell carcinoma, most frequently in tumors in the Waldeyer's ring (palatine tonsil and base of tongue). Several studies suggest that patients with HPV-positive tumors have better survival with either concurrent chemoradiation therapy or surgery followed by radiation compared with HPV-negative patients. However, some possible confounding clinicopathologic variables may challenge the validity of this statement, for example, some authors used the TNM (tumor, node, metastasis) grouping stage while others used the primary tumor (T stage), and other studies have demonstrated that tumors with advanced T stage were less likely to be infected with HPV. A large clinical trial with stratification of patients according to all known tumor prognostic factors is crucial to solve the question. PMID:20948869

  15. Advanced Plasma Propulsion for Human Missions to Jupiter

    NASA Technical Reports Server (NTRS)

    Donahue, Benjamin B.; Pearson, J. Boise

    1999-01-01

    This paper will briefly identify a promising fusion plasma power source, which when coupled with a promising electric thruster technology would provide for an efficient interplanetary transfer craft suitable to a 4 year round trip mission to the Jovian system. An advanced, nearly radiation free Inertial Electrostatic Confinement scheme for containing fusion plasma was judged as offering potential for delivering the performance and operational benefits needed for such high energy human expedition missions, without requiring heavy superconducting magnets for containment of the fusion plasma. Once the Jovian transfer stage has matched the heliocentric velocity of Jupiter, the energy requirements for excursions to its outer satellites (Callisto, Ganymede and Europa) by smaller excursion craft are not prohibitive. The overall propulsion, power and thruster system is briefly described and a preliminary vehicle mass statement is presented.

  16. Advancing our understanding of the human microbiome using QIIME

    PubMed Central

    Navas-Molina, José A.; Peralta-Sánchez, Juan M.; González, Antonio; McMurdie, Paul J.; Vázquez-Baeza, Yoshiki; Xu, Zhenjiang; Ursell, Luke K.; Lauber, Christian; Zhou, Hongwei; Song, Se Jin; Huntley, James; Ackermann, Gail L.; Berg-Lyons, Donna; Holmes, Susan; Caporaso, J. Gregory; Knight, Rob

    2014-01-01

    High-throughput DNA sequencing technologies, coupled with advanced bioinformatics tools, have enabled rapid advances in microbial ecology and our understanding of the human microbiome. QIIME (Quantitative Insights Into Microbial Ecology) is an open-source bioinformatics software package designed for microbial community analysis based on DNA sequence data, which provides a single analysis framework for analysis of raw sequence data through publication quality statistical analyses and interactive visualizations. In this paper, we demonstrate the use of the QIIME pipeline to analyze microbial communities obtained from several sites on the bodies of transgenic and wild-type mice, as assessed using 16S rRNA gene sequences generated on the Illumina MiSeq platform. We present our recommended pipeline for performing microbial community analysis, and provide guidelines for making critical choices in the process. We present examples of some of the types of analyses that are enabled by QIIME, and discuss how other tools, such as phyloseq and R, can be applied to expand upon these analyses. PMID:24060131

  17. Zebrafish Models of Human Leukemia: Technological Advances and Mechanistic Insights

    PubMed Central

    Harrison, Nicholas R.; Laroche, Fabrice J.F.; Gutierrez, Alejandro

    2016-01-01

    Insights concerning leukemic pathophysiology have been acquired in various animal models and further efforts to understand the mechanisms underlying leukemic treatment resistance and disease relapse promise to improve therapeutic strategies. The zebrafish (Danio rerio) is a vertebrate organism with a conserved hematopoietic program and unique experimental strengths suiting it for the investigation of human leukemia. Recent technological advances in zebrafish research including efficient transgenesis, precise genome editing, and straightforward transplantation techniques have led to the generation of a number of leukemia models. The transparency of the zebrafish when coupled with improved lineage-tracing and imaging techniques has revealed exquisite details of leukemic initiation, progression, and regression. With these advantages, the zebrafish represents a unique experimental system for leukemic research and additionally, advances in zebrafish-based high-throughput drug screening promise to hasten the discovery of novel leukemia therapeutics. To date, investigators have accumulated knowledge of the genetic underpinnings critical to leukemic transformation and treatment resistance and without doubt, zebrafish are rapidly expanding our understanding of disease mechanisms and helping to shape therapeutic strategies for improved outcomes in leukemic patients. PMID:27165361

  18. Human Exploration Spacecraft Testbed for Integration and Advancement (HESTIA)

    NASA Technical Reports Server (NTRS)

    Banker, Brian F.; Robinson, Travis

    2016-01-01

    The proposed paper will cover ongoing effort named HESTIA (Human Exploration Spacecraft Testbed for Integration and Advancement), led at the National Aeronautics and Space Administration (NASA) Johnson Space Center (JSC) to promote a cross-subsystem approach to developing Mars-enabling technologies with the ultimate goal of integrated system optimization. HESTIA also aims to develop the infrastructure required to rapidly test these highly integrated systems at a low cost. The initial focus is on the common fluids architecture required to enable human exploration of mars, specifically between life support and in-situ resource utilization (ISRU) subsystems. An overview of the advancements in both integrated technologies, in infrastructure, in simulation, and in modeling capabilities will be presented, as well as the results and findings of integrated testing,. Due to the enormous mass gear-ratio required for human exploration beyond low-earth orbit, (for every 1 kg of payload landed on Mars, 226 kg will be required on Earth), minimization of surface hardware and commodities is paramount. Hardware requirements can be minimized by reduction of equipment performing similar functions though for different subsystems. If hardware could be developed which meets the requirements of both life support and ISRU it could result in the reduction of primary hardware and/or reduction in spares. Minimization of commodities to the surface of mars can be achieved through the creation of higher efficiency systems producing little to no undesired waste, such as a closed-loop life support subsystem. Where complete efficiency is impossible or impractical, makeup commodities could be manufactured via ISRU. Although, utilization of ISRU products (oxygen and water) for crew consumption holds great promise of reducing demands on life support hardware, there exist concerns as to the purity and transportation of commodities. To date, ISRU has been focused on production rates and purities for

  19. Morphology of atherosclerotic coronary arteries

    NASA Astrophysics Data System (ADS)

    Holme, Margaret N.; Schulz, Georg; Deyhle, Hans; Hieber, Simone Elke; Weitkamp, Timm; Beckmann, Felix; Herzen, Julia; Lobrinus, Johannes A.; Montecucco, Fabrizio; Mach, François; Zumbuehl, Andreas; Saxer, Till; Müller, Bert

    2012-10-01

    Atherosclerosis, the narrowing of vessel diameter and build-up of plaques in coronary arteries, leads to an increase in the shear stresses present, which can be used as a physics-based trigger for targeted drug delivery. In order to develop appropriate nanometer-size containers, one has to know the morphology of the critical stenoses with isotropic micrometer resolution. Micro computed tomography in absorption and phase contrast mode provides the necessary spatial resolution and contrast. The present communication describes the pros and cons of the conventional and synchrotron radiation-based approaches in the visualization of diseased human and murine arteries. Using registered datasets, it also demonstrates that multi-modal imaging, including established histology, is even more powerful. The tomography data were evaluated with respect to cross-section, vessel radius and maximal constriction. The average cross-section of the diseased human artery (2.31 mm2) was almost an order of magnitude larger than the murine one (0.27 mm2), whereas the minimal radius differs only by a factor of two (0.51 mm versus 0.24 mm). The maximal constriction, however, was much larger for the human specimen (85% versus 49%). We could also show that a plastic model used for recent experiments in targeted drug delivery represents a very similar morphology, which is, for example, characterized by a maximal constriction of 82%. The tomography data build a sound basis for flow simulations, which allows for conclusions on shear stress distributions in stenosed blood vessels.

  20. Anti-Atherosclerotic Therapy Based on Botanicals

    PubMed Central

    Orekhov, Alexander N.; Sobenin, Igor A.; Korneev, Nikolay V.; Kirichenko, Tatyana V.; Myasoedova, Veronika A.; Melnichenko, Alexandra A.; Balcells, Mercedes; Edelman, Elazer R.; Bobryshev, Yuri V.

    2015-01-01

    Natural products including botanicals for both therapy of clinical manifestations of atherosclerosis and reduction of atherosclerosis risk factors are topics of recent patents. Only a few recent patents are relevant to the direct anti-atherosclerotic therapy leading to regression of atherosclerotic lesions. Earlier, using a cellular model we have developed and patented several anti-atherosclerotic drugs. The AMAR (Atherosclerosis Monitoring and Atherogenicity Reduction) study was designed to estimate the effect of two-year treatment with time-released garlic-based drug Allicor on the progression of carotid atherosclerosis in 196 asymptomatic men aged 40–74 in double-blinded placebo-controlled randomized clinical study. The primary outcome was the rate of atherosclerosis progression, measured by high-resolution B-mode ul-trasonography as the increase in carotid intima-media thickness (IMT) of the far wall of common carotid arteries. The mean rate of IMT changes in Allicor-treated group (−0.022±0.007 mm per year) was significantly different (P = 0.002) from the placebo group in which there was a moderate progression of 0.015±0.008 mm at the overall mean baseline IMT of 0.931±0.009 mm. A significant correlation was found between the changes in blood serum atherogenicity (the ability of serum to induce cholesterol accumulation in cultured cells) during the study and the changes in intima-media thickness of common carotid arteries (r = 0.144, P = 0.045). Thus, the results of AMAR study demonstrate that long-term treatment with Allicor has a direct anti-atherosclerotic effect on carotid atherosclerosis and this effect is likely to be due to serum atherogenicity inhibition. The beneficial effects of other botanicals including Inflaminat (calendula, elder and violet), phytoestrogen-rich Karinat (garlic powder, extract of grape seeds, green tea leafs, hop cones, β-carotene, α-tocopherol and ascorbic acid) on atherosclerosis have also been revealed in clinical

  1. Comparison of two murine models of thrombosis induced by atherosclerotic plaque injury.

    PubMed

    Hechler, Béatrice; Gachet, Christian

    2011-05-01

    Arterial thrombosis occurs at sites of erosion or rupture of atherosclerotic vascular lesions. To better study the pathophysiology of this complex phenomenon, there is a need for animal models of localised thrombosis at sites of atherosclerotic lesions with closer resemblance to the human pathology as compared to commonly used thrombosis models in healthy vessels. In the present study, we describe and compare a new model of thrombosis induced by atherosclerotic plaque rupture in the carotid artery from ApoE-/- mice using a suture needle to a milder model of ultrasound-induced plaque injury. Needle injury induces atherosclerotic plaque rupture with exposure of plaque material and formation of a thrombus that is larger, nearly occlusive and more stable as compared to that formed by application of ultrasounds. These two models have common features such as the concomitant involvement of platelet activation, thrombin generation and fibrin formation, which translates into sensitivity toward both antiplatelet drugs and anticoagulants. On the other hand, they display differences with respect to the role of the platelet collagen receptor GPVI, the plaque rupture model being less sensitive to its inhibition as compared to the ultrasound-induced injury, which may be related to the amount of thrombin generated. These models represent an improvement as compared to models in healthy vessels and may help identify specific plaque triggers of thrombosis. They should therefore be useful to evaluate new antithrombotic targets. PMID:21479341

  2. Quantification of Cellular Proliferation in Mouse Atherosclerotic Lesions.

    PubMed

    Fuster, José J

    2015-01-01

    Excessive cell proliferation within atherosclerotic plaques plays an important role in the progression of atherosclerosis. Macrophage proliferation in particular has become a major focus of attention in the cardiovascular field because it appears to mediate most of macrophage expansion in mouse atherosclerotic arteries. Therefore, quantification of cell proliferation is an essential part of the characterization of atherosclerotic plaques in experimental studies. This chapter describes two variants of a simple immunostaining protocol that allow for the quantification of cellular proliferation in mouse atherosclerotic lesions based on the detection of the proliferation-associated antigen Ki-67. PMID:26445791

  3. Reflection spectroscopy of atherosclerotic plaque

    NASA Astrophysics Data System (ADS)

    Lilledahl, Magnus B.; Haugen, Olav A.; Barkost, Marianne; Svaasand, Lars O.

    2006-03-01

    Heart disease is the primary cause of death in the western world. Many of these deaths are caused by the rupture of vulnerable plaque. Vulnerable plaques are characterized by a large lipid core covered by a thin fibrous cap. One method for detecting these plaques is reflection spectroscopy. Several studies have investigated this method using statistical methods. A more analytic and quantitative study might yield more insight into the sensitivity of this detection modality. This is the approach taken in this work. Reflectance spectra in the spectral region from 400 to 1700 nm are collected from 77 measurement points from 23 human aortas. A measure of lipid content in a plaque based on reflection spectra is presented. The measure of lipid content is compared with the thickness of the lipid core, determined from histology. Defining vulnerable plaque as having a lipid core >500 µm and fibrous cap <500 µm, vulnerable plaques are detected with a sensitivity of 88% and a specificity of 94%. Although the method can detect lipid content, it is not very sensitive to the thickness of the fibrous cap. Another detection modality is necessary to detect this feature.

  4. Dual-modality fiber-based OCT-TPL imaging system for simultaneous microstructural and molecular analysis of atherosclerotic plaques

    PubMed Central

    Wang, Tianyi; McElroy, Austin; Halaney, David; Vela, Deborah; Fung, Edmund; Hossain, Shafat; Phipps, Jennifer; Wang, Bingqing; Yin, Biwei; Feldman, Marc D.; Milner, Thomas E.

    2015-01-01

    New optical imaging techniques that provide contrast to study both the anatomy and composition of atherosclerotic plaques can be utilized to better understand the formation, progression and clinical complications of human coronary artery disease. We present a dual-modality fiber-based optical imaging system for simultaneous microstructural and molecular analysis of atherosclerotic plaques that combines optical coherence tomography (OCT) and two-photon luminescence (TPL) imaging. Experimental results from ex vivo human coronary arteries show that OCT and TPL optical contrast in recorded OCT-TPL images is complimentary and in agreement with histological analysis. Molecular composition (e.g., lipid and oxidized-LDL) detected by TPL imaging can be overlaid onto plaque microstructure depicted by OCT, providing new opportunities for atherosclerotic plaque identification and characterization. PMID:26137371

  5. Endovascular revascularization for aortoiliac atherosclerotic disease

    PubMed Central

    Aggarwal, Vikas; Waldo, Stephen W; Armstrong, Ehrin J

    2016-01-01

    Atherosclerotic iliac artery disease is increasingly being treated with endovascular techniques. A number of new stent technologies can be utilized with high long-term patency, including self-expanding stents, balloon-expandable stents, and covered stents, but comparative data on these stent types and in more complex lesions are lacking. This article provides a review of currently available iliac stent technologies, as well as complex procedural aspects of iliac artery interventions, including approaches to the treatment of iliac bifurcation disease, long segment occlusions, choice of stent type, and treatment of iliac artery in-stent restenosis. PMID:27099509

  6. Atherosclerotic renal artery stenosis: current status.

    PubMed

    Kwon, Soon Hyo; Lerman, Lilach O

    2015-05-01

    Atherosclerotic renal artery stenosis (ARAS) remains a major cause of secondary hypertension and kidney failure. Randomized prospective trials show that medical treatment should constitute the main therapeutic approach in ARAS. Regardless of intensive treatment and adequate blood pressure control, however, renal and extrarenal complications are not uncommon. Yet, the precise mechanisms, accurate detection, and optimal treatment in ARAS remain elusive. Strategies oriented to early detection and targeting these pathogenic pathways might prevent development of clinical end points. Here, we review the results of recent clinical trials, current understanding of the pathogenic mechanisms, novel imaging techniques to assess kidney damage in ARAS, and treatment options. PMID:25908472

  7. Multimodal nonlinear optical imaging of atherosclerotic plaque development in myocardial infarction-prone rabbits

    NASA Astrophysics Data System (ADS)

    Ko, Alex C. T.; Ridsdale, Andrew; Smith, Michael S. D.; Mostaço-Guidolin, Leila B.; Hewko, Mark D.; Pegoraro, Adrian F.; Kohlenberg, Elicia K.; Schattka, Bernie; Shiomi, Masashi; Stolow, Albert; Sowa, Michael G.

    2010-03-01

    Label-free imaging of bulk arterial tissue is demonstrated using a multimodal nonlinear optical microscope based on a photonic crystal fiber and a single femtosecond oscillator operating at 800 nm. Colocalized imaging of extracellular elastin fibers, fibrillar collagen, and lipid-rich structures within aortic tissue obtained from atherosclerosis-prone myocardial infarction-prone Watanabe heritable hyperlipidemic (WHHLMI) rabbits is demonstrated through two-photon excited fluorescence, second harmonic generation, and coherent anti-Stokes Raman scattering, respectively. These images are shown to differentiate healthy arterial wall, early atherosclerotic lesions, and advanced plaques. Clear pathological changes are observed in the extracellular matrix of the arterial wall and correlated with progression of atherosclerotic disease as represented by the age of the WHHLMI rabbits.

  8. Antibody-Labeled Liposomes for CT Imaging of Atherosclerotic Plaques

    PubMed Central

    Danila, Delia; Partha, Ranga; Elrod, Don B.; Lackey, Melinda; Casscells, S. Ward; Conyers, Jodie L.

    2009-01-01

    We evaluated the specific binding of anti-intercellular adhesion molecule 1 (ICAM-1) conjugated liposomes (immunoliposomes, or ILs) to activated human coronary artery endothelial cells (HCAEC) with the purpose of designing a computed tomographic imaging agent for early detection of atherosclerotic plaques. Covalent attachment of anti-ICAM-1 monoclonal antibodies to pre-formed liposomes stabilized with polyethylene glycol yielded ILs, with a coupling efficiency of the ICAM-1 to the liposomes of 10% to 24%. The anti-ICAM-1–labeled ILs had an average diameter of 136 nm as determined by dynamic light-scattering and cryogenic electron microscopy. The ILs' encapsulation of 5-[N-acetyl-(2,3-dihydroxypropyl)-amino)-N, N′-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-benzene-1,3-dicarboxamide (iohexol) was determined to be 18% to 19% by a dialysis technique coupled with ultraviolet detection of free iohexol. This encapsulation corresponded to 30 to 38 mg iodine per mL IL solution, and the ILs exhibited 91% to 98.5% iohexol retention at room temperature and under physiologic conditions. The specific binding of the ILs to cultured, activated HCAEC was measured using flow cytometry, enzyme-linked immunosorbent assays, and fluorescence microscopy. The immunosorbent assays demonstrated the specificity of binding of anti-ICAM-1 to ICAM-1 compared with control studies using nonspecific immunoglobulin G-labeled ILs. Flow cytometry and fluorescence microscopy experiments demonstrated the expression of ICAM-1 on the surface of activated HCAEC. Therefore, our iohexol-filled ILs demonstrated potential for implementation in computed tomographic angiography to noninvasively detect atherosclerotic plaques that are prone to rupture. PMID:19876414

  9. Dengue human infection models to advance dengue vaccine development.

    PubMed

    Larsen, Christian P; Whitehead, Stephen S; Durbin, Anna P

    2015-12-10

    Dengue viruses (DENV) currently infect approximately 400 million people each year causing millions to seek care and overwhelming the health care infrastructure in endemic areas. Vaccines to prevent dengue and therapeutics to treat dengue are not currently available. The efficacy of the most advanced candidate vaccine against symptomatic dengue in general and DENV-2 in particular was much lower than expected, despite the ability of the vaccine to induce neutralizing antibody against all four DENV serotypes. Because seroconversion to the DENV serotypes following vaccination was thought to be indicative of induced protection, these results have made it more difficult to assess which candidate vaccines should or should not be evaluated in large studies in endemic areas. A dengue human infection model (DHIM) could be extremely valuable to down-select candidate vaccines or therapeutics prior to engaging in efficacy trials in endemic areas. Two DHIM have been developed to assess the efficacy of live attenuated tetravalent (LATV) dengue vaccines. The first model, developed by the Laboratory of Infectious Diseases at the U. S. National Institutes of Health, utilizes a modified DENV-2 strain DEN2Δ30. This virus was derived from the DENV-2 Tonga/74 that caused only very mild clinical infection during the outbreak from which it was recovered. DEN2Δ30 induced viremia in 100%, rash in 80%, and neutropenia in 27% of the 30 subjects to whom it was given. The Walter Reed Army Institute of Research (WRAIR) is developing a DHIM the goal of which is to identify DENV that cause symptomatic dengue fever. WRAIR has evaluated seven viruses and has identified two that meet dengue fever criteria. Both of these models may be very useful in the evaluation and down-selection of candidate dengue vaccines and therapeutics. PMID:26424605

  10. The contemporary management of intracranial atherosclerotic disease.

    PubMed

    Leng, Xinyi; Wong, Ka Sing; Leung, Thomas W

    2016-06-01

    Intracranial atherosclerotic disease is the most common cause of cerebral vasculopathy and an important stroke etiology worldwide, with a higher prevalence in Asian, Hispanic and African ethnicities. Symptomatic intracranial atherosclerotic disease portends a recurrent stroke risk as high as 18% at one year. The key to secondary prevention is an understanding of the underlying stroke mechanism and aggressive control of conventional cardiovascular risks. Contemporary treatment includes antiplatelet therapy, optimal glycemic and blood pressure control, statin therapy and lifestyle modifications. For patients with high-grade (70-99%) symptomatic steno-occlusion, short-term dual antiplatelet therapy with aspirin and clopidogrel followed by life-long single antiplatelet therapy may reduce the recurrent risk. Current evidence does not advocate percutaneous transluminal angioplasty and stenting as an initial treatment. External counterpulsation, encephaloduroarteriosynangiosis and remote limb ischemic preconditioning are treatments under investigation. Future studies should aim at predicting patients prone to recurrence despite of medical therapies and testing the efficacy of emerging therapies. PMID:27082149

  11. Thermal compression and molding of atherosclerotic vascular tissue with use of radiofrequency energy: implications for radiofrequency balloon angioplasty

    SciTech Connect

    Lee, B.I.; Becker, G.J.; Waller, B.F.; Barry, K.J.; Connolly, R.J.; Kaplan, J.; Shapiro, A.R.; Nardella, P.C.

    1989-04-01

    The combined delivery of pressure and thermal energy may effectively remodel intraluminal atherosclerotic plaque and fuse intimal tears. To test these hypotheses with use of a non-laser thermal energy source, radiofrequency energy was delivered to postmortem human atherosclerotic vessels from a metal hot-tip catheter, block-mounted bipolar electrodes and from a prototype radiofrequency balloon catheter. Sixty-two radiofrequency doses delivered from a metal electrode tip produced dose-dependent ablation of atherosclerotic plaque, ranging from clean and shallow craters with histologic evidence of thermal compression at doses less than 40 J to tissue charring and vaporization at higher (greater than 80 J) doses. Lesion dimensions ranged between 3.14 and 3.79 mm in diameter and 0.20 and 0.47 mm in depth. Tissue perforation was not observed. To test the potential for radiofrequency fusion of intimal tears, 5 atm of pressure and 200 J radiofrequency energy were delivered from block-mounted bipolar electrodes to 48 segments of human atherosclerotic aorta, which had been manually separated into intima-media and media-adventitial layers. Significantly stronger tissue fusion resulted (28.5 +/- 3.3 g) with radiofrequency compared with that with pressure alone (4.8 +/- 0.26 g; p less than 0.0001). A prototype radiofrequency balloon catheter was used to deliver 3 atm of balloon pressure with or without 200 J radiofrequency energy to 20 postmortem human atherosclerotic arterial segments. In 10 of 10 radiofrequency-treated vessels, thermal molding of both normal and atherosclerotic vessel wall segments resulted with increased luminal diameter and histologic evidence of medial myocyte damage.

  12. Treating cardiovascular atherosclerotic plaques with Tongmaijiangzhi (TMJZ) capsule.

    PubMed

    Ren, Hong-Qiang; Zhao, Li; Zhang, Zhong Shuang; Wang, Zhong; Wang, Li; Duan, Jun Cang; Li, Li; Zhai, Zhi Hong; Qu, De Tao; Huang, Hui

    2013-01-01

    Atherosclerotic plaques can cause serious syndromes and mortality. Cholesterol accumulation in the plaques can disrupt the arterial flow, with lumen narrowing and stenosis, which contributes to heart attack and sudden cardiac death. The pharmacological treatment to atherosclerotic plaques can be anti-hypertensives, anti-cholesterol, and cleaning of the existed plaques. This work examined the effects of pharmacological Tongmaijiangzhi (TMJZ) capsule on atherosclerotic plaques. The radiological findings of the atherosclerotic plaques of 107 patients receiving TMJZ treatment were analyzed. We found that the TMJZ administration decreases plaque volume and alters the composition in a relatively short period, showing highly promising effects. TMJZ treatment is able to remove the existed atherosclerotic plaques with no side effects observed. PMID:24311866

  13. Human factors of advanced technology (glass cockpit) transport aircraft

    NASA Technical Reports Server (NTRS)

    Wiener, Earl L.

    1989-01-01

    A three-year study of airline crews at two U.S. airlines who were flying an advanced technology aircraft, the Boeing 757 is discussed. The opinions and experiences of these pilots as they view the advanced, automated features of this aircraft, and contrast them with previous models they have flown are discussed. Training for advanced automation; (2) cockpit errors and error reduction; (3) management of cockpit workload; and (4) general attitudes toward cockpit automation are emphasized. The limitations of the air traffic control (ATC) system on the ability to utilize the advanced features of the new aircraft are discussed. In general the pilots are enthusiastic about flying an advanced technology aircraft, but they express mixed feelings about the impact of automation on workload, crew errors, and ability to manage the flight.

  14. The development and evaluation of human factors guidelines for the review of advanced human-system interfaces

    SciTech Connect

    O`Hara, J.M.

    1992-09-01

    Advanced control rooms for future nuclear power plants are being designed utilizing computer-based technologies. The US Nuclear Regulatory Commission reviews the human engineering of such control rooms to ensure that they are designed to good human factors engineering principles and that operator performance and reliability are approximately supported in order to protect public health and safety. This paper describes the rationale, general approach, and initial development of an NRC Advanced Control Room Design Review Guideline.

  15. The development and evaluation of human factors guidelines for the review of advanced human-system interfaces

    SciTech Connect

    O'Hara, J.M.

    1992-01-01

    Advanced control rooms for future nuclear power plants are being designed utilizing computer-based technologies. The US Nuclear Regulatory Commission reviews the human engineering of such control rooms to ensure that they are designed to good human factors engineering principles and that operator performance and reliability are approximately supported in order to protect public health and safety. This paper describes the rationale, general approach, and initial development of an NRC Advanced Control Room Design Review Guideline.

  16. Low Testosterone Concentration and Atherosclerotic Disease Markers in Male Patients With Type 2 Diabetes

    PubMed Central

    Tinetti, Matias; Khoury, Marina; Umpierrez, Guillermo E.

    2014-01-01

    Background: Low total T is associated with an increased risk of atherosclerotic complications. However, the magnitude of this association in middle-aged patients with type 2 diabetes (T2D) has not been determined. Materials and Methods: This cross-sectional study evaluated atherosclerotic disease markers in T2D patients with normal and low plasma total T. A total of 115 male patients, aged younger than 70 years, without a history of cardiovascular events, and with normal [≥3.5 ng/mL (≥12.1 nmol/L), n = 79] or low [< 3.5 ng/mL (≤12.1 nmol/L), n = 36] total T underwent the measurement of highly sensitive C-reactive protein, carotid artery carotid intima-media thickness (IMT), and atherosclerotic plaque by high-resolution B-mode ultrasound and to asses endothelial function by brachial artery flow-mediated dilation. Results: Carotid IMT was negatively correlated with total T concentration (r = −0.39, P < .0001). Compared with subjects with normal T, a higher proportion of patients with low total T had carotid IMT of 0.1 cm or greater [80% vs 39%, odds ratio (OR) 6.41; 95% CI 2.5–16.4, P < .0001], atherosclerotic plaques (68.5% vs 44.8%, OR 2.60, 95% CI 1.12–6.03, P < .0001); endothelial dysfunction (80.5% vs 42.3%, OR 5.77, 95% CI 2.77–14.77, P < .003), and higher highly sensitive C-reactive protein levels (2.74 ± 5.82 vs 0.89 ± 0.88 mg/L, P < .0001). Similar results were found when free T was considered. Multiple logistic regression analyses adjusted for age, diabetes mellitus duration, hemoglobin A1c, lipids, treatment effect, and body mass index reported that a low total T level was independently associated with greater IMT [OR 8.43 (95% CI 2.5–25.8)] and endothelial dysfunction [OR 5.21 (95% CI 1.73–15.66)] but not with the presence of atherosclerotic plaques (OR 1.77, 95% CI 0.66–4.74). Conclusions: Low T is associated with more advanced atherosclerotic disease markers in middle-aged patients with T2D. PMID:25322269

  17. Phage display selection of peptides that home to atherosclerotic plaques: IL-4 receptor as a candidate target in atherosclerosis

    PubMed Central

    Hong, Hai-yan; Lee, Hwa Young; Kwak, Wonjung; Yoo, Jeongsoo; Na, Moon-Hee; So, In Seop; Kwon, Tae-Hwan; Park, Heon-Sik; Huh, Seung; Oh, Goo Taeg; Kwon, Ick-Chan; Kim, In-San; Lee, Byung-Heon

    2008-01-01

    Imaging or drug delivery tools for atherosclerosis based on the plaque biology are still insufficient. Here, we attempted to identify peptides that selectively home to atherosclerotic plaques using phage display. A phage library containing random peptides was ex viv screened for binding to human atheroma tissues. After three to four rounds of selection, the DNA inserts of phage clones wer sequenced. A peptide sequence, CRKRLDRNC, was the most frequently occurring one. Intravenously injected phage displaying the CRKRLDRNC peptide was observed to home to atherosclerotic aortic tissues of low-density lipoprotein receptor-deficient (Ldlr−/–) mice at higher levels than to normal aortic tissues of wild-type mice. Moreover, a fluorescein- or radioisotope-conjugated synthetic CRKRLDRNC peptide, but not a control peptide, homed in vivo to atherosclerotic plaques in Ldlr−/– mice, while homing of the peptide to other organs such as brain was minimal. The homing peptide co-localized with endothelial cells, macrophages and smooth muscle cells a mouse and human atherosclerotic plaques. Homology search revealed that the CRKRLDRNC peptide shares a motif of interleukin-receptor (IL-4) that is critical for binding to its receptor. The peptide indeed co-localized with IL-4 receptor (IL-4R) at atherosclerotic plaques. Moreover, the peptide bound to cultured cells expressing IL-4R on the cell surface and the binding was inhibited by the knock-down of IL-4R. These results show that the CRKRLDRNC peptide homes to atherosclerotic plaques through binding to IL-4R as its target and may be a useful tool for selective drug delivery and molecular imaging of atherosclerosis. PMID:19012727

  18. Potential Anti-Atherosclerotic Properties of Astaxanthin.

    PubMed

    Kishimoto, Yoshimi; Yoshida, Hiroshi; Kondo, Kazuo

    2016-02-01

    Astaxanthin is a naturally occurring red carotenoid pigment classified as a xanthophyll, found in microalgae and seafood such as salmon, trout, and shrimp. This review focuses on astaxanthin as a bioactive compound and outlines the evidence associated with its potential role in the prevention of atherosclerosis. Astaxanthin has a unique molecular structure that is responsible for its powerful antioxidant activities by quenching singlet oxygen and scavenging free radicals. Astaxanthin has been reported to inhibit low-density lipoprotein (LDL) oxidation and to increase high-density lipoprotein (HDL)-cholesterol and adiponectin levels in clinical studies. Accumulating evidence suggests that astaxanthin could exert preventive actions against atherosclerotic cardiovascular disease (CVD) via its potential to improve oxidative stress, inflammation, lipid metabolism, and glucose metabolism. In addition to identifying mechanisms of astaxanthin bioactivity by basic research, much more epidemiological and clinical evidence linking reduced CVD risk with dietary astaxanthin intake is needed. PMID:26861359

  19. Potential Anti-Atherosclerotic Properties of Astaxanthin

    PubMed Central

    Kishimoto, Yoshimi; Yoshida, Hiroshi; Kondo, Kazuo

    2016-01-01

    Astaxanthin is a naturally occurring red carotenoid pigment classified as a xanthophyll, found in microalgae and seafood such as salmon, trout, and shrimp. This review focuses on astaxanthin as a bioactive compound and outlines the evidence associated with its potential role in the prevention of atherosclerosis. Astaxanthin has a unique molecular structure that is responsible for its powerful antioxidant activities by quenching singlet oxygen and scavenging free radicals. Astaxanthin has been reported to inhibit low-density lipoprotein (LDL) oxidation and to increase high-density lipoprotein (HDL)-cholesterol and adiponectin levels in clinical studies. Accumulating evidence suggests that astaxanthin could exert preventive actions against atherosclerotic cardiovascular disease (CVD) via its potential to improve oxidative stress, inflammation, lipid metabolism, and glucose metabolism. In addition to identifying mechanisms of astaxanthin bioactivity by basic research, much more epidemiological and clinical evidence linking reduced CVD risk with dietary astaxanthin intake is needed. PMID:26861359

  20. Atherosclerotic carotid stenosis and cognitive function.

    PubMed

    Wang, Tao; Mei, Bin; Zhang, Junjian

    2016-07-01

    Atherosclerosis carotid stenosis is associated with stroke and cognitive impairment. Progressive cognitive decline may be an even greater problem than stroke, but it has not been widely recognized and therefore must be adequately addressed. Although both Carotid Endarterectomy (CEA) and Carotid Artery Stenting (CAS) have been proven can prevent future stroke in patients with atherosclerotic carotid stenosis, the influence of CEA and CAS on cognitive function is not clear. In the first part of this review, we evaluated the literature concerning carotid stenosis and the risk of cognitive impairment. Studies have suggested that both symptomatic and asymptomatic carotid stenosis are associated with cognitive impairment. In the second part, we reviewed the impact of CEA and CAS on cognitive function, some studies have shown benefits, but others have not. PMID:27152468

  1. [Advancement and goals of the aviation human engineering].

    PubMed

    Stupakov, G P; Ushakov, I B; Turzin, P S

    1997-01-01

    Analyzed were the efforts of the State Scientific-Research Test Institute of Aviation and Space Medicine to weigh and account the human factor in designing and upgrading avionics and aviation machinery. Described are the policy of human engineering support to the development, evaluation, and operation of aviation machinery, and the benefits from the human factor knowledge to the specifications for aviation machinery and allowance for the psychophysiological aptitudes of human on different phases of development of ergatic aviation systems. Outlined is the mainstream of ergonomic enhancement of the quality and safety, and humanization of the activities of different aviation specialists. PMID:9156675

  2. A statin-loaded reconstituted high-density lipoprotein nanoparticle inhibits atherosclerotic plaque inflammation

    NASA Astrophysics Data System (ADS)

    Duivenvoorden, Raphaël; Tang, Jun; Cormode, David P.; Mieszawska, Aneta J.; Izquierdo-Garcia, David; Ozcan, Canturk; Otten, Maarten J.; Zaidi, Neeha; Lobatto, Mark E.; van Rijs, Sarian M.; Priem, Bram; Kuan, Emma L.; Martel, Catherine; Hewing, Bernd; Sager, Hendrik; Nahrendorf, Matthias; Randolph, Gwendalyn J.; Stroes, Erik S. G.; Fuster, Valentin; Fisher, Edward A.; Fayad, Zahi A.; Mulder, Willem J. M.

    2014-01-01

    Inflammation is a key feature of atherosclerosis and a target for therapy. Statins have potent anti-inflammatory properties but these cannot be fully exploited with oral statin therapy due to low systemic bioavailability. Here we present an injectable reconstituted high-density lipoprotein (rHDL) nanoparticle carrier vehicle that delivers statins to atherosclerotic plaques. We demonstrate the anti-inflammatory effect of statin-rHDL in vitro and show that this effect is mediated through the inhibition of the mevalonate pathway. We also apply statin-rHDL nanoparticles in vivo in an apolipoprotein E-knockout mouse model of atherosclerosis and show that they accumulate in atherosclerotic lesions in which they directly affect plaque macrophages. Finally, we demonstrate that a 3-month low-dose statin-rHDL treatment regimen inhibits plaque inflammation progression, while a 1-week high-dose regimen markedly decreases inflammation in advanced atherosclerotic plaques. Statin-rHDL represents a novel potent atherosclerosis nanotherapy that directly affects plaque inflammation.

  3. A Statin-Loaded Reconstituted High-Density Lipoprotein Nanoparticle Inhibits Atherosclerotic Plaque Inflammation

    PubMed Central

    Duivenvoorden, Raphaël; Tang, Jun; Cormode, David P.; Mieszawska, Aneta J.; Izquierdo-Garcia, David; Ozcan, Canturk; Otten, Maarten J.; Zaidi, Neeha; Lobatto, Mark E.; van Rijs, Sarian M.; Priem, Bram; Kuan, Emma L.; Martel, Catherine; Hewing, Bernd; Sager, Hendrik; Nahrendorf, Matthias; Randolph, Gwendalyn J.; Stroes, Erik S.G.; Fuster, Valentin; Fisher, Edward A.; Fayad, Zahi A.; Mulder, Willem J.M.

    2014-01-01

    Inflammation is a key feature of atherosclerosis and a target for therapy. Statins have potent anti-inflammatory properties but these cannot be fully exploited with oral statin therapy due to low systemic bioavailability. Here we present an injectable reconstituted high-density lipoprotein (rHDL) nanoparticle carrier vehicle that delivers statins to atherosclerotic plaques. We demonstrate the anti-inflammatory effect of statin-rHDL in vitro and show this effect is mediated through inhibition of the mevalonate pathway. We also apply statin-rHDL nanoparticles in vivo in an apolipoprotein E-knockout mouse model of atherosclerosis and show they accumulate in atherosclerotic lesions where they directly affect plaque macrophages. Finally we demonstrate that a three-month low-dose statin-rHDL treatment regimen inhibits plaque inflammation progression, while a one-week high-dose regimen markedly decreases inflammation in advanced atherosclerotic plaques. Statin-rHDL represents a novel potent atherosclerosis nanotherapy that directly affects plaque inflammation. PMID:24445279

  4. Subsurface ablation of atherosclerotic plaque using ultrafast laser pulses

    PubMed Central

    Lanvin, Thomas; Conkey, Donald B.; Frobert, Aurelien; Valentin, Jeremy; Goy, Jean-Jacques; Cook, Stéphane; Giraud, Marie-Noelle; Psaltis, Demetri

    2015-01-01

    We perform subsurface ablation of atherosclerotic plaque using ultrafast pulses. Excised mouse aortas containing atherosclerotic plaque were ablated with ultrafast near-infrared (NIR) laser pulses. Optical coherence tomography (OCT) was used to observe the ablation result, while the physical damage was inspected in histological sections. We characterize the effects of incident pulse energy on surface damage, ablation hole size, and filament propagation. We find that it is possible to ablate plaque just below the surface without causing surface damage, which motivates further investigation of ultrafast ablation for subsurface atherosclerotic plaque removal. PMID:26203381

  5. Detection of Intraplaque Hemorrhage in Mouse Atherosclerotic Lesions.

    PubMed

    Sluimer, Judith C; Gijbels, Marion J; Heeneman, Sylvia

    2015-01-01

    Intraplaque hemorrhage is defined as the presence of fresh or lysed erythrocytes, iron deposits in macrophages, and/or a fibrin clot in an atherosclerotic plaque. These features can be detected by hematoxylin and eosin, Martius scarlet Blue, and Perl's iron histological stainings. It is noteworthy that intraplaque hemorrhage is only present in murine atherosclerotic plaques after additional interventions or additional genetic traits affecting matrix degradation or thrombosis. In this chapter, we describe methods to detect intraplaque hemorrhage in mouse atherosclerotic lesions. PMID:26445801

  6. Endothelial cells and macrophages, partners in atherosclerotic plaque progression.

    PubMed

    Antohe, Felicia

    2006-01-01

    Heart disease and stroke, the main cardiovascular diseases (CVD), have become global epidemics in our days. High levels of cholesterol and other abnormal lipids are among the main risk factors of atherosclerosis, the number one killer in the world. However, recent advances in CVD treatment together with improvements in surgical techniques have increased the quality of life and reduced premature death rates and disabilities. Nevertheless, they still add a heavy burden to the rising global costs of health care. The medical priorities highlight not only the need for early recognition of the warning signs of a heart attack, but also the need for early biomarkers for prevention. Two active partners in the development and progression of atherosclerotic plaques are the macrophages and endothelial cells that influence each other and modify the microenvironment composition of the plaque leading to either rapid progression or regression of individual lesions in patients. In this review we address two specific aspects related to atherosclerosis: i) the way in which folic acid and folic acid conjugates may be helpful to identify activated macrophages and ii) the high potential of proteomic analysis to evidence and identify the multiple changes induced in activated vascular cells. PMID:17178598

  7. Planetary protection issues in advance of human exploration of Mars.

    PubMed

    McKay, C P; Davis, W L

    1989-01-01

    Current planetary quarantine considerations focus on robotic missions and attempt a policy of no biological contamination. The presence of humans on Mars, however, will inevitably result in biological contamination and physical alteration of the local environment. The focus of planetary quarantine must therefore shift toward defining and minimizing the inevitable contamination associated with humans. This will involve first determining those areas that will be affected by the presence of a human base, then verifying that these environments do not harbor indigenous life nor provide sites for Earth bacteria to grow. Precursor missions can provide salient information that can make more efficient the planning and design of human exploration missions. In particular, a robotic sample return mission can help to eliminate the concern about returning samples with humans or the return of humans themselves from a planetary quarantine perspective. Without a robotic return the cost of quarantine that would have to be added to a human mission may well exceed the cost of a robotic return mission. Even if the preponderance of scientific evidence argues against the presence of indigenous life, it must be considered as part of any serious planetary quarantine analysis for missions to Mars. If there is life on Mars, the question of human exploration assumes an ethical dimension. PMID:11537372

  8. Human Intelligence: An Introduction to Advances in Theory and Research.

    ERIC Educational Resources Information Center

    Lohman, David F.

    1989-01-01

    Recent advances in three research traditions are summarized: trait theories of intelligence, information-processing theories of intelligence, and general theories of thinking. Work on fluid and crystallized abilities by J. Horn and R. Snow, mental speed, spatial visualization, cognitive psychology, artificial intelligence, and the construct of…

  9. Planetary protection issues in advance of human exploration of Mars

    NASA Technical Reports Server (NTRS)

    Mckay, Christopher P.; Davis, Wanda L.

    1989-01-01

    The major planetary quarantine issues associated with human exploration of Mars, which is viewed as being more likely to harbor indigenous life than is the moon, are discussed. Special attention is given to the environmental impact of human missions to Mars due to contamination and mechanical disturbances of the local environment, the contamination issues associated with the return of humans, and the planetary quarantine strategy for a human base. It is emphasized that, in addition to the question of indigenous life, there may be some concern of returning to earth the earth microorganisms that have spent some time in the Martian environment. It is suggested that, due to the fact that a robot system can be subjected to more stringent controls and protective treatments than a mission involving humans, a robotic sample return mission can help to eliminate many planetary-quarantine concerns about returning samples.

  10. Imaging of oxidation-specific epitopes with targeted nanoparticles to detect high-risk atherosclerotic lesions: Progress and future directions

    PubMed Central

    Briley-Saebo, Karen; Yeang, Calvin; Witztum, Joseph L.; Tsimikas, Sotirios

    2014-01-01

    Oxidation-specific epitopes (OSE) within developing atherosclerotic lesions are key antigens that drive innate and adaptive immune responses in atherosclerosis, leading to chronic inflammation. Oxidized phospholipids and malondialdehyde-lysine epitopes are well-characterized OSE present in human atherosclerotic lesions, particularly in pathologically defined vulnerable plaques. Using murine and human OSE-specific antibodies as targeting agents, we have developed radionuclide and magnetic resonance based nanoparticles, containing gadolinium, manganese or lipid-coated ultrasmall superparamagnetic iron oxide, to noninvasively image OSE within experimental atherosclerotic lesions. These methods quantitate plaque burden, allow detection of lesion progression and regression, plaque stabilization, and accumulation of OSE within macrophage-rich areas of the artery wall, suggesting they detect the most active lesions. Future studies will focus on using “natural” antibodies, lipopeptides and mimotopes for imaging applications. These approaches should enhance the clinical translation of this technique to image, monitor, evaluate efficacy of novel therapeutic agents and guide optimal therapy of high-risk atherosclerotic lesions. PMID:25297940

  11. Imaging of oxidation-specific epitopes with targeted nanoparticles to detect high-risk atherosclerotic lesions: progress and future directions.

    PubMed

    Briley-Saebo, Karen; Yeang, Calvin; Witztum, Joseph L; Tsimikas, Sotirios

    2014-11-01

    Oxidation-specific epitopes (OSE) within developing atherosclerotic lesions are key antigens that drive innate and adaptive immune responses in atherosclerosis, leading to chronic inflammation. Oxidized phospholipids and malondialdehyde-lysine epitopes are well-characterized OSE present in human atherosclerotic lesions, particularly in pathologically defined vulnerable plaques. Using murine and human OSE-specific antibodies as targeting agents, we have developed radionuclide and magnetic resonance based nanoparticles, containing gadolinium, manganese or lipid-coated ultrasmall superparamagnetic iron oxide, to non-invasively image OSE within experimental atherosclerotic lesions. These methods quantitate plaque burden, allow detection of lesion progression and regression, plaque stabilization, and accumulation of OSE within macrophage-rich areas of the artery wall, suggesting they detect the most active lesions. Future studies will focus on using "natural" antibodies, lipopeptides, and mimotopes for imaging applications. These approaches should enhance the clinical translation of this technique to image, monitor, evaluate efficacy of novel therapeutic agents, and guide optimal therapy of high-risk atherosclerotic lesions. PMID:25297940

  12. A single-photon fluorescence and multi-photon spectroscopic study of atherosclerotic lesions

    NASA Astrophysics Data System (ADS)

    Smith, Michael S. D.; Ko, Alex C. T.; Ridsdale, Andrew; Schattka, Bernie; Pegoraro, Adrian; Hewko, Mark D.; Shiomi, Masashi; Stolow, Albert; Sowa, Michael G.

    2009-06-01

    In this study we compare the single-photon autofluorescence and multi-photon emission spectra obtained from the luminal surface of healthy segments of artery with segments where there are early atherosclerotic lesions. Arterial tissue was harvested from atherosclerosis-prone WHHL-MI rabbits (Watanabe heritable hyperlipidemic rabbit-myocardial infarction), an animal model which mimics spontaneous myocardial infarction in humans. Single photon fluorescence emission spectra of samples were acquired using a simple spectrofluorometer set-up with 400 nm excitation. Samples were also investigated using a home built multi-photon microscope based on a Ti:sapphire femto-second oscillator. The excitation wavelength was set at 800 nm with a ~100 femto-second pulse width. Epi-multi-photon spectroscopic signals were collected through a fibre-optics coupled spectrometer. While the single-photon fluorescence spectra of atherosclerotic lesions show minimal spectroscopic difference from those of healthy arterial tissue, the multi-photon spectra collected from atherosclerotic lesions show marked changes in the relative intensity of two-photon excited fluorescence (TPEF) and second-harmonic generation (SHG) signals when compared with those from healthy arterial tissue. The observed sharp increase of the relative SHG signal intensity in a plaque is in agreement with the known pathology of early lesions which have increased collagen content.

  13. Modeling of Mechanical Stress Exerted by Cholesterol Crystallization on Atherosclerotic Plaques

    PubMed Central

    Cui, Dongyao; Yu, Xiaojun; Chen, Si; Liu, Xinyu; Tang, Hongying; Wang, Xianghong; Liu, Linbo

    2016-01-01

    Plaque rupture is the critical cause of cardiovascular thrombosis, but the detailed mechanisms are not fully understood. Recent studies have found abundant cholesterol crystals in ruptured plaques, and it has been proposed that the rapid expansion of cholesterol crystals in a limited space during crystallization may contribute to plaque rupture. To evaluate the effect of cholesterol crystal growth on atherosclerotic plaques, we modeled the expansion of cholesterol crystals during the crystallization process in the necrotic core and estimated the stress on the thin cap with different arrangements of cholesterol crystals. We developed a two-dimensional finite element method model of atherosclerotic plaques containing expanding cholesterol crystals and investigated the effect of the magnitude and distribution of crystallization on the peak circumferential stress born by the cap. Using micro-optical coherence tomography (μOCT), we extracted the cross-sectional geometric information of cholesterol crystals in human atherosclerotic aorta tissue ex vivo and applied the information to the model. The results demonstrate that (1) the peak circumference stress is proportionally dependent on the cholesterol crystal growth; (2) cholesterol crystals at the cap shoulder impose the highest peak circumference stress; and (3) spatial distributions of cholesterol crystals have a significant impact on the peak circumference stress: evenly distributed cholesterol crystals exert less peak circumferential stress on the cap than concentrated crystals. PMID:27149381

  14. Automated tissue characterization of in vivo atherosclerotic plaques by intravascular optical coherence tomography images

    PubMed Central

    Ughi, Giovanni Jacopo; Adriaenssens, Tom; Sinnaeve, Peter; Desmet, Walter; D’hooge, Jan

    2013-01-01

    Intravascular optical coherence tomography (IVOCT) is rapidly becoming the method of choice for the in vivo investigation of coronary artery disease. While IVOCT visualizes atherosclerotic plaques with a resolution <20µm, image analysis in terms of tissue composition is currently performed by a time-consuming manual procedure based on the qualitative interpretation of image features. We illustrate an algorithm for the automated and systematic characterization of IVOCT atherosclerotic tissue. The proposed method consists in a supervised classification of image pixels according to textural features combined with the estimated value of the optical attenuation coefficient. IVOCT images of 64 plaques, from 49 in vivo IVOCT data sets, constituted the algorithm’s training and testing data sets. Validation was obtained by comparing automated analysis results to the manual assessment of atherosclerotic plaques. An overall pixel-wise accuracy of 81.5% with a classification feasibility of 76.5% and per-class accuracy of 89.5%, 72.1% and 79.5% for fibrotic, calcified and lipid-rich tissue respectively, was found. Moreover, measured optical properties were in agreement with previous results reported in literature. As such, an algorithm for automated tissue characterization was developed and validated using in vivo human data, suggesting that it can be applied to clinical IVOCT data. This might be an important step towards the integration of IVOCT in cardiovascular research and routine clinical practice. PMID:23847728

  15. Advanced human-system interface design review guideline. Evaluation procedures and guidelines for human factors engineering reviews

    SciTech Connect

    O`Hara, J.M.; Brown, W.S.; Baker, C.C.; Welch, D.L.; Granda, T.M.; Vingelis, P.J.

    1994-07-01

    Advanced control rooms will use advanced human-system interface (HSI) technologies that may have significant implications for plant safety in that they will affect the operator`s overall role in the system, the method of information presentation, and the ways in which operators interact with the system. The U.S. Nuclear Regulatory Commission (NRC) reviews the HSI aspects of control rooms to ensure that they are designed to good human factors engineering principles and that operator performance and reliability are appropriately supported to protect public health and safety. The principal guidance available to the NRC, however, was developed more than ten years ago, well before these technological changes. Accordingly, the human factors guidance needs to be updated to serve as the basis for NRC review of these advanced designs. The purpose of this project was to develop a general approach to advanced HSI review and the human factors guidelines to support. NRC safety reviews of advanced systems. This two-volume report provides the results of the project. Volume I describes the development of the Advanced HSI Design Review Guideline (DRG) including (1) its theoretical and technical foundation, (2) a general model for the review of advanced HSIs, (3) guideline development in both hard-copy and computer-based versions, and (4) the tests and evaluations performed to develop and validate the DRG. Volume I also includes a discussion of the gaps in available guidance and a methodology for addressing them. Volume 2 provides the guidelines to be used for advanced HSI review and the procedures for their use.

  16. Management of atherosclerotic renovascular disease after Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL).

    PubMed

    Herrmann, Sandra M S; Saad, Ahmed; Textor, Stephen C

    2015-03-01

    Many patients with occlusive atherosclerotic renovascular disease (ARVD) may be managed effectively with medical therapy for several years without endovascular stenting, as demonstrated by randomized, prospective trials including the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) trial, the Angioplasty and Stenting for Renal Artery Lesions (ASTRAL) trial and the Stent Placement and Blood Pressure and Lipid-Lowering for the Prevention of Progression of Renal Dysfunction Caused by Atherosclerotic Ostial Stenosis of the Renal Artery (STAR) and ASTRAL. These trials share the limitation of excluding subsets of patients with high-risk clinical presentations, including episodic pulmonary edema and rapidly progressing renal failure and hypertension. Although hemodynamically significant, ARVD can reduce renal blood flow and glomerular filtration rate; adaptive mechanisms preserve both cortical and medullary oxygenation over a wide range of vascular occlusion. Progression of ARVD to severe vascular compromise eventually produces cortical hypoxia, however, associated with active inflammatory cytokine release and cellular infiltration of the renal parenchyma. In such cases ARVD produces a loss of glomerular filtration rate that no longer is reversible simply by restoring vessel patency with technically successful renal revascularization. Each of these trials reported adverse renal functional outcomes ranging between 16 and 22% over periods of 2-5 years of follow-up. Blood pressure control and medication adjustment may become more difficult with declining renal function and may prevent the use of angiotensin receptor blocker and angiotensin-converting enzyme inhibitors. The objective of this review is to evaluate the current management of ARVD for clinical nephrologists in the context of recent randomized clinical trials and experimental research. PMID:24723543

  17. Advance techniques for monitoring human tolerance to positive Gz accelerations

    NASA Technical Reports Server (NTRS)

    Pelligra, R.; Sandler, H.; Rositano, S.; Skrettingland, K.; Mancini, R.

    1973-01-01

    Tolerance to positive g accelerations was measured in ten normal male subjects using both standard and advanced techniques. In addition to routine electrocardiogram, heart rate, respiratory rate, and infrared television, monitoring techniques during acceleration exposure included measurement of peripheral vision loss, noninvasive temporal, brachial, and/or radial arterial blood flow, and automatic measurement of indirect systolic and diastolic blood pressure at 60-sec intervals. Although brachial and radial arterial flow measurements reflected significant cardiovascular changes during and after acceleration, they were inconsistent indices of the onset of grayout or blackout. Temporal arterial blood flow, however, showed a high correlation with subjective peripheral light loss.

  18. ACTIVATION OF T LYMPHOCYTES IN ATHEROSCLEROTIC PLAQUES

    PubMed Central

    Grivel, Jean-Charles; Ivanova, Oxana; Pinegina, Natalia; Blank, Paul S.; Shpektor, Alexander; Margolis, Leonid B.; Vasilieva, Elena

    2011-01-01

    Objective To decipher the immunological mechanisms of plaque maturation and rupture, it is necessary to analyze the phenotypes and distribution of individual lymphocytes which migrate to the plaques as well as their activation at different stages of plaque formation. Methods and Results We developed a protocol to isolate plaque-residing immune cells and analyze their status using polychromatic flow cytometry. We found that the composition and phenotype of T lymphocytes in the plaques differs from that in blood. CD4 and, in particular, CD8+ T cells in plaques are highly activated; the fraction of CD8 T cells co-expressing CD25 and HLA-DR in plaques was 10 times larger than in blood. Conclusions The first flow-cytoanalysis of individual T cells in atherosclerotic plaques indicates that plaques represent a separate immunological compartment from blood with lymphocytes characterized by a high level of T cells activation, which is compatible with the presence of antigen(s) that trigger infiltration activation of these cells. The ability to isolate and characterize these cells may lead to the identification of such antigens. PMID:21960562

  19. Modeling of Experimental Atherosclerotic Plaque Delamination.

    PubMed

    Leng, Xiaochang; Chen, Xin; Deng, Xiaomin; Sutton, Michael A; Lessner, Susan M

    2015-12-01

    A cohesive zone model (CZM) approach is applied to simulate atherosclerotic plaque delamination experiments in mouse abdominal aorta specimens. A three-dimensional finite element model is developed for the experiments. The aortic wall is treated as a fiber-reinforced, highly deformable, incompressible material, and the Holzapfel-Gasser-Ogden (HGO) model is adopted for the aortic bulk material behavior. Cohesive elements are placed along the plaque-media interface along which delamination occurs. The 3D specimen geometry is created based on images from the experiments and certain simplifying approximations. A set of HGO and CZM parameter values is determined based on values suggested in the literature and through matching simulation predictions of the load vs. load-point displacement curve with experimental measurements for one loading-delamination-unloading cycle. Using this set of parameter values, simulation predictions for four other loading-delamination-unloading cycles are obtained, which show good agreement with experimental measurements. The findings of the current study demonstrate the applicability of the CZM approach in arterial tissue failure simulations. PMID:26101030

  20. Human Factors Evaluation of Advanced Electric Power Grid Visualization Tools

    SciTech Connect

    Greitzer, Frank L.; Dauenhauer, Peter M.; Wierks, Tamara G.; Podmore, Robin

    2009-04-01

    This report describes initial human factors evaluation of four visualization tools (Graphical Contingency Analysis, Force Directed Graphs, Phasor State Estimator and Mode Meter/ Mode Shapes) developed by PNNL, and proposed test plans that may be implemented to evaluate their utility in scenario-based experiments.

  1. Human Relationships That Nurture and Advance the Construction of Knowledge.

    ERIC Educational Resources Information Center

    Herman, William E.; Gwaltney, Thomas M.

    This paper reviews the historical antecedents and theoretical foundation for a constructivist approach to teaching and learning. One neglected characteristic of constructivism apparent in the professional literature is the need to better understand that human relationships in the classroom are often pivotal in helping students construct knowledge.…

  2. Total Human Exposure Risk Database and Advance Simulaiton Environment

    EPA Science Inventory

    THERdbASE is no longer supported by EPA and is no longer available as download.

    THERdbASE is a collection of databases and models that are useful to assist in conducting assessments of human exposure to chemical pollutants, especial...

  3. Human Factors Engineering Review Model for advanced nuclear power reactors

    SciTech Connect

    O'Hara, J.; Higgins, J. ); Goodman, C.; Galletti, G.: Eckenrode, R. )

    1993-01-01

    One of the major issues to emerge from the initial design reviews under the certification process was that detailed human-systems interface (HSI) design information was not available for staff review. To address the lack of design detail issue. The Nuclear Regulatory Commission (NRC) is performing the design certification reviews based on a design process plan which describes the human factors engineering (HFE) program elements that are necessary and sufficient to develop an acceptable detailed design specification. Since the review of a design process is unprecedented in the nuclear industry. The criteria for review are not addressed by current regulations or guidance documents and. therefore, had to be developed. Thus, an HFE Program Review Model was developed. This paper will describe the model's rationale, scope, objectives, development, general characteristics. and application.

  4. Human Factors Engineering Review Model for advanced nuclear power reactors

    SciTech Connect

    O`Hara, J.; Higgins, J.; Goodman, C.; Galletti, G.: Eckenrode, R.

    1993-05-01

    One of the major issues to emerge from the initial design reviews under the certification process was that detailed human-systems interface (HSI) design information was not available for staff review. To address the lack of design detail issue. The Nuclear Regulatory Commission (NRC) is performing the design certification reviews based on a design process plan which describes the human factors engineering (HFE) program elements that are necessary and sufficient to develop an acceptable detailed design specification. Since the review of a design process is unprecedented in the nuclear industry. The criteria for review are not addressed by current regulations or guidance documents and. therefore, had to be developed. Thus, an HFE Program Review Model was developed. This paper will describe the model`s rationale, scope, objectives, development, general characteristics. and application.

  5. Advances in Analysis of Human Milk Oligosaccharides123

    PubMed Central

    Ruhaak, L. Renee; Lebrilla, Carlito B.

    2012-01-01

    Oligosaccharides in human milk strongly influence the composition of the gut microflora of neonates. Because it is now clear that the microflora play important roles in the development of the infant immune system, human milk oligosaccharides (HMO) are studied frequently. Milk samples contain complex mixtures of HMO, usually comprising several isomeric structures that can be either linear or branched. Traditionally, HMO profiling was performed using HPLC with fluorescence or UV detection. By using porous graphitic carbon liquid chromatography MS, it is now possible to separate and identify most of the isomers, facilitating linkage-specific analysis. Matrix-assisted laser desorption ionization time-of-flight analysis allows fast profiling, but does not allow isomer separation. Novel MS fragmentation techniques have facilitated structural characterization of HMO that are present at lower concentrations. These techniques now facilitate more accurate studies of HMO consumption as well as Lewis blood group determinations. PMID:22585919

  6. Advances in functional magnetic resonance imaging of the human brainstem.

    PubMed

    Beissner, Florian; Schumann, Andy; Brunn, Franziska; Eisenträger, Daniela; Bär, Karl-Jürgen

    2014-02-01

    The brainstem is of tremendous importance for our daily survival, and yet the functional relationships between various nuclei, their projection targets, and afferent regulatory areas remain poorly characterized. The main reason for this lies in the sub-optimal performance of standard neuroimaging methods in this area. In particular, fMRI signals are much harder to detect in the brainstem region compared to cortical areas. Here we describe and validate a new approach to measure activation of brainstem nuclei in humans using standard fMRI sequences and widely available tools for statistical image processing. By spatially restricting an independent component analysis to an anatomically defined brainstem mask, we excluded those areas from the analysis that were strongly affected by physiological noise. This allowed us to identify for the first time intrinsic connectivity networks in the human brainstem and to map brainstem-cortical connectivity purely based on functionally defined regions of interest. PMID:23933038

  7. Oncolytic virotherapy for human malignant mesothelioma: recent advances

    PubMed Central

    Boisgerault, Nicolas; Achard, Carole; Delaunay, Tiphaine; Cellerin, Laurent; Tangy, Frédéric; Grégoire, Marc; Fonteneau, Jean-François

    2015-01-01

    Cancer virotherapy is an attractive alternative to conventional treatments because it offers a wide range of antitumor effects due to 1) the diversity of the oncolytic viruses that are now available and 2) their multifaceted activities against both tumor cells and tumor vessels, in addition to their ability to induce antitumor immune responses. In this review, we summarize preclinical and clinical data regarding the targeting of malignant mesothelioma (MM) by oncolytic viruses. We also discuss the potential of other oncolytic viruses that have already shown antitumor effects against several malignancies in advanced clinical trials but are yet to be tested against MM cells. Finally, we review how the activation of the immune system and combinations with other types of anticancer treatments could support the development of oncolytic virotherapy for the treatment of MM. PMID:27512676

  8. Setaria digitata in advancing our knowledge of human lymphatic filariasis.

    PubMed

    Perumal, A N I; Gunawardene, Y I N S; Dassanayake, R S

    2016-03-01

    Setaria digitata is a filarial parasite that causes fatal cerebrospinal nematodiasis in goats, sheep and horses, resulting in substantial economic losses in animal husbandry in the tropics. Due to its close resemblance to Wuchereria bancrofti, this nematode is also frequently used as a model organism to study human lymphatic filariasis. This review highlights numerous insights into the morphological, histological, biochemical, immunological and genetic aspects of S. digitata that have broadened our understanding towards the control and eradication of filarial diseases. PMID:25924635

  9. Advance techniques for monitoring human tolerance to +Gz accelerations.

    NASA Technical Reports Server (NTRS)

    Pelligra, R.; Sandler, H.; Rositano, S.; Skrettingland, K.; Mancini, R.

    1972-01-01

    Standard techniques for monitoring the acceleration-stressed human subject have been augmented by measuring (1) temporal, brachial and/or radial arterial blood flow, and (2) indirect systolic and diastolic blood pressure at 60-sec intervals. Results show that the response of blood pressure to positive accelerations is complex and dependent on an interplay of hydrostatic forces, diminishing venous return, redistribution of blood, and other poorly defined compensatory reflexes.

  10. Recent Advances in Computational Mechanics of the Human Knee Joint

    PubMed Central

    Kazemi, M.; Dabiri, Y.; Li, L. P.

    2013-01-01

    Computational mechanics has been advanced in every area of orthopedic biomechanics. The objective of this paper is to provide a general review of the computational models used in the analysis of the mechanical function of the knee joint in different loading and pathological conditions. Major review articles published in related areas are summarized first. The constitutive models for soft tissues of the knee are briefly discussed to facilitate understanding the joint modeling. A detailed review of the tibiofemoral joint models is presented thereafter. The geometry reconstruction procedures as well as some critical issues in finite element modeling are also discussed. Computational modeling can be a reliable and effective method for the study of mechanical behavior of the knee joint, if the model is constructed correctly. Single-phase material models have been used to predict the instantaneous load response for the healthy knees and repaired joints, such as total and partial meniscectomies, ACL and PCL reconstructions, and joint replacements. Recently, poromechanical models accounting for fluid pressurization in soft tissues have been proposed to study the viscoelastic response of the healthy and impaired knee joints. While the constitutive modeling has been considerably advanced at the tissue level, many challenges still exist in applying a good material model to three-dimensional joint simulations. A complete model validation at the joint level seems impossible presently, because only simple data can be obtained experimentally. Therefore, model validation may be concentrated on the constitutive laws using multiple mechanical tests of the tissues. Extensive model verifications at the joint level are still crucial for the accuracy of the modeling. PMID:23509602

  11. Prevalence of Foam Cells and Helper-T cells in Atherosclerotic Plaques of Korean Patients with Carotid Atheroma

    PubMed Central

    Lee, Won-Ha; Ko, Young-Hyeh; Kim, Dong-Ik; Lee, Byung-Boong; Park, Jeong-Euy

    2000-01-01

    Background Inflammation and activation of immune cells have important roles in the pathogenesis of atherosclerosis. We analyzed the involvement of various immune cells in the pathogenesis of atherosclerosis. Methods We investigated the presence of foam cells, lymphocytes and killer cells in 11 atherosclerotic plaque specimens removed from Korean patients who underwent carotid endoarterectomy. Atherosclerotic plaques were analyzed by immunohistochemistry using monoclonal antibody specific to foam cells (anti-CD68), pan-T cells (anti-CD3), helper-T cells (anti-CD4), cytotoxic T cells (anti-CD8), granular component of killer cells (anti-TIA-1) and pan-B cells (anti-CD20). Results Analysis revealed a general infiltration of immune cells not only in atherosclerotic plaques but also in the vascular wall adjacent to the plaque. Heavy infiltration of CD68+ macrophage was observed in all cases. In addition, significant infiltration of CD3+ T-lymphocytes was observed in all cases, while CD20+ B-cells were observed in only a few cases. Majority of the CD3+ cells was found to be CD4+ helper-T cells. CD8+ cytotoxic T cells and TIA-1+ cells were less prominent. Conclusion Analysis of the human atherosclerotic plaques suggested that helper-T cells and foam cells had a major role in the plaque development. PMID:10992723

  12. Atherosclerotic vascular disease in systemic lupus erythematosus.

    PubMed Central

    Liang, Matthew H.; Mandl, Lisa A.; Costenbader, Karen; Fox, Ervin; Karlson, Elizabeth

    2002-01-01

    In the United States, systemic lupus erythematosus (SLE) disproportionately affects African Americans. It has become a chronic disease with long-term morbidity including chronic renal disease, osteoporosis, cataracts, psychosocial impairment, and importantly, atherosclerotic vascular disease (ASVD). The latter (myocardial infarction, angina, peripheral vascular disease and stroke) are strikingly accelerated, occurring in subjects who are predominantly premenopausal women at an age when ASVD is rare or unusual. Although much is known about the biology, risk factors, and the prevention of atherosclerosis in normal individuals, little work has been done in SLE. In fact, ASVD in people with SLE may be a different disease. Approximately 1.5% of SLE patients per year will have a myocardial infarction or equivalent; about 0.5% of SLE patients per year will have a stroke. The risk factors for ASVD in SLE are based on small, retrospective, single center studies. These suggest that the risk factors known for the general population (i.e., smoking, obesity, sedentary lifestyle, high LDL cholesterol, etc.) are also observed in SLE. The best study of risk factors shows that even accounting for the known factors, SLE and/or its treatment (glucocorticoids) is by far the most important. Our current management of cardiovascular risk factors in SLE patients with ASVD is substandard and our adherence to national guidelines for prevention is substandard. It is not known whether improving either will prevent these disastrous outcomes. Very little is known about the risk factors in African Americans with SLE, although there is data to suggest that they may not be identical to those seen in Caucasian populations. The study of the best and most effective means to prevent ASVD in SLE and in African Americans with SLE and in African Americans with SLE should be a major priority. PMID:12392045

  13. Advanced human-system interface design review guideline. General evaluation model, technical development, and guideline description

    SciTech Connect

    O`Hara, J.M.

    1994-07-01

    Advanced control rooms will use advanced human-system interface (HSI) technologies that may have significant implications for plant safety in that they will affect the operator`s overall role in the system, the method of information presentation, and the ways in which operators interact with the system. The U.S. Nuclear Regulatory Commission (NRC) reviews the HSI aspects of control rooms to ensure that they are designed to good human factors engineering principles and that operator performance and reliability are appropriately supported to protect public health and safety. The principal guidance available to the NRC, however, was developed more than ten years ago, well before these technological changes. Accordingly, the human factors guidance needs to be updated to serve as the basis for NRC review of these advanced designs. The purpose of this project was to develop a general approach to advanced HSI review and the human factors guidelines to support NRC safety reviews of advanced systems. This two-volume report provides the results of the project. Volume I describes the development of the Advanced HSI Design Review Guideline (DRG) including (1) its theoretical and technical foundation, (2) a general model for the review of advanced HSIs, (3) guideline development in both hard-copy and computer-based versions, and (4) the tests and evaluations performed to develop and validate the DRG. Volume I also includes a discussion of the gaps in available guidance and a methodology for addressing them. Volume 2 provides the guidelines to be used for advanced HSI review and the procedures for their use.

  14. The dark and bright side of atherosclerotic calcification.

    PubMed

    Pugliese, Giuseppe; Iacobini, Carla; Blasetti Fantauzzi, Claudia; Menini, Stefano

    2015-02-01

    Vascular calcification is an unfavorable event in the natural history of atherosclerosis that predicts cardiovascular morbidity and mortality. However, increasing evidence suggests that different calcification patterns are associated with different or even opposite histopathological and clinical features, reflecting the dual relationship between inflammation and calcification. In fact, initial calcium deposition in response to pro-inflammatory stimuli results in the formation of spotty or granular calcification ("microcalcification"), which induces further inflammation. This vicious cycle favors plaque rupture, unless an adaptive response prevails, with blunting of inflammation and survival of vascular smooth muscle cells (VSMCs). VSMCs promote fibrosis and also undergo osteogenic transdifferentiation, with formation of homogeneous or sheet-like calcification ("macrocalcification"), that stabilizes the plaque by serving as a barrier towards inflammation. Unfortunately, little is known about the molecular mechanisms regulating this adaptive response. The advanced glycation/lipoxidation endproducts (AGEs/ALEs) have been shown to promote vascular calcification and atherosclerosis. Recent evidence suggests that two AGE/ALE receptors, RAGE and galectin-3, modulate in divergent ways, not only inflammation, but also vascular osteogenesis, by favoring "microcalcification" and "macrocalcification", respectively. Galectin-3 seems essential for VSMC transdifferentiation into osteoblast-like cells via direct modulation of the WNT-β-catenin signaling, thus driving formation of "macrocalcification", whereas RAGE favors deposition of "microcalcification" by promoting and perpetuating inflammation and by counteracting the osteoblastogenic effect of galectin-3. Further studies are required to understand the molecular mechanisms regulating transition from "microcalcification" to "macrocalcification", thus allowing to design therapeutic strategies which favor this adaptive process

  15. Development of a quantitative mechanical test of atherosclerotic plaque stability.

    PubMed

    Wang, Ying; Ning, Jinfeng; Johnson, John A; Sutton, Michael A; Lessner, Susan M

    2011-09-01

    Atherosclerotic plaque rupture is the main cause of myocardial infarction and stroke. Both clinical and computational studies indicate that the shoulder region, where a plaque joins the vessel wall, is rupture-prone. Previous mechanistic studies focused on mechanical properties of the fibrous cap and tensile stresses, which could lead to tearing of the cap. Based on clinical observations of "mobile floating plaques," we postulate that de-adhesion between the fibrous cap and the underlying vessel wall may also play a role in plaque failure. Thus, measuring adhesive strength of the bond between plaque and vascular wall may provide useful new insights into plaque stability. Delamination experiments, widely used in examining inter-laminar adhesive strength of biological materials, were used to measure adhesive strength of advanced plaques in apolipoprotein E-knockout (apoE-KO) mice after 8 months on Western diet. We measured adhesive strength in terms of local energy release rate, G, during controlled plaque delamination. As a measure of the fracture energy required to delaminate a unit area of plaque from the underlying internal elastic lamina (IEL), G provides a quantitative measure of local adhesive strength of the plaque-IEL interface. The values for G acquired from 16 plaques from nine apoE-KO mouse aortas formed a positively skewed distribution with a mean of 24.5 J/m(2), median of 19.3 J/m(2), first quartile of 10.8 J/m(2), and third quartile of 34.1 J/m(2). These measurements are in the lower range of values reported for soft tissues. Histological studies confirmed delamination occurred at the interface between plaque and IEL. PMID:21757197

  16. Decreased early atherosclerotic lesions in hypertriglyceridemic mice expressing cholesteryl ester transfer protein transgene.

    PubMed Central

    Hayek, T; Masucci-Magoulas, L; Jiang, X; Walsh, A; Rubin, E; Breslow, J L; Tall, A R

    1995-01-01

    The human cholesteryl ester transfer protein (CETP) facilitates the transfer of cholesteryl ester from HDL to triglyceride-rich lipoproteins. The activity of CETP results in a reduction in HDL cholesterol levels, but CETP may also promote reverse cholesterol transport. Thus, the net impact of CETP expression on atherogenesis is uncertain. The influence of hypertriglyceridemia and CETP on the development of atherosclerotic lesions in the proximal aorta was assessed by feeding transgenic mice a high cholesterol diet for 16 wk. 13 out of 14 (93%) hypertriglyceridemic human apo CIII (HuCIII) transgenic (Tg) mice developed atherosclerotic lesions, compared to 18 out of 29 (62%) controls. In HuCIII/CETPTg, human apo AI/CIIITg and HuAI/CIII/CETPTg mice, 7 of 13 (54%), 5 of 10 (50%), and 5 of 13 (38%), respectively, developed lesions in the proximal aorta (P < .05 compared to HuCIIITg). The average number of aortic lesions per mouse in HuCIIITg and controls was 3.4 +/- 0.8 and 2.7 +/- 0.6, respectively in HuCIII/CETPTg, HuAI/CIIIg, and HuAI/CIII/CETPTg mice the number of lesions was significantly lower than in HuCIIITg and control mice: 0.9 +/- 0.4, 1.5 +/- 0.5, and 0.9 +/- 0.4, respectively. There were parallel reductions in mean lesion area. In a separate study, we found an increased susceptibility to dietary atherosclerosis in nonhypertriglyceridemic CETP transgenic mice compared to controls. We conclude that CETP expression inhibits the development of early atherosclerotic lesions but only in hypertriglyceridemic mice. PMID:7560101

  17. Detection of atherosclerotic vascular tissue from optical coherence tomography images

    NASA Astrophysics Data System (ADS)

    Prakash, Ammu; Hewko, Mark; Sowa, Mike; Sherif, Sherif

    2012-10-01

    Atherosclerotic coronary artery disease continues to be one of the major causes of mortality. Prevention, diagnosis and treatment of atherosclerotic coronary artery disease are dependent on the detection of high risk atherosclerotic plaque. As age is one of the most important risk factors, atherosclerosis worsens steadily with increasing age. Automatic characterization of atherosclerotic plaque using the optical coherence tomography (OCT) images provides a powerful tool to classify patients with high risk plaque. In this study we develop an automatic classifier to detect atherosclerotic plaque in young and old Watanabe heritable hyperlipidemic (WHHL) rabbits, using OCT images without reliance on visual inspection. Our classifier based on texture analysis technique may provide an efficient tool for detecting invisible changes in tissue structure. We extracted a set of 22 statistical textural features for each image using the spatial gray level dependence matrix (SGLDM) method. An optimal scalar feature selection process was carried to select the best discriminating features that employ the Fisher discriminant ratio (FDR) criterion, and cross correlation measure between the pairs of features. Using these optimal features, we formed a combination of 5 best classification features using an exhaustive search method. A combined feature set was finally employed for the classification of plaque. We obtained correct classification rate and validation of 76.67% and 75% respectively.

  18. Ultrafast laser ablation for targeted atherosclerotic plaque removal

    NASA Astrophysics Data System (ADS)

    Lanvin, Thomas; Conkey, Donald B.; Descloux, Laurent; Frobert, Aurelien; Valentin, Jeremy; Goy, Jean-Jacques; Cook, Stéphane; Giraud, Marie-Noelle; Psaltis, Demetri

    2015-07-01

    Coronary artery disease, the main cause of heart disease, develops as immune cells and lipids accumulate into plaques within the coronary arterial wall. As a plaque grows, the tissue layer (fibrous cap) separating it from the blood flow becomes thinner and increasingly susceptible to rupturing and causing a potentially lethal thrombosis. The stabilization and/or treatment of atherosclerotic plaque is required to prevent rupturing and remains an unsolved medical problem. Here we show for the first time targeted, subsurface ablation of atherosclerotic plaque using ultrafast laser pulses. Excised atherosclerotic mouse aortas were ablated with ultrafast near-infrared (NIR) laser pulses. The physical damage was characterized with histological sections of the ablated atherosclerotic arteries from six different mice. The ultrafast ablation system was integrated with optical coherence tomography (OCT) imaging for plaque-specific targeting and monitoring of the resulting ablation volume. We find that ultrafast ablation of plaque just below the surface is possible without causing damage to the fibrous cap, which indicates the potential use of ultrafast ablation for subsurface atherosclerotic plaque removal. We further demonstrate ex vivo subsurface ablation of a plaque volume through a catheter device with the high-energy ultrafast pulse delivered via hollow-core photonic crystal fiber.

  19. Application of infrared fiber optic imaging in atherosclerotic plaques

    NASA Astrophysics Data System (ADS)

    Guo, Bujin; Casscells, S. W.; Bearman, Gregory H.; McNatt, Janice; Naghevi, Morteza; Malik, Basit A.; Gul, Khawar; Willerson, James T.

    1999-07-01

    Rupture of atherosclerotic plaques - the main cause of heart attach and stokes - is not predictable. Hence even treadmill stress tests fail to detect many persons at risk. Fatal plaques are found at autopsies to be associated with active inflammatory cells. Classically, inflammation is detected by its swelling, red color, pain and heat. We have found that heat accurately locates the dangerous plaques that are significantly warmer then atherosclerotic plaques without the same inflammation. In order to develop a non-surgical method of locating these plaques, an IR fiber optic imaging system has been developed in our laboratory to evalute the causes and effect of heat in atherosclerotic plaques. The fiber optical imagin bundle consists of 900 individual As2S3 chalcogenide glass fibers which transmit IR radiation from 0.7 micrometers 7 micrometers with little energy loss. By combining that with a highly sensitive Indium Antimonide IR focal plane array detector, we are able to obtain thermal graphic images in situ. The temperature heterogeneity of atherosclerotic plaques developed in the arteral of the experimental animal models is under study with the new device. The preliminary experimental results from the animal model are encouraging. The potential of using this new technology in diagnostic evaluation of the vulnerable atherosclerotic plaques is considerable.

  20. Guidelines for the optimization of microsurgery in atherosclerotic patients.

    PubMed

    Chen, Hung-Chi; Coskunfirat, O Koray; Ozkan, Omer; Mardini, Samir; Cigna, Emanuele; Salgado, Christopher J; Spanio, Stefano

    2006-01-01

    We review the pathogenesis of atherosclerosis and the issues that must be taken into consideration when performing microsurgery in atherosclerotic patients. Atherosclerosis is a systemic disease, and may affect the success of microsurgery. Atherosclerotic patients have a tendency toward thrombosis, because the nature of the arteries is changed. Such patients are usually old and have additional medical problems. To increase the success rate of microsurgery in atherosclerotic patients, special precautions should be considered. Patients must be evaluated properly for the suitability of microsurgery. The microsurgical technique requires a meticulous approach, and various technical tricks can be used to avoid thrombosis. Recipient-vessel selection, anastomotic technique, and the use of vein grafts are all important issues. Prophylactic anticoagulation is recommended in severely atherosclerotic patients. Close monitoring of the patient and flap is necessary after the operation, as with routine microvascular free-tissue transfers. We conclude that atherosclerosis is not a contraindication for microsurgery. If the microsurgeon knows how to deal with the difficulties in atherosclerotic patients, microsurgery can be performed safely. PMID:16761266

  1. Human mortality at very advanced age might be constant.

    PubMed

    Klemera, P; Doubal, S

    1997-11-01

    An attempt was made to identify the course of the mortality rate at the upper tail of human age. The only known data suitable for this purpose were published by Riggs and Millecchia (J.E. Riggs, R.J. Millecchia, Mech. Ageing Dev. 62 (1992) 191-199) and our analysis follows up their results. By means of mathematical elaboration it was proved that these data imply a constant mortality rate (approx. 25% per year) at ages above 113 years for men and above 116 years for women. Indirect arguments supporting the validity of the source data are discussed. Nevertheless, even if the source data are mistaken, we proved they cannot be the product of purely random errors and our results may contribute to the elucidation of the origin of those systematic errors. PMID:9379712

  2. Decreased type II/type I TGF-beta receptor ratio in cells derived from human atherosclerotic lesions. Conversion from an antiproliferative to profibrotic response to TGF-beta1.

    PubMed Central

    McCaffrey, T A; Consigli, S; Du, B; Falcone, D J; Sanborn, T A; Spokojny, A M; Bush, H L

    1995-01-01

    Atherosclerosis and postangioplasty restenosis may result from abnormal wound healing. The present studies report that normal human smooth muscle cells are growth inhibited by TGF-beta1, a potent wound healing agent, and show little induction of collagen synthesis to TGF-beta1, yet cells grown from human vascular lesions are growth stimulated by TGF-beta1 and markedly increase collagen synthesis. Both cell types increase plasminogen activator inhibitor-1 production, switch actin phenotypes in response to TGF-beta1, and produce similar levels of TGF-beta activity. Membrane cross-linking of 125I-TGF-beta1 indicates that normal human smooth muscle cells express type I, II, and III receptors. The type II receptor is strikingly decreased in lesion cells, with little change in the type I or III receptors. RT-PCR confirmed that the type II TGF-beta1 receptor mRNA is reduced in lesion cells. Transfection of the type II receptor into lesion cells restores the growth inhibitory response to TGF-beta1, implying that signaling remains responsive. Because TGF-beta1 is overexpressed in fibroproliferative vascular lesions, receptor-variant cells would be allowed to grow in a slow, but uncontrolled fashion, while overproducing extracellular matrix components. This TGF-beta1 receptor dysfunction may be relevant for atherosclerosis, restenosis and related fibroproliferative diseases. Images PMID:8675633

  3. Recent advances on separation and characterization of human milk oligosaccharides.

    PubMed

    Mantovani, Veronica; Galeotti, Fabio; Maccari, Francesca; Volpi, Nicola

    2016-06-01

    Free human milk oligosaccharides (HMOs) are unique due to their highly complex nature and important emerging biological and protective functions during early life such as prebiotic activity, pathogen deflection, and epithelial and immune cell modulation. Moreover, four genetically determined heterogeneous HMO secretory groups are known to be based on their structure and composition. Over the years, several analytical techniques have been applied to characterize and quantitate HMOs, including nuclear magnetic resonance spectroscopy, high-performance liquid chromatography (HPLC), high pH anion-exchange chromatography, off-line and on-line mass spectrometry (MS), and capillary electrophoresis (CE). Even if these techniques have proven to be efficient and simple, most glycans have no significant UV absorption and derivatization with fluorophore groups prior to separation usually results in higher sensitivity and an improved chromatographic/electrophoretic profile. Consequently, the analysis by HPLC/CE of derivatized milk oligosaccharides with different chromophoric active tags has been developed. However, UV or fluorescence detection does not provide specific structural information and this is a key point in particular related to the highly complex nature of the milk glycan mixtures. As a consequence, for a specific determination of complex mixtures of oligomers, analytical separation is usually required with evaluation by means of MS, which has been successfully applied to HMOs, resulting in efficient compositional analysis and profiling in various milk samples. This review aims to give an overview of the current state-of-the-art techniques used in HMO analysis. PMID:26801168

  4. Advanced UV Absorbers for the Protection of Human Skin.

    PubMed

    Hüglin, Dietmar

    2016-01-01

    The increasing awareness of the damaging effects of UV radiation to human skin triggered the market introduction of new cosmetic UV absorbers. This article summarizes the outcome of a multi-year research program, in which the author contributed to the development of different new UV filters. First of all, the molecular design and the basic properties of bis-ethylhexyloxyphenol methoxyphenyl triazine (BEMT) will be presented. This oil-soluble filter, which today is widely used in both beach products and skin care products, exhibits inherent photostability and strong broad-spectrum UV-A+B absorbance. Based on the concept of micronized organic UV absorbers, the UV-B filter tris biphenyl triazine (TBPT) will be introduced. At present TBPT exhibits the highest efficacy of all cosmetic UV absorbers in the market (measured by area under the UV spectrum). Finally, the concept of liposomogenic UV absorbers will be featured. This approach was developed to create water-resistant UV filters, as liposomogenic structures are thought to integrate into the lipids of the horny layer. Due to prohibitively high costs, this technology did not result in a commercial product so far. PMID:27561611

  5. Advanced Nuclear Power Concepts for Human Exploration Missions

    SciTech Connect

    Robert L. Cataldo; Lee S. Mason

    2000-06-04

    The design reference mission for the National Aeronautics and Space Administration's (NASA's) human mission to Mars supports a philosophy of living off the land in order to reduce crew risk, launch mass, and life-cycle costs associated with logistics resupply to a Mars base. Life-support materials, oxygen, water, and buffer gases, and the crew's ascent-stage propellant would not be brought from Earth but rather manufactured from the Mars atmosphere. The propellants would be made over {approx}2 yr, the time between Mars mission launch window opportunities. The production of propellants is very power intensive and depends on type, amount, and time to produce the propellants. Closed-loop life support and food production are also power intensive. With the base having several habitats, a greenhouse, and propellant production capability, total power levels reach well over 125 kW(electric). The most mass-efficient means of satisfying these requirements is through the use of nuclear power. Studies have been performed to identify a potential system concept, described in this paper, using a mobile cart to transport the power system away from the Mars lander and provide adequate separation between the reactor and crew. The studies included an assessment of reactor and power conversion technology options, selection of system and component redundancy, determination of optimum separation distance, and system performance sensitivity to some key operating parameters.

  6. High shear stress induces atherosclerotic vulnerable plaque formation through angiogenesis

    PubMed Central

    Wang, Yi; Qiu, Juhui; Luo, Shisui; Xie, Xiang; Zheng, Yiming; Zhang, Kang; Ye, Zhiyi; Liu, Wanqian; Gregersen, Hans; Wang, Guixue

    2016-01-01

    Rupture of atherosclerotic plaques causing thrombosis is the main cause of acute coronary syndrome and ischemic strokes. Inhibition of thrombosis is one of the important tasks developing biomedical materials such as intravascular stents and vascular grafts. Shear stress (SS) influences the formation and development of atherosclerosis. The current review focuses on the vulnerable plaques observed in the high shear stress (HSS) regions, which localizes at the proximal region of the plaque intruding into the lumen. The vascular outward remodelling occurs in the HSS region for vascular compensation and that angiogenesis is a critical factor for HSS which induces atherosclerotic vulnerable plaque formation. These results greatly challenge the established belief that low shear stress is important for expansive remodelling, which provides a new perspective for preventing the transition of stable plaques to high-risk atherosclerotic lesions. PMID:27482467

  7. High-Resolution MRI of Intracranial Atherosclerotic Disease

    PubMed Central

    Kwak, Hyo-Sung; Jahng, Geon-Ho; Lee, Han Na

    2014-01-01

    Intracranial atherosclerotic disease (ICAD) causes up to 10% of all ischemic strokes, and the rate of recurrent vascular ischemic events is very high. Important predictors of vulnerability in atherosclerotic plaques include the degree of stenosis and the underlying plaque morphology. Vascular wall MRI can provide information about wall structures and atherosclerotic plaque components. High-resolution (HR)-MRI in ICAD poses a greater challenge in the neurologic fields, because a high in-plane resolution and a high signal-to-noise ratio are required for vessel wall imaging of ICAD. Until now, plaque imaging of ICAD has focused on assessing the presence of a plaque and evaluating the plaque load. Going forward, evaluation of plaque vulnerability through analysis of imaging characteristics will be a critical area of research. This review introduces the acquisition protocol for HR-MRI in ICAD and the current issues associated with imaging. PMID:24644529

  8. Targeting Cellular Antioxidant Enzymes for Treating Atherosclerotic Vascular Disease

    PubMed Central

    Kang, Dong Hoon; Kang, Sang Won

    2013-01-01

    Atherosclerotic vascular dysfunction is a chronic inflammatory process that spreads from the fatty streak and foam cells through lesion progression. Therefore, its early diagnosis and prevention is unfeasible. Reactive oxygen species (ROS) play important roles in the pathogenesis of atherosclerotic vascular disease. Intracellular redox status is tightly regulated by oxidant and antioxidant systems. Imbalance in these systems causes oxidative or reductive stress which triggers cellular damage or aberrant signaling, and leads to dysregulation. Paradoxically, large clinical trials have shown that non-specific ROS scavenging by antioxidant vitamins is ineffective or sometimes harmful. ROS production can be locally regulated by cellular antioxidant enzymes, such as superoxide dismutases, catalase, glutathione peroxidases and peroxiredoxins. Therapeutic approach targeting these antioxidant enzymes might prove beneficial for prevention of ROS-related atherosclerotic vascular disease. Conversely, the development of specific antioxidant enzyme-mimetics could contribute to the clinical effectiveness. PMID:24009865

  9. High shear stress induces atherosclerotic vulnerable plaque formation through angiogenesis.

    PubMed

    Wang, Yi; Qiu, Juhui; Luo, Shisui; Xie, Xiang; Zheng, Yiming; Zhang, Kang; Ye, Zhiyi; Liu, Wanqian; Gregersen, Hans; Wang, Guixue

    2016-12-01

    Rupture of atherosclerotic plaques causing thrombosis is the main cause of acute coronary syndrome and ischemic strokes. Inhibition of thrombosis is one of the important tasks developing biomedical materials such as intravascular stents and vascular grafts. Shear stress (SS) influences the formation and development of atherosclerosis. The current review focuses on the vulnerable plaques observed in the high shear stress (HSS) regions, which localizes at the proximal region of the plaque intruding into the lumen. The vascular outward remodelling occurs in the HSS region for vascular compensation and that angiogenesis is a critical factor for HSS which induces atherosclerotic vulnerable plaque formation. These results greatly challenge the established belief that low shear stress is important for expansive remodelling, which provides a new perspective for preventing the transition of stable plaques to high-risk atherosclerotic lesions. PMID:27482467

  10. A Distributed Simulation Facility to Support Human Factors Research in Advanced Air Transportation Technology

    NASA Technical Reports Server (NTRS)

    Amonlirdviman, Keith; Farley, Todd C.; Hansman, R. John, Jr.; Ladik, John F.; Sherer, Dana Z.

    1998-01-01

    A distributed real-time simulation of the civil air traffic environment developed to support human factors research in advanced air transportation technology is presented. The distributed environment is based on a custom simulation architecture designed for simplicity and flexibility in human experiments. Standard Internet protocols are used to create the distributed environment, linking all advanced cockpit simulator, all Air Traffic Control simulator, and a pseudo-aircraft control and simulation management station. The pseudo-aircraft control station also functions as a scenario design tool for coordinating human factors experiments. This station incorporates a pseudo-pilot interface designed to reduce workload for human operators piloting multiple aircraft simultaneously in real time. The application of this distributed simulation facility to support a study of the effect of shared information (via air-ground datalink) on pilot/controller shared situation awareness and re-route negotiation is also presented.

  11. Advancing human health risk assessment: integrating recent advisory committee recommendations.

    PubMed

    Dourson, Michael; Becker, Richard A; Haber, Lynne T; Pottenger, Lynn H; Bredfeldt, Tiffany; Fenner-Crisp, Penelope A

    2013-07-01

    Over the last dozen years, many national and international expert groups have considered specific improvements to risk assessment. Many of their stated recommendations are mutually supportive, but others appear conflicting, at least in an initial assessment. This review identifies areas of consensus and difference and recommends a practical, biology-centric course forward, which includes: (1) incorporating a clear problem formulation at the outset of the assessment with a level of complexity that is appropriate for informing the relevant risk management decision; (2) using toxicokinetics and toxicodynamic information to develop Chemical Specific Adjustment Factors (CSAF); (3) using mode of action (MOA) information and an understanding of the relevant biology as the key, central organizing principle for the risk assessment; (4) integrating MOA information into dose-response assessments using existing guidelines for non-cancer and cancer assessments; (5) using a tiered, iterative approach developed by the World Health Organization/International Programme on Chemical Safety (WHO/IPCS) as a scientifically robust, fit-for-purpose approach for risk assessment of combined exposures (chemical mixtures); and (6) applying all of this knowledge to enable interpretation of human biomonitoring data in a risk context. While scientifically based defaults will remain important and useful when data on CSAF or MOA to refine an assessment are absent or insufficient, assessments should always strive to use these data. The use of available 21st century knowledge of biological processes, clinical findings, chemical interactions, and dose-response at the molecular, cellular, organ and organism levels will minimize the need for extrapolation and reliance on default approaches. PMID:23844697

  12. Advancing human health risk assessment: Integrating recent advisory committee recommendations

    PubMed Central

    Becker, Richard A.; Haber, Lynne T.; Pottenger, Lynn H.; Bredfeldt, Tiffany; Fenner-Crisp, Penelope A.

    2013-01-01

    Over the last dozen years, many national and international expert groups have considered specific improvements to risk assessment. Many of their stated recommendations are mutually supportive, but others appear conflicting, at least in an initial assessment. This review identifies areas of consensus and difference and recommends a practical, biology-centric course forward, which includes: (1) incorporating a clear problem formulation at the outset of the assessment with a level of complexity that is appropriate for informing the relevant risk management decision; (2) using toxicokinetics and toxicodynamic information to develop Chemical Specific Adjustment Factors (CSAF); (3) using mode of action (MOA) information and an understanding of the relevant biology as the key, central organizing principle for the risk assessment; (4) integrating MOA information into dose–response assessments using existing guidelines for non-cancer and cancer assessments; (5) using a tiered, iterative approach developed by the World Health Organization/International Programme on Chemical Safety (WHO/IPCS) as a scientifically robust, fit-for-purpose approach for risk assessment of combined exposures (chemical mixtures); and (6) applying all of this knowledge to enable interpretation of human biomonitoring data in a risk context. While scientifically based defaults will remain important and useful when data on CSAF or MOA to refine an assessment are absent or insufficient, assessments should always strive to use these data. The use of available 21st century knowledge of biological processes, clinical findings, chemical interactions, and dose–response at the molecular, cellular, organ and organism levels will minimize the need for extrapolation and reliance on default approaches. PMID:23844697

  13. Validating a bimodal intravascular ultrasound (IVUS) and near-infrared fluorescence (NIRF) catheter for atherosclerotic plaque detection in rabbits

    PubMed Central

    Abran, Maxime; Stähli, Barbara E.; Merlet, Nolwenn; Mihalache-Avram, Teodora; Mecteau, Mélanie; Rhéaume, Eric; Busseuil, David; Tardif, Jean-Claude; Lesage, Frédéric

    2015-01-01

    Coronary artery disease is characterized by atherosclerotic plaque formation. Despite impressive advances in intravascular imaging modalities, in vivo molecular plaque characterization remains challenging, and different multimodality imaging systems have been proposed. We validated an engineered bimodal intravascular ultrasound imaging (IVUS) / near-infrared fluorescence (NIRF) imaging catheter in vivo using a balloon injury atherosclerosis rabbit model. Rabbit aortas and right iliac arteries were scanned in vivo after indocyanine green (ICG) injection, and compared to corresponding ex vivo fluorescence and white light images. Areas of ICG accumulation were colocalized with macroscopic atherosclerotic plaque formation. In vivo imaging was performed with the bimodal catheter integrating ICG-induced fluorescence signals into cross-sectional IVUS imaging. In vivo ICG accumulation corresponded to ex vivo fluorescence signal intensity and IVUS identified plaques. PMID:26504648

  14. Divergent JAM-C Expression Accelerates Monocyte-Derived Cell Exit from Atherosclerotic Plaques

    PubMed Central

    Miljkovic-Licina, Marijana; Lee, Boris P.; Fischer, Nicolas; Fish, Richard J.; Kwak, Brenda; Fisher, Edward A.; Imhof, Beat A.

    2016-01-01

    Atherosclerosis, caused in part by monocytes in plaques, continues to be a disease that afflicts the modern world. Whilst significant steps have been made in treating this chronic inflammatory disease, questions remain on how to prevent monocyte and macrophage accumulation in atherosclerotic plaques. Junctional Adhesion Molecule C (JAM-C) expressed by vascular endothelium directs monocyte transendothelial migration in a unidirectional manner leading to increased inflammation. Here we show that interfering with JAM-C allows reverse-transendothelial migration of monocyte-derived cells, opening the way back out of the inflamed environment. To study the role of JAM-C in plaque regression we used a mouse model of atherosclerosis, and tested the impact of vascular JAM-C expression levels on monocyte reverse transendothelial migration using human cells. Studies in-vitro under inflammatory conditions revealed that overexpression or gene silencing of JAM-C in human endothelium exposed to flow resulted in higher rates of monocyte reverse-transendothelial migration, similar to antibody blockade. We then transplanted atherosclerotic, plaque-containing aortic arches from hyperlipidemic ApoE-/- mice into wild-type normolipidemic recipient mice. JAM-C blockade in the recipients induced greater emigration of monocyte-derived cells and further diminished the size of atherosclerotic plaques. Our findings have shown that JAM-C forms a one-way vascular barrier for leukocyte transendothelial migration only when present at homeostatic copy numbers. We have also shown that blocking JAM-C can reduce the number of atherogenic monocytes/macrophages in plaques by emigration, providing a novel therapeutic strategy for chronic inflammatory pathologies. PMID:27442505

  15. A Framework for Human Performance Criteria for Advanced Reactor Operational Concepts

    SciTech Connect

    Jacques V Hugo; David I Gertman; Jeffrey C Joe

    2014-08-01

    This report supports the determination of new Operational Concept models needed in support of the operational design of new reactors. The objective of this research is to establish the technical bases for human performance and human performance criteria frameworks, models, and guidance for operational concepts for advanced reactor designs. The report includes a discussion of operating principles for advanced reactors, the human performance issues and requirements for human performance based upon work domain analysis and current regulatory requirements, and a description of general human performance criteria. The major findings and key observations to date are that there is some operating experience that informs operational concepts for baseline designs for SFR and HGTRs, with the Experimental Breeder Reactor-II (EBR-II) as a best-case predecessor design. This report summarizes the theoretical and operational foundations for the development of a framework and model for human performance criteria that will influence the development of future Operational Concepts. The report also highlights issues associated with advanced reactor design and clarifies and codifies the identified aspects of technology and operating scenarios.

  16. Advanced Placement Human Geography and the Annual Meetings of the National Council for Geographic Education

    ERIC Educational Resources Information Center

    Sublett, Michael D.

    2007-01-01

    Members of the National Council for Geographic Education have been instrumental in the creation, launch, and early success of Advanced Placement Human Geography. Annual meetings of the Council have served as a forum for spreading the word about the course and its follow-up national examination and in helping teachers develop content confidence and…

  17. Placing Advanced Placement® Human Geography: Its Role in U.S. Geography Education

    ERIC Educational Resources Information Center

    Bednarz, Sarah Witham

    2016-01-01

    This article examines Advanced Placement Human Geography (AP HG) in the context of its place in efforts to reform geography education. It presents a critical analysis of the AP program and its curriculum, asserting that it represents "powerful knowledge" as conceptualized by Young. It concludes with a call for research in AP HG aligned…

  18. Perspectives on the Development and Future of Advanced Placement® Human Geography

    ERIC Educational Resources Information Center

    Hildebrant, Barbara

    2016-01-01

    Advanced Placement (AP) Human Geography faced a number of hurdles that nearly derailed the course before it launched in 2000-2001. A dedicated cadre of geography professionals and high school teachers rose to the challenge and the course remains one of the fastest growing AP courses currently offered by College Board. Seventeen readers and leaders…

  19. 78 FR 8546 - National Center for Advancing Translational Sciences (NCATS) and National Human Genome Research...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-06

    ...The National Center for Advancing Translational Sciences (NCATS) and the National Human Genome Research Institute (NHGRI), the National Institutes of Health (NIH), are seeking Cooperative Research and Development Agreement (CRADA) partners to collaborate in the final stages of lead optimization, evaluation and preclinical development of a novel selective series of non-inhibitory chaperones of......

  20. The Success of Advanced Learning Technologies for Instruction: Research and Evaluation of Human Factors Issues.

    ERIC Educational Resources Information Center

    Coldeway, Dan O.

    2002-01-01

    Data from three graduate programs using advanced learning technologies (ALTs) identified important human factors issues in technology use in three categories: learners (needs, skills, support, and motivation related to ALTs); faculty (attitudes, skills, support, and motivation related to ALTs); and technical staff (methods of providing assistance,…

  1. Advancing Human Circadian Rhythms with Afternoon Melatonin and Morning Intermittent Bright Light

    PubMed Central

    Revell, Victoria L.; Burgess, Helen J.; Gazda, Clifford J.; Smith, Mark R.; Fogg, Louis F.; Eastman, Charmane I.

    2013-01-01

    Context Both light and melatonin can be used to phase shift the human circadian clock, but the phase advancing effect of the combination has not been extensively investigated. Objective The objective of the study was to determine whether phase advances induced by morning intermittent bright light and a gradually advancing sleep schedule could be increased with afternoon melatonin. Participants Healthy adults (25 males, 19 females, between the ages of 19 and 45 yr) participated in the study. Design There were 3 d of a gradually advancing sleep/dark period (wake time 1 h earlier each morning), bright light on awakening [ four 30-min bright-light pulses (∼5000 lux) alternating with 30 min room light < 60 lux] and afternoon melatonin, either 0.5 or 3.0 mg melatonin timed to induce maximal phase advances, or matching placebo. The dim light melatonin onset was measured before and after the treatment to determine the phase advance. Results There were significantly larger phase advances with 0.5 mg (2.5 h, n = 16) and 3.0 mg melatonin (2.6 h, n = 13), compared with placebo (1.7 h, n = 15), but there was no difference between the two melatonin doses. Subjects did not experience jet lag-type symptoms during the 3-d treatment Conclusions Afternoon melatonin, morning intermittent bright light, and a gradually advancing sleep schedule advanced circadian rhythms almost 1 h/d and thus produced very little circadian misalignment. This treatment could be used in any situation in which people need to phase advance their circadian clock, such as before eastward jet travel or for delayed sleep phase syndrome. PMID:16263827

  2. Advances in Robotic, Human, and Autonomous Systems for Missions of Space Exploration

    NASA Technical Reports Server (NTRS)

    Gross, Anthony R.; Briggs, Geoffrey A.; Glass, Brian J.; Pedersen, Liam; Kortenkamp, David M.; Wettergreen, David S.; Nourbakhsh, I.; Clancy, Daniel J.; Zornetzer, Steven (Technical Monitor)

    2002-01-01

    Space exploration missions are evolving toward more complex architectures involving more capable robotic systems, new levels of human and robotic interaction, and increasingly autonomous systems. How this evolving mix of advanced capabilities will be utilized in the design of new missions is a subject of much current interest. Cost and risk constraints also play a key role in the development of new missions, resulting in a complex interplay of a broad range of factors in the mission development and planning of new missions. This paper will discuss how human, robotic, and autonomous systems could be used in advanced space exploration missions. In particular, a recently completed survey of the state of the art and the potential future of robotic systems, as well as new experiments utilizing human and robotic approaches will be described. Finally, there will be a discussion of how best to utilize these various approaches for meeting space exploration goals.

  3. Workshop on Critical Issues in Microgravity Fluids, Transport, and Reaction Processes in Advanced Human Support Technology

    NASA Technical Reports Server (NTRS)

    Chiaramonte, Francis P.; Joshi, Jitendra A.

    2004-01-01

    This workshop was designed to bring the experts from the Advanced Human Support Technologies communities together to identify the most pressing and fruitful areas of research where success hinges on collaborative research between the two communities. Thus an effort was made to bring together experts in both advanced human support technologies and microgravity fluids, transport and reaction processes. Expertise was drawn from academia, national laboratories, and the federal government. The intent was to bring about a thorough exchange of ideas and develop recommendations to address the significant open design and operation issues for human support systems that are affected by fluid physics, transport and reaction processes. This report provides a summary of key discussions, findings, and recommendations.

  4. In vivo determination of arterial collagen synthesis in atherosclerotic rabbits

    SciTech Connect

    Opsahl, W.P.; DeLuca, D.J.; Ehrhart, L.A.

    1986-03-01

    Collagen and non-collagen protein synthesis rates were determined in vivo in tissues from rabbits fed a control or atherogenic diet supplemented with 2% peanut oil and 0.25% cholesterol for 4 months. Rabbits received a bolus intravenous injection of L-(/sup 3/H)-proline (1.0 mCi/kg) and unlabeled L-proline (7 mmoles/kg) in 0.9% NaCl. Plasma proline specific activity decreased only 20% over 5 hr and was similar to the specific activity of free proline in tissues. Thoracic aortas from atherosclerotic rabbits exhibited raised plaques covering at least 75% of the surface. Thoracic intima plus a portion of the media (TIM) was separated from the remaining media plus adventitia (TMA). Dry delipidated weight, total collagen content, and collagen as a percent of dry weight were increased significantly in the TIM of atherosclerotic rabbits. Collagen synthesis rates and collagen synthesis as a percent of total protein synthesis were likewise increased both in the TIM and in the abdominal aortas. No differences from controls either in collagen content or collagen synthesis rates were observed in the TMA, lung or skin. These results demonstrate for the first time in vivo that formation of atherosclerotic plaques is associated with increased rates of collagen synthesis. Furthermore, as previously observed with incubations in vitro, collagen synthesis was elevated to a greater extent than noncollagen protein synthesis in atherosclerotic aortas from rabbits fed cholesterol plus peanut oil.

  5. Atherosclerotic changes of vessels caused by restriction of movement

    NASA Technical Reports Server (NTRS)

    Gvishiani, G. S.; Kobakhidze, N. G.; Mchedlishvili, M. G.; Dekanosidze, T. I.

    1980-01-01

    The effect of restriction of movement on the development of atheroscelerosis was studied in rabbits. Drastic restriction of movement for 20 and 30 days causes atherosclerotic alterations of the aorta and shifts in ECG which are characteristic of coronary atherosclerosis. At the same time, shortening of the duration of blood coagulation and an increase in the content of catecholamines and beta-lipoproteids occur.

  6. Cap buckling as a potential mechanism of atherosclerotic plaque vulnerability.

    PubMed

    Abdelali, Maria; Reiter, Steven; Mongrain, Rosaire; Bertrand, Michel; L'Allier, Philippe L; Kritikou, Ekaterini A; Tardif, Jean-Claude

    2014-04-01

    Plaque rupture in atherosclerosis is the primary cause of potentially deadly coronary events, yet about 40% of ruptures occur away from the plaque cap shoulders and cannot be fully explained with the current biomechanical theories. Here, cap buckling is considered as a potential destabilizing factor which increases the propensity of the atherosclerotic plaque to rupture and which may also explain plaque failure away from the cap shoulders. To investigate this phenomenon, quasistatic 2D finite element simulations are performed, considering the salient geometrical and nonlinear material properties of diverse atherosclerotic plaques over the range of physiological loads. The numerical results indicate that buckling may displace the location of the peak von Mises stresses in the deflected caps. Plaque buckling, together with its deleterious effects is further observed experimentally in plaque caps using a physical model of deformable mock coronary arteries with fibroatheroma. Moreover, an analytical approach combining quasistatic equilibrium equations with the Navier-Bresse formulas is used to demonstrate the buckling potential of a simplified arched slender cap under intraluminal pressure and supported by foundations. This analysis shows that plaque caps - calcified, fibrotic or cellular - may buckle in specific undulated shapes once submitted to critical loads. Finally, a preliminary analysis of intravascular ultrasonography recordings of patients with atherosclerotic coronary arteries corroborates the numerical, experimental and theoretical findings and shows that various plaque caps buckle in vivo. By displacing the sites of high stresses in the plaque cap, buckling may explain the atherosclerotic plaque cap rupture at various locations, including cap shoulders. PMID:24491969

  7. Evaluation of the radiolabeled boronic acid-based FAP inhibitor MIP-1232 for atherosclerotic plaque imaging.

    PubMed

    Meletta, Romana; Müller Herde, Adrienne; Chiotellis, Aristeidis; Isa, Malsor; Rancic, Zoran; Borel, Nicole; Ametamey, Simon M; Krämer, Stefanie D; Schibli, Roger

    2015-01-01

    Research towards the non-invasive imaging of atherosclerotic plaques is of high clinical priority as early recognition of vulnerable plaques may reduce the incidence of cardiovascular events. The fibroblast activation protein alpha (FAP) was recently proposed as inflammation-induced protease involved in the process of plaque vulnerability. In this study, FAP mRNA and protein levels were investigated by quantitative polymerase chain reaction and immunohistochemistry, respectively, in human endarterectomized carotid plaques. A published boronic-acid based FAP inhibitor, MIP-1232, was synthetized and radiolabeled with iodine-125. The potential of this radiotracer to image plaques was evaluated by in vitro autoradiography with human carotid plaques. Specificity was assessed with a xenograft with high and one with low FAP level, grown in mice. Target expression analyses revealed a moderately higher protein level in atherosclerotic plaques than normal arteries correlating with plaque vulnerability. No difference in expression was determined on mRNA level. The radiotracer was successfully produced and accumulated strongly in the FAP-positive SK-Mel-187 melanoma xenograft in vitro while accumulation was negligible in an NCI-H69 xenograft with low FAP levels. Binding of the tracer to endarterectomized tissue was similar in plaques and normal arteries, hampering its use for atherosclerosis imaging. PMID:25633335

  8. CCL19 and CCL21 modulate the inflammatory milieu in atherosclerotic lesions

    PubMed Central

    Akhavanpoor, Mohammadreza; Gleissner, Christian A; Gorbatsch, Stephanie; Doesch, Andreas O; Akhavanpoor, Hamidreza; Wangler, Susanne; Jahn, Frederik; Lasitschka, Felix; Katus, Hugo A; Erbel, Christian

    2014-01-01

    Despite advances in the pharmacologic and interventional treatment of coronary artery disease, atherosclerosis remains the leading cause of death worldwide. Atherosclerosis is a chronic inflammatory disease, and elevated expression of CCL19 and CCL21 has been observed in ruptured lesions of coronary arteries of patients with myocardial infarction and carotid plaques of patients with ischemic symptoms, as well as in plasma of coronary artery disease patients. However, the exact role of CCL19 and CCL21 in atherosclerosis remains unknown. In order to identify CCL19 and CCL21 as a novel therapeutic target, we performed bone marrow transplantation as an immunomodulatory treatment concept. Bone marrow of plt/plt mice (lacking CCL19 and CCL21-Ser) was transplanted into atherogenic Ldlr−/− mice. The study demonstrated a significantly increased inflammatory cellular infiltration into the lesions of plt/plt/Ldlr−/− mice versus controls. Although the level of chemoattraction was increased, messenger ribonucleic acid and protein levels in thoracic aorta and serum of several proinflammatory cytokines (TNFα, IFNγ, IL-6, IL-12, and IL-17) were significantly reduced in plt/plt/Ldlr−/− versus control mice. Increased influx, accompanied by reduced activation of leukocytes in atherosclerotic lesion, was accompanied by increased plaque stability but unchanged lesion development. In conclusion, modulation of the chemokines CCL19 and CCL21 represents a potent immunoregulatory treatment approach, and thus represents a novel therapeutic target to stabilize atherosclerotic lesions. PMID:25473269

  9. CCL19 and CCL21 modulate the inflammatory milieu in atherosclerotic lesions.

    PubMed

    Akhavanpoor, Mohammadreza; Gleissner, Christian A; Gorbatsch, Stephanie; Doesch, Andreas O; Akhavanpoor, Hamidreza; Wangler, Susanne; Jahn, Frederik; Lasitschka, Felix; Katus, Hugo A; Erbel, Christian

    2014-01-01

    Despite advances in the pharmacologic and interventional treatment of coronary artery disease, atherosclerosis remains the leading cause of death worldwide. Atherosclerosis is a chronic inflammatory disease, and elevated expression of CCL19 and CCL21 has been observed in ruptured lesions of coronary arteries of patients with myocardial infarction and carotid plaques of patients with ischemic symptoms, as well as in plasma of coronary artery disease patients. However, the exact role of CCL19 and CCL21 in atherosclerosis remains unknown. In order to identify CCL19 and CCL21 as a novel therapeutic target, we performed bone marrow transplantation as an immunomodulatory treatment concept. Bone marrow of plt/plt mice (lacking CCL19 and CCL21-Ser) was transplanted into atherogenic Ldlr(-/-) mice. The study demonstrated a significantly increased inflammatory cellular infiltration into the lesions of plt/plt/Ldlr(-/-) mice versus controls. Although the level of chemoattraction was increased, messenger ribonucleic acid and protein levels in thoracic aorta and serum of several proinflammatory cytokines (TNFα, IFNγ, IL-6, IL-12, and IL-17) were significantly reduced in plt/plt/Ldlr(-/-) versus control mice. Increased influx, accompanied by reduced activation of leukocytes in atherosclerotic lesion, was accompanied by increased plaque stability but unchanged lesion development. In conclusion, modulation of the chemokines CCL19 and CCL21 represents a potent immunoregulatory treatment approach, and thus represents a novel therapeutic target to stabilize atherosclerotic lesions. PMID:25473269

  10. Human Factors Engineering (HFE) insights for advanced reactors based upon operating experience

    SciTech Connect

    Higgins, J.; Nasta, K.

    1997-01-01

    The NRC Human Factors Engineering Program Review Model (HFE PRM, NUREG-0711) was developed to support a design process review for advanced reactor design certification under 10CFR52. The HFE PRM defines ten fundamental elements of a human factors engineering program. An Operating Experience Review (OER) is one of these elements. The main purpose of an OER is to identify potential safety issues from operating plant experience and ensure that they are addressed in a new design. Broad-based experience reviews have typically been performed in the past by reactor designers. For the HFE PRM the intent is to have a more focussed OER that concentrates on HFE issues or experience that would be relevant to the human-system interface (HSI) design process for new advanced reactors. This document provides a detailed list of HFE-relevant operating experience pertinent to the HSI design process for advanced nuclear power plants. This document is intended to be used by NRC reviewers as part of the HFE PRM review process in determining the completeness of an OER performed by an applicant for advanced reactor design certification. 49 refs.