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1

Irbesartan  

MedlinePLUS

... or in combination with other medications to treat high blood pressure. It is also used to treat kidney disease ... the amount of sugar in the blood) and high blood pressure. Irbesartan is in a class of medications called ...

2

Suppressive Effects of Irbesartan on Inflammation and Apoptosis in Atherosclerotic Plaques of apoE?/? Mice: Molecular Imaging with 14C-FDG and 99mTc-Annexin A5  

PubMed Central

Objectives To investigate the effects of irbesartan on inflammation and apoptosis in atherosclerotic plaques by histochemical examination and molecular imaging using 14C-FDG and 99mTc-annexin A5. Background Irbesartan has a peroxisome proliferator-activated receptor gamma (PPAR?) activation property in addition to its ability to block the AT1 receptor. Accordingly, irbesartan may exert further anti-inflammatory and anti-apoptotic effects in atherosclerotic plaques. However, such effects of irbesartan have not been fully investigated. Molecular imaging using 18F-FDG and 99mTc-annexin A5 is useful for evaluating inflammation and apoptosis in atherosclerotic plaques. Methods Female apoE?/? mice were treated with irbesartan-mixed (50 mg/kg/day) or irbesartan-free (control) diet for 12 weeks (n?=?11/group). One week after the treatment, the mice were co-injected with 14C-FDG and 99mTc-annexin A5, and cryostat sections of the aortic root were prepared. Histochemical examination with Movat's pentachrome (plaque size), Oil Red O (lipid deposition), Mac-2 (macrophage infiltration), and TUNEL (apoptosis) stainings were performed. Dual-tracer autoradiography was carried out to evaluate the levels of 14C-FDG and 99mTc-annexin A5 in plaques (%ID×kg). In vitro experiments were performed to investigate the mechanism underlying the effects. Results Histological examination indicated that irbesartan treatment significantly reduced plaque size (to 56.4%±11.1% of control), intra-plaque lipid deposition (53.6%±20.2%) and macrophage infiltration (61.9%±20.8%) levels, and the number of apoptotic cells (14.5%±16.6%). 14C-FDG (43.0%±18.6%) and 99mTc-annexin A5 levels (45.9%±16.8%) were also significantly reduced by irbesartan treatment. Irbesartan significantly suppressed MCP-1 mRNA expression in TNF-? stimulated THP-1 monocytes (64.8%±8.4% of un-treated cells). PPAR? activation was observed in cells treated with irbesartan (134%±36% at 3 µM to 3329%±218% at 81 µM) by a PPAR? reporter assay system. Conclusions Remissions of inflammation and apoptosis as potential therapeutic effects of irbesartan on atherosclerosis were observed. The usefulness of molecular imaging using 18F-FDG and 99mTc-annexin A5 for evaluating the therapeutic effects of irbesartan on atherosclerosis was also suggested. PMID:24586699

Zhao, Songji; Kobayashi, Tatsuo; Fukao, Keita; Tanaka, Yoshikazu; Nakano, Toru; Yoshida, Tetsuya; Takemoto, Hiroshi; Tamaki, Nagara; Kuge, Yuji

2014-01-01

3

Atherosclerosis  

MedlinePLUS

Atherosclerosis Updated:May 12,2014 View an animation of atherosclerosis Atherosclerosis, or hardening of the arteries, is ... the arteries as you get older. How does atherosclerosis start and progress? It's a complex process. Exactly ...

4

Atherosclerosis  

MedlinePLUS

... my body? Atherosclerosis is the primary cause of cardiovascular disease. Cardiovascular disease is the leading cause of death in the United States. Types of cardiovascular disease include: Coronary artery disease: Coronary artery disease occurs ...

5

Apocynin suppresses the progression of atherosclerosis in apoE-deficient mice by inactivation of macrophages  

SciTech Connect

Highlights: ? We examined the anti-athrogenic effect of apocynin in atherosclerotic model mice. ? Apocynin prevented atherosclerotic lesion formation. ? Apocynin suppressed ROS production in aorta and in macrophages. ? Apocynin suppressed cytokine expression and cell proliferation in macrophages. ? Apocynin may be beneficial compound for the prevention of atherosclerosis. -- Abstract: Production of reactive oxygen species (ROS) and other proinflammatory substances by macrophages plays an important role in atherogenesis. Apocynin (4-hydroxy-3-methoxy-acetophenone), which is well known as a NADPH oxidase inhibitor, has anti-inflammatory effects including suppression of the generation of ROS. However, the suppressive effects of apocynin on the progression of atherosclerosis are not clearly understood. Thus, we investigated anti-atherosclerotic effects of apocynin using apolipoprotein E-deficient (apoE{sup –/–}) mice in vivo and in mouse peritoneal macrophages in vitro. In atherosclerosis-prone apoE{sup –/–} mice, apocynin suppressed the progression of atherosclerosis, decreased 4-hydroxynonenal-positive area in atherosclerotic lesions, and mRNA expression of monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6) in aorta. In mouse peritoneal macrophages, apocynin suppressed the Ox-LDL-induced ROS generation, mRNA expression of MCP-1, IL-6 and granulocyte/macrophage colony-stimulating factor, and cell proliferation. Moreover, immunohistochemical studies revealed that apocynin decreased the number of proliferating cell nuclear antigen-positive macrophages in atherosclerotic lesions of apoE{sup –/–} mice. These results suggested that apocynin suppressed the formation of atherosclerotic lesions, at least in part, by inactivation of macrophages. Therefore, apocynin may be a potential therapeutic material to prevent the progression of atherosclerosis.

Kinoshita, Hiroyuki [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556 (Japan)] [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556 (Japan); Matsumura, Takeshi, E-mail: takeshim@gpo.kumamoto-u.ac.jp [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556 (Japan)] [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556 (Japan); Ishii, Norio; Fukuda, Kazuki; Senokuchi, Takafumi; Motoshima, Hiroyuki; Kondo, Tatsuya; Taketa, Kayo; Kawasaki, Shuji; Hanatani, Satoko [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556 (Japan)] [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556 (Japan); Takeya, Motohiro [Department of Cell Pathology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556 (Japan)] [Department of Cell Pathology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556 (Japan); Nishikawa, Takeshi; Araki, Eiichi [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556 (Japan)] [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556 (Japan)

2013-02-08

6

Ginkgo suppresses atherosclerosis through downregulating the expression of connexin 43 in rabbits  

PubMed Central

Introduction Ginkgo biloba extract (GBE) EGb761 is widely used for cardiovascular prevention. Here, we investigated the effects of GBE on atherosclerotic lesion development in rabbits with a high-fat diet. Material and methods Forty New Zealand white male rabbits were randomly divided into four groups. The first two were the normal diet group (C) and the high-fat group (HF). The remaining two groups were those who received a high cholesterol diet supplemented with either the standard drug (simvastatin 2 mg/kg/day) or GBE (3 mg/kg/day). At 12 weeks, histopathological and chemical analyses were performed. Results Plasma lipid measurement showed that GBE inhibited high-fat diet-induced increase of serum triglyceride (TG), total cholesterol (TC), and low density lipoprotein cholesterol (LDL-C) by 59.1% (0.9 ±0.2 4 mmol/l vs. 2.2 ±0.4 mmol/l), 18.2% (31.1 ±1.4 mmol/l vs. 38.0 ±0.4 mmol/l) and 15% (28.9 ±1.3 mmol/l vs. 34.0±1.0 mmol/l), respectively, at 12 weeks (p < 0.01). The en face Sudan IV-positive lesion area of the aorta in the GBE group (51.7 ±3.1%) was significantly lower compared with that in the HF group (88.2 ±2.2%; p < 0.01). The mean atherosclerotic lesion area of the GBE group was reduced by 53.2% compared with the HF group (p < 0.01). Immunohistochemistry and western blot analysis showed that GBE markedly suppressed high-fat diet-induced upregulation of connexin 43 (Cx43) in rabbits (p < 0.01). Conclusions Thus, our study revealed that GBE prevented atherosclerosis progress through modulating plasma lipid, suppressing atherosclerotic lesion development, and attenuating the expression of Cx43 protein. PMID:23671447

Wang, Xin; Gong, Hui; Shi, Yi Jun; Zou, Yunzeng

2013-01-01

7

Suppression of Coronary Atherosclerosis by Helix B Surface Peptide, a Nonerythropoietic, Tissue-Protective Compound Derived from Erythropoietin  

PubMed Central

Erythropoietin (EPO), a type I cytokine originally identified for its critical role in hematopoiesis, has been shown to have nonhematopoietic, tissue-protective effects, including suppression of atherosclerosis. However, prothrombotic effects of EPO hinder its potential clinical use in nonanemic patients. In the present study, we investigated the antiatherosclerotic effects of helix B surface peptide (HBSP), a nonerythropoietic, tissue-protective compound derived from EPO, by using human umbilical vein endothelial cells (HUVECs) and human monocytic THP-1 cells in vitro and Watanabe heritable hyperlipidemic spontaneous myocardial infarction (WHHLMI) rabbits in vivo. In HUVECs, HBSP inhibited apoptosis (?70%) induced by C-reactive protein (CRP), a direct mediator of atherosclerosis. By using a small interfering RNA approach, Akt was shown to be a key molecule in HBSP-mediated prevention of apoptosis. HBSP also attenuated CRP-induced production of tumor necrosis factor (TNF)-? and matrix metalloproteinase-9 in THP-1 cells. In the WHHLMI rabbit, HBSP significantly suppressed progression of coronary atherosclerotic lesions as assessed by mean cross-sectional stenosis (HBSP 21.3 ± 2.2% versus control peptide 38.0 ± 2.7%) and inhibited coronary artery endothelial cell apoptosis with increased activation of Akt. Furthermore, TNF-? expression and the number of M1 macrophages and M1/M2 macrophage ratio in coronary atherosclerotic lesions were markedly reduced in HBSP-treated animals. In conclusion, these data demonstrate that HBSP suppresses coronary atherosclerosis, in part by inhibiting endothelial cell apoptosis through activation of Akt and in association with decreased TNF-? production and modified macrophage polarization in coronary atherosclerotic lesions. Because HBSP does not have the prothrombotic effects of EPO, our study may provide a novel therapeutic strategy that prevents progression of coronary artery disease. PMID:23648638

Ueba, Hiroto; Shiomi, Masashi; Brines, Michael; Yamin, Michael; Kobayashi, Tsutomu; Ako, Junya; Momomura, Shin-ichi; Cerami, Anthony; Kawakami, Masanobu

2013-01-01

8

Suppression of accelerated diabetic atherosclerosis by the soluble receptor for advanced glycation endproducts  

Microsoft Academic Search

Accelerated atherosclerosis in patients with diabetes is a major cause of their morbidity and mortality, and it is unresponsive to therapy aimed at restoring relative euglycemia. In hyperglycemia, nonenzymatic glycation and oxidation of proteins and lipids results in the accumulation of irreversibly formed advanced glycation endproducts. These advanced glycation endproducts engage their receptor in cells of the blood vessel wall,

Lisa Park; Kathleen G. Raman; Kenneth J. Lee; Yan Lu; Luis J. Ferran; Wing Sun Chow; David Stern; Ann Marie Schmidt

1998-01-01

9

Acidic Polysaccharide Extracts from Gastrodia Rhizomes Suppress the Atherosclerosis Risk Index through Inhibition of the Serum Cholesterol Composition in Sprague Dawley Rats Fed a High-Fat Diet  

PubMed Central

Obesity is associated with a broad spectrum of cardio-metabolic disturbances, including atherosclerosis and cardiovascular disease (CDV). A high-fat diet has been shown to cause an elevation of the plasma cholesterol levels in humans, and the control of serum cholesterol has been demonstrated to be important in the prevention of CVD and atherosclerosis. The aims of this study were to demonstrate that crude and acidic polysaccharide extracts from Gastrodia rhizomes suppress atherosclerosis through the regulation of serum lipids in Sprague Dawley (SD) rats fed a high-fat diet. We examined the concentrations of serum lipids, including total cholesterol, triglycerides, high-density lipoproteins (HDL) cholesterol, and low-density lipoproteins (LDL) cholesterol, in SD rats fed a high-fat diet and evaluated the atherogenic index. Here, we show that both crude and acidic polysaccharide extracts from Gastrodia rhizomes inhibited the total cholesterol and LDL levels. Moreover, there was a significantly suppressed atherosclerosis risk due to the acidic polysaccharide extract from Gastrodia rhizome. Taken together, our results suggested that acidic polysaccharide extracts from Gastrodia rhizomes might be beneficial for lowering the incidence of CVD and atherosclerosis by reducing the de novo synthesis of total cholesterol and the LDL levels. PMID:22408412

Kim, Kui-Jin; Lee, Ok-Hwan; Han, Chan-Kyu; Kim, Young-Chan; Hong, Hee-Do

2012-01-01

10

Novel angiotensin II AT(1) receptor antagonist irbesartan prevents thromboxane A(2)-induced vasoconstriction in canine coronary arteries and human platelet aggregation.  

PubMed

This study was conducted to investigate whether the novel orally active nonpeptide angiotensin II (Ang II) AT(1) receptor antagonist irbesartan interacts with the thromboxane A(2)/prostaglandin endoperoxide H(2) (TxA(2)/PGH(2)) receptor in canine coronary arteries and human platelets. Coronary artery rings were isolated from male dog hearts (n = 18) and isometric tension of vascular rings was measured continuously at optimal basal tension in organ chambers. Autoradiographic binding of [(3)H]SQ29,548, a TxA(2) receptor antagonist, in canine coronary sections was determined. Blood for platelet aggregation studies was collected by venous puncture from healthy human volunteers (n = 6) who were free of aspirin-like agents for at least 2 weeks. Vascular reactivity and platelet aggregation in response to the TxA(2) analogs U46619 and autoradioagraphic receptor binding to the TxA(2) receptor antagonist [(3)H]SQ29,548 were studied with and without irbesartan. The TxA(2) analog U46619 produced dose-dependent vasoconstriction in coronary rings (EC(50) = 11.6 +/- 1.5 nM). Pretreatment with irbesartan inhibited U46619-induced vasoconstriction, and the dose-response curve was shifted to the right in a dose-dependent manner. The EC(50) of U46619 was increased 6- and 35-fold in the presence of 1 and 10 microM of irbesartan without a change of maximal contraction. At 1 microM, irbesartan is 2-fold more potent than the AT(1) receptor antagonist losartan in the inhibition of U46619-induced vasoconstriction in canine coronary arteries. In contrast, neither AT(1) receptor antagonists (CV11974 and valsartan), the AT(2) receptor antagonist PD123319, nor the angiotensin converting enzyme inhibitor lisinopril had any effect on U46619-induced coronary vasoconstriction. Irbesartan did not change potassium chloride-induced vasoconstriction; however, irbesartan did inhibit the vasoconstriction mediated by another TxA(2)/PGH(2) receptor agonist prostaglandin F(2alpha) (PGF(2alpha)). Neither the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester nor the cyclooxygenase inhibitor indomethacin had any effect on irbesartan's attenuation of U46619-induced vasoconstriction. Irbesartan specifically reversed U46619-preconstricted coronary artery rings with and without endothelium in a dose-dependent manner. Irbesartan at high concentrations significantly competed for [(3)H]SQ29,548 binding in canine coronary sections. U46619 stimulated dose-dependent human platelet aggregation of platelet-rich plasma. Preincubation with irbesartan significantly inhibited platelet aggregation in a concentration-dependent manner. In conclusion, the dual antagonistic actions of irbesartan by acting at both the AT(1) and TxA(2) receptors in blood vessels and platelets may overall enhance its therapeutic profile in the treatment of hypertension, atherosclerosis, and arterial thrombosis. PMID:10604953

Li, P; Fukuhara, M; Diz, D I; Ferrario, C M; Brosnihan, K B

2000-01-01

11

Atherosclerosis (image)  

MedlinePLUS

Atherosclerosis is a disease of the arteries in which fatty material is deposited in the vessel wall, ... muscle leads to symptoms such as chest pain. Atherosclerosis shows no symptoms until a complication occurs.

12

The anti-atherosclerotic effect of olive leaf extract is related to suppressed inflammatory response in rabbits with experimental atherosclerosis  

Microsoft Academic Search

Background  The anti-atherogenic effect of olive leaf extract is supposed to be related to its activities of anti-oxidation and anti-inflammation.\\u000a \\u000a \\u000a \\u000a Aim of the study  To prove the effect of anti-atherosclerosis by olive leaf extract (OLE) and to elucidate the mechanism behind.\\u000a \\u000a \\u000a \\u000a Methods  Twenty-four rabbits were assigned to the control, high lipid diet (HLD) and OLE group that were fed with standard diet, HLD

Lihui Wang; Chengyan Geng; Liping Jiang; Dezheng Gong; Dayu Liu; Hiroyuki Yoshimura; Laifu Zhong

2008-01-01

13

Targeting annexin A7 by a small molecule suppressed the activity of phosphatidylcholine-specific phospholipase C in vascular endothelial cells and inhibited atherosclerosis in apolipoprotein E?/? mice  

PubMed Central

Phosphatidylcholine-specific phospholipase C (PC-PLC) is a key factor in apoptosis and autophagy of vascular endothelial cells (VECs), and involved in atherosclerosis in apolipoprotein E?/? (apoE?/?) mice. But the endogenous regulators of PC-PLC are not known. We recently found a small chemical molecule (6-amino-2, 3-dihydro-3-hydroxymethyl-1, 4-benzoxazine, ABO) that could inhibit oxidized low-density lipoprotein (oxLDL)-induced apoptosis and promote autophagy in VECs, and further identified ABO as an inhibitor of annexin A7 (ANXA7) GTPase. Based on these findings, we hypothesize that ANXA7 is an endogenous regulator of PC-PLC, and targeting ANXA7 by ABO may inhibit atherosclerosis in apoE?/? mice. In this study, we tested our hypothesis. The results showed that ABO suppressed oxLDL-induced increase of PC-PLC level and activity and promoted the co-localization of ANXA7 and PC-PLC in VECs. The experiments of ANXA7 knockdown and overexpression demonstrated that the action of ABO was ANXA7-dependent in cultured VECs. To investigate the relation of ANXA7 with PC-PLC in atherosclerosis, apoE?/? mice fed with a western diet were treated with 50 or 100?mg/kg/day ABO. The results showed that ABO decreased PC-PLC levels in the mouse aortic endothelium and PC-PLC activity in serum, and enhanced the protein levels of ANXA7 in the mouse aortic endothelium. Furthermore, both dosages of ABO significantly enhanced autophagy and reduced apoptosis in the mouse aortic endothelium. As a result, ABO significantly reduced atherosclerotic plaque area and effectively preserved a stable plaques phenotype, including reduced lipid deposition and pro-inflammatory macrophages, increased anti-inflammatory macrophages, collagen content and smooth muscle cells, and less cell death in the plaques. In conclusion, ANXA7 was an endogenous regulator of PC-PLC, and targeting ANXA7 by ABO inhibited atherosclerosis in apoE?/? mice. PMID:24052074

Li, H; Huang, S; Wang, S; Zhao, J; Su, L; Zhao, B; Zhang, Y; Zhang, S; Miao, J

2013-01-01

14

Endothelial function, blood pressure control, and risk modification: impact of irbesartan alone or in combination  

PubMed Central

Irbesartan, an angiotensin II type 1 receptor antagonist, is approved as monotherapy, or in combination with other drugs, for the treatment of hypertension in many countries worldwide. Data in the literature suggest that irbesartan is effective for reducing blood pressure over a 24-hour period with once-daily administration, and slows the progression of renal disease in patients with hypertension and type 2 diabetes. Furthermore, irbesartan shows a good safety and tolerability profile, compared with angiotensin II inhibitors and other angiotensin II type 1 receptor antagonists. Thus, irbesartan appears to be a useful treatment option for patients with hypertension, including those with type 2 diabetes and nephropathy. Irbesartan has an inhibitory effect on the pressor response to angiotensin II and improves arterial stiffness, vascular endothelial dysfunction, and inflammation in hypertensive patients. There has been considerable interest recently in the renoprotective effect of irbesartan, which appears to be independent of reductions in blood pressure. In particular, mounting data suggests that irbesartan improves endothelial function, oxidative stress, and inflammation in the kidneys. Recent studies have highlighted a possible role for irbesartan in improving coronary artery inflammation and vascular dysfunction. In this review we summarize and comment on the most important data available with regard to antihypertensive effect, endothelial function improvement, and cardiovascular risk reduction with irbesartan. PMID:21949618

Derosa, Giuseppe; Salvadeo, Sibilla AT

2010-01-01

15

Rutaecarpine suppresses atherosclerosis in ApoE-/- mice through upregulating ABCA1 and SR-BI within RCT.  

PubMed

ABCA1 and scavenger receptor class B type I (SR-BI)/CD36 and lysosomal integral membrane protein II analogous 1 (CLA-1) are the key transporter and receptor in reverse cholesterol transport (RCT). Increasing the expression level of ABCA1 and SR-BI/CLA-1 is antiatherogenic. The aim of the study was to find novel antiatherosclerotic agents upregulating expression of ABCA1 and SR-BI/CLA-1 from natural compounds. Using the ABCA1p-LUC and CLA-1p-LUC HepG2 cell lines, we found that rutaecarpine (RUT) triggered promoters of ABCA1 and CLA-1 genes. RUT increased ABCA1 and SR-BI/CLA-1 expression in vitro related to liver X receptor alpha and liver X receptor beta. RUT induced cholesterol efflux in RAW264.7 cells. ApoE-deficient (ApoE(-/-)) mice treated with RUT for 8 weeks showed ?68.43, 70.23, and 85.56% less en face lesions for RUT (L), RUT (M), and RUT (H) groups, respectively, compared with the model group. Mouse macrophage-specific antibody and filipin staining indicated that RUT attenuated macrophages and cholesterol accumulations in atherosclerotic lesions, respectively. Additionally, ABCA1 and SR-BI expression was highly induced by RUT in livers of ApoE(-/-) mice. Meanwhile, RUT treatment significantly increased the fecal (3)H-cholesterol excretion, which demonstrated that RUT could promote RCT in vivo. RUT was identified to be a candidate that protected ApoE(-/-) mice from developing atherosclerosis through preferentially promoting activities of ABCA1 and SR-BI within RCT. PMID:24908654

Xu, Yanni; Liu, Qi; Xu, Yang; Liu, Chang; Wang, Xiao; He, Xiaobo; Zhu, Ningyu; Liu, Jikai; Wu, Yexiang; Li, Yongzhen; Li, Ni; Feng, Tingting; Lai, Fangfang; Zhang, Murui; Hong, Bin; Jiang, Jian-Dong; Si, Shuyi

2014-06-01

16

What Causes Atherosclerosis?  

MedlinePLUS

... page from the NHLBI on Twitter. What Causes Atherosclerosis? The exact cause of atherosclerosis isn't known. ... Rate This Content: Next >> Featured Video What is atherosclerosis? 10/14/2014 August 4, 2014 Atherosclerosis Clinical ...

17

Irbesartan increased PPAR{gamma} activity in vivo in white adipose tissue of atherosclerotic mice and improved adipose tissue dysfunction  

SciTech Connect

Research highlights: {yields} Atherosclerotic apolipoprotein E-deficient (ApoEKO) mice were treated with irbesartan. {yields} Irbesartan decreased white adipose tissue weight without affecting body weight. {yields} DNA-binding for PPAR{gamma} was increased in white adipose tissue in vivo by irbesartan. {yields} Irbesartan increased adipocyte number in white adipose tissue. {yields} Irbesatan increased the expression of adiponectin and leptin in white adipose tissue. -- Abstract: The effect of the PPAR{gamma} agonistic action of an AT{sub 1} receptor blocker, irbesartan, on adipose tissue dysfunction was explored using atherosclerotic model mice. Adult male apolipoprotein E-deficient (ApoEKO) mice at 9 weeks of age were treated with a high-cholesterol diet (HCD) with or without irbesartan at a dose of 50 mg/kg/day for 4 weeks. The weight of epididymal and retroperitoneal adipose tissue was decreased by irbesartan without changing food intake or body weight. Treatment with irbesartan increased the expression of PPAR{gamma} in white adipose tissue and the DNA-binding activity of PPAR{gamma} in nuclear extract prepared from adipose tissue. The expression of adiponectin, leptin and insulin receptor was also increased by irbesartan. These results suggest that irbesartan induced activation of PPAR{gamma} and improved adipose tissue dysfunction including insulin resistance.

Iwai, Masaru; Kanno, Harumi; Senba, Izumi; Nakaoka, Hirotomo; Moritani, Tomozo [Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Shitsukawa, Tohon, Ehime 791-0295 (Japan)] [Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Shitsukawa, Tohon, Ehime 791-0295 (Japan); Horiuchi, Masatsugu, E-mail: horiuchi@m.ehime-u.ac.jp [Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Shitsukawa, Tohon, Ehime 791-0295 (Japan)] [Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Shitsukawa, Tohon, Ehime 791-0295 (Japan)

2011-03-04

18

Increased Expression of Chitinase 3-Like 1 in Aorta of Patients with Atherosclerosis and Suppression of Atherosclerosis in Apolipoprotein E-Knockout Mice by Chitinase 3-Like 1 Gene Silencing  

PubMed Central

Introduction. The purpose of this study was to investigate the changes of chitinase 3-like 1 (CHI3L1) in the aorta of patients with coronary atherosclerosis and to determine whether inhibition of CHI3L1 by lentivirus-mediated RNA interference could stabilize atherosclerotic plaques in apolipoprotein E-knockout (ApoE?/?) mice. Methods. We collected discarded aortic specimens from patients undergoing coronary artery bypass graft surgery and renal arterial tissues from kidney donors. A lentivirus carrying small interfering RNA targeting the expression of CHI3L1 was constructed. Fifty ApoE?/? mice were divided into control group and CHI3L1 gene silenced group. A constrictive collar was placed around carotid artery to induce plaques formation. Then lentivirus was transfected into carotid plaques. Results. We found that CHI3L1 was overexpressed in aorta of patients with atherosclerosis and its expression was correlated with the atherosclerotic risk factors. After lentivirus transduction, mRNA and protein expression of CHI3L1 were attenuated in carotid plaques, leading to reduced plaque content of lipids and macrophages, and increased plaque content of collagen and smooth muscle cells. Moreover, CHI3L1 gene silencing downregulated the expression of local proinflammatory mediators. Conclusions. CHI3L1 is overexpressed in aorta from patients with atherosclerosis and the lentivirus-mediated CHI3L1 gene silencing could represent a new strategy to inhibit plaques progression. PMID:24729664

Gong, Zushun; Xing, Shanshan; Zheng, Fei; Xing, Qichong

2014-01-01

19

Fixed combination of irbesartan and hydrochlorothiazide in the management of hypertension  

PubMed Central

Approximately 25% of the adult population worldwide is hypertensive and thus at risk of cardiovascular morbidity and mortality. Despite the availability of many antihypertensive drugs, at least 50% of patients do not achieve blood pressure (BP) targets and thus remain at increased cardiovascular risk. Fixed-dose (FD) irbesartan/hydrochlorothiazide (HCTZ) is an antihypertensive combination therapy approved for the treatment of patients whose BP is not adequately controlled on monotherapy and for initial treatment of patients likely to need multiple drugs to achieve their BP goal. The efficacy and tolerability of FD irbesartan/HCTZ has been demonstrated in both patient populations in large multicenter studies. In patients failing antihypertensive monotherapy, FD irbesartan/HCTZ (150/12.5 mg) has been shown to be more effective than FD valsartan/HCTZ (80/12.5 mg) and at least comparable to FD losartan/HCTZ (50/12.5 mg). In patients with moderate or severe hypertension receiving FD irbesartan/HCTZ as initial therapy, this combination achieved more rapid BP reductions compared with irbesartan monotherapy and enabled a greater proportion of patients with severe hypertension to achieve their BP target. FD irbesartan/HCTZ is thus a valuable addition to the clinician’s armamentarium for the management of hypertension and should help more patients achieve their BP target. PMID:19436667

Bramlage, Peter

2009-01-01

20

Long-term use and tolerability of irbesartan for control of hypertension  

PubMed Central

In this review, we discuss the pharmacological and clinical properties of irbesartan, a noncompetitive angiotensin II receptor type 1 antagonist, successfully used for more than a decade in the treatment of essential hypertension. Irbesartan exerts its antihypertensive effect through an inhibitory effect on the pressure response to angiotensin II. Irbesartan 150–300 mg once daily confers a lasting effect over 24 hours, and its antihypertensive efficacy is further enhanced by the coadministration of hydrochlorothiazide. Additionally and partially beyond its blood pressure-lowering effect, irbesartan reduces left ventricular hypertrophy, favors right atrial remodeling in atrial fibrillation, and increases the likelihood of maintenance of sinus rhythm after cardioversion in atrial fibrillation. In addition, the renoprotective effects of irbesartan are well documented in the early and later stages of renal disease in type 2 diabetics. Furthermore, both the therapeutic effectiveness and the placebo-like side effect profile contribute to a high adherence rate to the drug. Currently, irbesartan in monotherapy or combination therapy with hydrochlorothiazide represent a rationale pharmacologic approach for arterial hypertension and early-stage and late-stage diabetic nephropathy in hypertensive type II diabetics. PMID:21949635

Forni, Valentina; Wuerzner, Grégoire; Pruijm, Menno; Burnier, Michel

2011-01-01

21

Potential of the angiotensin receptor blockers (ARBs) telmisartan, irbesartan, and candesartan for inhibiting the HMGB1/RAGE axis in prevention and acute treatment of stroke.  

PubMed

Stroke is a major cause of mortality and disability worldwide. The main cause of stroke is atherosclerosis, and the most common risk factor for atherosclerosis is hypertension. Therefore, antihypertensive treatments are recommended for the prevention of stroke. Three angiotensin receptor blockers (ARBs), telmisartan, irbesartan and candesartan, inhibit the expression of the receptor for advanced glycation end-products (RAGE), which is one of the pleiotropic effects of these drugs. High mobility group box 1 (HMGB1) is the ligand of RAGE, and has been recently identified as a lethal mediator of severe sepsis. HMGB1 is an intracellular protein, which acts as an inflammatory cytokine when released into the extracellular milieu. Extracellular HMGB1 causes multiple organ failure and contributes to the pathogenesis of hypertension, hyperlipidemia, diabetes mellitus, atherosclerosis, thrombosis, and stroke. This is the first review of the literature evaluating the potential of three ARBs for the HMGB1-RAGE axis on stroke therapy, including prevention and acute treatment. This review covers clinical and experimental studies conducted between 1976 and 2013. We propose that ARBs, which inhibit the HMGB1/RAGE axis, may offer a novel option for prevention and acute treatment of stroke. However, additional clinical studies are necessary to verify the efficacy of ARBs. PMID:24065095

Kikuchi, Kiyoshi; Tancharoen, Salunya; Ito, Takashi; Morimoto-Yamashita, Yoko; Miura, Naoki; Kawahara, Ko-ichi; Maruyama, Ikuro; Murai, Yoshinaka; Tanaka, Eiichiro

2013-01-01

22

Potential of the Angiotensin Receptor Blockers (ARBs) Telmisartan, Irbesartan, and Candesartan for Inhibiting the HMGB1/RAGE Axis in Prevention and Acute Treatment of Stroke  

PubMed Central

Stroke is a major cause of mortality and disability worldwide. The main cause of stroke is atherosclerosis, and the most common risk factor for atherosclerosis is hypertension. Therefore, antihypertensive treatments are recommended for the prevention of stroke. Three angiotensin receptor blockers (ARBs), telmisartan, irbesartan and candesartan, inhibit the expression of the receptor for advanced glycation end-products (RAGE), which is one of the pleiotropic effects of these drugs. High mobility group box 1 (HMGB1) is the ligand of RAGE, and has been recently identified as a lethal mediator of severe sepsis. HMGB1 is an intracellular protein, which acts as an inflammatory cytokine when released into the extracellular milieu. Extracellular HMGB1 causes multiple organ failure and contributes to the pathogenesis of hypertension, hyperlipidemia, diabetes mellitus, atherosclerosis, thrombosis, and stroke. This is the first review of the literature evaluating the potential of three ARBs for the HMGB1-RAGE axis on stroke therapy, including prevention and acute treatment. This review covers clinical and experimental studies conducted between 1976 and 2013. We propose that ARBs, which inhibit the HMGB1/RAGE axis, may offer a novel option for prevention and acute treatment of stroke. However, additional clinical studies are necessary to verify the efficacy of ARBs. PMID:24065095

Kikuchi, Kiyoshi; Tancharoen, Salunya; Ito, Takashi; Morimoto-Yamashita, Yoko; Miura, Naoki; Kawahara, Ko-ichi; Maruyama, Ikuro; Murai, Yoshinaka; Tanaka, Eiichiro

2013-01-01

23

The antihypertensive response to irbesartan treatment from a pharmacogenetic perspective.  

PubMed

Coronary heart disease is the leading cause of death in the Western world. Approximately half of all the people who have their 1st heart attack and 2/3 of those with their first stroke have high blood pressure levels. Hypertension affects approximately 25% of the adult population. By treating hypertension and risk factors that contribute to cardiovascular disease both mortality and morbidity can be reduced. Many drugs have proven to be effective in treating hypertension, although the individual patient's response to antihypertensive treatment varies over a wide range and cannot be predicted with methods used today. Between 30-60% of the blood pressure variation is determined by genetic factors. Also the variation in drug response is in part heritable, which defines pharmacogenetics. This review gives a general background to pharmacogenetics and its potential usage. In addition, results from recent pharmacogenetics studies on the antihypertensive effect of the angiotensin II type 1 receptor antagonist irbesartan are presented. PMID:14605589

Kurland, L

2003-08-01

24

Living with Atherosclerosis  

MedlinePLUS

... page from the NHLBI on Twitter. Living With Atherosclerosis Improved treatments have reduced the number of deaths ... Rate This Content: Next >> Featured Video What is atherosclerosis? 10/14/2014 August 4, 2014 Atherosclerosis Clinical ...

25

Extractive-spectrophotometric determination of disopyramide and irbesartan in their pharmaceutical formulation  

NASA Astrophysics Data System (ADS)

Picric acid, bromocresol green, bromothymol blue, cobalt thiocyanate and molybdenum(V) thiocyanate have been tested as spectrophotometric reagents for the determination of disopyramide and irbesartan. Reaction conditions have been optimized to obtain coloured comoplexes of higher sensitivity and longer stability. The absorbance of ion-pair complexes formed were found to increases linearity with increases in concentrations of disopyramide and irbesartan which were corroborated by correction coefficient values. The developed methods have been successfully applied for the determination of disopyramide and irbesartan in bulk drugs and pharmaceutical formulations. The common excipients and additives did not interfere in their determination. The results obtained by the proposed methods have been statistically compared by means of student t-test and by the variance ratio F-test. The validity was assessed by applying the standard addition technique. The results were compared statistically with the official or reference methods showing a good agreement with high precision and accuracy.

Abdellatef, Hisham E.

2007-04-01

26

Extractive-spectrophotometric determination of disopyramide and irbesartan in their pharmaceutical formulation.  

PubMed

Picric acid, bromocresol green, bromothymol blue, cobalt thiocyanate and molybdenum(V) thiocyanate have been tested as spectrophotometric reagents for the determination of disopyramide and irbesartan. Reaction conditions have been optimized to obtain coloured comoplexes of higher sensitivity and longer stability. The absorbance of ion-pair complexes formed were found to increases linearity with increases in concentrations of disopyramide and irbesartan which were corroborated by correction coefficient values. The developed methods have been successfully applied for the determination of disopyramide and irbesartan in bulk drugs and pharmaceutical formulations. The common excipients and additives did not interfere in their determination. The results obtained by the proposed methods have been statistically compared by means of student t-test and by the variance ratio F-test. The validity was assessed by applying the standard addition technique. The results were compared statistically with the official or reference methods showing a good agreement with high precision and accuracy. PMID:16920393

Abdellatef, Hisham E

2007-04-01

27

Improved gastric emptying in diabetic rats by irbesartan via decreased serum leptin and ameliorated gastric microcirculation.  

PubMed

Diabetic gastroparesis (DG) is a common clinical complication of diabetes mellitus. Leptin may cause delayed gastric emptying in the central and peripheral pathways. Microcirculatory disturbances in the stomach make gastric smooth muscles and nerves hypoxic-ischemic, thereby impairing gastric motility. Irbesartan is an angiotensin II (ATII) receptor blocker that indirectly decreases serum leptin levels and improves blood vessel endothelia. This study examined the effect of irbesartan on DG and its relationship with serum leptin levels and microcirculatory disturbances of the stomach. Sprague-Dawley rats were injected with streptozotocin to induce diabetes and were then treated with or without 0.012 g·kg(-1)·d(-1) irbesartan by gavage. After six weeks of treatment, the gastric evacuation rate (GER) was measured using phenol red. Serum leptin levels were detected using enzyme-linked immunosorbent assays. Endothelin (ET) in the stomach tissue was examined using a radioimmunoassay, whereas chemical colorimetry was used to measure the nitric oxide synthase (NOS) activity of stomach tissues. The mRNA expression of the ATII receptor (AT1R) was assessed using reverse transcription-polymerase chain reaction. Treatment with irbesartan significantly increased the GER of diabetic rats and reduced the serum leptin levels, as well as decreased the ET content and AT1R mRNA expression in the stomach (P<0.05). Changes in the cNOS activity after irbesartan intervention were not significant (P>0.05), whereas iNOS activity was significantly decreased (P<0.05). Irbesartan can alleviate hyperglycemia-induced delayed gastric emptying, which is associated with decreased serum leptin levels and improved microcirculation in the stomach. PMID:25222222

He, L; Sun, Y; Zhu, Y; Ren, R; Zhang, Y; Wang, F

2014-01-01

28

Atherosclerosis and Stroke  

MedlinePLUS

Atherosclerosis and Stroke Updated:Sep 16,2014 Excerpted and adapted from "When Risk Factors Unite," appearing in the Stroke Connection Magazine ... it can cause difficulty walking and eventually gangrene. Stroke and atherosclerosis There are two types of ischemic ...

29

Naringenin and Atherosclerosis: a Review of Literatures.  

PubMed

Atherosclerosis is a multifactorial disease mainly caused by deposition of low-density lipoprotein cholesterol in macrophages of arterial walls. Atherosclerosis leads to heart attacks as well as stroke. Epidemiological studies showed that there is inverse correlation between fruit and vegetable consumption and risk of atherosclerosis. The promising effect of high vegetable and fruit containing diet on atherosclerosis is approved by several experimental studies on isolated phytochemicals such as flavonoids. Flavonoids are known to up-regulate endogenous antioxidant system, suppress oxidative and nitrosative stress, decrease macrophage oxidative stress through cellular oxygenase inhibition as well as interaction with several signal transduction pathways and from these ways, have therapeutic effects against atherosclerosis. Naringenin is a well known flavonoid belonging to the chemical class of flavanones. It is especially abundant in citrus fruits specially grapefruits. A plethora of evidences ascribes to naringenin anti-atherosclerotic effects. Naringenin abilities to decrease low-density lipoprotein (LDL) and triglycerides as well as inhibit glucose uptake; increase high-density lipoprotein (HDL); co-oxidation of NADH; suppress protein oxidation; protect against intercellular adhesion molecule-1(ICAM-1); Suppress macrophage inflammation; inhibit leukotriene B4, monocyte adhesion and foam cell formation; induce of HO-1 and G 0/G 1 cell cycle arrest in vascular smooth muscle cells (VSMC) and down regulate atherosclerosis related genes are believed to have crucial role in the promising role against atherosclerosis. In the present review, we have summarized the available literature data on the anti-atherosclerotic effects of naringenin and its possible mechanisms of actions. PMID:25483717

Orhan, Ilkay Erdogan; Nabavi, Seyed Fazel; Daglia, Maria; Tenore, Gian Carlo; Mansouri, Kowsar; Nabavi, Seyed Mohammad

2014-12-01

30

Effects of low-dose spironolactone combined with irbesartan on cardiac hypertrophy induced by pressure overload in rats  

PubMed Central

Background: The mineralocorticoid receptor (MR) blockade in the heart is an attractive therapeutic option for the treatment of heart failure. However, the use of MR antagonist is limited by an increased incidence of hyperkalemia owing to MR blockade in the kidney. This study was designed to evaluate and compare the effectiveness of a low, non-pressure-lowering dose of spironolactone (Sp) with that of a conventional blood pressure-lowering dose combined with irbesartan on pathological cardiac remodeling as well as serum potassium level in pressure-overload rats. Methods: The pressure-overloaded myocardial remodelling was produced by partial abdominal aortic constriction (PAAC) in rats. Four weeks after PAAC, animals were respectively treated with vehicle, irbesartan (15 mg/kg) alone, low-dose Sp (1 mg/kg) or conventional-dose of Sp (20 mg/kg) in combination with irbesartan for consecutive four weeks. Results: The result demonstrated that compared to irbesartan monotherapy, the combination of irbesartan and spironolactone both in low- and conventional-dose exhibited additional cardioprotection against PAAC-induced cardiac remodelling. Low-dose spironolactone was as effective in inhibiting cardiac hypertrophy, fibrosis and in improving diastolic function as high dose. Low-dose spironolactone did not lead to a rise in potassium serum levels, but high dose did. Conclusions: This study suggests that combined low dose of spironolactone and irbesartan may be an effective and safety therapeutic strategy for cardiac hypertrophy and heart failure.

Ma, Jingtao; Zhang, Hongxue; Guo, Huicai; Xu, Yanfang

2014-01-01

31

Vinpocetine attenuates lipid accumulation and atherosclerosis formation  

SciTech Connect

Highlights: •Vinpocetine attenuates hyperlipidemia-induced atherosclerosis in a mouse model. •Vinpocetine antagonizes ox-LDL uptake and accumulation in macrophages. •Vinpocetine blocks the induction of ox-LDL receptor LOX-1 in vitro and in vivo. -- Abstract: Atherosclerosis, the major cause of myocardial infarction and stroke, is a chronic arterial disease characterized by lipid deposition and inflammation in the vessel wall. Cholesterol, in low-density lipoprotein (LDL), plays a critical role in the pathogenesis of atherosclerosis. Vinpocetine, a derivative of the alkaloid vincamine, has long been used as a cerebral blood flow enhancer for treating cognitive impairment. Recent study indicated that vinpocetine is a potent anti-inflammatory agent. However, its role in the pathogenesis of atherosclerosis remains unexplored. In the present study, we show that vinpocetine significantly reduced atherosclerotic lesion formation in ApoE knockout mice fed with a high-fat diet. In cultured murine macrophage RAW264.7 cells, vinpocetine markedly attenuated oxidized LDL (ox-LDL) uptake and foam cell formation. Moreover, vinpocetine greatly blocked the induction of ox-LDL receptor 1 (LOX-1) in cultured macrophages as well as in the LOX-1 level in atherosclerotic lesions. Taken together, our data reveal a novel role of vinpocetine in reduction of pathogenesis of atherosclerosis, at least partially through suppressing LOX-1 signaling pathway. Given the excellent safety profile of vinpocetine, this study suggests vinpocetine may be a therapeutic candidate for treating atherosclerosis.

Cai, Yujun [Aab Cardiovascular Research Institute, Department of Medicine, University of Rochester, 601 Elmwood Ave, Rochester, NY 14642 (United States)] [Aab Cardiovascular Research Institute, Department of Medicine, University of Rochester, 601 Elmwood Ave, Rochester, NY 14642 (United States); Li, Jian-Dong [Center for Inflammation, Immunity and Infection, and Department of Biology, Georgia State University, Atlanta, GA 30303 (United States)] [Center for Inflammation, Immunity and Infection, and Department of Biology, Georgia State University, Atlanta, GA 30303 (United States); Yan, Chen, E-mail: Chen_Yan@urmc.rochester.edu [Aab Cardiovascular Research Institute, Department of Medicine, University of Rochester, 601 Elmwood Ave, Rochester, NY 14642 (United States)] [Aab Cardiovascular Research Institute, Department of Medicine, University of Rochester, 601 Elmwood Ave, Rochester, NY 14642 (United States)

2013-05-10

32

Genetic Variation and Atherosclerosis  

PubMed Central

A family history of atherosclerosis is independently associated with an increased incidence of cardiovascular events. The genetic factors underlying the importance of inheritance in atherosclerosis are starting to be understood. Genetic variation, such as mutations or common polymorphisms has been shown to be involved in modulation of a range of risk factors, such as plasma lipoprotein levels, inflammation and vascular calcification. This review presents examples of present studies of the role of genetic polymorphism in atherosclerosis. PMID:19424482

Biros, Erik; Karan, Mirko; Golledge, Jonathan

2008-01-01

33

Dendritic cells in atherosclerosis.  

PubMed

Atherosclerosis is a chronic inflammatory disease with activation of both the innate and adaptive arms of the immune system. Dendritic cells (DCs) are potent activators of adaptive immunity and have been identified in the normal arterial wall and within atherosclerotic lesions. Recent evidence points to a functional role for DCs in all stages of atherosclerosis because of their myriad functions including lipid uptake, antigen presentation, efferocytosis, and inflammation resolution. Moreover, DC-based vaccination strategies are currently being developed for the treatment of atherosclerosis. This review will focus on the current evidence as well as the proposed roles for DCs in the pathogenesis of atherosclerosis and discuss future therapeutic strategies. PMID:24196454

Subramanian, Manikandan; Tabas, Ira

2014-01-01

34

Fibrinolytic\\/hemostatic variables in arterial hypertension: response to treatment with irbesartan or atenolol  

Microsoft Academic Search

Essential hypertension is often accompanied by abnormalities of the coagulation\\/fibrinolytic system, predisposing to a procoagulant state. The aim of the present study was to compare the effects of atenolol (?1-blocker agent) and irbesartan (angiotensin II type 1 receptor antagonist) on plasma levels of hemostatic\\/fibrinolytic and endothelial function markers in a cohort of previously untreated hypertensives. Fifty-four patients were randomly assigned

Thomas K. Makris; George A. Stavroulakis; Panagiota G. Krespi; Anthony N. Hatzizacharias; Filippos K. Triposkiadis; Caterina G. Tsoukala; Vasilios V. Votteas; Michael K. Kyriakidis

2000-01-01

35

Bioequivalence study of two oral formulations of irbesartan 300?mg in healthy volunteers.  

PubMed

A bioequivalence study of 2 irbesartan (CAS 138402-11-6) film-coated tablet formulations was carried out in 40 healthy volunteers according to an open label, randomized, 2-period, 2-sequence, crossover, single dose and fasting conditions design. The test and reference formulations were administered in 2 treatment days, separated by a washout period of 7 days. Blood samples were drawn up to 96?h following drug administration. Plasma concentrations of irbesartan were obtained by a validated HPLC method using MS/MS detection. Log-transformed AUC0-t and Cmax values were tested for bioequivalence based on the ratios of the geometric LSmeans (test/reference). tmax was analysed nonparametrically. The 90% confidence intervals of the geometric LSmean values for the test/reference ratios for AUC0-t (98.06-109.48%, point estimator 103.61%) and Cmax (88.93-100.87%, point estimator 94.72%) were within the bioequivalence acceptance range of 80-125%. According to the European Guideline on the Investigation of Bioequivalence it may be therefore concluded that test formulation of irbesartan 300?mg film-coated tablet is bioequivalent to the reference formulation. Overall, it was judged that the study was conducted with a good tolerance of the subjects to both study drugs. PMID:24048950

Cánovas, M; Cabré, F; Polonio, F

2014-01-01

36

Vinpocetine attenuates lipid accumulation and atherosclerosis formation.  

PubMed

Atherosclerosis, the major cause of myocardial infarction and stroke, is a chronic arterial disease characterized by lipid deposition and inflammation in the vessel wall. Cholesterol, in low-density lipoprotein (LDL), plays a critical role in the pathogenesis of atherosclerosis. Vinpocetine, a derivative of the alkaloid vincamine, has long been used as a cerebral blood flow enhancer for treating cognitive impairment. Recent study indicated that vinpocetine is a potent anti-inflammatory agent. However, its role in the pathogenesis of atherosclerosis remains unexplored. In the present study, we show that vinpocetine significantly reduced atherosclerotic lesion formation in ApoE knockout mice fed with a high-fat diet. In cultured murine macrophage RAW264.7 cells, vinpocetine markedly attenuated oxidized LDL (ox-LDL) uptake and foam cell formation. Moreover, vinpocetine greatly blocked the induction of ox-LDL receptor 1 (LOX-1) in cultured macrophages as well as in the LOX-1 level in atherosclerotic lesions. Taken together, our data reveal a novel role of vinpocetine in reduction of pathogenesis of atherosclerosis, at least partially through suppressing LOX-1 signaling pathway. Given the excellent safety profile of vinpocetine, this study suggests vinpocetine may be a therapeutic candidate for treating atherosclerosis. PMID:23583194

Cai, Yujun; Li, Jian-Dong; Yan, Chen

2013-05-10

37

Vinpocetine Attenuates Lipid Accumulation and Atherosclerosis Formation  

PubMed Central

Atherosclerosis, the major cause of myocardial infarction and stroke, is a chronic arterial disease characterized by lipid deposition and inflammation in the vessel wall. Cholesterol, in low-density lipoprotein (LDL), plays a critical role in the pathogenesis of atherosclerosis. Vinpocetine, a derivative of the alkaloid vincamine, has long been used as a cerebral blood flow enhancer for treating cognitive impairment. Recent study indicated that vinpocetine is a potent inflammatory agent. However, its role in the pathogenesis of atherosclerosis remains unexplored. In the present study, we show that vinpocetine significantly reduced atherosclerotic lesion formation in ApoE knockout mice fed with a high-fat diet. In cultured murine macrophage RAW264.7 cells, vinpocetine markedly attenuated oxidized LDL (ox-LDL) uptake and foam cell formation. Moreover, vinpocetine greatly blocked the induction of ox-LDL receptor 1 (LOX-1) in cultured macrophages as well as in the LOX-1 level in atherosclerotic lesions. Taken together, our data reveal a novel role of vinpocetine in reduction of pathogenesis of atherosclerosis, at least partially through suppressing LOX-1 signaling pathway. Given the excellent safety profile of vinpocetine, this study suggests vinpocetine may be a therapeutic candidate for treating atherosclerosis PMID:23583194

Cai, Yujun; Li, Jian-Dong; Yan, Chen

2013-01-01

38

Animal models of atherosclerosis  

PubMed Central

In this mini-review several commonly used animal models of atherosclerosis have been discussed. Among them, emphasis has been made on mice, rabbits, pigs and non-human primates. Although these animal models have played a significant role in our understanding of induction of atherosclerotic lesions, we still lack a reliable animal model for regression of the disease. Researchers have reported several genetically modified and transgenic animal models that replicate human atherosclerosis, however each of current animal models have some limitations. Among these animal models, the apolipoprotein (apo) E-knockout (KO) mice have been used extensively because they develop spontaneous atherosclerosis. Furthermore, atherosclerotic lesions developed in this model depending on experimental design may resemble humans’ stable and unstable atherosclerotic lesions. This mouse model of hypercholesterolemia and atherosclerosis has been also used to investigate the impact of oxidative stress and inflammation on atherogenesis. Low density lipoprotein (LDL)-r-KO mice are a model of human familial hypercholesterolemia. However, unlike apo E-KO mice, the LDL-r-KO mice do not develop spontaneous atherosclerosis. Both apo E-KO and LDL-r-KO mice have been employed to generate other relevant mouse models of cardiovascular disease through breeding strategies. In addition to mice, rabbits have been used extensively particularly to understand the mechanisms of cholesterol-induced atherosclerosis. The present review paper details the characteristics of animal models that are used in atherosclerosis research. PMID:24868511

Kapourchali, Fatemeh Ramezani; Surendiran, Gangadaran; Chen, Li; Uitz, Elisabeth; Bahadori, Babak; Moghadasian, Mohammed H

2014-01-01

39

Matrix metalloproteinases and atherosclerosis  

Microsoft Academic Search

Atherosclerosis is a major cause of coronary heart disease, and matrix metalloproteinases (MMPs) play an important role in\\u000a atherosclerosis by degrading the extracellular matrix, which results in cardiovascular remodeling. Recent studies have identified\\u000a enhanced expression of MMPs in the atherosclerotic lesion and their contribution to weakening of the vascular wall by degrading\\u000a the extracellular matrix. The transcription, enzyme processing, and

Noboru Watanabe; Uichi Ikeda

2004-01-01

40

The Mechanics of Atherosclerosis  

NSDL National Science Digital Library

In this module, developed as part of Cornell's Learning Initiative in Medicine and Bioengineering (CLIMB), students will understand how arterial stiffness contributes to disturbed blood flow and the progression of atherosclerosis. This is done using polymer chemistry, fabricating gels of varying stiffness, and designing experiments to quantify gel stiffness. This module contains a teacher's guide, powerpoint instructional lecture "Atherosclerosis", instructional student activity sheets for laboratory activities, and multiple choice quizzes. CLIMB is part of the NSF GK-12 program.

CLIMB: Cornell's Learning Initiative in Medicine and Bioengineering

41

[AII antagonists (candesartan and irbesartan) in the treatment of cardiovascular diseases].  

PubMed

Treatment of hypertension with angiotensin II receptor antagonists (AIIA) was first limited to diabetics and patients with microalbuminuria. So far, results of several large clinical trials with AIIAs were published, confirming significant renoprotective effect of these agents compared to placebo (RENAAL and IRMA), amlodipin (MARVAL and IDNT) and a combination of ACEI and AIIA (CALM). In 2002, results of 2 large comparator studies in hypertension were published: LIFE - Losartan Intervention For Endpoints and SCOPE - the Study on COgnition and Prognosis in Elderly hypertensives. In 2003, a series of the CHARM studies involving patients with heart failure were published and, from than, AIIA have been used as an alternative to ACEI or in a combination with ACEI. MOSES study - Morbidity and mortality after stroke, eprosartan compared with nitrendipine for secondary prevention - results were published in 2005 and ONTARGET study, focusing on secondary prevention of ischemic heart disease, was published in 2008. The CORD study - Comparison of recommended doses - and the ACTIVE I study (AF Clopidogrel Trial with Irbesartan for prevention of Vascular Events) were published in 2009. Candesartan was used in the CALM, SCOPE, RESOLVED and CHARM studies, irbesartan in the IRMA, IDNT and ACTIVE I. PMID:23121062

Spinar, J; Vítovec, J

2012-10-01

42

Atherosclerosis and inflammation.  

PubMed

The pathophysiology of coronary atherosclerosis is complex and multifactorial. The probability of the development of symptomatic coronary heart disease may be predicted by standard risk factor stratification involving hypertension, dyslipidemia, age, positive family history, and diabetes. However, risk factor stratification has been demonstrated to have significant limitations in the individual patient, which has generated a search for more specific and sensitive markers. Evidence is increasing that atherosclerosis is a disease characterized by inflammation, beginning with the earliest identifiable lesion (fatty streak) to the advanced vulnerable plaque. Clinical markers of inflammation, including C-reactive protein, modified low-density lipoprotein, homocysteine, tumor necrosis factor, and thermogenicity, have been identified as emerging risk factors that may add prognostic information in patient management. This review centers on inflammation as a potential pathogenetic factor in atherosclerosis and the role that clinical markers may play in the identification of patients at risk. PMID:11822971

Farmer, John A; Torre-Amione, Guillermo

2002-03-01

43

Macrophage Autophagy in Atherosclerosis  

PubMed Central

Macrophages play crucial roles in atherosclerotic immune responses. Recent investigation into macrophage autophagy (AP) in atherosclerosis has demonstrated a novel pathway through which these cells contribute to vascular inflammation. AP is a cellular catabolic process involving the delivery of cytoplasmic contents to the lysosomal machinery for ultimate degradation and recycling. Basal levels of macrophage AP play an essential role in atheroprotection during early atherosclerosis. However, AP becomes dysfunctional in the more advanced stages of the pathology and its deficiency promotes vascular inflammation, oxidative stress, and plaque necrosis. In this paper, we will discuss the role of macrophages and AP in atherosclerosis and the emerging evidence demonstrating the contribution of macrophage AP to vascular pathology. Finally, we will discuss how AP could be targeted for therapeutic utility. PMID:23401644

Maiuri, Maria Chiara; Grassia, Gianluca; Platt, Andrew M.; Carnuccio, Rosa; Ialenti, Armando; Maffia, Pasquale

2013-01-01

44

Insulin resistance and atherosclerosis.  

PubMed

Considerable evidence supports the association between insulin resistance and vascular disease, and this has led to wide acceptance of the clustering of hyperlipidemia, glucose intolerance, hypertension, and obesity as a clinical entity, the metabolic syndrome. While insulin resistance, by promoting dyslipidemia and other metabolic abnormalities, is part of the proatherogenic milieu, it is possible that insulin resistance itself in the vascular wall does not promote atherosclerosis. Recent findings suggest that insulin resistance and atherosclerosis could represent independent and ultimately maladaptive responses to the disruption of cellular homeostasis caused by the excess delivery of fuel. PMID:16823479

Semenkovich, Clay F

2006-07-01

45

Intercellular Communication in Atherosclerosis  

NSDL National Science Digital Library

Cell-to-cell communication is a process necessary for physiological tissue homeostasis and appears often altered during disease. Gap junction channels, formed by connexins, allow the direct intercellular communication between adjacent cells. After a brief review of the pathophysiology of atherosclerosis, we will discuss the role of connexins throughout the different stages of the disease.

Laurent Burnier (University of Lausanne)

2009-02-01

46

Genes Involved in Atherosclerosis  

Microsoft Academic Search

Atherosclerosis is a multifactorial disease that involves several genes and proteins. The purpose of this article is to focus on the arterial wall and to review lipoprotein receptors, growth factors, cytokines, chemokines, matrix metalloproteinases, adhesion molecules, and apoptosis genes and their involvement in atherogenesis.

Johanna Laukkanen; Seppo Ylä-Herttuala

2002-01-01

47

Treating atherosclerosis with regulatory T cells.  

PubMed

Regulatory T cells (Tregs) play an important role in the regulation of T-cell-mediated immune responses through suppression of T-cell proliferation and secretion of inhibitory cytokines, such as interleukin-10 and transforming growth factor-?. Impaired Treg numbers and function have been associated with numerous diseases, and an imbalance between proinflammatory/proatherogenic cells and Tregs promotes atherosclerotic disease. Restoration of this balance by inducing Tregs has great therapeutic potential to prevent cardiovascular disease. In addition to suppressing differentiation and function of effector T cells, Tregs have been shown to induce anti-inflammatory macrophages, inhibit foam cell formation and to influence cholesterol metabolism. Furthermore, Tregs suppress immune responses of endothelial cells and innate lymphoid cells. In this review, we focus on the recent knowledge on Treg subsets, their activity and function in atherosclerosis, and discuss promising strategies to use Tregs as a therapeutic tool to prevent cardiovascular disease. PMID:25414253

Foks, Amanda C; Lichtman, Andrew H; Kuiper, Johan

2015-02-01

48

Insulin resistance and atherosclerosis.  

PubMed

Insulin resistance characterizes type 2 diabetes and the metabolic syndrome, disorders associated with an increased risk of death due to macrovascular disease. In the past few decades, research from both the basic science and clinical arenas has enabled evidence-based use of therapeutic modalities such as statins and angiotensin-converting enzyme inhibitors to reduce cardiovascular (CV) mortality in insulin-resistant patients. Recently, promising drugs such as the thiazolidinediones have come under scrutiny for possible deleterious CV effects. Ongoing research has broadened our understanding of the pathophysiology of atherosclerosis, implicating detrimental effects of inflammation and the cellular stress response on the vasculature. In this review, we address current thinking that is shaping our molecular understanding of insulin resistance and atherosclerosis. PMID:18775354

Razani, Babak; Chakravarthy, Manu V; Semenkovich, Clay F

2008-09-01

49

Insulin Resistance and Atherosclerosis  

PubMed Central

Synopsis Insulin resistance characterizes type 2 diabetes and the metabolic syndrome, disorders associated with an increased risk of death due to macrovascular disease. In the past few decades, research from both the basic science and clinical arenas has enabled evidenced-based use of therapeutic modalities such as statins and angiotensin converting enzyme inhibitors to reduce cardiovascular (CV) mortality in insulin resistant patients. Recently, promising drugs such as the thiazolidinediones have come under scrutiny for possible deleterious CV effects. Ongoing research has broadened our understanding of the pathophysiology of atherosclerosis, implicating detrimental effects of inflammation and the cellular stress response on the vasculature. In this review, we address current thinking that is shaping our molecular understanding of insulin resistance and atherosclerosis. PMID:18775354

Razani, Babak; Chakravarthy, Manu V.; Semenkovich, Clay F.

2008-01-01

50

Atherosclerosis and cancer  

Microsoft Academic Search

Scientific and medical evidence over the past 30 years has established striking parallels between atherosclerosis and cancer—pathogenetic\\u000a relationships that cross the boundaries of fiction into the realm of reason. Both diseases in humans are characterized by\\u000a uncontrolled regulation of cellular growth and differentiation and share many common genomic targets during the course of\\u000a growth dysregulation. Such parallels can be reconciled

Kenneth S. Ramos; Charles R. Partridge

2005-01-01

51

Herbs and atherosclerosis  

Microsoft Academic Search

It is now widely accepted that atherosclerosis is a complex multicellular process involving oxidation of cholesterol and the\\u000a intracellular accumulation of oxidized cholesterol. This accumulation causes a cascade of inflammatory processes, resulting\\u000a in an unstable atherosclerotic plaque that ultimately bursts, causing myocardial infarction. Botanical dietary supplements\\u000a (herbs) can ameliorate this process and prevent cardiovascular disease at many steps in the

David Heber

2001-01-01

52

Irbesartan/HCTZ fixed combinations in patients of different racial/ethnic groups with uncontrolled systolic blood pressure on monotherapy.  

PubMed Central

The IrbesartaN/hydroChlorothiazide (HCTZ) bLood pressUre reductionS In diVErse patient populations (INCLUSIVE) trial was a multicenter, prospective, open-label, single-arm study evaluating the efficacy and safety of irbesartan/HCTZ fixed combinations in patients > or = 18 years old with uncontrolled systolic blood pressure (SBP, 140-159 mmHg; 130-159 mmHg for type-2 diabetes mellitus patients) after > or = 4 weeks of antihypertensive monotherapy. This analysis focused on different racial/ethnic subgroups. Treatment was sequential: placebo (4-5 weeks), HCTZ 12.5 mg (two weeks), irbesartan/HCTZ 150/12.5 mg (eight weeks) and irbesartan/HCTZ 300/25 mg (eight weeks). Overall, 515 Caucasians, 191 African Americans and 119 Hispanics/Latinos completing placebo treatment were enrolled. Mean SBP changes from baseline (placebo treatment end) to week 18 were -21.5 +/- 13.8 mmHg for Caucasians, -20.7 +/- 16.5 mmHg for African Americans and -22.9 +/- 13.2 mmHg for Hispanics/Latinos, respectively (p<0.001 for each). Mean diastolic BP (DBP) changes were statistically significant (p<0.001) and similar among racial/ethnic subgroups. By week 18, 70% (95% CI, 66%, 74%) of Caucasian, 66% (95% CI, 59%, 74%) of African-American and 65% (95% CI, 57%, 74%) of Hispanic/Latino patients achieved dual SBP/DBP goal. Treatments appeared to be well tolerated. In conclusion, irbesartan/HCTZ treatment provided SBP/DBP goal attainment in approximately two-thirds of Caucasian, African-American and Hispanic/Latino patients with SBP uncontrolled on antihypertensive monotherapy. PMID:16623075

Ofili, Elizabeth O.; Ferdinand, Keith C.; Saunders, Elijah; Neutel, Joel M.; Bakris, George L.; Cushman, William C.; Sowers, James R.; Weber, Michael A.

2006-01-01

53

Incretin hormones as immunomodulators of atherosclerosis  

PubMed Central

Atherosclerosis results from endothelial cell dysfunction and inflammatory processes affecting both macro- and microvasculature which are involved in vascular diabetic complications. Glucagon-like peptide-1 (GLP-1) is an incretin hormone responsible for amplification of insulin secretion when nutrients are given orally as opposed to intravenously and it retains its insulinotropic activity in patients with type 2 diabetes mellitus (T2D). GLP-1 based therapies, such as GLP-1 receptor (GLP-1R) agonists and inhibitors of dipeptidyl peptidase-4, an enzyme that degrades endogenous GLP-1 are routinely used to treat patients with T2D. Recent experimental model studies have established that GLP-1R mRNA is widely expressed in several immune cells. Moreover, its activation contributes to the regulation of both thymocyte and peripheral T cells proliferation and is involved in the maintenance of peripheral regulatory T cells. GLP-1R is also expressed in endothelial and smooth muscle cells. The effect of incretin hormones on atherosclerogenesis have recently been studied in animal models of apolipoprotein E-deficient mice (apoE-/-). These studies have demonstrated that treatment with incretin hormones or related compounds suppresses the progression of atherosclerosis and macrophage infiltration in the arterial wall as well as a marked anti-oxidative and anti-inflammatory effect on endothelial cells. This effect may have a major impact on the attenuation of atherosclerosis and may help in the design of new therapies for cardiovascular disease in patients with type 2 diabetes. PMID:22973260

Alonso, Nuria; Julián, M. Teresa; Puig-Domingo, Manuel; Vives-Pi, Marta

2012-01-01

54

Endothelial progenitor cells in atherosclerosis  

PubMed Central

Endothelial progenitor cells (EPCs) are involved in the maintenance of endothelial homoeostasis and in the process of new vessel formation. Experimental and clinical studies have shown that atherosclerosis is associated with reduced numbers and dysfunction of EPCs; and that medications alone are able to partially reverse the impairment of EPCs in patients with atherosclerosis. Therefore, novel EPC-based therapies may provide enhancement in restoring EPCs’ population and improvement of vascular function. Here, for a better understanding of the molecular mechanisms underlying EPC impairment in atherosclerosis, we provide a comprehensive overview on EPC characteristics, phenotypes, and the signaling pathways underlying EPC impairment in atherosclerosis. PMID:22652782

Du, Fuyong; Zhou, Jun; Gong, Ren; Huang, Xiao; Pansuria, Meghana; Virtue, Anthony; Li, Xinyuan; Wang, Hong; Yang, Xiao-Feng

2012-01-01

55

Monocyte fate in atherosclerosis.  

PubMed

Monocytes and their descendant macrophages are essential to the development and exacerbation of atherosclerosis, a lipid-driven inflammatory disease. Lipid-laden macrophages, known as foam cells, reside in early lesions and advanced atheromata. Our understanding of how monocytes accumulate in the growing lesion, differentiate, ingest lipids, and contribute to disease has advanced substantially over the last several years. These cells' remarkable phenotypic and functional complexity is a therapeutic opportunity: in the future, treatment and prevention of cardiovascular disease and its complications may involve specific targeting of atherogenic monocytes/macrophages and their products. PMID:25538208

Hilgendorf, Ingo; Swirski, Filip K; Robbins, Clinton S

2015-02-01

56

HPLC method with monolithic column for simultaneous determination of irbesartan and hydrochlorothiazide in tablets.  

PubMed

A simple, sensitive and accurate HPLC method with high throughput has been developed and validated for the simultaneous determination of irbesartan (IRB) and hydrochlorothiazide (HCT) in combined pharmaceutical dosage forms. The proposed method employed, for the first time, a monolithic column in the analysis. Optimal chromatographic separation of the analytes was achieved on Chromolith(®) Performance RP-18e column using a mobile phase consisting of phosphate buffer (pH 4)/acetonitrile (50:50, V/V) pumped isocratically at a flow rate of 1.0 mL min(-1). The eluted analytes were monitored with a UV detector set at 270 nm. Under the optimum chromatographic conditions, linear relationship with a good correlation coefficient (R ? 0.9997) was found between the peak area and the corresponding concentrations of both IRB and HCT in the ranges of 10-200 and 1-20 ng mL(-1). The limits of detection were 2.34 and 0.03 ng mL(-1) for IRB and HCT, respectively. The intra- and inter-assay precisions were satisfactory as the RSD values did not exceed 3 %. The accuracy of the proposed method was > 97 %. The proposed method had high throughput as the analysis involved a simple procedure and a very short run-time of < 3 min. The results demonstrated that the method is applicable in the quality control of combined pharmaceutical tablets containing IRB and HCT. PMID:24914719

Alanazi, Amer M; Abdelhameed, Ali S; Khalil, Nasr Y; Khan, Azmat A; Darwish, Ibrahim A

2014-06-01

57

Formulation and development of a self-nanoemulsifying drug delivery system of irbesartan  

PubMed Central

Irbesartan (IRB) is an angiotensin II receptor blocker antihypertensive agent. The aim of the present investigation was to develop a self-nanoemulsifying drug delivery system (SNEDDS) to enhance the oral bioavailability of poorly water-soluble IRB. The solubility of IRB in various oils was determined to identify the oil phase of SNEDDS. Various surfactants and co-surfactants were screened for their ability to emulsify the selected oil. Pseudoternary phase diagrams were constructed to identify the efficient self-emulsifying region. The optimized SNEDDS formulation contained IRB (75 mg), Cremophor® EL (43.33%), Carbitol® (21.67%) and Capryol® 90 (32%). SNEDDS was further evaluated for its percentage transmittance, emulsification time, drug content, phase separation, dilution, droplet size and zeta potential. The optimized formulation of IRB-loaded SNEDDS exhibited complete in vitro drug release in 15 min as compared with the plain drug, which had a limited dissolution rate. It was also compared with the pure drug solution by oral administration in male Wister rats. The in vivo study exhibited a 7.5-fold increase in the oral bioavailability of IRB from SNEDDS compared with the pure drug solution. These results suggest the potential use of SNEDDS to improve dissolution and oral bioavailability of poorly water-soluble IRB. PMID:22171286

Patel, Jaydeep; Patel, Anjali; Raval, Mihir; Sheth, Navin

2011-01-01

58

Cannabinoids and atherosclerosis.  

PubMed

The endocannabinoids are a family of lipid neurotransmitters that engage the same membrane receptors targeted by tetrahydrocannabinol and that mediate retrograde signal from postsynaptic neurons to presynaptic ones. Discovery of endogenous cannabinoids and studies of the physiological functions of the cannabinoid system in the brain and body are producing a number of important findings about the role of membrane lipids and fatty acids. The role of lipid membranes in the cannabinoid system follows from the fact that the source and supply of endogenous cannabinoids are derived from arachidonic acid. The study of molecules which influence the cannabinoid system in the brain and body is crucial in search of medical preparations with the therapeutic effects of the phytocannabinoids without the negative effects on cognitive function attributed to cannabis. Basic information about function and role of the endocannabinoid system is summarized in the paper; possible therapeutic action of cannabinoids, effects on atherosclerosis specially, is described at the close. PMID:19591373

Fisar, Zdenek

2009-01-01

59

MicroRNAs and atherosclerosis  

PubMed Central

MicroRNAs (miRNAs) are small (~22nucleotide) sequences of RNA that regulate gene expression at posttranscriptional level. MiRNA/mRNA base pairing complementarity provokes mRNA decay and consequent gene silencing. These endogenous gene expression inhibitors were primarily described in cancer but recent exciting findings have also demonstrated a key role in cardiovascular diseases (CVDs) including atherosclerosis. MiRNAs controls endothelial cell (EC), vascular smooth muscle cell (VSMC) and macrophage functions, and thereby regulate the progression of atherosclerosis. MiRNAs expression is modulated by different stimuli involved in every stage of atherosclerosis and conversely miRNAs modulates several pathways implicated in plaque development such as cholesterol metabolism. In the present review, we focus on the importance of miRNAs in atherosclerosis and we further discuss their potential use as biomarkers and therapeutic targets in CVDs. PMID:23512606

Madrigal-Matute, Julio; Rotllan, Noemi; Aranda, Juan F.; Fernández-Hernando, Carlos

2014-01-01

60

CD8{sup +}CD25{sup +} T cells reduce atherosclerosis in apoE(?/?) mice  

SciTech Connect

Highlights: •The role of a sub-population of CD8{sup +} T cells with suppressor functions was investigated in atherosclerosis. •CD8{sup +}CD25{sup +} T cells from adult apoE(?/?) mice had phenotype characteristics of T suppressor cells. •These CD8{sup +}CD25{sup +} T cells reduced CD4{sup +} T cell proliferation and CD8{sup +} cytotoxic activity in vitro. •Adoptive transfer of CD8{sup +}CD25{sup +} T cells significantly reduced atherosclerosis. •CD8{sup +}CD25{sup +} T cells have a suppressive function in atherosclerosis. -- Abstract: Background: It is increasingly evident that CD8{sup +} T cells are involved in atherosclerosis but the specific subtypes have yet to be defined. CD8{sup +}CD25{sup +} T cells exert suppressive effects on immune signaling and modulate experimental autoimmune disorders but their role in atherosclerosis remains to be determined. The phenotype and functional role of CD8{sup +}CD25{sup +} T cells in experimental atherosclerosis were investigated in this study. Methods and results: CD8{sup +}CD25{sup +} T cells were observed in atherosclerotic plaques of apoE(?/?) mice fed hypercholesterolemic diet. Characterization by flow cytometric analysis and functional evaluation using a CFSE-based proliferation assays revealed a suppressive phenotype and function of splenic CD8{sup +}CD25{sup +} T cells from apoE(?/?) mice. Depletion of CD8{sup +}CD25{sup +} from total CD8{sup +} T cells rendered higher cytolytic activity of the remaining CD8{sup +}CD25{sup ?} T cells. Adoptive transfer of CD8{sup +}CD25{sup +} T cells into apoE(?/?) mice suppressed the proliferation of splenic CD4{sup +} T cells and significantly reduced atherosclerosis in recipient mice. Conclusions: Our study has identified an athero-protective role for CD8{sup +}CD25{sup +} T cells in experimental atherosclerosis.

Zhou, Jianchang; Dimayuga, Paul C.; Zhao, Xiaoning; Yano, Juliana; Lio, Wai Man; Trinidad, Portia; Honjo, Tomoyuki; Cercek, Bojan; Shah, Prediman K.; Chyu, Kuang-Yuh, E-mail: Chyuk@cshs.org

2014-01-17

61

Targeting hydrogen sulfide as a promising therapeutic strategy for atherosclerosis.  

PubMed

Physiological concentrations of nitric oxide (NO) and carbon monoxide (CO) have multiple protective effects in the cardiovascular system. Recent studies have implicated hydrogen sulfide (H2S) as a new member of vasculoprotective gasotransmitter family, behaving similarly to NO and CO. H2S has been demonstrated to inhibit multiple key aspects of atherosclerosis, including atherogenic modification of LDL, monocytes adhesion to the endothelial cells, macrophage-derived foam cell formation and inflammation, smooth muscle cell proliferation, neointimal hyperplasia, vascular calcification, and thrombogenesis. H2S also decreases plasma homocysteine levels in experimental animal models. In the human body, H2S production is predominantly catalyzed by cystathionine-?-synthase (CBS) and cystathionine ?-lyase (CSE). CSE is the primary H2S-producing enzyme in the vasculature. Growing evidence suggests that atherosclerosis is associated with vascular CSE/H2S deficiency and that H2S supplementation by exogenous H2S donors (such as NaHS and GYY4137) attenuates, and H2S synthesis suppression by inhibitors (such as D, L-propargylglycine) aggravates the development of atherosclerotic plaques. However, it remains elusive whether CSE deficiency plays a causative role in atherosclerosis. A recent study (Circulation. 2013; 127: 2523-2534) demonstrates that decreased endogenous H2S production by CSE genetic deletion accelerates atherosclerosis in athero-prone ApoE-/- mice, pinpointing that endogenously produced H2S by CSE activation may be of benefit in the prevention and treatment of atherosclerosis. This study will facilitate the development of H2S-based pharmaceuticals with therapeutic applications in atherosclerosis-related cardiovascular diseases. PMID:24491853

Xu, Suowen; Liu, Zhiping; Liu, Peiqing

2014-03-15

62

Renal protection by low dose irbesartan in diabetic nephropathy is paralleled by a reduction of inflammation, not of endoplasmic reticulum stress.  

PubMed

Diabetes can disrupt endoplasmic reticulum (ER) homeostasis which leads to ER stress. ER stress-induced renal apoptosis seems to be involved in the development of diabetic nephropathy. The present study was designed to investigate the contribution of reduced ER stress to the beneficial effects of an angiotensin receptor blocker. Insulin-dependent diabetes mellitus was induced by streptozotocin injections to hypertensive mRen2-transgenic rats. After 2weeks animals were treated with 0.7mg/kg/day irbesartan. Blood glucose, blood pressure and protein excretion were assessed. Expression of ER stress markers was measured by real-time PCR. Immunohistochemistry was performed to detect markers of ER stress, renal damage and infiltrating cells. Glomerulosclerosis and apoptosis were evaluated. Diabetic mRen2-transgenic rats developed renal injury with proteinuria, tubulointerstitial cell proliferation as well as glomerulosclerosis and podocyte injury. Moreover, an increase in inflammation, podocyte ER stress and apoptosis was detected. Irbesartan somewhat lowered blood pressure and reduced proteinuria, tubulointerstitial cell proliferation and glomerulosclerosis. Podocyte damage was ameliorated but markers of ER stress (calnexin, grp78) and apoptosis were not reduced by irbesartan. On the other hand, inflammatory cell infiltration in the tubulointerstitium and the glomerulus was significantly attenuated. We conclude that irbesartan reduced renal damage even in a very low dose. The beneficial effects of low dose irbesartan were paralleled by a reduction of blood pressure and inflammation but not by a reduction of ER stress and apoptosis. Thus, sustained endoplasmic reticulum stress in the kidney does not necessarily lead to increased inflammation and tubulointerstitial or glomerular injury. PMID:24418215

Hartner, Andrea; Cordasic, Nada; Klanke, Bernd; Menendez-Castro, Carlos; Veelken, Roland; Schmieder, Roland E; Hilgers, Karl F

2014-04-01

63

Long-Term Effects of Irbesartan Treatment and Smoking on Nucleic Acid Oxidation in Patients With Type 2 Diabetes and Microalbuminuria  

PubMed Central

OBJECTIVE We tested whether long-term treatment with the angiotensin II receptor antagonist irbesartan reduces nucleic acid oxidation in patients with type 2 diabetes and microalbuminuria. RESEARCH DESIGN AND METHODS The Irbesartan in Patients With Type 2 Diabetes and Microalbuminuria (IRMA 2) study was a 2-year multicenter randomized double-blind trial comparing irbesartan (150 and 300 mg once daily) with placebo. We studied a subgroup of 50 patients where urine samples were available for analysis of albumin and the oxidatively modified guanine nucleosides 8-oxo-7,8-dihydro-2?-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo). RESULTS During the 2-year trial, no significant differences in 8-oxodG and 8-oxoGuo excretions between placebo and irbesartan treatment were seen. 8-oxodG and albumin excretion decreased with time (P = 0.0004 and P < 0.0001, respectively), whereas treatment-related differences were shown for albumin excretion (P = 0.0008) only, as previously reported. Important secondary findings were significant associations between changes in 8-oxodG excretion and changes in albumin excretion and glycated hemoglobin (HbA1c). During the study period, 8-oxodG excretion decreased by 3 and 26% in smokers and nonsmokers, respectively (P = 0.015), and urinary albumin excretion decreased 22% in smokers and 58% in nonsmokers (P = 0.011). CONCLUSIONS Irbesartan treatment was not significantly more effective than placebo in reducing nucleic acid oxidation. The results indicate that DNA oxidation in diabetes patients is reduced by various components in the treatment of diabetes where glycemic control seems to be important and addition of angiotensin II receptor antagonists does not lead to any substantial additional reduction. Furthermore, the reductions in DNA oxidation and albumin excretion seem to be counteracted by smoking. PMID:21454798

Broedbaek, Kasper; Henriksen, Trine; Weimann, Allan; Petersen, Morten; Andersen, Jon T.; Afzal, Shoaib; Jimenez-Solem, Espen; Persson, Frederik; Parving, Hans-Henrik; Rossing, Peter; Poulsen, Henrik E.

2011-01-01

64

What Are the Signs and Symptoms of Atherosclerosis?  

MedlinePLUS

... Twitter. What Are the Signs and Symptoms of Atherosclerosis? Atherosclerosis usually doesn't cause signs and symptoms ... Rate This Content: Next >> Featured Video What is atherosclerosis? 10/14/2014 August 4, 2014 Atherosclerosis Clinical ...

65

Irbesartan is projected to be cost and life saving in a Spanish setting for treatment of patients with type 2 diabetes, hypertension, and microalbuminuria  

Microsoft Academic Search

Irbesartan is projected to be cost and life saving in a Spanish setting for treatment of patients with type 2 diabetes, hypertension, and microalbuminuria.ObjectivesThe purpose of this study was to project the cumulative incidence of end-stage renal disease (ESRD), life expectancy, and costs in a Spanish setting of treating patients with diabetes, hypertension, and microalbuminuria with either standard hypertension treatment

Andrew J. Palmer; LIEVEN ANNEMANS; STÉPHANE ROZE; PABLO LAPUERTA; ROLAND CHEN; SYLVIE GABRIEL; PAULO CARITA; Roger A. Rodby; DICK DE ZEEUW; HANS-HENRIK PARVING; FERNANDO DE ALVARO

2005-01-01

66

A prospective, randomized, placebo-controlled, double-blind, multicenter study of the effects of irbesartan on aortic dilatation in Marfan syndrome (AIMS trial): study protocol  

PubMed Central

Background Cardiovascular complications are the leading cause of mortality and morbidity in Marfan syndrome (MFS), a dominantly inherited disorder caused by mutations in the gene that encodes fibrillin-1. There are approximately 18,000 patients in the UK with MFS. Current treatment includes careful follow-up, beta blockers, and prophylactic surgical intervention; however, there is no known treatment which effectively prevents the rate of aortic dilatation in MFS. Preclinical, neonatal, and pediatric studies have indicated that angiotensin receptor blockers (ARBs) may reduce the rate of aortic dilatation. This trial will investigate the effects of irbesartan on aortic dilatation in Marfan syndrome. Methods/Design The Aortic Irbesartan Marfan Study (AIMS) is an investigator-led, prospective, randomized, placebo-controlled, double-blind, phase III, multicenter trial. Currently, 26 centers in the UK will recruit 490 clinically confirmed MFS patients (aged ?6 to ?40 years) using the revised Ghent diagnostic criteria. Patients will be randomized to irbesartan or placebo. Aortic root dilatation will be measured by transthoracic echocardiography at baseline and annually thereafter. The primary outcome is the absolute change in aortic root diameter per year measured by echocardiography. The follow-up period will be a minimum of 36 months with an expected mean follow-up period of 48 months. Discussion This is the first clinical trial to evaluate the ARB irbesartan versus placebo in reducing the rate of aortic root dilatation in MFS. Not only will this provide useful information on the safety and efficacy of ARBs in MFS, it will also provide a rationale basis for potentially lifesaving therapy for MFS patients. Trial registration ISRCTN, 90011794 PMID:24289736

2013-01-01

67

Effect of combination tablets containing amlodipine 10 mg and irbesartan 100 mg on blood pressure and cardiovascular risk factors in patients with hypertension  

PubMed Central

Background Hypertension is one of the major risk factors for cardiovascular and cerebrovascular disease and mortality. Patients who receive insufficient doses of antihypertensive agents or who are poorly adherent to multidrug treatment regimens often fail to achieve adequate blood pressure (BP) control. The aim of this study was to determine the efficacy of an angiotensin II receptor blocker (ARB) and calcium channel blocker (CCB) combination tablet containing a regular dose of irbesartan (100 mg) and a high dose of amlodipine (10 mg) with regard to lowering BP and other risk factors for cardiovascular disease. Methods We retrospectively evaluated data from 68 patients with essential hypertension whose treatment regimen was changed either from combination treatment with an independent ARB and a low-dose or regular-dose CCB or from a combination tablet of ARB and a low-dose or regular-dose CCB to a combination tablet containing amlodipine 10 mg and irbesartan 100 mg, because of incomplete BP control. Previous treatments did not include irbesartan as the ARB. Results The combination tablet decreased systolic and diastolic BP. In addition, it significantly decreased serum uric acid, low-density lipoprotein cholesterol, and increased high-density lipoprotein cholesterol levels, independent of the BP-lowering effect. Treatment with the combination tablet did not affect serum triglycerides, plasma glucose, glycated hemoglobin, serum potassium or creatinine levels, or the urinary albumin excretion rate. Conclusion The combination tablet containing amlodipine 10 mg and irbesartan 100 mg had a greater BP-lowering effect than an ARB and a low-dose or regular-dose CCB. In addition, the combination tablet had more favorable effects on serum uric acid, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol levels in patients with hypertension.

Yagi, Shusuke; Takashima, Akira; Mitsugi, Minoru; Wada, Toshihiro; Hotchi, Junko; Aihara, Ken-ichi; Hara, Tomoya; Ishida, Masayoshi; Fukuda, Daiju; Ise, Takayuki; Yamaguchi, Koji; Tobiume, Takeshi; Iwase, Takashi; Yamada, Hirotsugu; Soeki, Takeshi; Wakatsuki, Tetsuzo; Shimabukuro, Michio; Akaike, Masashi; Sata, Masataka

2015-01-01

68

MRI of subclinical coronary atherosclerosis  

Microsoft Academic Search

Coronary artery disease (CAD) is the leading cause of morbidity and mortality in the Western world. Whereas atherosclerosis\\u000a alone is rarely fatal, sudden luminal thrombosis precipitates life-threatening clinical events such as acute coronary syndromes\\u000a and stroke. Plaques assumed to cause luminal thrombosis are referred to as vulnerable plaques, which tend to preserve a normal\\u000a vessel lumen. Today’s clinical assessment of

Christian H. P. Jansen; Marcus R. Makowski; Andrea J. Wiethoff; René M. Botnar

2009-01-01

69

Microorganisms in the aetiology of atherosclerosis  

PubMed Central

Recent publications have suggested that infective pathogens might play an important role in the pathogenesis of atherosclerosis. This review focuses on these microorganisms in the process of atherosclerosis. The results of in vitro studies, animal studies, tissue studies, and serological studies will be summarised, followed by an overall conclusion concerning the strength of the association of the microorganism with the pathogenesis of atherosclerosis. The role of the bacteria Chlamydia pneumoniae and Helicobacter pylori, and the viruses human immunodeficiency virus, coxsackie B virus, cytomegalovirus, Epstein-Barr virus, herpes simplex virus, and measles virus will be discussed. Key Words: atherosclerosis • Chlamydia pneumoniae • Helicobacter pylori PMID:11041053

Morre, S; Stooker, W; Lagrand, W; van den Brule, A J C; Niessen, H

2000-01-01

70

Cholesterol-Lowering Atherosclerosis Study (CLAS)  

ClinicalTrials.gov

Arterial Occlusive Diseases; Cardiovascular Diseases; Carotid Artery Diseases; Cerebral Arteriosclerosis; Cerebrovascular Disorders; Coronary Arteriosclerosis; Coronary Disease; Heart Diseases; Myocardial Ischemia; Atherosclerosis

2013-12-12

71

Multi-Ethnic Study of Atherosclerosis (MESA)  

ClinicalTrials.gov

Atherosclerosis; Cardiovascular Diseases; Heart Diseases; Coronary Artery Disease; Coronary Disease; Stroke; Myocardial Infarction; Heart Failure; Diabetes Mellitus, Type 2; Hypertension; Diabetes Mellitus

2012-04-26

72

Hypercholesterolemia links hematopoiesis with atherosclerosis  

PubMed Central

Atherosclerosis is characterized by the progressive accumulation of lipids and leukocytes in the arterial wall. Leukocytes such as macrophages accumulate oxidized lipoproteins in the growing atheromata and give rise to foam cells, which can then contribute to a lesion’s necrotic core. Lipids and leukocytes interact also in other important ways. In experimental models, systemic hypercholesterolemia is associated with severe neutrophilia and monocytosis. Recent evidence indicates that cholesterol sensing pathways control the proliferation of hematopoietic stem cell progenitors. Here we review some of the studies that are forging this particular link between metabolism and inflammation and propose several strategies that could target this axis for the treatment of cardiovascular disease. PMID:23228326

Soehnlein, Oliver; Swirski, Filip K.

2015-01-01

73

Therapeutic approaches to drug targets in atherosclerosis.  

PubMed

Non-communicable diseases such as cancer, atherosclerosis and diabetes are responsible for major social and health burden as millions of people are dying every year. Out of which, atherosclerosis is the leading cause of deaths worldwide. The lipid abnormality is one of the major modifiable risk factors for atherosclerosis. Both genetic and environmental components are associated with the development of atherosclerotic plaques. Immune and inflammatory mediators have a complex role in the initiation and progression of atherosclerosis. Understanding of all these processes will help to invent a range of new biomarkers and novel treatment modalities targeting various cellular events in acute and chronic inflammation that are accountable for atherosclerosis. Several biochemical pathways, receptors and enzymes are involved in the development of atherosclerosis that would be possible targets for improving strategies for disease diagnosis and management. Earlier anti-inflammatory or lipid-lowering treatments could be useful for alleviating morbidity and mortality of atherosclerotic cardiovascular diseases. However, novel drug targets like endoglin receptor, PPAR?, squalene synthase, thyroid hormone analogues, scavenger receptor and thyroid hormone analogues are more powerful to control the process of atherosclerosis. Therefore, the review briefly focuses on different novel targets that act at the starting stage of the plaque form to the thrombus formation in the atherosclerosis. PMID:25061401

Jamkhande, Prasad G; Chandak, Prakash G; Dhawale, Shashikant C; Barde, Sonal R; Tidke, Priti S; Sakhare, Ram S

2014-07-01

74

Scavenger Receptors, Oxidized LDL, and Atherosclerosis  

E-print Network

214 Scavenger Receptors, Oxidized LDL, and Atherosclerosis AGNES BOULLIER, DAVID A. BIRD, MI and specifically in atherogenesis, be- cause apoptosis is a prominent feature of late lesions. KEYWORDS: scavenger-534- 2005. dsteinberg@ucsd.edu #12;215BOULLIER et al.: SCAVENGER RECEPTORS, LDL, AND ATHEROSCLEROSIS

Dennis, Edward A.

75

Cranberry Flavonoids, Atherosclerosis and Cardiovascular Health  

Microsoft Academic Search

Atherosclerosis is the deposition of plaques containing cholesterol and lipids in arterial walls. Atherosclerosis causes cardiovascular disease that lead to heart attacks and stroke. Mortality from these diseases is the leading cause of death in the U.S. Atherogenisis starts with the uptake of oxidized LDL by endothelial macrophages, the accumulation of foam cells in the intima of the artery and

Jess Reed

2002-01-01

76

Therapeutic approaches to drug targets in atherosclerosis  

PubMed Central

Non-communicable diseases such as cancer, atherosclerosis and diabetes are responsible for major social and health burden as millions of people are dying every year. Out of which, atherosclerosis is the leading cause of deaths worldwide. The lipid abnormality is one of the major modifiable risk factors for atherosclerosis. Both genetic and environmental components are associated with the development of atherosclerotic plaques. Immune and inflammatory mediators have a complex role in the initiation and progression of atherosclerosis. Understanding of all these processes will help to invent a range of new biomarkers and novel treatment modalities targeting various cellular events in acute and chronic inflammation that are accountable for atherosclerosis. Several biochemical pathways, receptors and enzymes are involved in the development of atherosclerosis that would be possible targets for improving strategies for disease diagnosis and management. Earlier anti-inflammatory or lipid-lowering treatments could be useful for alleviating morbidity and mortality of atherosclerotic cardiovascular diseases. However, novel drug targets like endoglin receptor, PPAR?, squalene synthase, thyroid hormone analogues, scavenger receptor and thyroid hormone analogues are more powerful to control the process of atherosclerosis. Therefore, the review briefly focuses on different novel targets that act at the starting stage of the plaque form to the thrombus formation in the atherosclerosis. PMID:25061401

Jamkhande, Prasad G.; Chandak, Prakash G.; Dhawale, Shashikant C.; Barde, Sonal R.; Tidke, Priti S.; Sakhare, Ram S.

2013-01-01

77

Endothelium Preserving Microwave Treatment for Atherosclerosis  

NASA Technical Reports Server (NTRS)

This slide presentation reviews the use of microwave technology for treating Atherosclerosis while preserving the endothelium. The system uses catheter antennas as part of the system that is intended to treat atherosclerosis. The concept is to use a microwave catheter for heating the atherosclerotic lesions, and reduce constriction in the artery.

Fink, Patrick; Arndt, G. D.; Ngo, Phong

2003-01-01

78

The autoimmune concept of atherosclerosis  

PubMed Central

Purpose of review This review summarizes the recent data on the ‘Autoimmune Concept of Atherosclerosis’, according to which the first stage of this disease is due to an autoimmune reaction against arterial endothelial cells expressing heat shock protein 60 (HSP60) and adhesion molecules when stressed by classical atherosclerosis risk factors. Special emphasis is put on oxidized low-density lipoproteins as early endothelial stressors. Recent findings Plasma cholesterol and LDL levels considered ‘normal’ by the medical community are possibly too high from an evolutionary viewpoint. The proinflammatory milieu at sites of early atherosclerotic lesions could be conducive to oxidation of LDL in situ. LDL oxidation can also take place at nonvascular sites or in the circulation under general proinflammatory conditions explaining its proatherosclerotic role in ‘normocholesterolemic’ individuals. Summary We hypothesize that the plasma cholesterol and LDL levels currently considered normal are evolutionarily too high. Cholesterol and/or oxidized low-density lipoprotein, even as a mild HSP60-inducing endothelial stressor, function as a ubiquitous risk factor. If this hypothesis is true, most members of developed societies might be at risk to develop atherosclerotic plaques at anti-HSP60-immunity-triggered intimal inflammatory foci, irrespective of the primary risk-factor(s). PMID:21881502

Grundtman, Cecilia; Wick, Georg

2011-01-01

79

BIOLOGICAL IMAGING OF ATHEROSCLEROSIS: MOVING BEYOND ANATOMY  

PubMed Central

Biological or molecular imaging is now providing exciting new strategies to study atherosclerosis in both animals and humans. These technologies hold the promise to provide disease-specific, molecular information within the context of a systemic or organ-specific disease beyond traditional anatomical-based imaging. By integration of biological, chemical and anatomical imaging knowledge into diagnostic strategies, a more comprehensive and predictive picture of atherosclerosis is likely to emerge. As such, biological imaging is well-positioned to study different stages of atherosclerosis and its treatment, including the sequence of atheroma initiation, progression, and plaque rupture. In this review we describe the evolving concepts in atherosclerosis imaging with a focus on coronary artery disease, and we provide an overview of recent exciting translational developments in biological imaging. The illuminated examples and discussions will highlight how biological imaging is providing new clinical approaches to identify high-risk plaques, and to streamline the development process of new atherosclerosis therapies. PMID:23733542

Verjans, Johan W.; Jaffer, Farouc A.

2013-01-01

80

Atherosclerosis  

MedlinePLUS

... disease in which plaque builds up inside your arteries. Plaque is a sticky substance made up of ... blood. Over time, plaque hardens and narrows your arteries. That limits the flow of oxygen-rich blood ...

81

Atherosclerosis  

MedlinePLUS

... likely that blood clots will form in your arteries. Blood clots can partially or completely block blood flow. ... side of your neck (the carotid arteries). These arteries supply oxygen-rich blood to your brain. If blood flow to your ...

82

Vitamin D Deficiency Induces High Blood Pressure and Accelerates Atherosclerosis in Mice  

PubMed Central

Multiple epidemiological studies link vitamin D deficiency to increased cardiovascular disease (CVD), but causality and possible mechanisms underlying these associations are not established. To clarify the role of vitamin D-deficiency in CVD in vivo, we generated mouse models of diet-induced vitamin D deficiency in two backgrounds (LDL receptor- and ApoE-null mice) that resemble humans with diet-induced hypertension and atherosclerosis. Mice were fed vitamin D-deficient or -sufficient chow for 6 weeks and then switched to high fat (HF) vitamin D-deficient or –sufficient diet for 8–10 weeks. Mice with diet-induced vitamin D deficiency showed increased systolic and diastolic blood pressure, high plasma renin, and decreased urinary sodium excretion. Hypertension was reversed and renin was suppressed by returning chow-fed vitamin D-deficient mice to vitamin D-sufficient chow diet for 6 weeks. On a HF diet, vitamin D-deficient mice had ?2-fold greater atherosclerosis in the aortic arch and ?2–8-fold greater atherosclerosis in the thoracic and abdominal aorta compared to vitamin D-sufficient mice. In the aortic root, HF-fed vitamin D-deficient mice had increased macrophage infiltration with increased fat accumulation and endoplasmic reticulum (ER) stress activation, but a lower prevalence of the M1 macrophage phenotype within atherosclerotic plaques. Similarly, peritoneal macrophages from vitamin D-deficient mice displayed an M2-predominant phenotype with increased foam cell formation and ER stress. Treatment of vitamin D-deficient mice with the ER stress reliever PBA during HF feeding suppressed atherosclerosis, decreased peritoneal macrophage foam cell formation, and downregulated ER stress proteins without changing blood pressure. Thus, we suggest that vitamin D deficiency activates both the renin angiotensin system and macrophage ER stress to contribute to the development of hypertension and accelerated atherosclerosis, highlighting vitamin D replacement as a potential therapy to reduce blood pressure and atherosclerosis. PMID:23349943

Oh, Jisu; Riek, Amy E.; Chin, Kathleen; Garcia, Miguel; Bernal-Mizrachi, Carlos

2013-01-01

83

Atherosclerosis and disturbances in flow.  

PubMed

From experiments on flow in a tapered tube it was found that a ring vortex could be produced in certain circumstances. The parameter which determines the vortex formation is the product of peak reversed flow, Reynolds number, and the taper angle of the tube. Using dimensional analysis, conditions in a model were adjusted to simulate those in the unbranched superficial femoral artery. A vortex was formed when there was sufficiently strong reversed flow, and it did so over a range of nondimensional frequencies similar to those which occur in the artery in humans. When the vortex passes up the tube, the surface stresses oscillate at a frequency an order of magnitude higher than the pulse frequency. It is possible that this oscillating stress could trigger atherosclerosis. The initiating ring vortex could be induced by a slight stenosis distal to the site of atherogenesis. PMID:3228538

Charlesworth, D; Gerrard, J H

1988-01-01

84

Bioequivalence studies for 2 different strengths of irbesartan/hydrochlorothiazide combination in healthy volunteers: 300/25?mg and 300/12.5?mg film-coated tablets.  

PubMed

Two bioequivalence studies of irbesartan (CAS 138402-11-6) and hydrochlorothiazide (CAS 58-93-5) combination at 300/12.5?mg and 300/25?mg strengths were carried out in order to assess the bioequivalence of these film-coated tablet formulations in comparison with the marketed reference formulations.Both studies were performed with 30 healthy volunteers according to an open label, randomized, 2-period, 2-sequence, crossover, single dose and fasting conditions design. In each study, test and reference formulations were administered in 2 treatment days, separated by a washout period of 7 days. Blood samples were drawn up to 72?h following drug administration in case of irbesartan and up to 24?h in case of hydrochlorothiazide. Plasma concentrations of both analytes were obtained by a validated HPLC method using MS/MS detection. Log-transformed AUC0-t and Cmax values were tested for bioequivalence based on the ratios of the geometric LSmeans (test/reference).For both studies, the 90% confidence intervals of the geometric LSmean values for the test/reference ratios for AUC0-t [(irbesartan: 300/12.5?mgstrength: 95.33-111.74%. 300/25?mg strength: 91.27-103.93%) (hydrochlorothiazide: 300/12.5?mg strength: 99.63-107.50%. 300/25?mg strength: 95.72-102.24%)] and Cmax [(irbesartan: 300/12.5?mg strength: 98.73-115.03%. 300/25?mg strength: 97.27-112.12%) (hydrochlorothiazide: 300/12.5?mg strength: 97.34-112.06%. 300/25?mg strength: 93.29-106.38%)] were within the bio-equivalence acceptance range of 80-125%.According to the European Guideline on the Investigation of Bioequivalence it may be therefore concluded that both test formulations are bioequivalent to the corresponding reference formulations. Overall, it was judged that both studies were conducted with a good tolerance of the subjects to study drugs. PMID:24105103

Cánovas, M; Cabré, F; Polonio, F

2014-05-01

85

History of Discovery: Inflammation in Atherosclerosis  

PubMed Central

Experimental work has elucidated molecular and cellular pathways of inflammation that promote atherosclerosis. Unraveling the roles of cytokines as inflammatory messengers provided a mechanism whereby risk factors for atherosclerosis can alter arterial biology, and produce a systemic milieu that favors atherothrombotic events. The discovery of the immune basis of allograft arteriosclerosis demonstrated that inflammation per se can drive arterial hyperplasia, even in the absence of traditional risk factors. Inflammation regulates aspects of plaque biology that trigger the thrombotic complications of atherosclerosis. Translation of these discoveries to humans has enabled both novel mechanistic insights and practical clinical advances. PMID:22895665

Libby, Peter

2012-01-01

86

Clinical utility of biomarkers in premature atherosclerosis.  

PubMed

Atherosclerosis is a very complex procedure responsible for the development of coronary artery disease which is the leading cause of death in the civilized world. The obvious pandemic character of atherosclerosis augments the need to discover an ideal biomarker, which will be able to facilitate the clinical diagnosis of the atherosclerosis from the physicians especially in the early stages of the atherosclerotic process. Among the biomarkers that are already used there are classical ones, such as c-reactive protein, interleukins, tumour necrosis factor, apolipoproteins, fibrinogen, homocysteine, and novel promising ones such as lipoprotein-associated phospholipase, asymmetric dimethylarginine, myeloperoxidase, cathepsins and cystatin C. The possibility of combining circulating biomarkers with other methods such as non-invasive and invasive imaging is clinically attractive because this could contribute to the improved diagnosis and understanding of premature atherosclerosis pathogenesis. PMID:22489712

Kampoli, A-M; Tousoulis, D; Papageorgiou, N; Pallatza, Z; Vogiatzi, G; Briasoulis, A; Androulakis, E; Toutouzas, C; Stougianos, P; Tentolouris, C; Stefanadis, C

2012-01-01

87

Neutrophils in atherosclerosis: from mice to man.  

PubMed

Infiltration of leukocyte subsets is a driving force of atherosclerotic lesion growth, and during the past decade, neutrophils have received growing attention in chronic inflammatory processes, such as atherosclerosis. Equipped with various ready to be released mediators, evolved to fight invading pathogens, neutrophils may also hold key functions in affecting sterile inflammation, such as in atherosclerosis. Many of their secretion products might instruct or activate other immune cells (particularly monocytes) to, for example, enter atherosclerotic lesions or release proinflammatory mediators. Despite the emerging evidence for the mechanistic contribution of neutrophils to early atherosclerosis in mice, their role in human atherogenesis, atheroprogression, and atherosclerotic plaque destabilization is still poorly understood. This brief review will summarize latest findings on the role of neutrophils in atherosclerosis and will pay special attention to studies describing a translation approach by combining measurements in mouse and human. PMID:25147339

Döring, Yvonne; Drechsler, Maik; Soehnlein, Oliver; Weber, Christian

2015-02-01

88

MRI of Atherosclerosis: Diagnosis and Monitoring Therapy  

PubMed Central

Summary Atherosclerosis is a prevalent disease affecting millions of Americans. Despite our advances in diagnosis and treatment, atherosclerosis is the leading cause of death in America. High resolution MRI has overcome the limitations of current angiographic techniques and has emerged as a leading noninvasive imaging modality of atherosclerotic disease. Atherosclerosis of the arterial wall of human carotid, aortic, peripheral, and coronary arteries have all been successfully evaluated. In addition, the power of MRI to differentiate the major components of atherosclerotic plaque has been validated. The ability to image the vessel wall and risk stratify atherosclerotic plaque will create management decisions not previously faced and has the potential to change the way atherosclerosis is treated. PMID:17187458

Anderson, Justin D.; Kramer, Christopher M.

2014-01-01

89

Platelet-endothelial interactions in atherosclerosis  

Microsoft Academic Search

The pathogenesis of atherosclerosis, the leading cause of morbidity and mortality in the United States, is multifactorial.\\u000a Many factors that have been shown to influence the development of atherosclerosis also affect the function of the endothelium\\u000a through soluble or cell-cell interactions. Among these, interactions between platelets and endothelial cells have only recently\\u000a begun to receive systematic study. This article reviews

Bruce S. Sachais

2001-01-01

90

Nitric oxide function in atherosclerosis  

PubMed Central

Atherosclerosis is a chronic inflammatory process in the intima of conduit arteries, which disturbs the endothelium-dependent regulation of the vascular tone by the labile liposoluble radical nitric oxide (NO) formed by the constitutive endothelial nitric oxide synthase (eNOS). This defect predisposes to coronary vasospasm and cardiac ischaemia, with anginal pain as the typical clinical manifestation. It is now appreciated that endothelial dysfunction is an early event in atherogenesis and that it may also involve the microcirculation, in which atherosclerotic lesions do not develop. On the other hand, the inflammatory environment in atherosclerotic plaques may result in the expression of the inducible NO synthase (iNOS) isozyme. Whether the dysfunction in endothelial NO production is causal to, or the result of, atherosclerotic lesion formation is still highly debated. Most evidence supports the hypothesis that constitutive endothelial NO release protects against atherogenesis e.g. by preventing smooth muscle cell proliferation and leukocyte adhesion. Nitric oxide generated by the inducible isozyme may be beneficial by replacing the failing endothelial production but excessive release may damage the vascular wall cells, especially in combination with reactive oxygen intermediates. PMID:18472828

Matthys, K. E.

1997-01-01

91

Maximising antihypertensive effects of angiotensin II receptor blockers with thiazide diuretic combination therapy: focus on irbesartan/hydrochlorothiazide  

PubMed Central

Background Evidence-based guidelines for the management of hypertension are now well established. Studies have shown that more than 60% of patients with hypertension will require two or more drugs to achieve current treatment targets. Discussion Combination therapy is recommended as first-line treatment by the JNC-7 guidelines for patients with a blood pressure > 20 mmHg above the systolic goal or 10 mmHg above the diastolic goal, while the International Society of Hypertension in Blacks recommends combination therapy when BP exceeds targets by > 15/10 mmHg. Current European Society of Hypertension-European Society of Cardiology guidelines also recommend the use of low-dose combination therapy in the first-line setting. Furthermore, JNC-7 recommends that a thiazide-type diuretic should be part of initial first-line combination therapy. Thiazide/diuretic combinations are available for a variety of classes of antihypertensive, including ACE inhibitors, angiotensin receptor blockers (ARBs), beta blockers and centrally acting agents. This article focuses on clinical data investigating the combination of an ARB, irbesartan, with the diuretic, hydrochlorothiazide. Conclusions These data indicate that the ARB/HCTZ combination has greater potency and a similar side effect profile to ARB monotherapy and represents a highly effective approach for attaining goal BP levels using a therapeutic strategy that very effectively lowers BP, is well tolerated and minimises diuretic-induced metabolic effects. Review Criteria The PubMed and other searchable databases were utilized to collate information from original and review articles as well as from selected abstracts relevant to this topic. Message for the Clinic Diuretic-based combination antihypertensive drug therapy is a cornerstone of antihypertensive drug therapy. Most hypertensive patients will require more than one antihypertensive drug to lower blood pressure (BP) below target levels. The combination of diuretics with renin angiotensin system antagonists is highly logical given the significant augmentation of BP response and the minimization of drug-specific side effects (e.g., hypo- and hyperkalemia) when these two drug classes are combined. The combined use of angiotensin receptor blockers and diuretics is better tolerated, but more costly, than generic angiotensin converting enzyme inhibitors and diuretics, mostly because of the absence of cough and much lower incidence of angioedema. PMID:17887997

Flack, J M

2007-01-01

92

Gene delivery of suppressors of cytokine signaling (SOCS) inhibits inflammation and atherosclerosis development in mice.  

PubMed

Chronic activation of Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway contributes to vascular inflammation and atherosclerosis by inducing expression of genes involved in cell proliferation, differentiation and migration. We aimed to investigate whether enforced expression of negative regulators, the suppressors of cytokine signaling (SOCS1 and SOCS3), inhibits harmful JAK/STAT-mediated responses and affects atherosclerosis in apolipoprotein E knockout mice. Adenovirus-mediated SOCS1 transgene expression impaired the onset and progression of atherosclerosis without impact on lipid profile, whereas SOCS3 was only effective on early atherosclerosis. Mechanistically, SOCS gene delivery, primarily SOCS1, attenuated STAT1 and STAT3 activation and reduced the expression of STAT-dependent genes (chemokine/chemokine receptors, adhesion molecules, pro-inflammatory cytokines and scavenger receptors) in aortic tissue. Furthermore, atherosclerotic plaques exhibit a more stable phenotype characterized by lower lipids, T cells and M1 macrophages and higher M2 macrophages and collagen. Atheroprotection was accompanied by a systemic alteration of T helper- and T regulatory-related genes and a reduced activation state of circulating monocytes. In vascular smooth muscle cells and macrophages, SOCS gene delivery inhibited cytokine-induced STAT activation, pro-inflammatory gene expression, cell migration and proliferation. In conclusion, targeting SOCS proteins, predominantly SOCS1, to suppress pathological mechanisms involved in atheroma plaque progression and destabilization could be an interesting anti-atherosclerotic strategy. PMID:25604439

Recio, Carlota; Oguiza, Ainhoa; Mallavia, Beñat; Lazaro, Iolanda; Ortiz-Muñoz, Guadalupe; Lopez-Franco, Oscar; Egido, Jesus; Gomez-Guerrero, Carmen

2015-03-01

93

Nanoparticles Containing a Liver X Receptor Agonist Inhibit Inflammation and Atherosclerosis.  

PubMed

Liver X receptor (LXR) signaling pathways regulate lipid metabolism and inflammation, which has generated widespread interest in developing synthetic LXR agonists as potential therapeutics for the management of atherosclerosis. In this study, it is demonstrated that nanoparticles (NPs) containing the synthetic LXR agonist GW3965 (NP-LXR) exert anti-inflammatory effects and inhibit the development of atherosclerosis without causing hepatic steatosis. These NPs are engineered through self-assembly of a biodegradable diblock poly(lactide-co-glycolide)-b-poly(ethylene glycol) (PLGA-b-PEG) copolymer. NP-LXR is significantly more effective than free GW3965 at inducing LXR-target gene expression and suppressing inflammatory factors in macrophages in vitro and in vivo. Additionally, the NPs elicit negligible lipogenic gene stimulation in the liver. Using the Ldlr (-/-) mouse model of atherosclerosis, abundant colocalization of fluorescently labeled NPs within plaque macrophages following systemic administration is seen. Notably, six intravenous injections of NP-LXR over 2 weeks markedly reduce the CD68-positive cell (macrophage) content of plaques (by 50%) without increasing total cholesterol or triglycerides in the liver and plasma. Together, these findings identify GW3965-encapsulated PLGA-b-PEG NPs as a promising nanotherapeutic approach to combat atherosclerosis, providing the benefits of LXR agonists without their adverse effects on hepatic and plasma lipid metabolism. PMID:25156796

Zhang, Xue-Qing; Even-Or, Orli; Xu, Xiaoyang; van Rosmalen, Mariska; Lim, Lucas; Gadde, Suresh; Farokhzad, Omid C; Fisher, Edward A

2014-08-22

94

Functionally Defective High-Density Lipoprotein and Paraoxonase: A Couple for Endothelial Dysfunction in Atherosclerosis  

PubMed Central

The endothelium is the primary target for biochemical or mechanical injuries caused by the putative risk factors of atherosclerosis. Endothelial dysfunction represents the ultimate link between atherosclerotic risk factors that promote atherosclerosis. HDL-C is thought to exert at least some parts of its antiatherogenic facilities via stimulating endothelial NO production, nearby inhibiting oxidative stress and inflammation. HDL-C is capable of opposing LDL's inductive effects and avoiding the ox-LDL's inhibition of eNOS. Paraoxonase 1 (PON1) is an HDL-associated enzyme esterase which appears to contribute to the antioxidant and antiatherosclerotic capabilities of HDL-C. “Healthy HDL,” namely the particle that contains the active Paraoxonase 1, has the power to suppress the formation of oxidized lipids. “Dysfunctional HDL,” on the contrary, has reduced Paraoxonase 1 enzyme activity and not only fails in its mission but also potentially leads to greater formation of oxidized lipids/lipoproteins to cause endothelial dysfunction. The association of HDL-C PON1 and endothelial dysfunction depends largely on the molecules with exact damaging effect on NO synthase coupling. Loss of nitric oxide bioavailability has a pivotal role in endothelial dysfunction preceding the appearance of atherosclerosis. Analyses of HDL-C and Paraoxonase1 would be more important in the diagnosis and treatment of atherosclerosis in the very near future. PMID:24222847

Eren, Esin; Yilmaz, Necat; Aydin, Ozgur

2013-01-01

95

Macrophage Mitochondrial Oxidative Stress Promotes Atherosclerosis and NF-?B-Mediated Inflammation in Macrophages  

PubMed Central

Rationale Mitochondrial oxidative stress (mitoOS) has been shown to correlate with the progression of human atherosclerosis. However, definitive cell-type specific causation studies in vivo are lacking, and the molecular mechanisms of potential pro-atherogenic effects remain to be determined. Objective To assess the importance of macrophage mitoOS in atherogenesis and explore the underlying molecular mechanisms. Methods & Results We first validated Western-type diet-fed Ldlr-/- mice as a model of human mitoOS-atherosclerosis association by showing that a marker of mitoOS in lesional macrophages, non-nuclear oxidative DNA damage, correlates with aortic root lesion development. To investigate the importance of macrophage-mitoOS, we used a genetic engineering strategy in which the OS suppressor catalase was ectopically expressed in mitochondria (mCAT) in macrophages. MitoOS in lesional macrophages was successfully suppressed in these mice, and this led to a significant reduction in aortic root lesional area. The mCAT lesions had less monocyte-derived cells, less Ly6chi monocyte infiltration into lesions, and lower levels of the monocyte chemotactic protein-1 (MCP-1). The decrease in lesional MCP-1 was associated with suppression of other markers of inflammation and with decreased phosphorylation of RelA (NF-?B p65), indicating decreased activation of the pro-inflammatory NF-?B pathway. Using models of mitoOS in cultured macrophages, we showed that mCAT suppressed MCP-1 expression by decreasing activation of the I?-kinase-RelA NF-?B pathway. Conclusions MitoOS in lesional macrophages amplifies atherosclerotic lesion development by promoting NF-?B-mediated entry of monocytes and other inflammatory processes. In view of the mitoOS-atherosclerosis link in human atheromata, these findings reveal a potentially new therapeutic target to prevent the progression of atherosclerosis. PMID:24297735

Wang, Ying; Wang, Gary Z.; Rabinovitch, Peter S.; Tabas, Ira

2014-01-01

96

Genetic Modifiers of Atherosclerosis in Mice  

PubMed Central

Atherosclerosis is a complex, multifactorial disease with both genetic and environmental determinants. Experimental investigation of the effects of these determinants on the development and progression of atherosclerosis has been greatly facilitated by the use of targeted mouse models of the disease, particularly those resulting from the absence of functional genes for apolipoprotein E or the low density lipoprotein receptor (LDLR). This review focuses on the influence on atherosclerosis of combining apoE or LDLR deficiencies with factors affecting atherogenesis, including (1) inflammatory processes, (2) glucose metabolism, (3) blood pressure, and (4) coagulation and fibrinolysis. We also discuss the general problem of using the mouse to test the effects on atherogenesis of human polymorphic variations and future ways of enhancing the usefulness of these mouse models. PMID:11073835

Knowles, Joshua W.; Maeda, Nobuyo

2009-01-01

97

[Progress in researches on ancient history of atherosclerosis].  

PubMed

Atherosclerosis has been thought to be a disease of modern society, and its occurrence was closely related to contemporary diet and lifestyle. However, a series of investigations on ancient mummies by autopsy and CT scan concluded that atherosclerosis was commonly seen in ancient times. The presence of atherosclerosis in ancient human beings suggested that aging and genetic predisposition might be essential risk factors for atherosclerosis. PMID:24432667

Chen, Ke-Ji; Fu, Chang-Geng

2013-10-01

98

Beta3 integrin deficiency promotes atherosclerosis and pulmonary inflammation in high-fat-fed, hyperlipidemic mice.  

PubMed

Hyperlipidemia promotes the chronic inflammatory disease atherosclerosis through poorly understood mechanisms. Atherogenic lipoproteins activate platelets, but it is unknown whether platelets contribute to early inflammatory atherosclerotic lesions. To address the role of platelet aggregation in diet-induced vascular disease, we studied beta3 integrin-deficient mice (lacking platelet integrin alphaIIbbeta3 and the widely expressed nonplatelet integrin alphavbeta3) in two models of atherosclerosis, apolipoprotein E (apoE)-null and low-density lipoprotein receptor (LDLR)-null mice. Unexpectedly, a high-fat, Western-type (but not a low-fat) diet caused death in two-thirds of the beta3-/-apoE-/- and half of the beta3-/-LDLR-/- mice due to noninfectious pneumonitis. In animals from both models surviving high-fat feeding, pneumonitis was absent, but aortic atherosclerosis was 2- to 6-fold greater in beta3-/- compared with beta+/+ littermates. Expression of CD36, CD40L, and CD40 was increased in lungs of beta3-/-LDLR-/- mice. Each was also increased in smooth muscle cells cultured from beta3-deficient mice and suppressed by retroviral reconstitution of beta3. These data show that the platelet defect caused by alphaIIbbeta3 deficiency does not impair atherosclerotic lesion initiation. They also suggest that alphavbeta3 has a suppressive effect on inflammation, the loss of which induces atherogenic mediators that are amplified by diet-induced hyperlipidemia. PMID:12746502

Weng, Sherry; Zemany, Laura; Standley, Kara N; Novack, Deborah V; La Regina, Marie; Bernal-Mizrachi, Carlos; Coleman, Trey; Semenkovich, Clay F

2003-05-27

99

Interleukins and atherosclerosis: a dysfunctional family grows.  

PubMed

Atherosclerosis is driven by the release of cytokines from macrophages, and the ? isoform of interleukin-1 (IL-1?) is a prime suspect in disease progression. Freigang et al. (2013) now suggest that IL-1?, a close relative, is selectively induced by fatty acids independent of the inflammasome to promote vascular inflammation. PMID:24206661

Spears, Larry D; Razani, Babak; Semenkovich, Clay F

2013-11-01

100

Interleukins and Atherosclerosis: a Dysfunctional Family Grows  

PubMed Central

Atherosclerosis is driven by the release of cytokines from macrophages, and the ? isoform of interleukin 1 (IL-1?) is a prime suspect in disease progression. Freigang et al. (2013) now suggest that IL-1?, a close relative, is selectively induced by fatty acids independent of the inflammasome to promote vascular inflammation. PMID:24206661

Spears, Larry D.; Razani, Babak; Semenkovich, Clay F.

2013-01-01

101

Therapeutic targeting of chemokine interactions in atherosclerosis  

Microsoft Academic Search

Atherosclerosis is a chronic inflammatory disease of the arterial wall that is characterized by a disturbed equilibrium of immune responses and lipid accumulation, leading to the development of plaques. The atherogenic influx of mononuclear cells is orchestrated by chemokines and their receptors. Studies using gene-deficient mice and antagonists based on peptides and small molecules have generated insight into targeting chemokine–receptor

Rory R. Koenen; Christian Weber

2010-01-01

102

Inflammation, Atherosclerosis, and Coronary Artery Disease  

Microsoft Academic Search

ecent research has shown that inflammation plays a key role in coronary artery disease (CAD) and other manifestations of atherosclerosis. Immune cells dominate early atherosclerotic lesions, their effector molecules accelerate progression of the lesions, and activation of inflammation can elicit acute coronary syndromes. This review highlights the role of inflammation in the pathogen- esis of atherosclerotic CAD. It will recount

Göran K. Hansson

2005-01-01

103

Infectious burden and atherosclerosis: A clinical issue  

PubMed Central

Atherosclerotic cardiovascular diseases, chronic inflammatory diseases of multifactorial etiology, are the leading cause of death worldwide. In the last decade, more infectious agents, labeled as “infectious burden”, rather than any single pathogen, have been showed to contribute to the development of atherosclerosis through different mechanisms. Some microorganisms, such as Chlamydia pneumoniae (C. pneumoniae), human cytomegalovirus, etc. may act directly on the arterial wall contributing to endothelial dysfunction, foam cell formation, smooth muscle cell proliferation, platelet aggregation as well as cytokine, reactive oxygen specie, growth factor, and cellular adhesion molecule production. Others, such as Helicobacter pylori (H. pylori), influenza virus, etc. may induce a systemic inflammation which in turn may damage the vascular wall (e.g., by cytokines and proteases). Moreover, another indirect mechanism by which some infectious agents (such as H. pylori, C. pneumoniae, periodontal pathogens, etc.) may play a role in the pathogenesis of atherosclerosis is molecular mimicry. Given the complexity of the mechanisms by which each microorganism may contribute to atherosclerosis, defining the interplay of more infectious agents is far more difficult because the pro-atherogenic effect of each pathogen might be amplified. Clearly, continued research and a greater awareness will be helpful to improve our knowledge on the complex interaction between the infectious burden and atherosclerosis. PMID:25032197

Sessa, Rosa; Pietro, Marisa Di; Filardo, Simone; Turriziani, Ombretta

2014-01-01

104

Phosphatidylethanolamine binding protein 1 in vacular endothelial cell autophagy and atherosclerosis  

PubMed Central

We previously found that phosphatidylcholine-specific phospholipase C (PC-PLC) was a key inducing element of atherosclerosis, and might negatively regulate human umbilical vein endothelial cell (HUVEC) autophagy. To further investigate the mechanism of PC-PLC action, we initially identified phosphatidylethanolamine binding protein 1 (PEBP1) as a binding partner of PC-PLC by using mass spectrometry (MS, MALDI-TOF/TOF). We found that PEBP1 positively regulated PC-PLC activity in HUVECs, and inhibition of PC-PLC by its inhibitor D609 suppressed PEBP1 expression dramatically. Moreover, both PC-PLC and PEBP1 negatively regulated HUVEC autophagy independently of mammalian target of rapamycin (mTOR). Furthermore, the PEBP1 level was elevated during the development of atherosclerosis, while D609 significantly decreased the upregulated PEBP1 level in apoE?/? mice. PMID:23959677

Wang, Li; Li, HaiYing; Zhang, JinFeng; Lu, Wei; Zhao, Jing; Su, Le; Zhao, BaoXiang; Zhang, Yun; Zhang, ShangLi; Miao, JunYing

2013-01-01

105

Flow-dependent cellular mechanotransduction in atherosclerosis  

PubMed Central

Summary Atherosclerosis depends on risk factors such as hyperlipidemia, smoking, hypertension and diabetes. Although these risk factors are relatively constant throughout the arterial circulation, atherosclerotic plaques occur at specific sites where flow patterns are disturbed, with lower overall magnitude and complex changes in speed and direction. Research over the past few decades has provided new insights into the cellular mechanisms of force transduction and how mechanical effects act in concert with conventional risk factors to mediate plaque formation and progression. This Commentary summarizes our current understanding of how mechanotransduction pathways synergize with conventional risk factors in atherosclerosis. We attempt to integrate cellular studies with animal and clinical data, and highlight major questions that need to be answered to develop more effective therapies. PMID:24190880

Conway, Daniel E.; Schwartz, Martin A.

2013-01-01

106

Lipoprotein lipase: From gene to atherosclerosis.  

PubMed

Lipoprotein lipase (LPL) is a key enzyme in lipid metabolism and responsible for catalyzing lipolysis of triglycerides in lipoproteins. LPL is produced mainly in adipose tissue, skeletal and heart muscle, as well as in macrophage and other tissues. After synthesized, it is secreted and translocated to the vascular lumen. LPL expression and activity are regulated by a variety of factors, such as transcription factors, interactive proteins and nutritional state through complicated mechanisms. LPL with different distributions may exert distinct functions and have diverse roles in human health and disease with close association with atherosclerosis. It may pose a pro-atherogenic or an anti-atherogenic effect depending on its locations. In this review, we will discuss its gene, protein, synthesis, transportation and biological functions, and then focus on its regulation and relationship with atherosclerosis and potential underlying mechanisms. The goal of this review is to provide basic information and novel insight for further studies and therapeutic targets. PMID:25463094

Li, Yuan; He, Ping-Ping; Zhang, Da-Wei; Zheng, Xi-Long; Cayabyab, Fracisco S; Yin, Wei-Dong; Tang, Chao-Ke

2014-12-01

107

Inflammation, Atherosclerosis, and Coronary Artery Disease: PET/CT for the Evaluation of Atherosclerosis and Inflammation  

PubMed Central

Atherosclerosis is a prevalent cardiovascular disease marked by inflammation and the formation of plaque within arterial walls. As the disease progresses, there is an increased risk of major cardiovascular events. Owing to the nature of atherosclerosis, it is imperative to develop methods to further understand the physiological implications and progression of the disease. The combination of positron emission tomography (PET)/computed tomography (CT) has proven to be promising for the evaluation of atherosclerotic plaques and inflammation within the vessel walls. The utilization of the radiopharmaceutical tracer, 18F-fluorodeoxyglucose (18F-FDG), with PET/CT is invaluable in understanding the pathophysiological state involved in atherosclerosis. In this review, we will discuss the use of 18F-FDG-PET/CT imaging for the evaluation of atherosclerosis and inflammation both in preclinical and clinical studies. The potential of more specific novel tracers will be discussed. Finally, we will touch on the potential benefits of using the newly introduced combined PET/magnetic resonance imaging (MRI) for non-invasive imaging of atherosclerosis. PMID:25674025

Alie, Nadia; Eldib, Mootaz; Fayad, Zahi A; Mani, Venkatesh

2014-01-01

108

Computer assessment of atherosclerosis from angiographic images  

NASA Technical Reports Server (NTRS)

A computer method for detection and quantification of atherosclerosis from angiograms has been developed and used to measure lesion change in human clinical trials. The technique involves tracking the vessel edges and measuring individual lesions as well as the overall irregularity of the arterial image. Application of the technique to conventional arterial-injection femoral and coronary angiograms is outlined and an experimental study to extend the technique to analysis of intravenous angiograms of the carotid and cornary arteries is described.

Selzer, R. H.; Blankenhorn, D. H.; Brooks, S. H.; Crawford, D. W.; Cashin, W. L.

1982-01-01

109

Lysophosphatidic acid effects on atherosclerosis and thrombosis  

PubMed Central

Lysophosphatidic acid (LPA) has been found to accumulate in high concentrations in atherosclerotic lesions. LPA is a bioactive phospholipid produced by activated platelets and formed during the oxidation of LDL. Accumulating evidence suggests that this lipid mediator may serve as an important risk factor for development of atherosclerosis and thrombosis. The role of LPA in atherogenesis is supported by the evidence that LPA: stimulates endothelial cells to produce adhesion molecules and chemoattractants; induces smooth muscle cells to produce inflammatory cytokines; stimulates smooth muscle cell dedifferentiation, proliferation, and migration; increases monocyte migration and decreases monocyte-derived cell emigration from the vessel wall; induces hypertension and vascular neointimal formation in vivo; and promotes plaque progression in a mouse atherosclerosis model. The role of LPA in thrombogenesis is supported by the evidence that LPA markedly induces the aggregation of platelets and the expression of tissue factor, which is the principal initiator of blood coagulation. Recent experimental data indicate that LPA is produced by specific enzymes and that LPA binds to and activates multiple G-protein-coupled receptors, leading to intracellular signaling. Therapeutics targeting LPA biosynthesis, metabolism and signaling pathways could be viable for prevention and treatment of atherosclerosis and thrombosis. PMID:22162980

Cui, Mei-Zhen

2011-01-01

110

Is atherosclerosis fundamental to human aging? Lessons from ancient mummies.  

PubMed

Case reports from Johan Czermak, Marc Ruffer, and others a century or more ago demonstrated ancient Egyptians had atherosclerosis three millennia ago. The Horus study team extended their findings, demonstrating that atherosclerosis was prevalent among 76 ancient Egyptian mummies and among 61 mummies from each of the ancient cultures of Peru, the American Southwest, and the Aleutian Islands. These findings challenge the assumption that atherosclerosis is a modern disease caused by present day risk factors. An extensive autopsy of an ancient Egyptian teenage male weaver named Nakht found that he was infected with four parasites: Schistosoma haematobium, Taenia species, Trichinella spiralis, and Plasmodium falciparum. Modern day patients with chronic inflammatory disease such as rheumatoid arthritis, systemic lupus erythematosus, and human immunodeficiency virus experience premature atherosclerosis. Could the burden of chronic inflammatory disease have been a risk factor for atherosclerosis in these ancient cultures? The prevalence of atherosclerosis in four diverse ancient cultures is consistent with atherosclerosis being fundamental to aging. The impact of risk factors in modern times, and potentially in ancient times, suggests a strong gene-environmental interplay: human genes provide a vulnerability to atherosclerosis, the environment determines when and if atherosclerosis becomes manifest clinically. PMID:24582386

Clarke, Emily M; Thompson, Randall C; Allam, Adel H; Wann, L Samuel; Lombardi, Guido P; Sutherland, M Linda; Sutherland, James D; Cox, Samantha L; Soliman, Muhammad Al-Tohamy; Abd el-Maksoud, Gomaa; Badr, Ibrahem; Miyamoto, Michael I; Frohlich, Bruno; Nur el-din, Abdel-Halim; Stewart, Alexandre F R; Narula, Jagat; Zink, Albert R; Finch, Caleb E; Michalik, David E; Thomas, Gregory S

2014-05-01

111

RNA interference therapy: a new solution for intracranial atherosclerosis?  

PubMed Central

Intracranial atherosclerotic stenosis (ICAS) of a major intracranial artery, especially middle cerebral artery (MCA), is reported to be one leading cause of ischemic stroke throughout the world. Compared with other stroke subtypes, ICAS is associated with a higher risk of recurrent stroke despite aggressive medical therapy. Increased understanding of the pathophysiology of ICAS has highlighted several possible targets for therapeutic interventions. Both luminal stenosis and plaque components of ICAS have been found to be associated with ischemic stroke based a post-mortem study. Recent application of high-resolution magnetic resonance imaging (HRMRI) in evaluating ICAS provides new insight into the vascular biology of plaque morphology and component. High signal on T1-weighted fat-suppressed images (HST1) within MCA plaque of HRMRI, highly suggested of fresh or recent intraplaque hemorrhage, has been found to be associated with ipsilateral brain infarction. Thus, the higher prevalence of intraplaque hemorrhage and neovasculature in symptomatic patients with MCA stenosis may provide a potential target for plaque stabilization. We hypothesize that RNA interference (RNAi) therapy delivered by modified nanoparticles may achieve in vivo biomedical imaging and targeted therapy. With the rapid developments in studies about therapeutic and diagnostic nanomaterials, future studies further exploring the molecular biology of atherosclerosis may provide more drug targets for plaque stabilization. PMID:25333054

Tang, Tao; Wong, Ka-Sing

2014-01-01

112

Is the Use of Fullerene in Photodynamic Therapy Effective for Atherosclerosis?  

SciTech Connect

The purpose of this study was to evaluate Fullerene as a therapeutic photosensitizer in the treatment of atherosclerosis. An atherosclerotic experimental rabbit model was prepared by causing intimal injury to bilateral external iliac arteries using balloon expansion. In four atherosclerotic rabbits and one normal rabbit, polyethylene glycol-modified Fullerene (Fullerene-PEG) was infused into the left external iliac artery and illuminated by light emitting diode (LED), while the right external iliac artery was only illuminated by LED. Two weeks later, the histological findings for each iliac artery were evaluated quantitatively and comparisons were made among atherosclerotic Fullerene+LED artery (n = 4), atherosclerotic light artery (n = 4), normal Fullerene+LED artery (n = 1), and normal light artery (n = 1). An additional two atherosclerotic rabbits were studied by fluorescence microscopy, after Fullerene-PEG-Cy5 complex infusion into the left external iliac artery, for evaluation of Fullerene-PEG incorporated within the atherosclerotic lesions. The degree of atherosclerosis in the atherosclerotic Fullerene+LED artery was significantly (p < 0.05) more severe than that in the atherosclerotic LED artery. No pathological change was observed in normal Fullerene+LED and LED arteries. In addition, strong accumulation of Fullerene-PEG-Cy5 complex within the plaque of the left iliac artery of the two rabbits was demonstrated, in contrast to no accumulation in the right iliac artery. We conclude that infusion of a high concentration of Fullerene-PEG followed by photo-illumination resulted not in a suppression of atherosclerosis but in a progression of atherosclerosis in experimental rabbit models. However, this intervention showed no adverse effects on the normal iliac artery.

Nitta, Norihisa, E-mail: r34nitta@belle.shiga-med.ac.jp; Seko, Ayumi; Sonoda, Akinaga; Ohta, Shinichi; Tanaka, Toyohiko; Takahashi, Masashi; Murata, Kiyoshi [Shiga University of Medical Science, Department of Radiology (Japan); Takemura, Shizuki [Shiga University of Medical Science, Department of Pathology (Japan); Sakamoto, Tsutomu [Koka General Hospital, Department of Radiology (Japan); Tabata, Yasuhiko [Kyoto University, Department of Biomaterials, Field of Tissue Engineering (Japan)

2008-03-15

113

Association of Fat Density With Subclinical Atherosclerosis  

PubMed Central

Background Ectopic fat density is associated with cardiovascular disease (CVD) risk factors above and beyond fat volume. Volumetric measures of ectopic fat have been associated with CVD risk factors and subclinical atherosclerosis. The aim of this study was to investigate the association between fat density and subclinical atherosclerosis. Methods and Results Participants were drawn from the Multi?Detector Computed Tomography (MDCT) substudy of the Framingham Heart Study (n=3079; mean age, 50.1 years; 49.2% women). Fat density was indirectly estimated by computed tomography attenuation (Hounsfield Units [HU]) on abdominal scan slices. Visceral fat (VAT), subcutaneous fat (SAT), and pericardial fat HU and volumes were quantified using standard protocols; coronary and abdominal aortic calcium (CAC and AAC, respectively) were measured radiographically. Multivariable?adjusted logistic regression models were used to evaluate the association between adipose tissue HU and the presence of CAC and AAC. Overall, 17.1% of the participants had elevated CAC (Agatston score [AS]>100), and 23.3% had elevated AAC (AS>age?/sex?specific cutoffs). Per 5?unit decrement in VAT HU, the odds ratio (OR) for elevated CAC was 0.76 (95% confidence interval [CI], 0.65 to 0.89; P=0.0005), even after adjustment for body mass index or VAT volume. Results were similar for SAT HU. With decreasing VAT HU, we also observed an OR of 0.79 (95% CI, 0.67 to 0.92; P=0.004) for elevated AAC after multivariable adjustment. We found no significant associations between SAT HU and AAC. There was no significant association between pericardial fat HU and either CAC or AAC. Conclusions Lower VAT and SAT HU, indirect estimates of fat quality, are associated with a lower risk of subclinical atherosclerosis. PMID:25169793

Alvey, Nicholas J.; Pedley, Alison; Rosenquist, Klara J.; Massaro, Joseph M.; O'Donnell, Christopher J.; Hoffmann, Udo; Fox, Caroline S.

2014-01-01

114

Simultaneous determination of irbesartan and hydrochlorothiazide in human plasma by ultra high performance liquid chromatography tandem mass spectrometry and its application to a bioequivalence study.  

PubMed

An ultra high performance liquid chromatography tandem mass spectrometry (U-HPLC-MS/MS) method was developed and validated to determine irbesartan (IRB) and hydrochlorothiazide (HCTZ) in human plasma simultaneously. Plasma samples were prepared using protein precipitation with acetonitrile, the two analytes and the internal standard losartan were separated on an Acquity U-HPLC BEH C18 column and mass spectrometric analysis was performed using a QTrap5500 mass spectrometer coupled with an electro-spray ionization (ESI) source in the negative ion mode. The MRM transitions of m/z 427.2?206.9 and m/z 296.1?204.9 were used to quantify for IRB and HCTZ, respectively. The linearity of this method was found to be within the concentration range of 5-3000ng/mL for IRB, and 0.5-300ng/mL for HCTZ in human plasma, respectively. The lower limit of quantification (LLOQ) was 5ng/mL and 0.5ng/mL for IRB and HCTZ in human plasma, respectively. The relative standard deviations (RSD) of intra and inter precision were less than 12% for both IRB and HCTZ. The analysis time of per sample was 2.5min. The developed and validated method was successfully applied to a bioequivalence study of IRB (300mg) with HCTZ (12.5mg) tablet in Chinese healthy volunteers (N=20). PMID:24681823

Qiu, Xiangjun; Wang, Zhe; Wang, Bing; Zhan, Hui; Pan, Xiaofeng; Xu, Ren-ai

2014-04-15

115

Internal Carotid Artery Stenting for Intracranial Atherosclerosis  

PubMed Central

Intracranial atherosclerotic disease is a significant cause of stroke in the United States. Much like coronary atherosclerosis, this disease leads to arterial stenosis secondary to the buildup of lipid-based plaques in intracranial vessels. Ischemic stroke may occur following thromboembolic events near the site of stenosis or from watershed ischemia secondary to cerebral hypoperfusion. While this disease has been treated with intracranial angioplasty and stenting and cerebrovascular bypass surgery, the current literature supports aggressive medical management with dual antiplatelet therapy, treatment of comorbidities such as hypertension, diabetes, and hyperlipidemia, and lifestyle modification. Intracranial angioplasty and stenting is reserved for cases of medical failure. PMID:25624980

Osbun, Joshua W.; Kim, Louis J.

2014-01-01

116

Adiponectin Abates Atherosclerosis by Reducing Oxidative Stress  

PubMed Central

Background We investigated whether the anti-atherosclerosis of adiponectin (APN) relates to the reduction of oxidative stress. We observed the overexpression of adiponectin gene with different titers on atherosclerosis (AS) models of high-fat apolipoprotein E-deficient (ApoE?/?) mice. Material/Methods We divided 48 male ApoE?/? mice into 4 groups: control group, high-fat diet group, low adiponectin group, and high adiponectin group. The low and high adiponectin group mice were treated with recombinant adenovirus expressing mice adiponectin (Ad-APN) with low-dose adiponectin 1.0×108 p.f.u. and high-dose adiponectin 5.0×108 p.f.u. via the tail every 2 weeks and given a high-fat diet for the last 8 weeks. On the 14th day after injection, blood samples were obtained from the vena cava. Results Along with increased serum adiponectin, serum superoxide dismutase (SOD) activity increased (P<0.05) and concentration of malondialdehyde (MDA) was decreased (P<0.05). Levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) were decreased, especially TC and LDL-C (P<0.05). A real-time fluorescent quantitative polymerase chain reaction test was used to analyze levels of mRNA expression for endothelial nitric oxide synthase (eNOS) and adiponectin in the aorta. Along with increased adiponectin, the mRNA expression of eNOS in the aorta was increased significantly (P<0.05). The lesion formation in the aortic sinus was inhibited by 25% and 31% in the low-APN group and high-APN group, respectively (P<0.05). Along with the increase of adiponectin doses, the damage of atherosclerosis gradually eased. However, the differences between the low-APN group and high-APN group had no statistical significance. Conclusions Adiponectin may protect the aorta from atherosclerosis injury by reducing oxidative stress, reducing lesion formation size in the aortic root and reducing TC, TG, and LDL-C in serum. The molecular mechanism may involve preservation of SOD, reducing MDA in serum, and increasing eNOS and adiponectin mRNA expression in the aorta. PMID:25275545

Wang, Xuemei; Pu, Hongwei; Ma, Chuang; Jiang, Tao; Wei, Qin; Duan, Mingjun; Zhang, Chun; Shou, Xi; Su, Lipin; Zhang, Jianlong; Yang, Yining

2014-01-01

117

PPAR and Atherosclerosis Effects on Cell Growth and Movement  

Microsoft Academic Search

Atherosclerosis is a major vascular complication of diabetes and the primary cause of mortality in persons with this disease. Metabolic abnormalities related to the Insulin Resistance Syndrome or Metabolic Syndrome may importantly contribute to the increased risk of atherosclerosis associated with diabetes. Thiazolidinediones (TZDs) are oral insulin sensitizers in broad clinical use that enhance insulin-stimulated glucose uptake into skeletal muscle.

Willa A. Hsueh; Ronald E. Law

2001-01-01

118

Modulation of atherosclerosis by N-3 polyunsaturated fatty acids  

Technology Transfer Automated Retrieval System (TEKTRAN)

We have reviewed literature regarding the effects of n-3 polyunsaturated fatty acids (PUFA) on risk factors for atherosclerosis in human subjects. Dietary intervention with long chain n-3 PUFA decreased some risk factor (s) for atherosclerosis in most human studies reviewed. These benefits resulted ...

119

[The morphological substrate and histogenesis of systemic and ocular atherosclerosis].  

PubMed

The atherosclerosis is an complex pathologic process with thrombosis and vessels obstructions. At the cerebral level, atherosclerosis determines lesions especially at the Willis circle vessels, and his peripheral ramifications (ophthalmic artery). The authors presents the atherosclerotic lesions at the level of ocular vessels, and their consequence at the central retinal artery, and other ocular vessels. PMID:7766572

Dumitrache, M; Ani?escu, M; Gheorghe, L

1995-01-01

120

Cardiac CT: atherosclerosis to acute coronary syndrome  

PubMed Central

Coronary computed tomographic angiography (CCTA) is a robust non-invasive method to assess coronary artery disease (CAD). Qualitative and quantitative assessment of atherosclerotic coronary stenosis with CCTA has been favourably compared with invasive coronary angiography (ICA) and intravascular ultrasound (IVUS). Importantly, it allows the study of preclinical stages of atherosclerotic disease, may help improve risk stratification and monitor the progressive course of the disease. The diagnostic accuracy of CCTA in the assessment of coronary artery bypass grafts (CABG) is excellent and the constantly improving technology is making the evaluation of stents feasible. Novel techniques are being developed to assess the functional significance of coronary stenosis. The excellent negative predictive value of CCTA in ruling out disease enables early and safe discharge of patients with suspected acute coronary syndromes (ACS) in the Emergency Department (ED). In addition, CCTA is useful in predicting clinical outcomes based on the extent of coronary atherosclerosis and also based on individual plaque characteristics such as low attenuation plaque (LAP), positive remodelling and spotty calcification. In this article, we review the role of CCTA in the detection of coronary atherosclerosis in native vessels, stented vessels, calcified arteries and grafts; the assessment of plaque progression, evaluation of chest pain in the ED, assessment of functional significance of stenosis and the prognostic significance of CCTA. PMID:25610801

Munnur, Ravi Kiran; Cameron, James D.; Ko, Brian S.; Meredith, Ian T.

2014-01-01

121

Applications of stenting for intracranial atherosclerosis.  

PubMed

Intracranial atherosclerosis presents a therapeutic challenge to medical and surgical physicians alike. Despite maximal medical therapy, the stroke rate from this disease is still high, especially when arterial stenosis is severe and patients are symptomatic. Open surgical therapy has yet to be shown to be a more efficacious treatment than medical therapy alone, largely due to the relatively high rates of perioperative complications. Angioplasty has a similar fate, with the risk of periprocedural complications outweighing the overall benefit of treatment. With the advent of stents for use in intracranial vasculature, new hope has arisen for the treatment of intracranial atherosclerosis. The NEUROLINK system, the drug-eluting stents Taxus and Cypher, the flexible Wingspan stent, the Apollo stent, and the Pharos stent have all been used in various prospective and retrospective clinical studies with varying technical and clinical results. The authors' objective is to review and loosely compare the data presented for each of these stenting systems. While the Wingspan stent appears to have somewhat of an advantage with regard to technical success in comparison with the other stenting systems, the clinical follow-up time of its studies is too short to properly compare its complication rates with those of other stents. Before we continue to move forward with stenting for intracranial stenosis, a randomized prospective trial is ultimately needed to directly compare intracranial stenting to medical therapy. PMID:21631216

Ding, Dale; Liu, Kenneth C

2011-06-01

122

Molecular imaging of atherosclerosis in translational medicine.  

PubMed

Functional characterization of atherosclerosis is a promising application of molecular imaging. Radionuclide-based techniques for molecular imaging in the large arteries (e.g. aorta and carotids), along with ultrasound and magnetic resonance imaging (MRI), have been studied both experimentally and in clinical studies. Technical factors including cardiac and respiratory motion, low spatial resolution and partial volume effects mean that noninvasive molecular imaging of atherosclerosis in the coronary arteries is not ready for prime time. Positron emission tomography imaging with fluorodeoxyglucose can measure vascular inflammation in the large arteries with high reproducibility, and signal change in response to anti-inflammatory therapy has been described. MRI has proven of value for quantifying carotid artery inflammation when iron oxide nanoparticles are used as a contrast agent. Macrophage accumulation of the iron particles allows regression of inflammation to be measured with drug therapy. Similarly, contrast-enhanced ultrasound imaging is also being evaluated for functional characterization of atherosclerotic plaques. For all of these techniques, however, large-scale clinical trials are mandatory to define the prognostic importance of the imaging signals in terms of risk of future vascular events. PMID:21174089

Perrone-Filardi, Pasquale; Dellegrottaglie, Santo; Rudd, James H F; Costanzo, Pierluigi; Marciano, Caterina; Vassallo, Enrico; Marsico, Fabio; Ruggiero, Donatella; Petretta, Maria Piera; Chiariello, Massimo; Cuocolo, Alberto

2011-05-01

123

Obesity, atherosclerosis, and coronary artery disease.  

PubMed

Although several risk factors for heart disease including high blood pressure, diabetes mellitus, and lipid and lipoprotein abnormalities are associated with overweight, overweight is not consistently associated with coronary heart disease risk. Some prospective studies of white men (life insurance cohorts, airline pilots, cancer study volunteers, and the Framingham population) have shown a positive linear relationship of weight to coronary heart disease. Other epidemiologic studies show a negative association, no association, a U-shaped relationship, or a threshold effect. The inconsistencies do not appear to be explained by differences in the definition or distribution of obesity, duration of follow-up, or risk factor distribution. Neither misclassification bias nor confounding by cigarette smoking or chronic disease appears to explain the inconsistencies. No known protective effect of obesity could explain these divergent findings. Inconsistent results with regard to the nature, strength, and linearity of the association between obesity and atherosclerosis do not support the hypothesis that obesity causes atherosclerosis, despite its biological plausibility. PMID:3904565

Barrett-Connor, E L

1985-12-01

124

Collateral circulation in symptomatic intracranial atherosclerosis.  

PubMed

Collateral circulation in intracranial atherosclerosis has never been systematically characterized. We investigated collaterals in a multicenter trial of symptomatic intracranial atherosclerotic disease. Baseline angiography was reviewed for information on collaterals in stenoses of the internal carotid, middle cerebral, vertebral, and basilar arteries. A battery of angiographic scales was utilized to evaluate lesion site, arterial patency, antegrade flow, downstream territorial perfusion, and collateral circulation, blinded to all other data. Collateral circulation was adequately available for analysis in 287/569 (50%) subjects with proximal arterial stenoses ranging from 50% to 99%. Extent of collaterals was absent or none in 69%, slow or minimal in 10%, more rapid, yet incomplete perfusion of territory in 7%, complete but delayed perfusion in 11%, and rapid, complete collateral perfusion in 4%. Extent of collateral flow correlated with percentage of stenosis (P<0.0001), with more severe stenoses exhibiting greater compensation via collaterals. Overall, collateral grade increased with diminished antegrade flow across the lesion (thrombolysis in myocardial ischemia) and resultant downstream perfusion (thrombolysis in cerebral infarction) (both P<0.001). Our findings provide the initial detailed description of collaterals across a variety of stenoses, suggesting that collateral perfusion is a pivotal component in pathophysiology of intracranial atherosclerosis and implicating the need for further evaluation in ongoing studies. PMID:21157476

Liebeskind, David S; Cotsonis, George A; Saver, Jeffrey L; Lynn, Michael J; Cloft, Harry J; Chimowitz, Marc I

2011-05-01

125

Collateral circulation in symptomatic intracranial atherosclerosis  

PubMed Central

Collateral circulation in intracranial atherosclerosis has never been systematically characterized. We investigated collaterals in a multicenter trial of symptomatic intracranial atherosclerotic disease. Baseline angiography was reviewed for information on collaterals in stenoses of the internal carotid, middle cerebral, vertebral, and basilar arteries. A battery of angiographic scales was utilized to evaluate lesion site, arterial patency, antegrade flow, downstream territorial perfusion, and collateral circulation, blinded to all other data. Collateral circulation was adequately available for analysis in 287/569 (50%) subjects with proximal arterial stenoses ranging from 50% to 99%. Extent of collaterals was absent or none in 69%, slow or minimal in 10%, more rapid, yet incomplete perfusion of territory in 7%, complete but delayed perfusion in 11%, and rapid, complete collateral perfusion in 4%. Extent of collateral flow correlated with percentage of stenosis (P<0.0001), with more severe stenoses exhibiting greater compensation via collaterals. Overall, collateral grade increased with diminished antegrade flow across the lesion (thrombolysis in myocardial ischemia) and resultant downstream perfusion (thrombolysis in cerebral infarction) (both P<0.001). Our findings provide the initial detailed description of collaterals across a variety of stenoses, suggesting that collateral perfusion is a pivotal component in pathophysiology of intracranial atherosclerosis and implicating the need for further evaluation in ongoing studies. PMID:21157476

Liebeskind, David S; Cotsonis, George A; Saver, Jeffrey L; Lynn, Michael J; Cloft, Harry J; Chimowitz, Marc I

2011-01-01

126

Periodontitis as a Risk Factor of Atherosclerosis  

PubMed Central

Over the last two decades, the amount of evidence corroborating an association between dental plaque bacteria and coronary diseases that develop as a result of atherosclerosis has increased. These findings have brought a new aspect to the etiology of the disease. There are several mechanisms by which dental plaque bacteria may initiate or worsen atherosclerotic processes: activation of innate immunity, bacteremia related to dental treatment, and direct involvement of mediators activated by dental plaque and involvement of cytokines and heat shock proteins from dental plaque bacteria. There are common predisposing factors which influence both periodontitis and atherosclerosis. Both diseases can be initiated in early childhood, although the first symptoms may not appear until adulthood. The formation of lipid stripes has been reported in 10-year-old children and the increased prevalence of obesity in children and adolescents is a risk factor contributing to lipid stripes development. Endothelium damage caused by the formation of lipid stripes in early childhood may lead to bacteria penetrating into blood circulation after oral cavity procedures for children as well as for patients with aggressive and chronic periodontitis. PMID:24741613

Bartova, Jirina; Sommerova, Pavla; Lyuya-Mi, Yelena; Mysak, Jaroslav; Janatova, Tatjana; Podzimek, Stepan

2014-01-01

127

Atherosclerosis staging: imaging using FLIM technique  

NASA Astrophysics Data System (ADS)

In this work it was used fluorescence lifetime imaging (FLIM) to analyze biochemical composition of atherosclerotic plaque. For this purpose an animal experimentation was done with New Zealand rabbits divided into two groups: a control group of 4 rabbits that received a regular diet for 0, 20, 40 and 60 days; and an experimental group of 9 rabbits, divided in 3 subgroups, that were fed with 1% cholesterol diet for 20, 40 and 60 days respectively. The aortas slices stained with europium chlortetracycline were analyzed by FLIM exciting samples at 440 nm. The results shown an increase in the lifetime imaging of rabbits fed with cholesterol. It was observed that is possible to detect the metabolic changes associated with atherosclerosis at an early stage using FLIM technique exciting the tissue around 440 nm and observing autofluorescence lifetime. Lifetimes longer than 1.75 ns suggest the presence of porphyrins in the tissue and consequently, inflammation and the presence of macrophages.

Sicchieri, Leticia B.; Barioni, Marina Berardi; Silva, Mônica Nascimento; Monteiro, Andrea Moreira; Figueiredo Neto, Antonio Martins; Ito, Amando S.; Courrol, Lilia C.

2014-03-01

128

Chemokines: established and novel targets in atherosclerosis  

PubMed Central

In their role as small chemotactic cytokines, chemokines are crucial mediators and regulators of leukocyte trafficking during immune surveillance and inflammation. Their involvement in the development and progression of inflammatory diseases has been subject of intense investigation. Concordantly, the chemokine system has been explored in search for therapeutic targets to prevent or treat inflammatory disorders, such as atherosclerosis. Targeting the chemokine system offers various entry points for a causative treatment of this widespread and chronic illness. Although this approach has encountered some setbacks, several innovative compounds are currently in an advanced stage of development. In this review, the current standing of this dynamic field is highlighted and the potential advantages and drawbacks of particular strategies are discussed. PMID:22038924

Koenen, Rory R; Weber, Christian

2011-01-01

129

Laboratory medicine for molecular imaging of atherosclerosis.  

PubMed

Atherosclerotic plaques are the main cause of life threatening clinical endpoints like myocardial infarction and stroke. To prevent these endpoints, the improved early diagnosis and treatment of vulnerable atherosclerotic vascular lesions are essential. Although originally applied for anticancer treatment, recent advances have also showed the considerable potential of nanotechnology for atherosclerosis. Otherwise, one domain of laboratory medicine is the investigation of new biomarkers. Recent research activities have identified the usability of biomarker-targeted nanoparticles for molecular imaging and pharmacologic modification of vulnerable atherosclerotic lesions leading to myocardial infarction or stroke. These investigations have established a new research interface between laboratory medicine, nanotechnology, cardiology/neurology, and radiology. In this review, we discuss inflammatory pathophysiologic mechanisms and biomarkers associated with a vulnerable atherosclerotic plaque phenotype. Further, we will emphasize cardiovascular relevant functionalized nanoparticle biomarker constructs which were developed within the cooperation interface between Laboratory Medicine (anti-inflammatory biomarkers), Nano-Medicine (nanoparticle development), and Radiology (molecular imaging). PMID:25003647

Mangge, Harald; Almer, Gunter; Stelzer, Ingeborg; Reininghaus, Eva; Prassl, Ruth

2014-11-01

130

Children and Heart Disease (Atherosclerosis) (Beyond the Basics)  

MedlinePLUS

... times per week. Other options include joining a gym or YMCA, riding an exercise bike, or running ... children is available separately. (See "Overview of the management of the child at risk for atherosclerosis" .) HIGH ...

131

Multi-Ethnic Study of Atherosclerosis (MESA) - Ancillary Eye Study  

ClinicalTrials.gov

Atherosclerosis; Cardiovascular Diseases; Coronary Arteriosclerosis; Coronary Disease; Cerebrovascular Disorders; Heart Failure, Congestive; Myocardial Infarction; Heart Diseases; Diabetes Mellitus, Non-insulin Dependent; Hypertension; Diabetic Retinopathy; Macular Degeneration; Diabetes Mellitus

2014-03-12

132

Cholesterol and hematopoietic stem cells: inflammatory mediators of atherosclerosis.  

PubMed

Atherosclerosis causing heart attack and stroke is the leading cause of death in the modern world. Therapy for end-stage atherosclerotic disease using CD34(+) hematopoietic cells has shown promise in human clinical trials, and the in vivo function of hematopoietic and progenitor cells in atherogenesis is becoming apparent. Inflammation plays a central role in the pathogenesis of atherosclerosis. Cholesterol is a modifiable risk factor in atherosclerosis, but in many patients cholesterol levels are only mildly elevated. Those with high cholesterol levels often have elevated circulating monocyte and neutrophil counts. How cholesterol affects inflammatory cell levels was not well understood. Recent findings have provided new insight into the interaction among hematopoietic stem cells, cholesterol, and atherosclerosis. In mice, high cholesterol levels or inactivation of cholesterol efflux transporters have multiple effects on hematopoietic stem cells (HSPCs), including promoting their mobilization into the bloodstream, increasing proliferation, and differentiating HSPCs to the inflammatory monocytes and neutrophils that participate in atherosclerosis. Increased levels of interleukin-23 (IL-23) stimulate IL-17 production, resulting in granulocyte colony-stimulating factor (G-CSF) secretion, which subsequently leads to HSPC release into the bloodstream. Collectively, these findings clearly link elevated cholesterol levels to increased circulating HSPC levels and differentiation to inflammatory cells that participate in atherosclerosis. Seminal questions remain to be answered to understand how cholesterol affects HSPC-mobilizing cytokines and the role they play in atherosclerosis. Translation of findings in animal models to human subjects may include HSPCs as new targets for therapy to prevent or regress atherosclerosis in patients. PMID:24646491

Lang, Jennifer K; Cimato, Thomas R

2014-05-01

133

Essential Polyunsaturated Fatty Acids, Inflammation, Atherosclerosis and Cardiovascular Diseases  

Microsoft Academic Search

Atherosclerosis is the primary cause of coronary and cardiovascular diseases (CVD). Epidemiological studies have revealed\\u000a several important environmental (especially nutritional) factors associated with atherosclerosis. However, progress in defining\\u000a the cellular and molecular interactions involved has been hindered by the etiological complexity of the disease. Nevertheless,\\u000a our understanding of CVD has improved significantly over the past decade owing to the availability

Michel E. DE Lorgeril

134

Ambient Air Pollution and the Progression of Atherosclerosis in Adults  

Microsoft Academic Search

BackgroundCross-sectional studies suggest an association between exposure to ambient air pollution and atherosclerosis. We investigated the association between outdoor air quality and progression of subclinical atherosclerosis (common carotid artery intima-media thickness, CIMT).Methodology\\/Principal FindingsWe examined data from five double-blind randomized trials that assessed effects of various treatments on the change in CIMT. The trials were conducted in the Los Angeles area.

Nino Künzli; Michael Jerrett; Raquel Garcia-Esteban; Xavier Basagaña; Bernardo Beckermann; Frank Gilliland; Merce Medina; John Peters; Howard N. Hodis; Wendy J. Mack

2010-01-01

135

Atherosclerosis in CKD: differences from the general population  

Microsoft Academic Search

The prevalence of cardiovascular morbidity and mortality is higher in patients with chronic kidney disease (CKD)—especially those with end-stage renal disease—than in the general population. The contribution of atherosclerosis to cardiovascular disease in patients with CKD remains unclear. Researchers in the 1970s proposed that atherosclerosis was the main cause of cardiovascular disease in patients with CKD and that its progression,

Ziad A. Massy; Tilman B. Drüeke

2010-01-01

136

Helicobacter pylori-An Infectious Risk Factor for Atherosclerosis?  

PubMed

Accumulating evidence implicates Helicobacter pylori (H. pylori) infection in the pathogenesis of certain diseases localized outside the stomach, particularly those characterized by persistent and low-grade systematic inflammation. Recently, the role of H. pylori infection in the development of atherosclerosis and its clinical complications has received attention. Atherosclerosis is a high-cost disease, and acute events resulting from this condition rank first among morbidity and mortality statistics in most industrialized countries. Atherosclerosis is a multifactorial disorder, and traditional risk factors explain only 50% of its etiology. Therefore, identifying new risk factors for atherosclerosis is necessary. Serological studies indicate that chronic H. pylori infection, especially that with more virulent strains, may predispose patients to the onset of atherosclerosis and related adverse clinical events, and PCR studies have detected H. pylori DNA in atherosclerotic plaques, although this finding remains controversial. If this association were to be confirmed, its importance to public health would be substantial, as the eradication of H. pylori is more straightforward and less costly than the long-term treatment of other risk factors. This review investigates the potential relationship between H. pylori infection and atherosclerosis from both epidemiological and pathogenic perspectives and characterizes the potential mechanisms underlying this correlation. PMID:25342566

He, Cong; Yang, Zhen; Lu, Nong-Hua

2014-12-17

137

A major role for RCAN1 in atherosclerosis progression  

PubMed Central

Atherosclerosis is a complex inflammatory disease involving extensive vascular vessel remodelling and migration of vascular cells. As RCAN1 is implicated in cell migration, we investigated its contribution to atherosclerosis. We show RCAN1 induction in atherosclerotic human and mouse tissues. Rcan1 was expressed in lesional macrophages, endothelial cells and vascular smooth muscle cells and was induced by treatment of these cells with oxidized LDLs (oxLDLs). Rcan1 regulates CD36 expression and its genetic inactivation reduced atherosclerosis extension and severity in Apoe?/? mice. This effect was mechanistically linked to diminished oxLDL uptake, resistance to oxLDL-mediated inhibition of macrophage migration and increased lesional IL-10 and mannose receptor expression. Moreover, Apoe?/?Rcan1?/? macrophages expressed higher-than-Apoe?/? levels of anti-inflammatory markers. We previously showed that Rcan1 mediates aneurysm development and that its expression is not required in haematopoietic cells for this process. However, transplantation of Apoe?/?Rcan1?/? bone-marrow (BM) cells into Apoe?/? recipients confers atherosclerosis resistance. Our data define a major role for haematopoietic Rcan1 in atherosclerosis and suggest that therapies aimed at inhibiting RCAN1 expression or function might significantly reduce atherosclerosis burden. PMID:24127415

Méndez-Barbero, Nerea; Esteban, Vanesa; Villahoz, Silvia; Escolano, Amelia; Urso, Katia; Alfranca, Arantzazu; Rodríguez, Cristina; Sánchez, Susana A; Osawa, Tsuyoshi; Andrés, Vicente; Martínez-González, José; Minami, Takashi; Redondo, Juan Miguel; Campanero, Miguel R

2013-01-01

138

Aortic Atherosclerosis in Systemic Lupus Erythematosus  

PubMed Central

Aortic atherosclerosis (AoA) defined as intima-media thickening or plaques and aortic stiffness (AoS) also considered an atherosclerotic process and defined as decreased vessel distensibility (higher pulse pressure to achieve similar degree of vessel distension) are common in patients with SLE. Immune-mediated inflammation, thrombogenesis, traditional atherogenic factors, and therapy-related metabolic abnormalities are the main pathogenic factors of AoA and AoS. Pathology of AoA and AoS suggests an initial subclinical endothelialitis or vasculitis, which is exacerbated by thrombogenesis and atherogenic factors and ultimately resulting in AoA and AoS. Computed tomography (CT) for detection of arterial wall calcifications and arterial tonometry for detection of increased arterial pulse wave velocity are the most common diagnostic methods for detecting AoA and AoS, respectively. MRI may become a more applicable and accurate technique than CT. Although transesophageal echocardiography accurately detects earlier and advanced stages of AoA and AoS, it is semi-invasive and cannot be used as a screening method. Although imaging techniques demonstrate highly variable prevalence rates, on average about one third of adult SLE patients may have AoA or AoS. Age at SLE diagnosis; SLE duration; activity and damage; corticosteroid therapy; metabolic syndrome; chronic kidney disease; and mitral annular calcification are common independent predictors of AoA and AoS. Also, AoA and AoS are highly associated with carotid and coronary atherosclerosis. Earlier stages of AoA and AoS are usually subclinical. However, earlier stages of disease may be causally related or contribute to peripheral or cerebral embolism, pre-hypertension and hypertension, and increased left ventricular afterload resulting in left ventricular hypertrophy and diastolic dysfunction. Later stages of disease predisposes to visceral ischemia, aortic aneurysms and aortic dissection. Even earlier stages of AoA and AoS have been associated with increased cardiovascular and cerebrovascular morbidity and mortality of SLE patients. Aggressive non-steroidal immunosuppressive therapy and non-pharmacologic and pharmacologic interventions for control of atherogenic risk factors may prevent the development or progression of AoA and AoS and may decrease cardiovascular and cerebrovascular morbidity and mortality in SLE. PMID:25593786

Roldan, Paola C; Ratliff, Michelle; Snider, Richard; Macias, Leonardo; Rodriguez, Rodrigo; Sibbitt, Wilmer; Roldan, Carlos A.

2014-01-01

139

Study of Coronary Atherosclerosis by Modified American Heart Association Classification of Atherosclerosis-An Autopsy Study  

PubMed Central

Background: The study was designed to assess the atherosclerotic lesions in coronary arteries in cases subjected to autopsy to grade by applying Modified American Heart Association (AHA) classification, evaluate the atheromatous & vulnerable plaques to find out the to age and sex related prevalence of atherosclerosis in the semi-urban & urban population of Jamnagar, a district in Western India. Material & Methods: Autopsy was conducted on 264 cases whose age ranged from 8-79 years, by the conventional technique; heart was removed & dissected along the direction of blood flow. Microscopic assessment of the three main coronary arteries was done. Result: According to Modified AHA classification of atherosclerosis, maximum number of cases were in the 40-49 years age group. Intimal xanthoma was the most common type in all three coronary arteries. The number of males was 168(64%) and females was 96(36%). 59% males & 52% female were affected from atherosclerosis. An intermediate lesion was noted commonly in young individuals (10-39 years) and older individuals (40-79 years) were 46% & 41% respectively. Pathological Intimal thickening was more common in left anterior descending coronary artery compared to others. Thin fibrous cap atheroma was more common in Left circumflex artery than compared to Left anterior descending artery & Right coronary artery. Conclusion: The study highlights the impact of atherosclerotic lesions in the population of Jamnagar, a district in Gujarat state of Western India. The increased amount of intermediate atherosclerotic lesions found in the young population gives an indication that anti-atherogenic preventive measures and drastic dietary & life style modification need to be implemented in young individuals, this will help to prevent coronary artery disease from causing premature death that lead to huge financial burden on the economy and health sector of India. PMID:24392381

Bhanvadia, Viral M.; Desai, Nandini J.; Agarwal, Neeru M.

2013-01-01

140

Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis  

PubMed Central

Intestinal microbiota metabolism of choline/phosphatidylcholine produces trimethylamine (TMA), which is further metabolized to a proatherogenic species, trimethylamine-N-oxide (TMAO). Herein we demonstrate that intestinal microbiota metabolism of dietary L-carnitine, a trimethylamine abundant in red meat, also produces TMAO and accelerates atherosclerosis. Omnivorous subjects are shown to produce significantly more TMAO than vegans/vegetarians following ingestion of L-carnitine through a microbiota-dependent mechanism. Specific bacterial taxa in human feces are shown to associate with both plasma TMAO and dietary status. Plasma L-carnitine levels in subjects undergoing cardiac evaluation (n = 2,595) predict increased risks for both prevalent cardiovascular disease (CVD) and incident major adverse cardiac events (MI, stroke or death), but only among subjects with concurrently high TMAO levels. Chronic dietary L-carnitine supplementation in mice significantly altered cecal microbial composition, markedly enhanced synthesis of TMA/TMAO, and increased atherosclerosis, but not following suppression of intestinal microbiota. Dietary supplementation of TMAO, or either carnitine or choline in mice with intact intestinal microbiota, significantly reduced reverse cholesterol transport in vivo. Intestinal microbiota may thus participate in the well-established link between increased red meat consumption and CVD risk. PMID:23563705

Koeth, Robert A.; Wang, Zeneng; Levison, Bruce S.; Buffa, Jennifer A.; Org, Elin; Sheehy, Brendan T.; Britt, Earl B.; Fu, Xiaoming; Wu, Yuping; Li, Lin; Smith, Jonathan D.; DiDonato, Joseph A.; Chen, Jun; Li, Hongzhe; Wu, Gary D.; Lewis, James D.; Warrier, Manya; Brown, J. Mark; Krauss, Ronald M.; Tang, W. H. Wilson; Bushman, Frederic D.; Lusis, Aldons J.; Hazen, Stanley L.

2013-01-01

141

B Cells and Humoral Immunity in Atherosclerosis  

PubMed Central

Insights into the important contribution of inflammation and immune functions in the development and progression of atherosclerosis have greatly improved our understanding of this disease. Although the role of T cells has been extensively studied for decades, only recently has the role of B cells gained more attention. Recent studies have identified differential effects of different B-cell subsets and helped to clarify the still poorly understood mechanisms by which these act. B1 cells have been shown to prevent lesion formation, whereas B2 cells have been suggested to promote it. Natural IgM antibodies, mainly derived from B1 cells, have been shown to mediate atheroprotective effects, but the functional role of other immunoglobulin classes, particularly IgG, still remains elusive. In this review, we will focus on recent insights on the role of B cells and various immunoglobulin classes and how these may mediate their effects in atherosclerotic lesion formation. Moreover, we will highlight potential therapeutic approaches focusing on B-cell depletion that could be used to translate experimental evidence to human disease. PMID:24855199

Tsiantoulas, Dimitrios; Diehl, Cody J.; Witztum, Joseph L.; Binder, Christoph J.

2014-01-01

142

Molecular Imaging of Inflammation in Atherosclerosis  

PubMed Central

Acute rupture of vulnerable plaques frequently leads to myocardial infarction and stroke. Within the last decades, several cellular and molecular players have been identified that promote atherosclerotic lesion formation, maturation and plaque rupture. It is now widely recognized that inflammation of the vessel wall and distinct leukocyte subsets are involved throughout all phases of atherosclerotic lesion development. The mechanisms that render a stable plaque unstable and prone to rupture, however, remain unknown and the identification of the vulnerable plaque remains a major challenge in cardiovascular medicine. Imaging technologies used in the clinic offer minimal information about the underlying biology and potential risk for rupture. New imaging technologies are therefore being developed, and in the preclinical setting have enabled new and dynamic insights into the vessel wall for a better understanding of this complex disease. Molecular imaging has the potential to track biological processes, such as the activity of cellular and molecular biomarkers in vivo and over time. Similarly, novel imaging technologies specifically detect effects of therapies that aim to stabilize vulnerable plaques and silence vascular inflammation. Here we will review the potential of established and new molecular imaging technologies in the setting of atherosclerosis, and discuss the cumbersome steps required for translating molecular imaging approaches into the clinic. PMID:24312156

Wildgruber, Moritz; Swirski, Filip K.; Zernecke, Alma

2013-01-01

143

Oxidative stress in atherosclerosis and diabetes.  

PubMed

We measured the content of lipid peroxides in plasma LDL from patients with chronic CHD not accompanied by hypercholesterolemia; CHD and hypercholesterolemia; type 2 diabetes mellitus and decompensation of carbohydrate metabolism; and CHD, circulatory insufficiency, and type 2 diabetes mellitus (without hypercholesterolemia). The content of lipid peroxides in LDL isolated from blood plasma by differential ultracentrifugation in a density gradient was estimated by a highly specific method with modifications (reagent Fe(2+) xylene orange and triphenylphosphine as a reducing agent for organic peroxides). The content of lipid peroxides in LDL from patients was much higher than in controls (patients without coronary heart disease and diabetes). Hypercholesterolemia and diabetes can be considered as factors promoting LDL oxidation in vivo. Our results suggest that stimulation of lipid peroxidation in low-density lipoproteins during hypercholesterolemia and diabetes is associated with strong autooxidation of cholesterol and glucose during oxidative and carbonyl (aldehyde) stress, respectively. These data illustrate a possible mechanism of the progression of atherosclerosis in patients with diabetes mellitus. PMID:16254616

Lankin, V Z; Lisina, M O; Arzamastseva, N E; Konovalova, G G; Nedosugova, L V; Kaminnyi, A I; Tikhaze, A K; Ageev, F T; Kukharchuk, V V; Belenkov, Yu N

2005-07-01

144

Atherosclerosis, degenerative aortic stenosis and statins.  

PubMed

Aortic stenosis is the most common valvular heart disease among adult subjects in western countries The current treatment for aortic stenosis is aortic valve replacement. The possibility of a medical treatment that can slow the progression of aortic stenosis is very fascinating and statins have been tested to reduce the progression of degenerative aortic stenosis (DAS). The rationale for statin treatment in DAS has a deep pathophysiological substrate, in fact inflammation and lipid infiltration constitute the same histopathological pattern of both aortic stenosis and atherosclerosis and these two conditions have the same risk factors. Whether retrospective studies have shown some efficacy of statins in halting the progression of DAS, prospective trials have shown controversial results. A recently published large and randomized controlled trial SEAS found that statins have no significant effect on the progression of aortic stenosis, the ASTRONOMER, recently confirmed this data. The most plausible hypothesis is that coronary artery disease and DAS, have a common pathogenetic background and a distinct evolution due to different factors (mechanical stress, genetic factors, interaction between inflammatory cells and calcification mediators). Thus, treatment with statins is not recommended in patients with valvular aortic stenosis and without conventional indications to lipid-lowering treatment. PMID:20863278

Novo, Giuseppina; Fazio, Giovanni; Visconti, Claudia; Carità, Patrizia; Maira, Ermanno; Fattouch, Khalil; Novo, Salvatore

2011-01-01

145

Atherosclerosis: from biology to pharmacological treatment  

PubMed Central

A recent explosion in the amount of cardiovascular risk has swept across the globe. Primary prevention is the preferred method to lower cardiovascular risk. Lowering the prevalence of obesity is the most urgent matter, and is pleiotropic since it affects blood pressure, lipid profiles, glucose metabolism, inflammation, and atherothrombotic disease progression. Given the current obstacles, success of primary prevention remains uncertain. At the same time, the consequences of delay and inaction will inevitably be disastrous, and the sense of urgency mounts. Pathological and epidemiological data confirm that atherosclerosis begins in early childhood, and advances seamlessly and inexorably throughout life. Risk factors in childhood are similar to those in adults, and track between stages of life. When indicated, aggressive treatment should begin at the earliest indication, and be continued for many years. For those patients at intermediate risk according to global risk scores, C-reactive protein, coronary artery calcium, and carotid intima-media thickness are available for further stratification. Using statins for primary prevention is recommended by guidelines, is prevalent, but remains under prescribed. Statin drugs are unrivaled, evidence-based, major weapons to lower cardiovascular risk. Even when low density lipoprotein cholesterol targets are attained, over half of patients continue to have disease progression and clinical events. Though clinical evidence is incomplete, altering or raising the blood high density lipoprotein cholesterol level continues to be pursued. The aim of this review is to point out the attention of key aspects of vulnerable plaques regarding their pathogenesis and treatment. PMID:23097661

Riccioni, Graziano; Sblendorio, Valeriana

2012-01-01

146

Niemann-Pick C1 protects against atherosclerosis in mice via regulation of macrophage intracellular cholesterol trafficking.  

PubMed

Niemann-Pick C1 (NPC1) is a key participant in cellular cholesterol trafficking. Loss of NPC1 function leads to defective suppression of SREBP-dependent gene expression and failure to appropriately activate liver X receptor-mediated (LXR-mediated) pathways, ultimately resulting in intracellular cholesterol accumulation. To determine whether NPC1 contributes to regulation of macrophage sterol homeostasis in vivo, we examined the effect of NPC1 deletion in BM-derived cells on atherosclerotic lesion development in the Ldlr-/- mouse model of atherosclerosis. High-fat diet-fed chimeric Npc1-/- mice reconstituted with Ldlr-/-Npc1-/- macrophages exhibited accelerated atherosclerosis despite lower serum cholesterol compared with mice reconstituted with wild-type macrophages. The discordance between the low serum lipoprotein levels and the presence of aortic atherosclerosis suggested that intrinsic alterations in macrophage sterol metabolism in the chimeric Npc1-/- mice played a greater role in atherosclerotic lesion formation than did serum lipoprotein levels. Macrophages from chimeric Npc1-/- mice showed decreased synthesis of 27-hydroxycholesterol (27-HC), an endogenous LXR ligand; decreased expression of LXR-regulated cholesterol transporters; and impaired cholesterol efflux. Lower 27-HC levels were associated with elevated cholesterol oxidation products in macrophages and plasma of chimeric Npc1-/- mice and with increased oxidative stress. Our results demonstrate that NPC1 serves an atheroprotective role in mice through regulation of LXR-dependent cholesterol efflux and mitigation of cholesterol-induced oxidative stress in macrophages. PMID:18483620

Zhang, Jessie R; Coleman, Trey; Langmade, S Joshua; Scherrer, David E; Lane, Lindsay; Lanier, M Hunter; Feng, Chu; Sands, Mark S; Schaffer, Jean E; Semenkovich, Clay F; Ory, Daniel S

2008-06-01

147

Niemann-Pick C1 protects against atherosclerosis in mice via regulation of macrophage intracellular cholesterol trafficking  

PubMed Central

Niemann-Pick C1 (NPC1) is a key participant in cellular cholesterol trafficking. Loss of NPC1 function leads to defective suppression of SREBP-dependent gene expression and failure to appropriately activate liver X receptor–mediated (LXR-mediated) pathways, ultimately resulting in intracellular cholesterol accumulation. To determine whether NPC1 contributes to regulation of macrophage sterol homeostasis in vivo, we examined the effect of NPC1 deletion in BM-derived cells on atherosclerotic lesion development in the Ldlr–/– mouse model of atherosclerosis. High-fat diet–fed chimeric Npc1–/– mice reconstituted with Ldlr–/–Npc1–/– macrophages exhibited accelerated atherosclerosis despite lower serum cholesterol compared with mice reconstituted with wild-type macrophages. The discordance between the low serum lipoprotein levels and the presence of aortic atherosclerosis suggested that intrinsic alterations in macrophage sterol metabolism in the chimeric Npc1–/– mice played a greater role in atherosclerotic lesion formation than did serum lipoprotein levels. Macrophages from chimeric Npc1–/– mice showed decreased synthesis of 27-hydroxycholesterol (27-HC), an endogenous LXR ligand; decreased expression of LXR-regulated cholesterol transporters; and impaired cholesterol efflux. Lower 27-HC levels were associated with elevated cholesterol oxidation products in macrophages and plasma of chimeric Npc1–/– mice and with increased oxidative stress. Our results demonstrate that NPC1 serves an atheroprotective role in mice through regulation of LXR-dependent cholesterol efflux and mitigation of cholesterol-induced oxidative stress in macrophages. PMID:18483620

Zhang, Jessie R.; Coleman, Trey; Langmade, S. Joshua; Scherrer, David E.; Lane, Lindsay; Lanier, M. Hunter; Feng, Chu; Sands, Mark S.; Schaffer, Jean E.; Semenkovich, Clay F.; Ory, Daniel S.

2008-01-01

148

Diverse Roles of Macrophages in Atherosclerosis: From Inflammatory Biology to Biomarker Discovery  

PubMed Central

Cardiovascular disease, a leading cause of mortality in developed countries, is mainly caused by atherosclerosis, a chronic inflammatory disease. Macrophages, which differentiate from monocytes that are recruited from the blood, account for the majority of leukocytes in atherosclerotic plaques. Apoptosis and the suppressed clearance of apoptotic macrophages (efferocytosis) are associated with vulnerable plaques that are prone to rupture, leading to thrombosis. Based on the central functions of macrophages in atherogenesis, cytokines, chemokines, enzymes, or microRNAs related to or produced by macrophages have become important clinical prognostic or diagnostic biomarkers. This paper discusses the impact of monocyte-derived macrophages in early atherogenesis and advanced disease. The role and possible future development of macrophage inflammatory biomarkers are also described. PMID:22577254

Gui, Ting; Shimokado, Aiko; Sun, Yujing; Akasaka, Takashi; Muragaki, Yasuteru

2012-01-01

149

Suppression of adrenal ?arrestin1-dependent aldosterone production by ARBs: head-to-head comparison.  

PubMed

The known angiotensin II (AngII) physiological effect of aldosterone synthesis and secretion is mediated by either Gq/11 proteins or ?arrestin1 (?arr1), both of which can couple to its type 1 receptors (AT1Rs), present in adrenocortical zona glomerulosa (AZG) cell membranes. In the present study, we examined the relative potencies of all the currently used in the clinic AT1R antagonist drugs (angiotensin receptor blockers, ARBs, or sartans) at preventing activation of these two signaling mediators (G proteins and ?arrs) at the AngII-bound AT1R and, consequently, at suppression of aldosterone in vitro. All ARBs were found to be potent inhibitors of G protein activation at the AT1R. However, candesartan and valsartan were the most potent at blocking AngII-induced ?arr activation at this receptor, among the tetrazolo-biphenyl-methyl derivatives, translating into excellent efficacies at aldosterone suppression in H295R cells. Conversely, irbesartan and losartan were largely G protein-selective inhibitors at the AT1R, with very low potency towards ?arr inhibition. As a result, they were very weak suppressors of ?arr1-dependent aldosterone production in H295R cells. These findings provide important pharmacological insights into the drug class of ARBs and medicinal chemistry insights for future drug development in the field of AngII antagonism. PMID:25631300

Dabul, Samalia; Bathgate-Siryk, Ashley; Valero, Thairy Reyes; Jafferjee, Malika; Sturchler, Emmanuel; McDonald, Patricia; Koch, Walter J; Lymperopoulos, Anastasios

2015-01-01

150

Suppression of adrenal ?arrestin1-dependent aldosterone production by ARBs: head-to-head comparison  

PubMed Central

The known angiotensin II (AngII) physiological effect of aldosterone synthesis and secretion is mediated by either Gq/11 proteins or ?arrestin1 (?arr1), both of which can couple to its type 1 receptors (AT1Rs), present in adrenocortical zona glomerulosa (AZG) cell membranes. In the present study, we examined the relative potencies of all the currently used in the clinic AT1R antagonist drugs (angiotensin receptor blockers, ARBs, or sartans) at preventing activation of these two signaling mediators (G proteins and ?arrs) at the AngII-bound AT1R and, consequently, at suppression of aldosterone in vitro. All ARBs were found to be potent inhibitors of G protein activation at the AT1R. However, candesartan and valsartan were the most potent at blocking AngII-induced ?arr activation at this receptor, among the tetrazolo-biphenyl-methyl derivatives, translating into excellent efficacies at aldosterone suppression in H295R cells. Conversely, irbesartan and losartan were largely G protein-selective inhibitors at the AT1R, with very low potency towards ?arr inhibition. As a result, they were very weak suppressors of ?arr1-dependent aldosterone production in H295R cells. These findings provide important pharmacological insights into the drug class of ARBs and medicinal chemistry insights for future drug development in the field of AngII antagonism. PMID:25631300

Dabul, Samalia; Bathgate-Siryk, Ashley; Valero, Thairy Reyes; Jafferjee, Malika; Sturchler, Emmanuel; McDonald, Patricia; Koch, Walter J.; Lymperopoulos, Anastasios

2015-01-01

151

Anti-diabetic atherosclerosis effect of Prunella vulgaris in db/db mice with type 2 diabetes.  

PubMed

Diabetes mellitus is the leading cause of vascular complications such as atherosclerosis. This study was designed to investigate whether Prunella vulgaris (APV) would inhibit diabetic atherosclerosis in db/db mice with type 2 diabetes. The db/db mice were treated with high fat/high cholesterol (HFHC) diet and an aqueous extract of APV (100 and 200 mg/kg/day) for eight weeks to examine the long-term effect on metabolic abnormalities and diabetic atherosclerosis. APV treatment markedly lowered blood glucose and systolic blood pressure. The db/db mice experienced an increase in blood urea nitrogen as well as a decrease of creatinine clearance, the latter of which was restored by treatment with APV. Treatment with APV markedly decreased total plasma cholesterol, triglyceride, and LDL-cholesterol and also increased the HDL-cholesterol. In addition, malondialdehyde and TGF-?1 were decreased by treatment of APV. On the other hand, total NO level was decreased in db/db mice. However, the NO level was increased by treatment with APV, suggesting an association with vascular dysfunction. Vascular relaxation of aortic rings by acetylcholine or SNP-inducement was ameliorated by APV in a dose-dependent manner. Damage of vascular intima and hypertrophic of media were observed in db/db mice; however its dysfunction was improved by the treatment of APV. APV treatment significantly reduced the aortic expressions of ICAM-1, VCAM-1, ET-1, and nitrotyrosine. Furthermore, expression of eNOS in aortic was remarkably increased by APV treatment. Taken together, APV suppressed hyperglycemia and diabetic vascular dysfunction in HFHC diet-db/db mice. The present data suggest that Prunella vulgaris may prevent development of diabetic atherosclerosis. PMID:22928826

Hwang, Sun Mi; Kim, Jin Sook; Lee, Yun Jung; Yoon, Jung Joo; Lee, So Min; Kang, Dae Gill; Lee, Ho Sub

2012-01-01

152

Vascular respiratory uncoupling increases blood pressure and atherosclerosis.  

PubMed

The observations that atherosclerosis often occurs in non-smokers without elevated levels of low-density lipoprotein cholesterol, and that most atherosclerosis loci so far identified in mice do not affect systemic risk factors associated with atherosclerosis, suggest that as-yet-unidentified mechanisms must contribute to vascular disease. Arterial walls undergo regional disturbances of metabolism that include the uncoupling of respiration and oxidative phosphorylation, a process that occurs to some extent in all cells and may be characteristic of blood vessels being predisposed to the development of atherosclerosis. To test the hypothesis that inefficient metabolism in blood vessels promotes vascular disease, we generated mice with doxycycline-inducible expression of uncoupling protein-1 (UCP1) in the artery wall. Here we show that UCP1 expression in aortic smooth muscle cells causes hypertension and increases dietary atherosclerosis without affecting cholesterol levels. UCP1 expression also increases superoxide production and decreases the availability of nitric oxide, evidence of oxidative stress. These results provide proof of principle that inefficient metabolism in blood vessels can cause vascular disease. PMID:15917810

Bernal-Mizrachi, Carlos; Gates, Allison C; Weng, Sherry; Imamura, Takuji; Knutsen, Russell H; DeSantis, Pascual; Coleman, Trey; Townsend, R Reid; Muglia, Louis J; Semenkovich, Clay F

2005-05-26

153

Antigen-Induced Immunomodulation in the Pathogenesis of Atherosclerosis  

PubMed Central

Atherosclerosis is a chronic inflammatory disorder characterised by the accumulation of monocytes/macrophages, smooth muscle cells, and lymphocytes within the arterial wall in response to the release of proinflammatory molecules. Such accumulation results in the formation of the atherosclerotic plaque, which would eventually evolve to complications such as total artery occlusion, rupture, calcification, or aneurysm. Although the molecular mechanism responsible for the development of atherosclerosis is not completely understood, it is clear that the immune system plays a key role in the development of the atherosclerotic plaque and in its complications. There are multiple antigenic stimuli that have been associated with the pathogenesis of atherosclerosis. Most of these stimuli come from modified self-molecules such as oxidised low-density lipoproteins (oxLDLs), beta2glycoprotein1 (?2GP1), lipoprotein a (LP(a)), heat shock proteins (HSPs), and protein components of the extracellular matrix such as collagen and fibrinogen in the form of advanced glycation-end (AGE) products. In addition, several foreign antigens including bacteria such as Porphyromonas gingivalis and Chlamydia pneumoniae and viruses such as enterovirus and cytomegalovirus have been associated with atherosclerosis as potentially causative or bystander participants, adding another level of complexity to the analysis of the pathophysiology of atherosclerosis. The present review summarises the most important scientific findings published within the last two decades on the importance of antigens, antigen stimulation, and adaptive immune responses in the development of atherosclerotic plaques. PMID:18551190

Milioti, Natalia; Bermudez-Fajardo, Alexandra; Penichet, Manuel L.; Oviedo-Orta, Ernesto

2008-01-01

154

[Cyclooxygenase-2: a new therapeutic target in atherosclerosis?].  

PubMed

It is now widely accepted that atherosclerosis is a complex chronic inflammatory disorder of the arterial tree associated with several risk factors. From the initial phases to eventual rupture of vulnerable atherosclerotic plaques, a low-grade inflammation, also termed microinflammation, appears to play a key pathogenetic role. Systemic inflammatory markers (C reactive protein, cytokines adhesion molecules) also play a role in this process. Experimental and clinical evidence suggests that cyclooxygenase-2 (COX-2), an enzyme which catalyzes the generation of prostaglandins from arachidonic acid, also contributes to lesion formation. Recent reports by our group have demonstrated increased monocyte COX-2 activity and the production of prostaglandin E2 in relation to cardiovascular risk factors and subclinical atherosclerosis in asymptomatic subjects. Our findings support the notion that the COX-2/prostaglandin E2 axis may have a role, raising the question as to whether its selective inhibition might be an attractive therapeutic target in atherosclerosis. COX-2 inhibitors, collectively called "coxibs" (celecoxib, rofecoxib, valdecoxib, lumiracoxib, etc), held a promise as anti-inflammatory drugs without the some of the side effects of aspirin or non steroidal antiinflammatory agents. However, clinical studies raise several clinically relevant questions as to their beneficial role in atherosclerosis prevention, because of increased thrombogenicity and cardiovascular risk, and therefore coxibs should be restricted in atherosclerosis-prone patients. PMID:16792983

Páramo, José A; Beloqui, Oscar; Orbe, Josune

2006-05-27

155

G Protein-coupled Estrogen Receptor Protects from Atherosclerosis.  

PubMed

Coronary atherosclerosis and myocardial infarction in postmenopausal women have been linked to inflammation and reduced nitric oxide (NO) formation. Natural estrogen exerts protective effects on both processes, yet also displays uterotrophic activity. Here, we used genetic and pharmacologic approaches to investigate the role of the G protein-coupled estrogen receptor (GPER) in atherosclerosis. In ovary-intact mice, deletion of gper increased atherosclerosis progression, total and LDL cholesterol levels and inflammation while reducing vascular NO bioactivity, effects that were in some cases aggravated by surgical menopause. In human endothelial cells, GPER was expressed on intracellular membranes and mediated eNOS activation and NO formation, partially accounting for estrogen-mediated effects. Chronic treatment with G-1, a synthetic, highly selective small molecule agonist of GPER, reduced postmenopausal atherosclerosis and inflammation without uterotrophic effects. In summary, this study reveals an atheroprotective function of GPER and introduces selective GPER activation as a novel therapeutic approach to inhibit postmenopausal atherosclerosis and inflammation in the absence of uterotrophic activity. PMID:25532911

Meyer, Matthias R; Fredette, Natalie C; Howard, Tamara A; Hu, Chelin; Ramesh, Chinnasamy; Daniel, Christoph; Amann, Kerstin; Arterburn, Jeffrey B; Barton, Matthias; Prossnitz, Eric R

2014-01-01

156

Contrasting Roles of Different Endoglin Forms in Atherosclerosis  

PubMed Central

Endoglin (also known as CD105 or TGF-? type III receptor) is a co-receptor involved in TGF-? signaling. In atherosclerosis, TGF-? signaling is crucial in regulating disease progression owing to its anti-inflammatory effects as well as its inhibitory effects on smooth muscle cell proliferation and migration. Endoglin is a regulator of TGF-? signaling, but its role in atherosclerosis has yet to be defined. This review focuses on the roles of the various forms of endoglin in atherosclerosis. The expression of the two isoforms of endoglin (long-form and short-form) is increased in atherosclerotic lesions, and the expression of the soluble forms of endoglin is upregulated in sera of patients with hypercholesterolemia and atherosclerosis. Interestingly, long-form endoglin shows an atheroprotective effect via the induction of eNOS expression, while short-form and soluble endoglin enhance atherogenesis by inhibiting eNOS expression and TGF-? signaling. This review summarizes evidence suggesting that the different forms of endoglin have distinct roles in atherosclerosis. PMID:25360074

Jang, Young-Saeng

2014-01-01

157

Contrasting roles of different endoglin forms in atherosclerosis.  

PubMed

Endoglin (also known as CD105 or TGF-? type III receptor) is a co-receptor involved in TGF-? signaling. In atherosclerosis, TGF-? signaling is crucial in regulating disease progression owing to its anti-inflammatory effects as well as its inhibitory effects on smooth muscle cell proliferation and migration. Endoglin is a regulator of TGF-? signaling, but its role in atherosclerosis has yet to be defined. This review focuses on the roles of the various forms of endoglin in atherosclerosis. The expression of the two isoforms of endoglin (long-form and short-form) is increased in atherosclerotic lesions, and the expression of the soluble forms of endoglin is upregulated in sera of patients with hypercholesterolemia and atherosclerosis. Interestingly, long-form endoglin shows an atheroprotective effect via the induction of eNOS expression, while short-form and soluble endoglin enhance atherogenesis by inhibiting eNOS expression and TGF-? signaling. This review summarizes evidence suggesting that the different forms of endoglin have distinct roles in atherosclerosis. PMID:25360074

Jang, Young-Saeng; Choi, In-Hong

2014-10-01

158

G Protein-coupled Estrogen Receptor Protects from Atherosclerosis  

PubMed Central

Coronary atherosclerosis and myocardial infarction in postmenopausal women have been linked to inflammation and reduced nitric oxide (NO) formation. Natural estrogen exerts protective effects on both processes, yet also displays uterotrophic activity. Here, we used genetic and pharmacologic approaches to investigate the role of the G protein-coupled estrogen receptor (GPER) in atherosclerosis. In ovary-intact mice, deletion of gper increased atherosclerosis progression, total and LDL cholesterol levels and inflammation while reducing vascular NO bioactivity, effects that were in some cases aggravated by surgical menopause. In human endothelial cells, GPER was expressed on intracellular membranes and mediated eNOS activation and NO formation, partially accounting for estrogen-mediated effects. Chronic treatment with G-1, a synthetic, highly selective small molecule agonist of GPER, reduced postmenopausal atherosclerosis and inflammation without uterotrophic effects. In summary, this study reveals an atheroprotective function of GPER and introduces selective GPER activation as a novel therapeutic approach to inhibit postmenopausal atherosclerosis and inflammation in the absence of uterotrophic activity. PMID:25532911

Meyer, Matthias R.; Fredette, Natalie C.; Howard, Tamara A.; Hu, Chelin; Ramesh, Chinnasamy; Daniel, Christoph; Amann, Kerstin; Arterburn, Jeffrey B.; Barton, Matthias; Prossnitz, Eric R.

2014-01-01

159

Endogenous hydrogen sulfide is involved in the pathogenesis of atherosclerosis  

SciTech Connect

Atherosclerosis is a chronic, complex, and progressive pathological process in large and medium sized arteries. The exact mechanism of this process remains unclear. Hydrogen sulfide (H{sub 2}S), a novel gasotransmitter, was confirmed as playing a major role in the pathogenesis of many cardiovascular diseases. It plays a role in vascular smooth muscle cell (VSMC) proliferation and apoptosis, participates in the progress of hyperhomocysteinemia (HHCY), inhibits atherogenic modification of LDL, interferes with vascular calcification, intervenes with platelet function, and there are interactions between H{sub 2}S and inflammatory processes. The role of H{sub 2}S in atherosclerotic pathogenesis highlights the mysteries of atherosclerosis and inspires the search for innovative therapeutic strategies. Here, we review the studies to date that have considered the role of H{sub 2}S in atherosclerosis.

Qiao, Wang [Department of Pediatrics, Peking University First Hospital, Beijing 100034 (China)] [Department of Pediatrics, Peking University First Hospital, Beijing 100034 (China); Chaoshu, Tang [Department of Physiology and Pathophysiology, Health Sciences Center, Peking University, Beijing 100034 (China) [Department of Physiology and Pathophysiology, Health Sciences Center, Peking University, Beijing 100034 (China); Key Laboratory of Molecular Cardiovascular Medicine, Ministry of Education (China); Hongfang, Jin, E-mail: jinhongfang51@126.com [Department of Pediatrics, Peking University First Hospital, Beijing 100034 (China)] [Department of Pediatrics, Peking University First Hospital, Beijing 100034 (China); Junbao, Du, E-mail: junbaodu1@126.com [Department of Pediatrics, Peking University First Hospital, Beijing 100034 (China)] [Department of Pediatrics, Peking University First Hospital, Beijing 100034 (China)

2010-05-28

160

Adipokines as a novel link between obesity and atherosclerosis  

PubMed Central

The traditional perception of adipose tissue as a storage organ of fatty acids has been replaced by the notion that adipose tissue is an active endocrine organ, releasing various adipokines that are involved in the pathogenesis of obesity-related metabolic disturbances. Obesity is a well-known risk factor for atherosclerosis, and accelerates atherosclerosis by many mechanisms such as increase in blood pressure and glucose level, abnormal lipid profiles, and systemic inflammation. Furthermore, growing evidence suggests that some adipokines directly mediate the process of atherosclerosis by influencing the function of endothelial cells, arterial smooth muscle cells, and macrophages in vessel walls. In obese patients, the secretion and coordination of such adipokines is abnormal, and the secretion of specific adipokines increases or decreases. Accordingly, the discovery of new adipokines and elucidation of their functions might lead to a new treatment strategy for metabolic disorders related to obesity, including cardiovascular diseases. PMID:24936256

Yoo, Hye Jin; Choi, Kyung Mook

2014-01-01

161

Cell-derived microparticles in atherosclerosis: biomarkers and targets for pharmacological modulation?  

E-print Network

Cell-derived microparticles in atherosclerosis: biomarkers and targets for pharmacological, the pathophysiological properties of MPs may contribute to atherosclerosis development. In addition, pharmacological com in thrombosis · Pharmacological modulation of plasma MP concentrations - Statins - Anti-oxidants - Peroxisome

Paris-Sud XI, Université de

162

SUSCEPTIBILITY TO ATHEROSCLEROSIS IN AORTAS AND CORONARY ARTERIES OF SWINE WITH VON WILLEBRAND'S DISEASE  

EPA Science Inventory

The development of coronary and aortic atherosclerosis was determined after balloon catheter injury of coronary arteries and administration of an atherogenic diet in normal pigs and pigs that were homozygous and heterozygous for von Willebrand's disease. Coronary atherosclerosis ...

163

Celastrol may have an anti-atherosclerosis effect in a rabbit experimental carotid atherosclerosis model  

PubMed Central

Background: Celastrol may have an anti-atherosclerosis effect. This study aimed to investigate if celastrol had an anti-AS effect using a rabbit experimental carotid atherosclerosis model. Methods: Forty male Japanese white rabbits were divided into the sham group (normal diet), the model group (high fat diet), the group treated with celastrol (high fat diet) and the group treated with atorvastatin (high fat diet) randomly. The rabbits fed a high fat diet underwent balloon injury of the right common carotid artery and were treated with dimethyl sulfoxide (DMSO) (the model group, 3.5 ml/kg/d), celastrol and its dissolvent DMSO (the celastrol group, 1 mg/kg/d and 3.5 ml/kg/d) and atorvastatin and its dissolvent DMSO (the atorvastatin group, 2.5 mg/kg/d and 3.5 ml/kg/d) for 12 weeks by gavage. Results: The ratio of the plaque area and the arterial wall cross-section area in the celastrol group was significantly less than the model group (P < 0.001), and there was no significant difference compared with the atorvastatin group. The serum level of LDL-C of the celastrol group was significantly lower than the model group (P = 0.014), and there was no significant difference compared with the atorvastatin group. The expression of VEGF in the celastrol group was significantly less compared with the model group (P = 0.014), whereas the expression of VEGF in the atorvastatin group and the model group showed no significant differences. Conclusion: Our findings suggest that celastrol effectively reduced the plaque ratio, decreased the serum levels of LDL and downregulated the expression of VEGF, suggesting an anti-AS effect of celastrol. PMID:25126165

Zhu, Feng; Li, Cai; Jin, Xiao-Ping; Weng, Shou-Xiang; Fan, Li-Long; Zheng, Zhou; Li, Wei-Ling; Wang, Feng; Wang, Wan-Fen; Hu, Xiao-Fei; Lv, Chen-Ling; Liu, Peng

2014-01-01

164

Human genetic evidence for involvement of CD137 in atherosclerosis.  

PubMed

Atherosclerosis is an inflammatory disease and the main cause of cardiovascular disease. Inflammation promotes plaque instability and clinical disease, such as myocardial infarction, stroke and peripheral vascular disease. Subclinical atherosclerosis begins with thickening of the arterial intimal layer, and increased intima-media thickness (IMT) in the carotid artery is a widely used measurement of subclinical atherosclerosis. Activation of CD137 (tumor necrosis factor receptor super family 9) promotes inflammation and disease development in murine atherosclerosis. CD137 is expressed in human atherosclerosis, but its role is largely unknown. This study uses a genetic approach to investigate CD137 in human atherosclerotic disease. In publicly available data on genotype and gene expression from the HapMap project, the minor T allele of rs2453021, a single nucleotide polymorphism in CD137, was significantly associated with CD137 gene expression. In the PROCARDIS and Wellcome Trust Case Control Consortium (WTCCC) cohorts of 13,029 cases and controls, no significant association was detected between the minor T allele of rs2453021 and risk for coronary artery disease or myocardial infarction. However, in the IMPROVE multicenter study of 3,418 individuals, the minor T allele of rs2453021 was associated with increased IMT of the common carotid artery (CCA), as measured by ultrasonography, with presence of plaque in CCA and with increased incidence of adverse noncardiac vascular events. Taken together, this study shows that the minor T allele of rs2453021 is associated with increased IMT in the CCA and increased risk of incident noncardiac vascular events, thus providing the first human genetic evidence for involvement of CD137 in atherosclerosis. PMID:25032953

Söderström, Leif Å; Gertow, Karl; Folkersen, Lasse; Sabater-Lleal, Maria; Sundman, Eva; Sheikine, Yuri; Goel, Anuj; Baldassarre, Damiano; Humphries, Steve E; de Faire, Ulf; Watkins, Hugh; Tremoli, Elena; Veglia, Fabrizio; Hamsten, Anders; Hansson, Göran K; Olofsson, Peder S

2014-01-01

165

"Therapies Targeting Innate Immunity for Fighting Inflammation in Atherosclerosis"  

PubMed

Atherosclerosis is a smoldering disease of the vasculature that can lead to the occlusion of the arteries, resulting in ischemia of the heart and brain. For many years, the asserted underlying mechanism of atherosclerosis, supported by its epidemiology, was based on the "cholesterol hypothesis" that people with high blood cholesterol are at higher risk of developing cardiovascular disease. This hypothesis instigated a vigorous search for treatment that yielded the generation of statins, which specifically reduce LDL cholesterol. Since then, statins have revolutionized the way people are treated for the prevention of atherosclerosis. Nonetheless, despite this potent class of drugs, cardiovascular disease continues to be the leading cause of death in many parts of the world, suggesting that additional mechanisms are involved in disease pathogenesis. Intensive research has revealed that the atherosclerotic plaque is enriched with leukocytes, and that macrophages constitute the majority of immune cells in the lesion. Monocytes/macrophages are now recognized as the prime immune cells involved in the development of atherosclerosis and are implicated to affect the size, composition and vulnerability of the atherosclerotic plaque. While many of the macrophage-derived pro-inflammatory mechanisms associated with atherogenesis have been characterized, such as cell adhesion, cytokine production and protease secretion, there is a dearth of drugs that specifically target innate immunity for treating patients with atherosclerosis. This review presents pre-clinical studies, and in most cases following clinical trials with antagonists and agonists that have been designed to counteract inflammation in atherosclerosis and associated diseases, highlighting targets expressed predominantly in monocytes. PMID:25312734

Mendel, Itzhak; Yacov, Niva; Harats, Dror; Breitbart, Eyal

2014-10-13

166

Human Genetic Evidence for Involvement of CD137 in Atherosclerosis  

PubMed Central

Atherosclerosis is an inflammatory disease and the main cause of cardiovascular disease. Inflammation promotes plaque instability and clinical disease, such as myocardial infarction, stroke and peripheral vascular disease. Subclinical atherosclerosis begins with thickening of the arterial intimal layer, and increased intima-media thickness (IMT) in the carotid artery is a widely used measurement of subclinical atherosclerosis. Activation of CD137 (tumor necrosis factor receptor super family 9) promotes inflammation and disease development in murine atherosclerosis. CD137 is expressed in human atherosclerosis, but its role is largely unknown. This study uses a genetic approach to investigate CD137 in human atherosclerotic disease. In publicly available data on genotype and gene expression from the HapMap project, the minor T allele of rs2453021, a single nucleotide polymorphism in CD137, was significantly associated with CD137 gene expression. In the PROCARDIS and Wellcome Trust Case Control Consortium (WTCCC) cohorts of 13,029 cases and controls, no significant association was detected between the minor T allele of rs2453021 and risk for coronary artery disease or myocardial infarction. However, in the IMPROVE multicenter study of 3,418 individuals, the minor T allele of rs2453021 was associated with increased IMT of the common carotid artery (CCA), as measured by ultrasonography, with presence of plaque in CCA and with increased incidence of adverse noncardiac vascular events. Taken together, this study shows that the minor T allele of rs2453021 is associated with increased IMT in the CCA and increased risk of incident noncardiac vascular events, thus providing the first human genetic evidence for involvement of CD137 in atherosclerosis. PMID:25032953

Söderström, Leif Å; Gertow, Karl; Folkersen, Lasse; Sabater-Lleal, Maria; Sundman, Eva; Sheikine, Yuri; Goel, Anuj; Baldassarre, Damiano; Humphries, Steve E; de Faire, Ulf; Watkins, Hugh; Tremoli, Elena; Veglia, Fabrizio; Hamsten, Anders; Hansson, Göran K; Olofsson, Peder S

2014-01-01

167

What can ancient mummies teach us about atherosclerosis?  

PubMed

Ancient mummies have captivated a wide variety of audiences for centuries. In order to better understand the evolution and causative features of atherosclerosis, the Horus group is applying modern scientific methods to study ancient mummies. We have used CT scanning to detect calcification in arteries as an indication of the presence of atherosclerosis, and are correlating these results with cultural and lifestyle features of various populations of ancient people as represented by their ancient mummified remains. We are also pursuing related studies of ancient DNA to define genotypes associated with atherosclerotic phenotypes. PMID:25106086

Wann, Samuel; Thomas, Gregory S

2014-10-01

168

Leukocyte behavior in atherosclerosis, myocardial infarction, and heart failure  

PubMed Central

Cardiovascular diseases claim more lives worldwide than any other. Etiologically, the dominant trajectory involves atherosclerosis, a chronic inflammatory process of lipid-rich lesion growth in the vascular wall that can cause life-threatening myocardial infarction (MI). Those who survive MI can develop congestive heart failure, a chronic condition of inadequate pump activity that is frequently fatal. Leukocytes – white blood cells – are important participants at the various stages of cardiovascular disease progression and complication. This review will discuss leukocyte function in atherosclerosis, myocardial infarction, and heart failure. PMID:23307733

Swirski, Filip K.; Nahrendorf, Matthias

2013-01-01

169

Lipid Rafts and Redox Regulation of Cellular Signaling in Cholesterol Induced Atherosclerosis  

PubMed Central

Redox mediated signaling mechanisms play crucial roles in the pathogenesis of several cardiovascular diseases. Atherosclerosis is one of the most important disorders induced mainly by hypercholesterolemia. Oxidation products and related signaling mechanisms are found within the characteristic biomarkers of atherosclerosis. Several studies have shown that redox signaling via lipid rafts play a significant role in the regulation of pathogenesis of many diseases including atherosclerosis. This review attempts to summarize redox signaling and lipid rafts in hypercholesterolemia induced atherosclerosis. PMID:22043207

Catalgol, Betul; Kartal Ozer, Nesrin

2010-01-01

170

IRF5 Deficiency Ameliorates Lupus but Promotes Atherosclerosis and Metabolic Dysfunction in a Mouse Model of Lupus-Associated Atherosclerosis.  

PubMed

Premature atherosclerosis is a severe complication of lupus and other systemic autoimmune disorders. Gain-of-function polymorphisms in IFN regulatory factor 5 (IRF5) are associated with an increased risk of developing lupus, and IRF5 deficiency in lupus mouse models ameliorates disease. However, whether IRF5 deficiency also protects against atherosclerosis development in lupus is not known. In this study, we addressed this question using the gld.apoE(-/-) mouse model. IRF5 deficiency markedly reduced lupus disease severity. Unexpectedly, despite the reduction in systemic immune activation, IRF5-deficient mice developed increased atherosclerosis and also exhibited metabolic dysregulation characterized by hyperlipidemia, increased adiposity, and insulin resistance. Levels of the atheroprotective cytokine IL-10 were reduced in aortae of IRF5-deficient mice, and in vitro studies demonstrated that IRF5 is required for IL-10 production downstream of TLR7 and TLR9 signaling in multiple immune cell types. Chimera studies showed that IRF5 deficiency in bone marrow-derived cells prevents lupus development and contributes in part to the increased atherosclerosis. Notably, IRF5 deficiency in non-bone marrow-derived cells also contributes to the increased atherosclerosis through the generation of hyperlipidemia and increased adiposity. Together, our results reveal a protective role for IRF5 in lupus-associated atherosclerosis that is mediated through the effects of IRF5 in both immune and nonimmune cells. These findings have implications for the proposed targeting of IRF5 in the treatment of autoimmune disease as global IRF5 inhibition may exacerbate cardiovascular disease in these patients. PMID:25595782

Watkins, Amanda A; Yasuda, Kei; Wilson, Gabriella E; Aprahamian, Tamar; Xie, Yao; Maganto-Garcia, Elena; Shukla, Prachi; Oberlander, Lillian; Laskow, Bari; Menn-Josephy, Hanni; Wu, Yuanyuan; Duffau, Pierre; Fried, Susan K; Lichtman, Andrew H; Bonegio, Ramon G; Rifkin, Ian R

2015-02-15

171

Vitamin E suppresses isoprostane generation in vivo and reduces atherosclerosis in ApoE-deficient mice  

Microsoft Academic Search

Oxidative modification of low density lipoprotein (LDL) has been implicated in atherogenesis. Evidence consistent with this hypothesis includes the presence of oxidized lipids in atherosclerotic lesions, the newly discovered biological properties conferred on LDL by oxidation and the acceleration of atherogenesis by in vivo delivery of the gene for 15-lipoxygenase, an oxidizing enzyme present in atherosclerotic lesions. However, it is

Domenico Praticò; Rajendra K. Tangirala; Daniel J. Rader; Joshua Rokach; Garret A. FitzGerald

1998-01-01

172

The role of shear stress in the pathogenesis of atherosclerosis  

Microsoft Academic Search

Although the pathobiology of atherosclerosis is a complex multifactorial process, blood flow-induced shear stress has emerged as an essential feature of atherogenesis. This fluid drag force acting on the vessel wall is mechanotransduced into a biochemical signal that results in changes in vascular behavior. Maintenance of a physiologic, laminar shear stress is known to be crucial for normal vascular functioning,

Kristopher S Cunningham; Avrum I Gotlieb

2005-01-01

173

Cell signaling by reactive nitrogen and oxygen species in atherosclerosis  

NASA Technical Reports Server (NTRS)

The production of reactive oxygen and nitrogen species has been implicated in atherosclerosis principally as means of damaging low-density lipoprotein that in turn initiates the accumulation of cholesterol in macrophages. The diversity of novel oxidative modifications to lipids and proteins recently identified in atherosclerotic lesions has revealed surprising complexity in the mechanisms of oxidative damage and their potential role in atherosclerosis. Oxidative or nitrosative stress does not completely consume intracellular antioxidants leading to cell death as previously thought. Rather, oxidative and nitrosative stress have a more subtle impact on the atherogenic process by modulating intracellular signaling pathways in vascular tissues to affect inflammatory cell adhesion, migration, proliferation, and differentiation. Furthermore, cellular responses can affect the production of nitric oxide, which in turn can strongly influence the nature of oxidative modifications occurring in atherosclerosis. The dynamic interactions between endogenous low concentrations of oxidants or reactive nitrogen species with intracellular signaling pathways may have a general role in processes affecting wound healing to apoptosis, which can provide novel insights into the pathogenesis of atherosclerosis.

Patel, R. P.; Moellering, D.; Murphy-Ullrich, J.; Jo, H.; Beckman, J. S.; Darley-Usmar, V. M.

2000-01-01

174

CD36, a scavenger receptor implicated in atherosclerosis  

PubMed Central

CD36 is a membrane glycoprotein that is present on various types of cells, including monocytes, macrophages, microvascular endothelial cells, adipocytes and platelets. Macrophage CD36 participates in atherosclerotic arterial lesion formation through its interaction with oxidized low-density lipoprotein (oxLDL), which triggers signaling cascades for inflammatory responses. CD36 functions in oxLDL uptake and foam cell formation, which is the initial critical stage of atherosclerosis. In addition, oxLDL via CD36 inhibits macrophage migration, which may be a macrophage-trapping mechanism in atherosclerotic lesions. The role of CD36 was examined in in vitro studies and in vivo experiments, which investigated various functions of CD36 in atherosclerosis and revealed that CD36 deficiency reduces atherosclerotic lesion formation. Platelet CD36 also promotes atherosclerotic inflammatory processes and is involved in thrombus formation after atherosclerotic plaque rupture. Because CD36 is an essential component of atherosclerosis, defining the function of CD36 and its corresponding signaling pathway may lead to a new treatment strategy for atherosclerosis. PMID:24903227

Park, Young Mi

2014-01-01

175

Oversized vein grafts develop advanced atherosclerosis in hypercholesterolemic minipigs  

PubMed Central

Background Accelerated atherosclerosis is the main cause of late aortocoronary vein graft failure. We aimed to develop a large animal model for the study of pathogenesis and treatment of vein graft atherosclerosis. Methods An autologous reversed jugular vein graft was inserted end-to-end into the transected common carotid artery of ten hypercholesteroemic minipigs. The vein grafts were investigated 12-14 weeks later with ultrasound and angiograpy in vivo and microscopy post mortem. Results One minipig died during follow up (patent vein graft at autopsy), and one vein graft thrombosed early. In the remaining eight patent vein grafts, the mean (standard deviation) intima-media thickness was 712 ?m (276 ?m) versus 204 ?m (74 ?m) in the contralateral control internal jugular veins (P < .01). Advanced atherosclerotic plaques were found in three of four oversized vein grafts (diameter of graft > diameter of artery). No plaques were found in four non-oversized vein grafts (P < .05). Conclusions Our model of jugular vein graft in the common carotid artery of hypercholesterolemic minipigs displayed the components of human vein graft disease, i.e. thrombosis, intimal hyperplasia, and atherosclerosis. Advanced atherosclerosis, the main cause of late failure of human aortocoronary vein grafts was only seen in oversized grafts. This finding suggests that oversized vein grafts may have detrimental effects on patient outcome. PMID:22463679

2012-01-01

176

The role of heat shock proteins in atherosclerosis.  

PubMed

Atherosclerosis is a chronic, multifactorial disease that starts in youth, manifests clinically later in life, and can lead to myocardial infarction, stroke, claudication, and death. Although inflammatory processes have long been known to be involved in atherogenesis, interest in this subject has grown in the past 30-40 years. Animal experiments and human analyses of early atherosclerotic lesions have shown that the first pathogenic event in atherogenesis is the intimal infiltration of T cells at arterial branching points. These T cells recognize heat shock protein (HSP)60, which is expressed together with adhesion molecules by endothelial cells in response to classic risk factors for atherosclerosis. Although these HSP60-reactive T cells initiate atherosclerosis, antibodies to HSP60 accelerate and perpetuate the disease. All healthy humans develop cellular and humoral immunity against microbial HSP60 by infection or vaccination. Given that prokaryotic (bacterial) and eukaryotic (for instance, human) HSP60 display substantial sequence homology, atherosclerosis might be the price we pay for this protective immunity, if risk factors stress the vascular endothelial cells beyond physiological conditions. PMID:25027488

Wick, Georg; Jakic, Bojana; Buszko, Maja; Wick, Marius C; Grundtman, Cecilia

2014-09-01

177

Obstructive Sleep Apnea, Immuno-Inflammation and Atherosclerosis  

E-print Network

pharyngeal collapses occurring during sleep [1]. The upper airway closure could be complete, leadingObstructive Sleep Apnea, Immuno-Inflammation and Atherosclerosis Claire Arnaud1,2 , Maurice;31(1):113-25" DOI : 10.1007/s00281-009-0148-5 #12;2 ABSTRACT Obstructive sleep apnea (OSA) is a highly prevalent

Paris-Sud XI, Université de

178

Evaluation of the biomechanics of atherosclerosis by acoustic microscopy  

NASA Astrophysics Data System (ADS)

Acoustic microscopy provides not only the morphology, but also the biomechanical properties of the biological soft tissues. The biomechanics of atherosclerosis is important because the pathophysiology of atherosclerosis is closely related with mechanical properties and mechanical stress. Rupture of the fibrous cap of atheromatous plaque is the initial event in acute coronary syndrome such as acute myocardial infarction or unstable angina. In addition to extrinsic physical stresses to the plaque, the intrinsic biomechanical property of the plaque is important for assessing the mechanism of the rupture. Two sets of SAMs operating in 100 to 200 MHz and in 800 MHz to 1.3 GHz were equipped to measure the acoustic properties of atherosclerosis of human or mouse arteries. The values of attenuation and sound speed in the tissue components of atherosclerosis were measured by analyzing the frequency dependent characteristics of the amplitude and phase signals. Both values were highest in calcification and lowest in lipid pool. Although attenuation and sound speed were relatively high in intimal fibrosis, the inhomogeneity of acoustic parameters was found within the fibrous cap. Polarized microscopy for the collagen stained with Picrosirius red showed that the attenuation of ultrasound was significantly higher in type I collagen with orange polarized color compared to type III collagen with green color. SAM has shown the possibility to detect the plaque vulnerability and it might improve our understanding of the sudden rupture from micro-mechanical point of view.

Saijo, Yoshifumi; Nitta, Shin-ichi; Schiott Jorgensen, Claus; Falk, Erling

2001-07-01

179

Cell signaling by reactive nitrogen and oxygen species in atherosclerosis  

Microsoft Academic Search

The production of reactive oxygen and nitrogen species has been implicated in atherosclerosis principally as means of damaging low-density lipoprotein that in turn initiates the accumulation of cholesterol in macrophages. The diversity of novel oxidative modifications to lipids and proteins recently identified in atherosclerotic lesions has revealed surprising complexity in the mechanisms of oxidative damage and their potential role in

Rakesh P Patel; Douglas Moellering; Joanne Murphy-Ullrich; Hanjoong Jo; Joseph S Beckman; Victor M Darley-Usmar

2000-01-01

180

trans-Fatty acids in the diet stimulate atherosclerosis  

Microsoft Academic Search

Epidemiological evidence has associated dietary trans-fatty acids (TFAs) with coronary heart disease. It is assumed that TFAs stimulate atherosclerosis, but this has not been proven. The purpose of this study was to determine the effects of consuming 2 concentrations of TFAs obtained from commercially hydrogenated vegetable shortening on atherosclerotic development in the presence or absence of elevated dietary cholesterol. Low-density

Chantal M. C. Bassett; Richelle S. McCullough; Andrea L. Edel; Thane G. Maddaford; Elena Dibrov; David P. Blackwood; Jose A. Austria; Grant N. Pierce

2009-01-01

181

The Biology of Atherosclerosis: General Paradigms and Distinct Pathogenic Mechanisms Among HIV-Infected Patients  

PubMed Central

Complications of atherosclerosis, including myocardial infarction and stroke, are the leading cause of death and disability worldwide. Recent data strongly implicate cardiovascular death as a contributor to mortality among patients with human immunodeficiency virus (HIV) infection, with evidence suggesting increased incidence of atherosclerosis among these patients. Therefore, greater understanding of atherosclerotic mechanisms and how these responses may be similar or distinct in HIV-infected patients is needed. Key concepts in atherosclerosis are reviewed, including the evidence that inflammation and abnormal metabolism are major drivers of atherosclerosis, and connected to the current literature regarding atherosclerosis in the context of HIV. PMID:22577210

Lo, Janet

2012-01-01

182

Improved animal models for testing gene therapy for atherosclerosis.  

PubMed

Gene therapy delivered to the blood vessel wall could augment current therapies for atherosclerosis, including systemic drug therapy and stenting. However, identification of clinically useful vectors and effective therapeutic transgenes remains at the preclinical stage. Identification of effective vectors and transgenes would be accelerated by availability of animal models that allow practical and expeditious testing of vessel-wall-directed gene therapy. Such models would include humanlike lesions that develop rapidly in vessels that are amenable to efficient gene delivery. Moreover, because human atherosclerosis develops in normal vessels, gene therapy that prevents atherosclerosis is most logically tested in relatively normal arteries. Similarly, gene therapy that causes atherosclerosis regression requires gene delivery to an existing lesion. Here we report development of three new rabbit models for testing vessel-wall-directed gene therapy that either prevents or reverses atherosclerosis. Carotid artery intimal lesions in these new models develop within 2-7 months after initiation of a high-fat diet and are 20-80 times larger than lesions in a model we described previously. Individual models allow generation of lesions that are relatively rich in either macrophages or smooth muscle cells, permitting testing of gene therapy strategies targeted at either cell type. Two of the models include gene delivery to essentially normal arteries and will be useful for identifying strategies that prevent lesion development. The third model generates lesions rapidly in vector-naïve animals and can be used for testing gene therapy that promotes lesion regression. These models are optimized for testing helper-dependent adenovirus (HDAd)-mediated gene therapy; however, they could be easily adapted for testing of other vectors or of different types of molecular therapies, delivered directly to the blood vessel wall. Our data also supports the promise of HDAd to deliver long-term therapy from vascular endothelium without accelerating atherosclerotic disease. PMID:24528162

Du, Liang; Zhang, Jingwan; De Meyer, Guido R Y; Flynn, Rowan; Dichek, David A

2014-04-01

183

Habitual street food intake and subclinical carotid atherosclerosis.  

PubMed

Street food (SF) is defined as out-of-home food consumption, and generally consists of energy-dense meals rich in saturated fats and poor in fibers, vitamins and antioxidants. Though SF consumption may have unfavorable metabolic and cardiovascular effects, its possible association with atherosclerosis has not been considered. The association between habitual SF consumption and asymptomatic carotid atherosclerosis, defined as the presence of plaques and/or increased intima-media thickness, was therefore investigated. One thousand thirty-five randomly selected adult participants without known diabetes and atherosclerotic cardiovascular diseases were cross-sectionally investigated in Palermo, Italy. Each participant answered a food frequency questionnaire and underwent high-resolution ultrasonographic evaluation of both carotid arteries. Laboratory blood measurements were obtained in a subsample of 541 participants. A score of SF consumption was obtained by categorizing each of ten SFs consumed more or less than once a month. Participants were divided into three classes based on the tertiles of SF score distribution. Age, gender distribution, body mass index (BMI), prevalence of hypertension and of clinically silent carotid atherosclerosis (I tertile 20.8 %, II tertile 19.7 %, III tertile 19.0 %; P = 0.85) were not significantly different among the three groups. Clinically silent carotid atherosclerosis was independently associated with age, gender and hypertension. The score of SF consumption was significantly correlated with BMI (r = 0.10; P = 0.04), uric acid (r = 0.16; P = 0.002) and high-density lipoproteins-cholesterol (r = -0.13; P = 0.009) blood concentrations. In conclusion, this study suggests that SF consumption is not associated with clinically silent carotid atherosclerosis. However, given the association of SF consumption with other cardiovascular risk factors, caution requires that this category of food should be limited in patients at high cardiovascular risk. PMID:24151145

Buscemi, Silvio; Mattina, Alessandro; Rosafio, Giuseppe; Massenti, Fatima M; Galvano, Fabio; Grosso, Giuseppe; Amodio, Emanuele; Barile, Anna M; Maniaci, Vincenza; Bonura, Alice; Sprini, Delia; Rini, Giovam B

2014-09-01

184

Gradient Echo MRI Characterization of Development of Atherosclerosis in the Abdominal Aorta in Watanabe Heritable Hyperlipidemic Rabbits  

SciTech Connect

Purpose. The Watanabe Heritable Hyperlipidemic (WHHL) rabbit provides an important model of spontaneous atherosclerosis. With a strain of WHHL rabbits which do not develop abdominal aorta lumen stenosis even with advanced atherosclerosis, we studied the MRI-histology correlation, and the natural progression of atherosclerosis in the abdominal aorta. In addition, intra-reader segmentation repeatability and scan-rescan reproducibility were assessed. Methods. Two batches of female WHHL rabbits were used. The first batch of 6 rabbits was scanned at 20 weeks old. A second batch of 17 rabbits was scanned at 50 weeks old and then randomly divided into two subgroups: 8 were killed for histologic investigation; 9 were kept alive for follow-up, with repeat scanning a week later to assess scan-rescan reproducibility, and again at 73 weeks old to assess disease progression. MR images were acquired at 4.7 T using a chemical shift selective fat suppression gradient echo with a saturation band suppressing blood signal within the aortic lumen. Five slices per animal were acquired, centered around the renal artery region of the abdominal aorta, with in-plane resolution of 0.195 mm and slice thickness of 3 mm. Results. The coefficient of variation for intra-reader reproducibility for aortic wall thickness measurements was 2.5% for repeat segmentations of the same scans on the same day, but segmentations of these same scans made 8 months later showed a systematic change, suggesting that intra-reader bias as well as increased variability could compromise assessments made over time. Comparative analyses were therefore performed in one postprocessing session. The coefficient of variation for scan-rescan reproducibility for aortic wall thickness was 5.5% for nine pairs of scans acquired a week apart and segmented on the same day. Good MRI-histology correlation was obtained. The MRI-measured mean aortic wall thickness of animals at 20 weeks of age was 76% that of animals at 50 weeks of age (p < 0.001). There was a small increase in aortic wall thickness between 50 and 73 weeks of age, but this was not significant (p > 0.05). The corresponding differences in lumen cross-sectional areas at 20, 50, and 73 weeks of age were not significant. These results were consistent with in-house historical histology data on this strain of rabbits. Conclusions. High-resolution gradient echo MRI can follow disease progression in the WHHL rabbit spontaneous atherosclerosis disease model.

Wang, Yi-Xiang J., E-mail: yi-xiang.wang@astrazeneca.com; Kuribayashi, Hideto [AstraZeneca (United Kingdom); Wagberg, Maria [AstraZeneca (Sweden); Holmes, Andrew P.; Tessier, Jean J.; Waterton, John C. [AstraZeneca (United Kingdom)

2006-08-15

185

Socioeconomic differences in the progression of carotid atherosclerosis in middle-aged men and women with subclinical atherosclerosis in Sweden  

Microsoft Academic Search

While the persistence of socioeconomic differences in cardiovascular disease (CVD) has been recognized for many years, less is known about whether socioeconomic factors are of importance to CVD before symptoms of the disease appear. In this study the associations among educational level, occupational status and progression of atherosclerosis were investigated in 1016 Swedish middle-aged men and women with signs of

Maria Rosvall; Per-Olof Östergren; Bo Hedblad; Sven-Olof Isacsson; Lars Janzon; Göran Berglund

2006-01-01

186

Intravascular multispectral optoacoustic tomography of atherosclerosis: prospects and challenges  

PubMed Central

The progression of atherosclerosis involves complex changes in the structure, composition and biology of the artery wall. Currently, only anatomical plaque burden is routinely characterized in living patients, whereas compositional and biological changes are mostly inaccessible. However, anatomical imaging alone has proven to be insufficient for accurate diagnostics of the disease. Multispectral optoacoustic tomography offers complementary data to anatomical methods and is capable of imaging both tissue composition and, via the use of molecular markers, the biological activity therein. In this paper we review recent progress in multispectral optoacoustic tomography imaging of atherosclerosis with specific emphasis on intravascular applications. The potential capabilities of multispectral optoacoustic tomography are compared with those of established intravascular imaging techniques and current challenges on the road towards a clinically viable imaging modality are discussed. PMID:23144663

Rosenthal, Amir; Jaffer, Farouc A; Ntziachristos, Vasilis

2012-01-01

187

Probing nanoparticle translocation across the permeable endothelium in experimental atherosclerosis  

PubMed Central

Therapeutic and diagnostic nanomaterials are being intensely studied for several diseases, including cancer and atherosclerosis. However, the exact mechanism by which nanomedicines accumulate at targeted sites remains a topic of investigation, especially in the context of atherosclerotic disease. Models to accurately predict transvascular permeation of nanomedicines are needed to aid in design optimization. Here we show that an endothelialized microchip with controllable permeability can be used to probe nanoparticle translocation across an endothelial cell layer. To validate our in vitro model, we studied nanoparticle translocation in an in vivo rabbit model of atherosclerosis using a variety of preclinical and clinical imaging methods. Our results reveal that the translocation of lipid–polymer hybrid nanoparticles across the atherosclerotic endothelium is dependent on microvascular permeability. These results were mimicked with our microfluidic chip, demonstrating the potential utility of the model system. PMID:24395808

Kim, YongTae; Lobatto, Mark E.; Kawahara, Tomohiro; Lee Chung, Bomy; Mieszawska, Aneta J.; Sanchez-Gaytan, Brenda L.; Fay, Francois; Senders, Max L.; Calcagno, Claudia; Becraft, Jacob; Tun Saung, May; Gordon, Ronald E.; Stroes, Erik S. G.; Ma, Mingming; Farokhzad, Omid C.; Fayad, Zahi A.; Mulder, Willem J. M.; Langer, Robert

2014-01-01

188

Local proliferation dominates lesional macrophage accumulation in atherosclerosis  

PubMed Central

During the inflammatory response that drives atherogenesis, macrophages accumulate progressively in the expanding arterial wall1,2. The observation that circulating monocytes give rise to lesional macrophages3–9 has reinforced the concept that monocyte infiltration dictates macrophage build-up. Recent work indicates, however, that macrophages do not depend on monocytes in some inflammatory contexts10. We therefore revisited the mechanism of macrophage accumulation in atherosclerosis. We show that murine atherosclerotic lesions experience a surprisingly rapid, 4-week, cell turnover. Replenishment of macrophages in these experimental atheromata depends predominantly on local macrophage proliferation rather than monocyte influx. The microenvironment orchestrates macrophage proliferation via the involvement of scavenger receptor (SR)-A. Our study reveals macrophage proliferation as a key event in atherosclerosis and identifies macrophage self-renewal as a therapeutic target for cardiovascular disease. PMID:23933982

Robbins, Clinton S.; Hilgendorf, Ingo; Weber, Georg F.; Theurl, Igor; Iwamoto, Yoshiko; Figueiredo, Jose-Luiz; Gorbatov, Rostic; Sukhova, Galina K.; Gerhardt, Louisa M.S.; Smyth, David; Zavitz, Caleb C. J.; Shikatani, Eric A.; Parsons, Michael; van Rooijen, Nico; Lin, Herbert Y.; Husain, Mansoor; Libby, Peter; Nahrendorf, Matthias; Weissleder, Ralph; Swirski, Filip K.

2013-01-01

189

Omega-3 fatty acids: mechanisms underlying “protective effects” in atherosclerosis  

PubMed Central

Purpose of review This article provides an updated review on mechanistic and molecular studies relating to the effects of n-3 fatty acids (FA) on inhibiting atherogenesis. Recent findings The effects of n-3 FA on modulating arterial lipoprotein lipase (LpL) levels link to changes in lipid deposition in the arterial wall. LpL expression in the arterial wall also relates to local macrophage-mediated inflammatory processes. Increasing evidence suggests that n-3 FA ameliorate inflammation, another key component in the development of atherosclerosis, including decreases in pro-inflammatory cytokine production. n-3 FA inhibit atherogenic signaling pathways and modulate the phenotypes of inflammatory leukocytes and their recruitment in the arterial wall. Summary New mechanistic insights into the anti-atherogenic action of n-3 FA have emerged. These studies may contribute to future therapeutic advances in preventing mortality and morbidity associated with atherosclerosis. PMID:23594712

Chang, Chuchun L.; Deckelbaum, Richard J.

2014-01-01

190

Immune Effector Mechanisms Implicated in Atherosclerosis: From Mice to Humans  

PubMed Central

According to the traditional view, atherosclerosis results from a passive buildup of cholesterol in the artery wall. Yet, burgeoning evidence implicates inflammation and immune effector mechanisms in the pathogenesis of this disease. Both innate and adaptive immunity operate during atherogenesis and link many traditional risk factors to altered arterial functions. Inflammatory pathways have become targets in the quest for novel preventive and therapeutic strategies against cardiovascular disease, a growing contributor to morbidity and mortality worldwide. Here we review current experimental and clinical knowledge of the pathogenesis of atherosclerosis through an immunological lens and how host defense mechanisms essential for survival of the species actually contribute to this chronic disease but also present new opportunities for its mitigation. PMID:23809160

Libby, Peter; Lichtman, Andrew H.; Hansson, Göran K.

2013-01-01

191

[Morphological aspects of atherosclerosis lesion: past and present].  

PubMed

Atherosclerosis is an inflammatory process disease that involves the artery wall and that is characterized by the progressive accumulation of lipids. The term arteriosclerosis has been created by Lobstein in 1833. Subsequently, during the 19th century, the contribution of Rokitansky and Virchow was important to elucidate the pathogenesis of arteriosclerosis and the morphologic aspects of the plaque. In the beginning of the 20th century, Aschoff was a leading proponent who regarded the morphologically different intimal lipid deposits of children and adults as early and late stages of one disease and he called them atherosis and atherosclerosis, respectively. The first classification of atherosclerosis was made by the World Health Organization (WHO) in 1958 and it consisted of the following sequence: fatty streak, atheroma, fibrous plaque and complicated lesions. In 1990s, thanks to much more sensitive techniques, the American Heart Association (AHA) proposed a new morphological classification based on eight lesion types designated by Roman numerals which indicate the usual sequence of lesion progression. Finally, Virmani et al. (2000) described a classification with the add of a specific plaque type, not recognized by the AHA classification, called "thin fibrous cap atheroma" which is more likely to rupture. The atherosclerotic process is characterized by typical ultrastructural changes that mainly involve the endothelial and smooth muscle cells. The morphological alterations of the endothelium are associated with dysfunctions leading to a proinflammatory and prothrombotic phenotype. This process seems to be due to turbulent blood flow and low fluid shear stress that normally occurs in particular regions of the vascular tree. Inflammation has a key role in the pathogenesis of atherosclerosis and it is supported by numerous factors such as modified LDL, hypertension, diabetes mellitus, free radicals and, in particular, by infectious agents such as Chlamydia pneumoniae. PMID:16817503

Gaudio, E; Carpino, G; Grassi, M; Musca, A

2006-01-01

192

Platelets and their chemokines in atherosclerosis—clinical applications  

PubMed Central

The concept of platelets as important players in the process of atherogenesis has become increasingly accepted due to accumulating experimental and clinical evidence. Despite the progress in understanding the molecular details of atherosclerosis, particularly by using animal models, the inflammatory and thrombotic roles of activated platelet s especially in the human system remain difficult to dissect, as often only the complications of atherosclerosis, i.e., stroke and myocardial infarction are definable but not the plaque burden. Platelet indices including platelet count and mean platelet volume (MPV) and soluble mediators released by activated platelets are associated with atherosclerosis. The chemokine CXCL4 has multiple atherogenic activities, e.g., altering the differentiation of T cells and macrophages by inhibiting neutrophil and monocyte apoptosis and by increasing the uptake of oxLDL and synergizing with CCL5. CCL5 is released and deposited on endothelium by activated platelets thereby triggering atherogenic monocyte recruitment, which can be attenuated by blocking the corresponding chemokine receptor CCR5. Atheroprotective and plaque stabilizing properties are attributed to CXCL12, which plays an important role in regenerative processes by attracting progenitor cells. Its release from luminal attached platelets accelerates endothelial healing after injury. Platelet surface molecules GPIIb/IIIa, GP1b?, P-selectin, JAM-A and the CD40/CD40L dyade are crucially involved in the interaction with endothelial cells, leukocytes and matrix molecules affecting atherogenesis. Beyond the effects on the arterial inflammatory infiltrate, platelets affect cholesterol metabolism by binding, modifying and endocytosing LDL particles via their scavenger receptors and contribute to the formation of lipid laden macrophages. Current medical therapies for the prevention of atherosclerotic therapies enable the elucidation of mechanisms linking platelets to inflammation and atherosclerosis. PMID:25152735

von Hundelshausen, Philipp; Schmitt, Martin M. N.

2014-01-01

193

P2 receptors in atherosclerosis and postangioplasty restenosis.  

PubMed

Atherosclerosis is an immunoinflammatory process that involves complex interactions between the vessel wall and blood components and is thought to be initiated by endothelial dysfunction [Ross (Nature 362:801-809, 1993); Fuster et al. (N Engl J Med 326:242-250, 1992); Davies and Woolf (Br Heart J 69:S3-S11, 1993)]. Extracellular nucleotides that are released from a variety of arterial and blood cells [Di Virgilio and Solini (Br J Pharmacol 135:831-842, 2002)] can bind to P2 receptors and modulate proliferation and migration of smooth muscle cells (SMC), which are known to be involved in intimal hyperplasia that accompanies atherosclerosis and postangioplasty restenosis [Lafont et al. (Circ Res 76:996-1002, 1995)]. In addition, P2 receptors mediate many other functions including platelet aggregation, leukocyte adherence, and arterial vasomotricity. A direct pathological role of P2 receptors is reinforced by recent evidence showing that upregulation and activation of P2Y(2) receptors in rabbit arteries mediates intimal hyperplasia [Seye et al. (Circulation 106:2720-2726, 2002)]. In addition, upregulation of functional P2Y receptors also has been demonstrated in the basilar artery of the rat double-hemorrhage model [Carpenter et al. (Stroke 32:516-522, 2001)] and in coronary artery of diabetic dyslipidemic pigs [Hill et al. (J Vasc Res 38:432-443, 2001)]. It has been proposed that upregulation of P2Y receptors may be a potential diagnostic indicator for the early stages of atherosclerosis [Elmaleh et al. (Proc Natl Acad Sci U S A 95:691-695, 1998)]. Therefore, particular effort must be made to understand the consequences of nucleotide release from cells in the cardiovascular system and the subsequent effects of P2 nucleotide receptor activation in blood vessels, which may reveal novel therapeutic strategies for atherosclerosis and restenosis after angioplasty. PMID:18404429

Seye, Cheikh I; Kong, Qiongman; Yu, Ningpu; Gonzalez, Fernando A; Erb, Laurie; Weisman, Gary A

2007-03-01

194

Immune regulation in atherosclerosis and the hygiene hypothesis  

Microsoft Academic Search

Atherosclerosis is a chronic inflammatory disease of the arterial wall where both innate and adaptive immune responses contribute\\u000a to disease initiation and progression. The hygiene hypothesis implies that dysregulation of the immune response has led to\\u000a increased susceptibility to immuno-inflammatory diseases. Recent studies established that subtypes of T cells, regulatory\\u000a T cells, actively involved in the maintenance of immunological tolerance,

Hafid Ait-Oufella; Alain Tedgui; Ziad Mallat

195

Intermittent hypoxia-activated cyclooxygenase pathway: role in atherosclerosis.  

PubMed

Intermittent hypoxia, the main stimulus of obstructive sleep apnoea (OSA), induces inflammation, leading to early atherosclerosis. Whether the cyclooxygenase (COX) pathway contributes to intermittent hypoxia-induced atherosclerosis remains to be determined. We studied the effects of 8-weeks of intermittent hypoxia exposure on COX-pathway gene expression and atherosclerosis, and the influence of COX-1 inhibition by SC-560 on atherosclerosis progression in aortas of apolipoprotein E(-/-) mice. Urinary 11-dehydrothromboxane B2 (11-dTXB2) was assessed in 50 OSA subjects free of cardiovascular risk factor matched for age and body mass index with 25 controls, and 56 OSA with cardiovascular risk factor. Intermittent hypoxia significantly increased atherosclerotic lesion sizes, mRNA levels of COX-1 and thromboxane synthase (TXBS). Lesion sizes correlated to COX-1 (r = 0.654, p = 0.0003) and TXBS (r = 0.693, p<0.0001) mRNA levels. COX-1 inhibition reduced lesion progression in intermittent hypoxia mice only (p = 0.04). Urinary 11-dTXB2 was similar in OSA subjects free of cardiovascular risk factor and controls, but was increased by 13% (p = 0.007) in OSA subjects with cardiovascular risk factor compared with those without. Although OSA itself was not associated with increased urinary 11-dTXB2 concentration, the COX-1 pathway was activated in intermittent hypoxia-exposed mice and in OSA subjects presenting with cardiovascular risk factor, and may contribute to intermittent hypoxia-induced atherogenesis. COX-1 inhibition could be of clinical interest in the prevention of cardiovascular morbidity in OSA. PMID:23060635

Gautier-Veyret, Elodie; Arnaud, Claire; Bäck, Magnus; Pépin, Jean-Louis; Petri, Marcelo H; Baguet, Jean-Philippe; Tamisier, Renaud; Lévy, Patrick; Stanke-Labesque, Françoise

2013-08-01

196

IL-25 Inhibits Atherosclerosis Development in Apolipoprotein E Deficient Mice  

PubMed Central

Objective IL-25 has been implicated in the initiation of type 2 immunity and in the protection against autoimmune inflammatory diseases. Recent studies have identified the novel innate lymphoid type 2 cells (ILC2s) as an IL-25 target cell population. The purpose of this study was to evaluate if IL-25 has any influence on atherosclerosis development in mice. Methods and Results Administration of 1 ?g IL-25 per day for one week to atherosclerosis-prone apolipoprotein (apo)E deficient mice, had limited effect on the frequency of T cell populations, but resulted in a large expansion of ILC2s in the spleen. The expansion was accompanied by increased levels of anti-phosphorylcholine (PC) natural IgM antibodies in plasma and elevated levels of IL-5 in plasma and spleen. Transfer of ILC2s to apoE deficient mice elevated the natural antibody-producing B1a cell population in the spleen. Treatment of apoE/Rag-1 deficient mice with IL-25 was also associated with extensive expansion of splenic ILC2s and increased plasma IL-5, suggesting ILC2s to be the source of IL-5. Administration of IL-25 in IL-5 deficient mice resulted in an expanded ILC2 population, but did not stimulate generation of anti-PC IgM, indicating that IL-5 is not required for ILC2 expansion but for the downstream production of natural antibodies. Additionally, administration of 1 ?g IL-25 per day for 4 weeks in apoE deficient mice reduced atherosclerosis in the aorta both during initiation and progression of the disease. Conclusions The present findings demonstrate that IL-25 has a protective role in atherosclerosis mediated by innate responses, including ILC2 expansion, increased IL-5 secretion, B1a expansion and natural anti-PC IgM generation, rather than adaptive Th2 responses. PMID:25629516

Mantani, Polyxeni T.; Dunér, Pontus; Bengtsson, Eva; Alm, Ragnar; Ljungcrantz, Irena; Söderberg, Ingrid; Sundius, Lena; To, Fong; Nilsson, Jan; Björkbacka, Harry; Fredrikson, Gunilla Nordin

2015-01-01

197

Necrosis of the Penis with Multiple Vessel Atherosclerosis  

PubMed Central

Penile necrosis is a very rare complication because of its rich collateral supply. Conservative management is apt to be ineffective; thus penectomy is usually performed. We present a case of penile necrosis and claudication of both legs with multiple atherosclerosis in a type II diabetes mellitus patient who was successfully treated with angioplasty, penoplasty, and additional intracavernous injections of prostaglandin E1. The treatment resulted in relief of the leg pain and healing of the penile ischemic lesions. PMID:24872955

Kim, Sung Dae; Huh, Jung Sik

2014-01-01

198

Particulate air pollution, systemic oxidative stress, inflammation, and atherosclerosis  

Microsoft Academic Search

Air pollution has been associated with significant adverse health effects leading to increased overall morbidity and mortality\\u000a of worldwide significance. Epidemiological studies have shown that the largest portion of air pollution-related mortality\\u000a is due to cardiovascular diseases, predominantly those of ischemic nature. Human studies suggest an association with atherosclerosis\\u000a and increasing experimental animal data support that this association is likely

Jesus A. Araujo

2011-01-01

199

Bisphenol A Exposure Enhances Atherosclerosis in WHHL Rabbits  

PubMed Central

Bisphenol A (BPA) is an environmental endocrine disrupter. Excess exposure to BPA may increase susceptibility to many metabolic disorders, but it is unclear whether BPA exposure has any adverse effects on the development of atherosclerosis. To determine whether there are such effects, we investigated the response of Watanabe heritable hyperlipidemic (WHHL) rabbits to 400-µg/kg BPA per day, administered orally by gavage, over the course of 12 weeks and compared aortic and coronary atherosclerosis in these rabbits to the vehicle group using histological and morphometric methods. In addition, serum BPA, cytokines levels and plasma lipids as well as pathologic changes in liver, adipose and heart were analyzed. Moreover, we treated human umbilical cord vein endothelial cells (HUVECs) and rabbit aortic smooth muscle cells (SMCs) with different doses of BPA to investigate the underlying molecular mechanisms involved in BPA action(s). BPA treatment did not change the plasma lipids and body weights of the WHHL rabbits; however, the gross atherosclerotic lesion area in the aortic arch was increased by 57% compared to the vehicle group. Histological and immunohistochemical analyses revealed marked increases in advanced lesions (37%) accompanied by smooth muscle cells (60%) but no significant changes in the numbers of macrophages. With regard to coronary atherosclerosis, incidents of coronary stenosis increased by 11% and smooth muscle cells increased by 73% compared to the vehicle group. Furthermore, BPA-treated WHHL rabbits showed increased adipose accumulation and hepatic and myocardial injuries accompanied by up-regulation of endoplasmic reticulum (ER) stress and inflammatory and lipid metabolism markers in livers. Treatment with BPA also induced the expression of ER stress and inflammation related genes in cultured HUVECs. These results demonstrate for the first time that BPA exposure may increase susceptibility to atherosclerosis in WHHL rabbits. PMID:25333893

Fang, Chao; Ning, Bo; Waqar, Ahmed Bilal; Niimi, Manabu; Li, Shen; Satoh, Kaneo; Shiomi, Masashi; Ye, Ting; Dong, Sijun; Fan, Jianglin

2014-01-01

200

Early carotid atherosclerosis and cardiac diastolic abnormalities in hypertensive subjects  

Microsoft Academic Search

Despite the fact that it is known that hypertension may be associated to early atherosclerosis manifestations, few data are to date available on the relationship between early carotid abnormalities and left ventricular diastolic dysfunction. To address this issue, 142 hypertensive patients (64 females and 78 males) younger than 55 years, at the first diagnosis of mild-to-moderate essential hypertension (WHO\\/ISH criteria),

G Parrinello; D Colomba; P Bologna; A Licata; A Pinto; S Paterna; R Scaglione; G Licata

2004-01-01

201

Natural History of Stenosis From Intracranial Atherosclerosis by Serial Angiography  

Microsoft Academic Search

Background and Purpose—Knowledge of the natural history of stenoses due to intracranial atherosclerosis may be useful for evaluating possible treatments such as angioplasty. Methods—We retrospectively reviewed records over a 7-year period to identify patients with intracranial atherosclerotic stenoses and serial angiograms. Quantitative measurements of stenoses were made in a blinded manner, and clinical outcomes were reviewed. Results—We identified 21 patients

Paul T. Akins; Thomas K. Pilgram; DeWitte T. Cross III; Christopher J. Moran

202

LOX-1 in atherosclerosis: biological functions and pharmacological modifiers  

PubMed Central

Lectin-like oxidized LDL (oxLDL) receptor-1 (LOX-1, also known as OLR-1), is a class E scavenger receptor that mediates the uptake of oxLDL by vascular cells. LOX-1 is involved in endothelial dysfunction, monocyte adhesion, the proliferation, migration, and apoptosis of smooth muscle cells, foam cell formation, platelet activation, as well as plaque instability; all of these events are critical in the pathogenesis of atherosclerosis. These LOX-1-dependent biological processes contribute to plaque instability and the ultimate clinical sequelae of plaque rupture and life-threatening tissue ischemia. Administration of anti-LOX-1 antibodies inhibits atherosclerosis by decreasing these cellular events. Over the past decade, multiple drugs including naturally occurring antioxidants, statins, antiinflammatory agents, antihypertensive and antihyperglycemic drugs have been demonstrated to inhibit vascular LOX-1 expression and activity. Therefore, LOX-1 represents an attractive therapeutic target for the treatment of human atherosclerotic diseases. This review aims to integrate the current understanding of LOX-1 signaling, regulation of LOX-1 by vasculoprotective drugs, and the importance of LOX-1 in the pathogenesis of atherosclerosis. PMID:23124189

Xu, Suowen; Ogura, Sayoko; Chen, Jiawei; Little, Peter J.; Moss, Joel; Liu, Peiqing

2013-01-01

203

PPARgamma and atherosclerosis: effects on cell growth and movement.  

PubMed

Atherosclerosis is a major vascular complication of diabetes and the primary cause of mortality in persons with this disease. Metabolic abnormalities related to the Insulin Resistance Syndrome or Metabolic Syndrome may importantly contribute to the increased risk of atherosclerosis associated with diabetes. Thiazolidinediones (TZDs) are oral insulin sensitizers in broad clinical use that enhance insulin-stimulated glucose uptake into skeletal muscle. TZDs can also improve cardiovascular risk factors and exert direct effects on vascular cells to potentially retard the atherosclerotic process. Direct vascular effects of TZDs likely result from their activity as ligands for the nuclear receptor, PPARgamma. All of the major cell types in the vasculature express PPARgamma, including intimal macrophages and vascular smooth muscle cells (VSMCs) in human atheroma. TZDs block VSMC growth by inducing cell cycle arrest in G1 through an inhibition of retinoblastoma protein phosphorylation. Migration of monocytes and VSMCs is also inhibited by TZDs, possibly through decreased matrix metalloproteinase production. Activation of PPARgamma by TZDs in macrophages induces ABCA1 transporter expression to promote reverse cholesterol transport. These antiatherogenic activities may also occur in vivo because TZDs have been shown to inhibit lesion formation in several animal models. Thus, TZD activation of PPARgamma may protect against atherosclerosis both by normalizing proatherogenic metabolic abnormalities of the insulin resistance/diabetes milieu and through an inhibition of vascular cell growth and movement. PMID:11742860

Hsueh, W A; Law, R E

2001-12-01

204

Arterial remodeling of basilar atherosclerosis in isolated pontine infarction.  

PubMed

Isolated pontine infarctions are usually classified as paramedian pontine infarction (PPI) and lacunar pontine infarction (LPI). Although they have different shapes and locations, some recent studies proved that they might both be associated with basilar artery atherosclerosis in pathogenesis. This study aimed to explore the difference of basilar artery remodeling between two subtypes of pontine infarctions. Patients with PPI or LPI were scanned by High-resolution MRI (HR-MRI). The MR images of patients with basilar artery atherosclerosis were further analyzed to measure the vessel, lumen and wall areas at different segments of basilar arteries. Stenosis rate and remodeling index were calculated according to which arterial remodeling was divided into positive, intermediate and negative remodeling. Vascular risk factors and remodeling-related features were compared between PPI and LPI, and also between patients with and without positive remodeling. 34 patients with PPI and 21 patients with LPI had basilar artery atherosclerosis identified by HR-MRI. Positive remodeling was dominant in LPI group while in PPI group, three subtypes of remodeling were equal. Patients with positive remodeling had higher levels of low-density lipoprotein and homocysteine. Positive remodeling of basilar artery might reflect the low stability of basilar atherosclerotic plaques, which was more closely associated with LPI than PPI. PMID:25367406

Feng, Chao; Hua, Ting; Xu, Yu; Liu, Xue-Yuan; Huang, Jing

2014-11-01

205

IKK? links vascular inflammation to obesity and atherosclerosis.  

PubMed

I?B kinase ? (IKK?), a central coordinator of inflammatory responses through activation of NF-?B, has been implicated in vascular pathologies, but its role in atherogenesis remains elusive. Here, we demonstrate that IKK? functions in smooth muscle cells (SMCs) to regulate vascular inflammatory responses and atherosclerosis development. IKK? deficiency in SMCs driven by a SM22Cre-IKK?-flox system rendered low density lipoprotein receptor-null mice resistant to vascular inflammation and atherosclerosis induced by high-fat feeding. Unexpectedly, IKK?-deficient mice were also resistant to diet-induced obesity and metabolic disorders. Cell lineage analysis revealed that SM22Cre is active in primary adipose stromal vascular cells and deficiency of IKK? diminished the ability of these cells to differentiate, leading to accumulation of adipocyte precursor cells in adipose tissue. Mechanistically, reduction of IKK? expression or pharmacological inhibition of IKK? inhibited proteasome-mediated ?-catenin ubiquitination and degradation in murine preadipocytes, resulting in elevated ?-catenin levels and impaired adipocyte differentiation. Further, chronic treatment of mice with a potent IKK? inhibitor decreased adipogenesis and ameliorated diet-induced obesity. Our findings demonstrate a pivotal role of IKK? in linking vascular inflammation to atherosclerosis and adipose tissue development, and provide evidence for using appropriate IKK? inhibitors in the treatment of obesity and metabolic disorders. PMID:24799533

Sui, Yipeng; Park, Se-Hyung; Xu, Jinxian; Monette, Sébastien; Helsley, Robert N; Han, Seong-Su; Zhou, Changcheng

2014-05-01

206

Protective Role for Properdin in Progression of Experimental Murine Atherosclerosis  

PubMed Central

Genetic, dietary and immune factors contribute to the pathogenesis of atherosclerosis in humans and mice. Complement activation is an integral part of the innate immune defence but also shapes cellular responses and influences directly triglyceride synthesis. Deficiency of Factor B of the alternative pathway (AP) of complement is beneficial in LDLR?/? mice fed a high fat diet. The serum glycoprotein properdin is a key positive regulator of the AP but has not been studied in experimental atherosclerosis. Atherosclerosis was assessed after feeding low fat (LFD) or high fat (HFD) Western type diets to newly generated LDLR?/? ProperdinKO (LDLR?/?PKO) and LDLR?/?PWT mice. Lipids, lymphocytes and monocytes were similar among genotypes, genders and diets. Complement C3, but not C3adesarg, levels were enhanced in LDLR?/?PKO mice regardless of diet type or gender. Non-esterified fatty acids (NEFA) were decreased in male LDLR?/?PKO fed a HFD compared with controls. All mice showed significant atherosclerotic burden in aortae and at aortic roots but male LDLR?/? mice fed a LFD were affected to the greatest extent by the absence of properdin. The protective effect of properdin expression was overwhelmed in both genders of LDLR?/?mice when fed a HFD. We conclude that properdin plays an unexpectedly beneficial role in the development and progression of early atherosclerotic lesions. PMID:24667818

Byrne, Simon; Hughes, Timothy; Jayanthi, Archana; Guschina, Irina; Harwood, John; Cianflone, Katherine; Francis, Sheila

2014-01-01

207

Habitual fish intake and clinically silent carotid atherosclerosis  

PubMed Central

Background Fish consumption is recommended as part of a healthy diet. However, there is a paucity of data concerning the relation between fish consumption and carotid atherosclerosis. We investigated the association between habitual fish consumption and asymptomatic carotid atherosclerosis, defined as the presence of plaques and/or increased intima-media thickness (? 0.90 mm), in non-diabetic participants. Methods Nine hundred-sixty-one (range of age: 18–89 yrs; 37.1% males) adult participants without clinically known atherosclerotic disease were randomly recruited among the customers of a shopping mall in Palermo, Italy, and cross-sectionally investigated. Each participant answered a food frequency questionnaire and underwent high-resolution ultrasonographic evaluation of both carotid arteries. Routine laboratory blood measurements were obtained in a subsample of 507 participants. Results Based on habitual fish consumption, participants were divided into three groups: non-consumers or consumers of less than 1 serving a week (24.0%), consumers of 1 serving a week (38.8%), and consumers of???2 servings a week (37.2%). Age-adjusted prevalence of carotid atherosclerosis (presence of plaques or intima media thickness???0.9 mm) was higher in the low fish consumption group (13.3%, 12.1% and 6.6%, respectively; P?=?0.003). Multivariate analysis evidenced that carotid atherosclerosis was significantly associated with age (OR?=?1.12; 95% CI?=?1.09-1.14), hypertension on pharmacologic treatment (OR?=?1.81; 95% CI?=?1.16-2.82), and pulse pressure (OR?=?1.03; 95% CI?=?1.01-1.04), while consuming ?2 servings of fish weekly was protective compared with the condition of consumption of <1 serving of fish weekly (OR?=?0.46; 95% CI?=?0.26-0.80). Conclusions High habitual fish consumption seems to be associated with less carotid atherosclerosis, though adequate interventional trials are necessary to confirm the role of fish consumption in prevention of cardiovascular disease. PMID:24405571

2014-01-01

208

Lithium chloride suppresses LPS-mediated matrix metalloproteinase-9 expression in macrophages through phosphorylation of GSK-3?.  

PubMed

Abnormal degradation of matrix components due to dysregulated expression of matrix metalloproteinase (MMP)-9 in macrophages has been linked to progression of acute cerebral ischemia and atherosclerosis. We report that lithium chloride (LiCl) or CHIR99021, inhibitors of Wnt signaling pathway, enhance phosphorylation of glycogen synthase kinase-3beta and suppress lipopolysaccharide-mediated upregulation of MMP-9 expression in murine macrophage RAW264.7 cells in a dose-dependent manner. Suppression of MMP-9 expression by LiCl or CHIR99021 did not result after inhibition of kinases involved in NF?B or AP-1 family proteins, but from changes in the activity of histone deacetylases. Beneficial effects on atherosclerosis or cerebral ischemia in animal studies caused by LiCl may be in part explained by the suppression of MMP-9 gene expression. PMID:25053111

Kim, Sooho; Bong, Naeun; Kim, Ok Soo; Jin, JunYup; Kim, Dong-Eog; Lee, Dong Kun

2015-02-01

209

Hypertension Status Is the Major Determinant of Carotid Atherosclerosis A Community-Based Study in Taiwan  

Microsoft Academic Search

Background and Purpose—Extracranial carotid artery (ECCA) atherosclerosis has been associated with hypertension- related stroke. The present study was aimed at investigating the determinants of ECCA atherosclerosis in patients with hypertension in Taiwan. Methods—The extent and severity of ECCA atherosclerosis were measured by high-resolution B-mode ultrasonography and expressed as maximal intima-media thickness (IMT) of the common carotid artery, ECCA plaque score,

Ta-Chen Su; Jiann-Shing Jeng; Kuo-Liong Chien; Fung-Chang Sung; Hsiu-Ching Hsu; Yuan-Teh Lee

210

Progression and regression of atherosclerosis in APOE3Leiden transgenic mice: an immunohistochemical study  

Microsoft Academic Search

Apolipoprotein E3-Leiden (APOE3-Leiden) transgenic mice develop hyperlipidemia and are highly susceptible to diet-induced atherosclerosis. We have studied the progression and regression of atherosclerosis using immunohistochemistry. Female transgenic mice were fed a moderate fat diet to study atherosclerosis over a longer time period. Fatty streaks arose in the intima and consisted of lipid filled macrophages which differed in origin. All macrophages

Marion J. J Gijbels; Maarten van der Cammen; Luc J. W van der Laan; Jef J Emeis; Louis M Havekes; Marten H Hofker; Georg Kraal

1999-01-01

211

Atherosclerosis associated with pericardial effusion in a central bearded dragon (Pogona vitticeps).  

PubMed

Atherosclerosis is a common disease in pet birds, particularly in psittacines, and is frequently found when performing postmortem examinations on adult and old dogs, in which it is mainly associated with endocrine diseases, such as hypothyroidism and diabetes mellitus. However, atherosclerosis is poorly documented in reptiles and consequently poorly understood. In the current case report, atherosclerosis and pericardial effusion were diagnosed in a 2-year-old male central bearded dragon (Pogona vitticeps) based on ultrasound visualization, necropsy, and histologic examination. PMID:20807945

Schilliger, Lionel; Lemberger, Karin; Chai, Norin; Bourgeois, Aude; Charpentier, Maud

2010-09-01

212

Understanding the Pathogenesis of Accelerated Atherosclerosis in Systemic Lupus Erythematosus: A Role for T cell Dysregulation.  

E-print Network

?? Patients with the autoimmune disease systemic lupus erythematosus (SLE) have an increased risk of developing premature cardiovascular disease, most notably atherosclerosis. While the mechanisms… (more)

Wade, Nekeithia Shiana

2012-01-01

213

Akt3 Deficiency in Macrophages Promotes Foam Cell Formation and Atherosclerosis in Mice  

PubMed Central

Summary Akt, a serine-threonine protein kinase, exists as three isoforms. The Akt signaling pathway controls multiple cellular functions in the cardiovascular system, and the atheroprotective endothelial cell dependent role of Akt1 has been recently demonstrated. The role of Akt3 isoform in cardiovascular pathophysiology is not known. We explored the role of Akt3 in atherosclerosis using mice with a genetic ablation of the Akt3 gene. Using hyperlipidemic ApoE?/? mice, we demonstrated a macrophage dependent, atheroprotective role for Akt3. In vitro experiments demonstrated differential subcellular localization of Akt1 and Akt3 in macrophages, and showed that Akt3 specifically inhibits macrophage cholesteryl ester accumulation and foam cell formation, a critical early event in atherogenesis. Mechanistically, Akt3 suppresses foam cell formation by reducing lipoprotein uptake and promoting ACAT-1 degradation via the ubiquitin-proteasome pathway. These studies demonstrate the non-redundant atheroprotective role for Akt3 exerted via the previously unknown link between the Akt signaling pathway and cholesterol metabolism. PMID:22632897

Ding, Liang; Biswas, Sudipta; Morton, Richard E.; Smith, Jonathan D.; Hay, Nissim; Byzova, Tatiana; Febbraio, Maria; Podrez, Eugene

2012-01-01

214

A Crucial Role for CDC42 in Senescence-Associated Inflammation and Atherosclerosis  

PubMed Central

Risk factors for atherosclerosis accelerate the senescence of vascular endothelial cells and promote atherogenesis by inducing vascular inflammation. A hallmark of endothelial senescence is the persistent up-regulation of pro-inflammatory genes. We identified CDC42 signaling as a mediator of chronic inflammation associated with endothelial senescence. Inhibition of CDC42 or NF-?B signaling attenuated the sustained up-regulation of pro-inflammatory genes in senescent human endothelial cells. Endothelium-specific activation of the p53/p21 pathway, a key mediator of senescence, also resulted in up-regulation of pro-inflammatory molecules in mice, which was reversed by Cdc42 deletion in endothelial cells. Likewise, endothelial-specific deletion of Cdc42 significantly attenuated chronic inflammation and plaque formation in atherosclerotic mice. While inhibition of NF-?B suppressed the pro-inflammatory responses in acute inflammation, the influence of Cdc42 deletion was less marked. Knockdown of cdc-42 significantly down-regulated pro-inflammatory gene expression and restored the shortened lifespan to normal in mutant worms with enhanced inflammation. These findings indicate that the CDC42 pathway is critically involved in senescence-associated inflammation and could be a therapeutic target for chronic inflammation in patients with age-related diseases without compromising host defenses. PMID:25057989

Ito, Takashi K.; Yokoyama, Masataka; Yoshida, Yohko; Nojima, Aika; Kassai, Hidetoshi; Oishi, Kengo; Okada, Sho; Kinoshita, Daisuke; Kobayashi, Yoshio; Fruttiger, Marcus; Aiba, Atsu; Minamino, Tohru

2014-01-01

215

Effects of lisinopril, irbesartan, and amlodipine on the thrombogenic variables in the early and late stages of the treatment in hypertensive patients.  

PubMed

Regulation of the fibrinolytic balance between plasminogen activators and inhibitors is modulated by the renin-angiotensin system (RAS). Impaired fibrinolytic function, characterized by increased plasminogen activator inhibitor type 1 (PAI-1) levels and decreased tissue plasminogen activator (t-PA) activity, has been found in patients with hypertension and may account in part for the increased risk of atherosclerosis and its clinical complications in these patients. In this regard, data from the literature indicate that different antihypertensive drugs may vary in their influence on fibrinolysis. Angiotensin-converting enzyme (ACE) inhibitors (ACE-I) have generally been shown to improve the fibrinolytic balance by reducing plasma PAI-1 levels. Calcium-channel blockers (CCB) have been reported to increase t-PA activity, and angiotensin receptor blockers (ARB) seem to be neutral in their effect. In the light of these data, this study aimed to compare the effects of ACE-I, ARB, and CCB on the fibrinolytic system in the early and late stages of the treatment in hypertensive patients. These data that the beneficial effect of RAS inhibition on fibrinolysis related to decrease in Ang II during early period of treatment. Amlodipine may also improve thrombogenic risk related to lowering the effect on increased platelet activation reflected by p-selectin. The greater improvement in the early and late stages of the fibrinolytic balance because of the combined action of RAS inhibition and Ca antagonism represents a further indication to the use of combinations of RAS inhibition (ACE-I or ARB) and CCB in the treatment of hypertension. PMID:21967026

Tiryaki, Ozlem; Usalan, Celalettin; Buyukhatipoglu, Hakan; Sayiner, Zeynel Abidin; Kilisli, Hasan

2012-01-01

216

Influence of chronic exercise on carotid atherosclerosis in marathon runners  

PubMed Central

Objectives The effect of habitual, high-intensity exercise training on the progression of atherosclerosis is unclear. We assessed indices of vascular health (central systolic blood pressure (SBP) and arterial stiffness as well as carotid intima-medial thickness (cIMT)) in addition to cardiovascular risk factors of trained runners versus their untrained spouses or partners to evaluate the impact of exercise on the development of carotid atherosclerosis. Setting field study at Boston Marathon. Participants 42 qualifiers (mean age±SD: 46±13?years, 21 women) for the 2012 Boston Marathon and their sedentary domestic controls (46±12?years, n=21 women). Outcomes We measured medical and running history, vital signs, anthropometrics, blood lipids, C reactive protein (CRP), 10?years Framingham risk, central arterial stiffness and SBP and cIMT. Results Multiple cardiovascular risk factors, including CRP, non-high-density lipoprotein cholesterol, triglycerides, heart rate, body weight and body mass index (all p<0.05), were reduced in the runners. The left and right cIMT, as well as central SBP, were not different between the two groups (all p>0.31) and were associated with age (all r?0.41; p<0.01) and Framingham risk score (all r?0.44; p<0.01) independent of exercise group (all p>0.08 for interactions). The amplification of the central pressure waveform (augmentation pressure at heart rate 75?bpm) was also not different between the two groups (p=0.07) but was related to age (p<0.01) and group (p=0.02) in a multiple linear regression model. Conclusions Habitual endurance exercise improves the cardiovascular risk profile, but does not reduce the magnitude of carotid atherosclerosis associated with age and cardiovascular risk factors. PMID:24531453

Taylor, Beth A; Zaleski, Amanda L; Capizzi, Jeffrey A; Ballard, Kevin D; Troyanos, Christopher; Baggish, Aaron L; D'Hemecourt, Pierre A; Dada, Marcin R; Thompson, Paul D

2014-01-01

217

Experimental diet-induced atherosclerosis in Quaker parrots (Myiopsitta monachus).  

PubMed

Spontaneous atherosclerosis is common in psittaciformes, and clinical signs associated with flow-limiting stenosis are encountered in pet birds. Nevertheless, a psittacine model of atherosclerosis has not been developed for research investigations. Sixteen captive-bred Quaker parrots (Myiopsitta monachus) were used in this study. While 4 control birds were fed a maintenance diet, 12 other birds were fed an atherogenic diet composed of 1% cholesterol controlling for a calorie-to-protein ratio for periods ranging from 2 to 8 months. The birds were euthanized at the end of their respective food trial period. Histopathology, transmission electron microscopy, and cholesterol measurement were performed on the ascending aorta and brachiocephalic and pulmonary arteries. Plasma lipoproteins, cholesterol, and triglycerides were also measured on a monthly basis. Significant atherosclerotic lesions were induced within 2 months and advanced atherosclerotic lesions within 4 to 6 months. The advanced lesions were histologically similar to naturally occurring lesions identified in the same parrot species with a lipid core and a fibrous cap. Ultrastructurally, there were extracellular lipid, foam cell, and endothelial changes. Arterial cholesterol content increased linearly over time. Plasma cholesterol and low-density lipoprotein (LDL) significantly increased over time by an average of 5- and 15-fold, respectively, with a shift from high-density lipoprotein to LDL as the main plasma lipoprotein. Quaker parrots also exhibited high plasma cholesteryl ester transfer protein activity that increased, although not significantly, over time. This experiment demonstrates that in Quaker parrots fed 1% cholesterol, advanced atherosclerosis can be induced relatively quickly, and lesions resemble those found in other avian models and humans. PMID:23696447

Beaufrère, H; Nevarez, J G; Wakamatsu, N; Clubb, S; Cray, C; Tully, T N

2013-11-01

218

Fluorescence spectroscopic detection of virus-induced atherosclerosis  

NASA Astrophysics Data System (ADS)

Laser-induced fluorescence (LF) has been developed as a diagnostic tool for the detection of atherosclerosis. We have examined the use of LF for the identification of accelerated atherosclerotic plaque growth induced by Marek's Disease Virus (MDV) infection in White Leghorn rooster chicks (R) as well as plaque regression after treatment. Twenty-eight newborn R were infected with 12,000 cfu of MDV. Twelve parallel control R had saline injection. LF spectra were recorded from the arteries in vitro with a CeramOptec laser angioplasty catheter during 308 nm XeCl excimer laser excitation. Significant differences were detected at 440 to 475, 525, 550, 600, and 650 nm in MDV-R (p<0.05). In a subsequent study, 60 R were infected with 5,000 cfu of MDV, and were then treated with either Pravastatin (PRV) or placebo at 3 months post infection. These PRV-R were followed for 6 months to detect changes in atherosclerotic plaque development. PRV reduced intimal proliferation produced by MDV infection on histological examination (PRV-R 128.0+/- 44.0 micrometers , placebo-R 412.2+/- 91.5 micrometers , pequals0.007). MDV infected, PRV treated R were examined for LF changes that correlated with decreased atherosclerosis. There was an associated significant increase in LF intensity in PRV-R at 405 to 425 nm (p<0.001). In conclusion, LF can detect intimal proliferation in virus- induced atherosclerosis and atherosclerotic plaque regression after PRV therapy.

Yan, Wei-dong; Perk, Masis; Nation, Patric N.; Power, Robert F.; Liu, Liying; Jiang, Xiuyan; Lucas, Alexandra

1994-07-01

219

COLLATERALS DRAMATICALLY ALTER STROKE RISK IN INTRACRANIAL ATHEROSCLEROSIS  

PubMed Central

Objective Stroke risk due to intracranial atherosclerosis increases with degree of arterial stenosis. We evaluated the previously unexplored role of collaterals in modifying stroke risk in intracranial atherosclerosis and impact on subsequent stroke characteristics. Methods Collateral flow was graded in blind fashion on 287/569 baseline angiograms (stenoses of 50–99% and adequate collateral views) in the WASID trial. Statistical models predicted stroke in the symptomatic arterial territory based on collateral flow grade, percentage of stenosis, and previously demonstrated independent covariates. Results Across all stenoses, extent of collaterals was a predictor for subsequent stroke in the symptomatic arterial territory (HR none vs. good: 1.14, 95% CI 0.39 to 3.30, poor vs good: 4.36, 95% CI 1.46 to 13.07, p<0.0001). For 70–99% stenoses, more extensive collaterals diminished risk of subsequent territorial stroke (HR none vs. good: 4.60, 95% CI 1.03 to 20.56, poor vs good: 5.90, 95% CI 1.25 to 27.81, p=0.0427). At milder degrees of stenoses (50–69%), presence of collaterals was associated with greater likelihood of subsequent stroke (HR none vs. good: 0.18, 95% CI 0.04 to 0.82, poor vs good: 1.78, 95% CI 0.37 to 8.57, p<0.0001). In multivariate analyses, extent of collaterals was an independent predictor for subsequent stroke in the symptomatic arterial territory (HR none vs. good: 1.62, 95% CI 0.52 to 5.11, poor vs good: 4.78, 95% CI 1.55 to 14.7, p=0.0019). Interpretation Collateral circulation is a potent determinant of stroke risk in intracranial atherosclerosis, demonstrating a protective role with severe stenoses and identifying more unstable milder stenoses. PMID:21437932

Liebeskind, David S.; Cotsonis, George A.; Saver, Jeffrey L.; Lynn, Michael J.; Turan, Tanya N.; Cloft, Harry J.; Chimowitz, Marc I.

2010-01-01

220

The pigeon (Columba livia) model of spontaneous atherosclerosis.  

PubMed

Multiple animal models have been employed to study human atherosclerosis, the principal cause of mortality in the United States. Each model has individual advantages related to specific pathologies. Initiation, the earliest disease phase, is best modeled by the White Carneau (WC-As) pigeon. Atherosclerosis develops spontaneously in the WC-As without either external manipulation or known risk factors. Furthermore, susceptibility is caused by a single gene defect inherited in an autosomal recessive manner. The Show Racer (SR-Ar) pigeon is resistant to atherosclerosis. Breed differences in the biochemistry and metabolism of celiac foci cells have been described. For example, WC-As have lower oxidative metabolism but higher amounts of chondroitin-6-sulfate and nonesterified fatty acids compared with SR-Ar. Gene expression in aortic smooth muscle cells was compared between breeds using representational difference analysis and microarray analysis. Energy metabolism and cellular phenotype were the chief gene expression differences. Glycolysis and synthetic cell types were related to the WC-As but oxidative metabolism and contractile cell types were related to the SR-Ar. Rosiglitazone, a PPAR? agonist, blocked RNA binding motif (RBMS1) expression in WC-As cells. The drug may act through the c-myc oncogene as RBMS1 is a c-myc target. Proteomic tests of aortic smooth muscle cells supported greater glycosylation in the WC-As and a transforming growth factor ? effect in SR-Ar. Unoxidized fatty acids build up in WC-As cells because of their metabolic deficiency, ultimately preventing the contractile phenotype in these cells. The single gene responsible for the disease is likely regulatory in nature. PMID:25214557

Anderson, J L; Smith, S C; Taylor, R L

2014-11-01

221

Beta-carotene inhibits atherosclerosis in hypercholesterolemic rabbits.  

PubMed Central

Oxidatively damaged LDL may be of central importance in atherogenesis. Epidemiological evidence suggests that high dietary intakes of beta-carotene and vitamin E decreases the risk for atherosclerotic vascular disease, raising the possibility that lipid-soluble antioxidants slow vascular disease by protecting LDL from oxidation. To test this hypothesis, we fed male New Zealand White rabbits a high-cholesterol diet or the same diet supplemented with either 1% probucol, 0.01% vitamin E, 0.01% all-trans beta-carotene, or 0.01% 9-cis beta-carotene; then we assessed both the susceptibility of LDL to oxidation ex vivo and the extent of aortic atherosclerosis. As in earlier studies, probucol protected LDL from oxidation and inhibited lesion formation. In contrast, vitamin E modestly inhibited LDL oxidation but did not prevent atherosclerosis. While beta-carotene had no effect on LDL oxidation ex vivo, the all-trans isomer inhibited lesion formation to the same degree as probucol. Moreover, all-trans beta-carotene was undetectable in LDL isolated from rabbits fed the compound, although tissue levels of retinyl palmitate were increased. The effect of all-trans beta-carotene on atherogenesis can thus be separated from the resistance of LDL to oxidation, indicating that other mechanisms may account for the ability of this compound to prevent vascular disease. Our results suggest that metabolites derived from all-trans beta-carotene inhibit atherosclerosis in hypercholesterolemic rabbits, possibly via stereospecific interactions with retinoic acid receptors in the artery wall. PMID:7560102

Shaish, A; Daugherty, A; O'Sullivan, F; Schonfeld, G; Heinecke, J W

1995-01-01

222

[Determination of the intelligence quotient of pilots with incipient atherosclerosis].  

PubMed

Comprehensive examination, including clinical-functional and psychological testing, was given to 189 essentially healthy civil pilots and 235 pilots with atherosclerosis of aorta and trunks without considerable blood flow disturbance. The total of 835 investigations was performed. Distribution into health groups was conducted on clinical diagnosis. Pilots with cardiovascular pathologies were found to have the intelligence quotient significantly lowered. Associated clinical and psychological tests were effective in revealing and dynamic monitoring of incipient diseases, and taking reasoned disposition regarding pilot's fitness for flight duties. PMID:17405281

Krapivnitskaia, T A

2006-01-01

223

The graded effect of hyperhomocysteinemia on the severity and extent of coronary atherosclerosis  

Microsoft Academic Search

It is not clear to what extent methylenetetrahydrofolate reductase (MTHFR) gene and hyperhomocysteinemia effect the severity and extent of coronary atherosclerosis in Asian populations. We examined the MTHFR genotypes and plasma homocysteine (HCY) concentrations in 192 Taiwanese and investigated their relationship with coronary artery disease (CAD), and the severity and extent of coronary atherosclerosis. The distribution of MTHFR genotypes was

Chia-Lun Chao; Hui-Hsin Tsai; Chii-Ming Lee; Su-Ming Hsu; Jau-Tsuen Kao; Kuo-Liong Chien; Fung-Chang Sung; Yuan-Teh Lee

1999-01-01

224

Circle of Willis atherosclerosis: association with Alzheimer’s disease, neuritic plaques and neurofibrillary tangles  

Microsoft Academic Search

The role of intracranial atherosclerosis in Alzheimer’s disease (AD) has been a subject of debate since the first decade of the last century. The initial “vascular hypothesis” of AD was rejected after a series of mid-twentieth century gross anatomical postmortem studies that showed an inconstant relationship between intracranial atherosclerosis and senile dementia. These early studies did not utilize statistical methods,

Thomas G. Beach; Jeffrey R. Wilson; Lucia I. Sue; Amanda Newell; Marissa Poston; Raquel Cisneros; Yoga Pandya; Chera Esh; Donald J. Connor; Marwan Sabbagh; Douglas G. Walker; Alex E. Roher

2007-01-01

225

Repeated exposure to stressors do not accelerate atherosclerosis in ApoE ?\\/? mice  

Microsoft Academic Search

Psychosocial stress is suggested to play a significant role in development of cardiovascular disease. To evaluate the effects of repeated exposure to stress on atherosclerosis in atherosclerosis-prone ApoE?\\/? mice we used five different stressors. We further sought to determine whether stress combined with high salt diet induces dysfunctional neurohormonal regulation and impaired salt excretion, thus amplifying the atherogenic potential of

Evelina Bernberg; Irene J. Andersson; Sofia Tidstrand; Maria E. Johansson; Göran Bergström

2009-01-01

226

Atherosclerosis and ischemic cardiomyopathy in a captive, adult red-tailed hawk (Buteo jamaicensis).  

PubMed

An adult, male, captive red-tailed hawk (Buteo jamaicensis) of at least 19 years of age presented in dorsal recumbency. The hawk was nonresponsive, and despite initial supportive care, died shortly after presentation. Gross postmortem revealed no abnormal findings. Histologic examination demonstrated atherosclerosis and ischemic cardiomyopathy. This is the first reported case of atherosclerosis in a red-tailed hawk. PMID:18939649

Shrubsole-Cockwill, Alana; Wojnarowicz, Chris; Parker, Dennilyn

2008-09-01

227

Aortic smooth muscle cell proteoglycan synthesis in relation to atherosclerosis  

SciTech Connect

Proteoglycans (PG) are implicated in atherogenesis by their effects on tissue permeability and cell proliferation and their interaction with plasma low density lipoproteins. Using the pigeon model in which an atherosclerosis-susceptible (WC) and -resistant (SR) breed can be compared, PG synthesis by cultured aortic smooth muscle cells was examined by the use of ({sup 35}S)-sodium sulfate and ({sup 3}H)-serine or ({sup 3}H)-glucosamine as labeling precursors. In both SR and WC cells, the majority of newly synthesized PG were secreted into the media. Chondroitin sulfate (CS) PG and dermatan sulfate (DS) PG were the major PG produced. Total PG production was consistently lower in WC compared to SR cultures due in part to reduce PG synthesis but also to degradation of newly synthesized PG. Since increased DS-PG accompanines atherosclerosis progression, experiments were designed to test the hypothesis that macrophages modulate smooth muscle cell metabolism to cause increase DS-PG production. Cultured WC aortic smooth muscle cells were exposed to the media of cholesteryl ester-loaded pigeon peritoneal macrophages or a macrophage cell line P388D1 and the production of PG examined. Increasing concentration of conditioned media from both types of macrophages caused increased incorporation of {sup 35}S-sulfate into secreted PG, but no change in cell-associated PG. Lipopolysaccharide activation of P388D1 cells enhanced the effect.

Edwards, I.J.

1989-01-01

228

Does atherosclerosis contribute the development of Fahr’s Syndrome?  

PubMed Central

Fahr’s syndrome is a rare neurological condition in which calcification of vessels in the basal ganglia and cerebellum usually occurs. Impaired glucose tolerance (IGT) may be present, causing multiple organ complications by means of atherosclerosis. We report a case of Fahr’s syndrome associated with hypoparathyroidism and IGT. We present the case of a 52-year-old man with Fahr’s syndrome and IGT. The patient’s neurological examination was normal except for bilateral tremor. Laboratory investigations showed that the level of serum Ca (calcium) was 5.9 mg/dl, the parathormone (PTH) level was 1.95 pg/ml (normal level 15–65 pg/ml) and the phosphate (P) level was 5.45 mg/dl (normal level 2–6 mg/dl). Bilateral and symmetric calcifications in the basal ganglia, the centrum semiovale, and the cerebellum were demonstrated with a computerized scan of the head (CT) and magnetic resonance imaging (MRI). Therefore, the patient was diagnosed with Fahr’s syndrome. An endocrinologist was consulted, and treatment was started according to the suggestions of the endocrinologist. Here we report a case of Fahr’s syndrome associated with hypoparathyroidism and IGT. Atherosclerosis due to IGT may contribute to the calcification of brain vessels. Further investigations will be needed to clarify the pathogenesis of Fahr’s syndrome.

Varoglu, Asuman Orhan

2008-01-01

229

MicroRNAs and lipoproteins: a connection beyond atherosclerosis?  

PubMed Central

MicroRNAs (miRNAs) are involved in the pathogenesis of a number of cardiovascular diseases. In this review article, we have summarized the role of miRNAs in regulating lipid metabolism and how their therapeutical inhibition may lead to new approaches to treat cardiometabolic diseases, including atherosclerosis and metabolic syndrome. Specific miRNAs, such as miR-33a and -33b, represent one of the most interesting and attractive targets for metabolic-related disorders and anti-miR33 approaches are under intensive investigation. In addition to miR-33, other miRNAs, including miR-122, are also emerging as key players in lipid metabolism. More recently miRNAs were shown to exert their activities in a paracrine manner and also systemically. The latter is possible due to lipid-carriers, including lipoproteins, that transport and protect miRNAs from degradation. The emerging strong connection between miRNAs, lipoproteins and lipid metabolism indicates the existence of a reciprocal modulation that might go beyond atherosclerosis. PMID:23260873

Norata, Giuseppe Danilo; Sala, Federica; Catapano, Alberico Luigi; Fernández-Hernando, Carlos

2014-01-01

230

Apheresis technology for prevention and regression of atherosclerosis: an overview.  

PubMed

Low density lipoprotein (LDL) apheresis is at present one method of treatment in homozygous cases of familial hypercholesterolemia (FH). It is also effective in the prevention of the development of coronary atherosclerosis in patients with heterozygous FH and other types of mild hypercholesterolemia, leading to the regression of the stenosing lesions. In this paper, an overview is presented on the development of the devices for LDL apheresis and its short- and long-term effects on FH mainly based upon experience with the Liposorber system. LDL apheresis has served to protect the lives of patients from life threatening diseases like myocardial infarction although observations for more than 10 years in some laboratories have shown that the progression of atherosclerosis has taken place in many patients, and more importantly, the involvement of the aortic valve with calcification has developed, especially in patients who had homozygous FH, making this the most obstinate complication of FH. Therefore, more aggressive treatment or the combination of LDL apheresis with other therapies is required in the future. LDL apheresis has also been approved for the treatment of glomerulosclerosis and arteriosclerosis obliterans. PMID:10225745

Yamamoto, A; Kawaguchi, A; Harada-Shiba, M; Tsushima, M; Kojima, S

1997-08-01

231

Regression of Atherosclerosis: Insights from Animal and Clinical Studies  

PubMed Central

Based on studies that extend back to the 1920s, regression and stabilization of atherosclerosis in humans has gone from just a dream to one that is achievable. Review of the literature indicates that the successful attempts at regression generally applied robust measures to improve plasma lipoprotein profiles. Examples include extensive lowering of plasma concentrations of atherogenic apolipoprotein B and enhancement of reverse cholesterol transport from atheromata to the liver. Possible mechanisms responsible for lesion shrinkage include decreased retention of atherogenic apolipoprotein B within the arterial wall, efflux of cholesterol and other toxic lipids from plaques, emigration of lesional foam cells out of the arterial wall, and influx of healthy phagocytes that remove necrotic debris as well as other components of the plaque. However, currently available clinical agents cause less dramatic changes in plasma lipoprotein levels, and thereby fail to stop most cardiovascular events. There is, therefore, a clear need for preclinical and clinical testing of new agents expected to facilitate atherosclerosis regression with the hope that additional mechanistic insights will allow further progress. PMID:24751561

Feig, Jonathan E.

2014-01-01

232

Elastin fragmentation and atherosclerosis progression: the elastokine concept.  

PubMed

Atherosclerosis is a progressive multifaceted inflammatory disease affecting large- and medium-sized arteries. Typical feature of this disease is the formation and build-up of atherosclerotic plaques characterized by vascular extracellular matrix degradation and remodeling. Many studies have documented degradation of native elastin, the main extracellular matrix protein responsible for resilience and elasticity of arteries, by local release of elastases, leading to the production of elastin-derived peptides (EDP). These peptides have been proposed to actively participate in the progression of the disease by accelerating different biological processes, such as LDL oxidation and calcification of the vascular wall. These pathophysiological effects are mediated by the binding of EDP on a peculiar heterotrimeric receptor named elastin receptor complex (ERC). In this article, we review the contribution of elastin in biological processes involved in atherosclerosis progression from its initial elastase-driven degradation to its ultimate cellular effects. Finally, we discuss the ERC and its derived signaling pathways as promising therapeutic targets. PMID:23561795

Maurice, Pascal; Blaise, Sébastien; Gayral, Stéphanie; Debelle, Laurent; Laffargue, Muriel; Hornebeck, William; Duca, Laurent

2013-08-01

233

Zebrafish models of dyslipidemia: Relevance to atherosclerosis and angiogenesis  

PubMed Central

Lipid and lipoprotein metabolism in zebrafish and in humans are remarkably similar. Zebrafish express all major nuclear receptors, lipid transporters, apolipoproteins and enzymes involved in lipoprotein metabolism. Unlike mice, zebrafish express cetp and the Cetp activity is detected in zebrafish plasma. Feeding zebrafish a high cholesterol diet, without any genetic intervention, results in significant hypercholesterolemia and robust lipoprotein oxidation, making zebrafish an attractive animal model to study mechanisms relevant to early development of human atherosclerosis. These studies are facilitated by the optical transparency of zebrafish larvae and the availability of transgenic zebrafish expressing fluorescent proteins in endothelial cells and macrophages. Thus, vascular processes can be monitored in live animals. In this review article we discuss recent advances in using dyslipidemic zebrafish in atherosclerosis-related studies. We also summarize recent work connecting lipid metabolism with regulation of angiogenesis, the work that considerably benefited from using the zebrafish model. These studies uncovered the role of aibp, abca1, abcg1, mtp, apoB and apoC2 in regulation of angiogenesis in zebrafish and paved the way for future studies in mammals, which may suggest new therapeutic approaches to modulation of excessive or diminished angiogenesis contributing to the pathogenesis of human disease. PMID:24095954

Fang, Longhou; Liu, Chao; Miller, Yury I.

2013-01-01

234

Cyclin-dependent kinase 9 may as a novel target in downregulating the atherosclerosis inflammation (Review)  

PubMed Central

Inflammation is a key component of atherosclerosis. Genes coding for inflammatory or anti-inflammatory molecules are considered good candidates for estimating the risk of developing atherosclerosis. Cyclin-dependent kinase 9 (CDK9), the kinase of positive transcription elongation factor b (P-TEFb), is crucial in the cell cycle and apoptosis. Previous studies have focused on its inhibition of immune cells for the resolution of inflammation. Considering the effects of inflammation in the pathogenicity of atherosclerosis, decreasing inflammation through the inhibition of CDK9 may be useful for the prognosis of atherosclerosis. The aim of this review was to examine whether inhibition of the CDK9 monocyte may affect the process of inflammation by acting on the cytokine secretion and interacting with endothelial cells (ECs). Thus, CDK9 may be a novel target for the diagnosis and therapy of atherosclerosis. PMID:25279144

HAN, YEMING; ZHAN, YANG; HOU, GUIHUA; LI, LI

2014-01-01

235

Postmortem coronary atherosclerosis findings in general aviation accident pilot fatalities: 1975-77.  

PubMed

The autopsies of 764 pilots involved in fatal general aviation accidents during the years 1975-77 were reviewed to appraise the age specific prevalence of coronary atherosclerosis among the autopsied group. Of the pilots killed in aircraft accidents and autopsied during 1975-77, 51% were found to have some degree of coronary atherosclerosis ranging from minimal to severe. However, only about 5% of the autopsied group were categorized as having severe coronary atherosclerosis. The rate per 1,000 of severe coronary atherosclerosis increased with age from 14.5 for ages less than 30, to 89.9 for ages 50 years and above; the rate nearly tripled from ages 30-39 to 40-49 (22.1 to 63.6). The prevalence of coronary atherosclerosis among this group of autopsied airmen is less than would have been expected based on the results of other recent studies. PMID:7213283

Booze, C F; Pidkowicz, J K; Davis, A W; Bolding, F A

1981-01-01

236

PPAR activation differently affects microparticle content in atherosclerotic lesions and liver of a mouse model of atherosclerosis and NASH  

E-print Network

: Atherosclerosis and non-alcoholic fatty liver disease (NAFLD) are complex pathologies characterized by lipid actors in these pathologies. The apoE2-KI mouse is a model of atherosclerosis and NAFLD. Activation and plasma during atherosclerosis and NASH progression in apoE2-KI mice, and 2) to study whether PPAR

Boyer, Edmond

237

Fire Suppression and Response  

NASA Technical Reports Server (NTRS)

This report is concerned with the following topics regarding fire suppression:What is the relative effectiveness of candidate suppressants to extinguish a representative fire in reduced gravity, including high-O2 mole fraction, low -pressure environments? What are the relative advantages and disadvantages of physically acting and chemically-acting agents in spacecraft fire suppression? What are the O2 mole fraction and absolute pressure below which a fire cannot exist? What effect does gas-phase radiation play in the overall fire and post-fire environments? Are the candidate suppressants effective to extinguish fires on practical solid fuels? What is required to suppress non-flaming fires (smoldering and deep seated fires) in reduced gravity? How can idealized space experiment results be applied to a practical fire scenario? What is the optimal agent deployment strategy for space fire suppression?

Ruff, Gary A.

2004-01-01

238

Prospects for prevention of atherosclerosis in the young.  

PubMed

There appears to be a need to protect our young from an atherogenic way of life. The average male child today has one chance in three of a cardiovascular catastrophe before age 60. Atherosclerosis and the conditions which predispose appear to have their onset in childhood. Correctable precursors of cardiovascular disease have been identified, and their contribution to risk has been estimated not only for adults but for college students as well. An analysis of the combined impact of atherogenic risk factors indicates that they exert greater force early in life than later. Although the optimal time to begin prophylaxis is not established, there is evidence to suggest that measures instituted late in life when lesions are advanced is of only limited value. Prevention of atherosclerosis is best viewed as a family affair since the propensity to disease and contributing factors tend to be shared by family members. It is also difficult to implement effectively preventive measures which include dietary changes, weight control, exercise and restriction of cigarettes for one family member without involving the rest of the family. Optimal levels of the correctable precursors of cardiovascular disease are not established for children. However, the rise in serum lipids, blood pressure, weight and blood sugar observed in transition from childhood to adult life is not inevitable, or desirable. Paediatricians can alter the appalling cardiovascular mortality statistics by not allowing the process or the habits and conditions which promote it to reach an irreversible stage. Cardiovascular disease may well begin in childhood with "medical trivia" such as a tendency to obesity, moderate cholesterol and blood pressure elevations, lack of exercise and the cigarette habit. In some respects a heart attack at age 45 can be regarded as a failure of the paediatrician. Awaiting proof of the efficacy of the indicated prophylactic measures is not acceptable since this will be a long time in coming. We must learn how to correct risk factors effectively in childhood as soon as they appear. We must establish goals based on optimal as distinct from usual levels of risk factors. Paediatricians' resolve about prevention of atherosclerosis in childhood needs to be strengthened and we must develop a sense of urgency about this. PMID:1071869

Kannel, W B

1976-10-01

239

Establishment and ultrasound characteristics of atherosclerosis in rhesus monkey  

PubMed Central

Background Atherosclerosis is one of the main risk factors cause acute cerebral-cardio vascular diseases. It's of great significance to establish an atherosclerosis animal model that can mimic the characteristics and nature course of human patients. Therefore, a rhesus monkey model was induced by high-fat diet to monitor their lipid profile and intima-media thickness (IMT) of artery walls and study atherosclerosis progression. Methods Fifty male rhesus monkeys were enrolled in this study. All of these monkeys were aged 7 to 14 years with BMI >30 kg/m2. They were fed with high-fat diet containing 10% of fat for the first 48 weeks. Use ultrasound to measure the IMT at bilateral common carotid arteries and their bifurcations and aorta (AO) of the monkeys, and screen out the individuals with thickened IMT for the next phase. In the next 48 weeks, some of these monkeys (n = 4) were fed with standard diet containing 3% fat. Meanwhile the other monkeys (n = 5) were fed with high-fat diet for another 48 weeks. Their serum lipid level was monitored and arterial IMT was also determined periodically. Results Serum lipid level of all 50 monkeys elevated after fed with high-fat diet for the first 48 weeks. IMT thickening at right common carotid bifurcation and aorta (AO) was thickened in 9 monkeys. Furthermore, 4 of these 9 monkeys were fed with standard diet and other 5 monkeys were fed with high-fat diet in the following 48 weeks. The serum lipid level of the 4 monkeys recovered and their IMT at RBIF and AO did not progress. However, the lipid level of other 5 monkeys remained high, and their IMT thickening of AO progressed, and plaques and calcification focuses were found at the anterior wall of aorta near the bifurcation of common iliac artery. Conclusions After high-fat diet induction for 96 weeks, serum lipid levels of rhesus monkeys elevated significantly, which subsequently caused IMT thickening and plaques formation. When IMT thickening occurred, further vascular injury may be prevented by reducing diet fat content. Our study indicates that vascular injury of high-fat diet induced rhesus monkey is similar to that of human in position and progression. PMID:25602196

2015-01-01

240

Interleukin-10 protects against atherosclerosis by modulating multiple atherogenic macrophage function.  

PubMed

Atherosclerosis is primarily a disorder of lipid metabolism, but there is also a prominent chronic inflammatory component that drives the atherosclerotic lesion progression in the artery wall. During hyperlipidaemic conditions, there is a rapid influx of circulating monocytes into the atherosclerosis-prone areas of the arterial intima. These infiltrated monocytes differentiate into macrophages and take up the atherogenic lipoproteins in the intima of the vessel wall that have been modified within the lesion environment. Interleukin (IL)-10 is a prototypic anti-inflammatory cytokine made primarily by the macrophages and Th2 subtype T lymphocytes. In terms of atherosclerosis its major roles include inhibition of macrophage activation as well as inhibition of matrix metalloproteinase, pro-inflammatory cytokines and cyclooxygenase-2 expression in lipid-loaded and activated macrophage foam cells. Recent discoveries suggest another important role of IL-10 in atherosclerosis: its ability to alter lipid metabolism in macrophages. The current review will highlight the present knowledge on multiple ways in which IL-10 mediates atherosclerosis. As macrophages play a critical role in all stages of atherosclerosis, the review will concentrate on how IL-10 regulates the activities of macrophages that are especially important in the development of atherosclerosis. PMID:25373619

Han, X; Boisvert, W A

2014-11-01

241

CD40 in Clinical Inflammation: From Multiple Sclerosis to Atherosclerosis  

PubMed Central

The interactions of CD40 and CD40L have been known for some time to critically regulate B-cell responses with respect to proliferation, isotype switching, antibody production, and memory formation. More recent findings demonstrated that CD40 can be expressed on several other antigen-presenting cell (APC) types such as macrophages, dendritic cells, and fibroblasts. This expression of CD40 regulates T-cell-APC interaction and is centrally involved in a wide array of inflammatory events. Here, currently available data are reviewed demonstrating that CD40- CD40L interactions are operational in two chronic inflammatory clinical conditions, namely, multiple sclerosis and atherosclerosis. The functional correlates of these interactions are discussed in the light of recent other findings, shedding light on the multiple effects of CD40- CD40L interactions. PMID:9814595

De Boer, Mark; Hart, Bert A. 'T

1998-01-01

242

Dynamic Aspects of Macrophage Polarization during Atherosclerosis Progression and Regression  

PubMed Central

It is well recognized that macrophages in many contexts in vitro and in vivo display a spectrum of inflammatory features and functional properties. A convenient system to group together different subsets of macrophages has been the M1 (inflammatory)/M2 (anti-inflammatory) classification. In addition to other sites of inflammation, it is now established that atherosclerotic plaques contain both M1 and M2 macrophages. We review results made possible by a number of recent mouse models of atherosclerotic regression that, taken with other literature, have shown the M1/M2 balance in plaques to be dynamic, with M1 predominating in disease progression and M2 in regression. The regulation of the macrophage phenotype in plaques and the functional consequences of the M1 and M2 states in atherosclerosis will also be discussed. PMID:25429291

Peled, Michael; Fisher, Edward A.

2014-01-01

243

Genetics of leukocyte telomere length and its role in atherosclerosis.  

PubMed

Humans display a large inter-individual variation in leukocyte telomere length (LTL), which is influenced by heredity, sex, race/ethnicity, paternal age at conception and environmental exposures. LTL dynamics (birth LTL and its age-dependent attrition thereafter) mirror telomere dynamics in hematopoietic stem cells (HSCs). LTL at birth is evidently a major determinant of LTL throughout the human lifespan, such that individuals endowed with short (or long) LTL at birth probably have short (or long) LTL later in life. Therefore, the associations of short LTL with atherosclerosis and with diminished survival in the elderly may relate to short birth LTL, accelerated age-dependent LTL attrition, or both. The mechanisms underlying these associations are still not well understood, but they stem in part from genetic factors in control of telomere maintenance and the rate of HSC replication. PMID:21600224

Aviv, Abraham

2012-02-01

244

Extracellular matrix synthesis in vascular disease: hypertension, and atherosclerosis  

PubMed Central

Extracellular matrix (ECM) within the vascular network provides both a structural and regulatory role. The ECM is a dynamic composite of multiple proteins that form structures connecting cells within the network. Blood vessels are distended by blood pressure and, therefore, require ECM components with elasticity yet with enough tensile strength to resist rupture. The ECM is involved in conducting mechanical signals to cells. Most importantly, ECM regulates cellular function through chemical signaling by controlling activation and bioavailability of the growth factors. Cells respond to ECM by remodeling their microenvironment which becomes dysregulated in vascular diseases such hypertension, restenosis and atherosclerosis. This review examines the cellular and ECM components of vessels, with specific emphasis on the regulation of collagen type I and implications in vascular disease. PMID:24474961

Ponticos, Markella; Smith, Barbara D.

2014-01-01

245

Plasma Cholesterol–Induced Lesion Networks Activated before Regression of Early, Mature, and Advanced Atherosclerosis  

PubMed Central

Plasma cholesterol lowering (PCL) slows and sometimes prevents progression of atherosclerosis and may even lead to regression. Little is known about how molecular processes in the atherosclerotic arterial wall respond to PCL and modify responses to atherosclerosis regression. We studied atherosclerosis regression and global gene expression responses to PCL (?80%) and to atherosclerosis regression itself in early, mature, and advanced lesions. In atherosclerotic aortic wall from Ldlr?/?Apob100/100Mttpflox/floxMx1-Cre mice, atherosclerosis regressed after PCL regardless of lesion stage. However, near-complete regression was observed only in mice with early lesions; mice with mature and advanced lesions were left with regression-resistant, relatively unstable plaque remnants. Atherosclerosis genes responding to PCL before regression, unlike those responding to the regression itself, were enriched in inherited risk for coronary artery disease and myocardial infarction, indicating causality. Inference of transcription factor (TF) regulatory networks of these PCL-responsive gene sets revealed largely different networks in early, mature, and advanced lesions. In early lesions, PPARG was identified as a specific master regulator of the PCL-responsive atherosclerosis TF-regulatory network, whereas in mature and advanced lesions, the specific master regulators were MLL5 and SRSF10/XRN2, respectively. In a THP-1 foam cell model of atherosclerosis regression, siRNA targeting of these master regulators activated the time-point-specific TF-regulatory networks and altered the accumulation of cholesterol esters. We conclude that PCL leads to complete atherosclerosis regression only in mice with early lesions. Identified master regulators and related PCL-responsive TF-regulatory networks will be interesting targets to enhance PCL-mediated regression of mature and advanced atherosclerotic lesions. PMID:24586211

Björkegren, Johan L. M.; Hägg, Sara; Jain, Rajeev K.; Cedergren, Cecilia; Shang, Ming-Mei; Rossignoli, Aránzazu; Takolander, Rabbe; Melander, Olle; Hamsten, Anders; Michoel, Tom; Skogsberg, Josefin

2014-01-01

246

Chlorogenic Acid Protects against Atherosclerosis in ApoE?/? Mice and Promotes Cholesterol Efflux from RAW264.7 Macrophages  

PubMed Central

Chlorogenic acid (CGA) is one of the most abundant polyphenols in the human diet and is suggested to be a potential antiatherosclerotic agent due to its proposed hypolipidemic, anti-inflammatory and antioxidative properties. The aim of this study was to evaluate the effect of CGA on atherosclerosis development in ApoE?/? mice and its potential mechanism. ApoE?/? mice were fed a cholesterol-rich diet without (control) or with CGA (200 and 400 mg/kg) or atorvastatin (4 mg/kg) for 12 weeks. During the study plasma lipid and inflammatory parameters were determined. Treatment with CGA (400 mg/kg) reduced atherosclerotic lesion area and vascular dilatation in the aortic root, comparable to atorvastatin. CGA (400 mg/kg) also significantly decreased plasma levels of total cholesterol, triglycerides and low-density lipoprotein-cholesterol as well as inflammatory markers. Supplementation with CGA or CGA metabolites-containing serum suppressed oxidized low-density lipoprotein (oxLDL)-induced lipid accumulation and stimulated cholesterol efflux from RAW264.7 cells. CGA significantly increased the mRNA levels of PPAR?, LXR?, ABCA1 and ABCG1 as well as the transcriptional activity of PPAR?. Cholesterol efflux assay showed that three major metabolites, caffeic, ferulic and gallic acids, significantly stimulated cholesterol efflux from RAW264.7 cells. These results suggest that CGA potently reduces atherosclerosis development in ApoE?/? mice and promotes cholesterol efflux from RAW264.7 macrophages. Caffeic, ferulic and gallic acids may be the potential active compounds accounting for the in vivo effect of CGA. PMID:25187964

Wu, Chongming; Luan, Hong; Zhang, Xue; Wang, Shuai; Zhang, Xiaopo; Sun, Xiaobo; Guo, Peng

2014-01-01

247

Nanoparticle PET-CT imaging of macrophages in inflammatory atherosclerosis  

PubMed Central

Background Macrophages (Mø) participate centrally in atherosclerosis and Mø markers (e.g. CD68, MAC-3) correlate well with lesion severity and therapeutic modulation. Based on the avidity of lesional Mø for polysaccharide containing supramolecular structures such as nanoparticles, we have developed a new positron emission tomography (PET) agent with optimized pharmacokinetics to allow in vivo imaging at tracer concentrations. Methods and Results A dextranated and DTPA-modified magnetofluorescent 20nm nanoparticle was labeled with the PET tracer 64Cu (1 mCi/0.1mg NP) to yield a PET, MR and optically detectable imaging agent. Peak PET activity 24 hours after i.v. injection into mice deficient in apolipoprotein E (apoE-/-) with experimental atherosclerosis mapped to areas of high plaque load identified by CT, such as the aortic root and arch, and correlated with magnetic resonance and optical imaging. Accumulated dose in apoE-/- aortas determined by gammacounting was 260% and in carotids 392% of respective wild type organs (p<0.05 both). Autoradiography of aortas demonstrated uptake of the agent into Mø-rich atheromata identified by Oil red O staining of lipid deposits. The novel nanoagent accumulated predominantly in Mø as determined by fluorescence microscopy and flow cytometry of cells dissociated from aortas. Conclusion This report establishes the capability of a novel tri-modality nanoparticle to directly detect Mø in atherosclerotic plaques. Advantages include improved sensitivity, direct correlation of PET signal with an established biomarker (CD68), ability to readily quantify the PET signal, perform whole body vascular surveys, the ability to spatially localize and follow the tri-reporter by microscopy, and the clinical translatability of the agent given similarities to MRI probes in clinical trials. PMID:18158358

Nahrendorf, Matthias; Zhang, Hanwen; Hembrador, Sheena; Panizzi, Peter; Sosnovik, David E.; Aikawa, Elena; Libby, Peter; Swirski, Filip K.; Weissleder, Ralph

2009-01-01

248

Metabolic Syndrome and Subclinical Atherosclerosis in Patients Infected with HIV  

PubMed Central

Background The present study examines the association between carotid and coronary atherosclerosis and metabolic syndrome in human immunodeficiency virus (HIV)–infected adults. Methods We measured the common and internal carotid intima-media thickness (c-IMT) using B-mode ultrasonography, and we measured coronary artery calcium (CAC) using high-resolution, electrocardiographic, synchronized, computed tomography, for 314 HIV-infected men and women. Metabolic syndrome was defined by National Cholesterol Education Program/Adult Treatment Panel III criteria. We compared the c-IMT measurements and CAC scores of patients with metabolic syndrome with the scores of those without metabolic syndrome using a Wilcoxon test for continuous variables and a ?2 test for categorical variables. To examine the association between surrogate markers and metabolic syndrome, we used logistic regression analysis. Results Participants with metabolic syndrome were more likely to have a common c-IMT measurement >0.8 mm than were those without metabolic syndrome (17% vs.7%; P=.009), but both groups were equally likely to have an internal c-IMT measurement >1.0 mm (20% vs. 13%; P=.15). Any positive CAC score was more likely to occur for participants with metabolic syndrome (80.3% vs. 46.7%; P < .0001). In a multivariate model adjusted for sex, age, ethnicity, and smoking status, participants with metabolic syndrome were more likely than those without metabolic syndrome to have an abnormal common c-IMT measurement (odds ratio [OR], 2.9; P= .020) and detectable CAC scores (OR, 4.9; P < .0001) but not a higher internal c-IMT measurement (OR, 1.6; P=.255). Conclusion Our study demonstrates that HIV-infected individuals with metabolic syndrome may be at increased risk for subclinical atherosclerosis and supports screening for metabolic syndrome among HIV-infected patients at risk for cardiovascular disease. PMID:17443477

Mangili, Alexandra; Jacobson, Denise L.; Gerrior, Jul; Polak, Joseph F.; Gorbach, Sherwood L.; Wanke, Christine A.

2009-01-01

249

Soluble TWEAK independently predicts atherosclerosis in renal transplant patients  

PubMed Central

Background Cardiovascular risk is increased in the early stages of chronic kidney disease (CKD) and also found to be ongoing in renal transplant (Rtx) patients. As a sign of atherosclerosis, increased carotid intima-media thickness (CIMT) has been widely accepted as a strong predictor of cardiovascular disease (CVD) and mortality in CKD patients. A novel markers, soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) and neutrophil-to-lymphocyte ratio (NLR) were introduced as potential markers in inflammatory disorders including CKD. The role of Rtx in terms of atherogenesis is still unclear. We aimed to investigate the relationship between sTWEAK, NLR and CIMT in Rtx patients without overt CVD and to compare these results with those obtained from healthy subjects. Methods Cross-sectional analysis in which CIMT measurements, NLR and serum TWEAK levels were assessed in 70 Rtx patients (29 females; mean age, 40.6?±?12.4 years) and 25 healthy subjects (13 females, mean age; 37.4±8.8 years). Results sTWEAK levels were significantly decreased (p=0.01) and hs-CRP, NLR and CIMT levels of Rtx patients were significantly increased compared to healthy subjects (p<0.0001, p=0.001, p<0.0001, respectively). sTWEAK was also found to be decreased when eGFR was decreased (p=0.04 between all groups). CIMT was positively correlated with sTWEAK and NLR in Rtx patients (r=0.81, p<0.0001 and r=0.33, p=0.006, respectively). sTWEAK was also positively correlated with NLR (r=0.37, p=0.002). In the multivariate analysis only sTWEAK was found to be an independent variable of increased CIMT. Conclusion sTWEAK might have a role in the pathogenesis of ongoing atherosclerosis in Rtx patients. PMID:23849432

2013-01-01

250

Peculiarities of spectroscopic information of whole blood in atherosclerosis  

NASA Astrophysics Data System (ADS)

The coefficient of diffuse reflection and light transmission measurements in an optically thick layer of blood at atherosclerosis conditions under multiple scattering of light in the visual and nearest IR-spectra region (590 -900 nm) were measured for calculation of the absorption coefficients of the material of particles and surrounding medium K((lambda) ) and parameter Q (the latter parameter was defined by the sizes of erythrocytes and aggregates and by refraction coefficient of red cells relative to plasma at atherosclerosis). For the main quantitative spectroscopy of particles the K1((lambda) ) for known value of K((lambda) ) and the parameter Q determinations it is necessary to have the knowledge of relative volume part H occupied by particles. In the case of a high concentration of particles H >= 0.2 as it takes place in the blood the parameters Q and K((lambda) ) are in dependence of H (H - is hematocrit ration for the case of whole blood). It should be noted that spectroscopy of multiple scattering light can give some information out of main absorption bands with the higher accuracy and higher light scattering. The latter value provides the opportunity of determination of faint absorption bands which couldn't be achieved by other methods. The method proposed is characterized by absence of probe preparations, approach to in viva conditions, expressivity, and high informativity of each experiment. A many-fold investigation of the blood of healthy men in the spectral region 650 - 810 nm shows the electron spectrum of absorption of molecular hemoglobin hem is the most optically active blood spectra component K((lambda) ). The broadening of spectral investigations, as in short wave or long wave areas of the spectrum, by the use of multiple scattering methods for calculations of K((lambda) ) and Q((lambda) ) enlarges the number of chromophores studied.

Khairullina, Alphiya Y.; Oleinik, Tatiana V.; Yusupova, Lira B.; Prigoun, Natalia

1995-01-01

251

Subclinical Atherosclerosis Measures for Cardiovascular Prediction in CKD.  

PubMed

Whether inclusion of the coronary artery calcium score improves cardiovascular risk prediction in individuals with CKD, a population with unique calcium-phosphate homeostasis, is unknown. Among 6553 participants ages 45-84 years without prior cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis, coronary artery calcium score was assessed for cardiovascular risk prediction beyond the Framingham predictors in those with (n=1284) and without CKD and contrasted with carotid intima-media thickness and ankle-brachial index (two other measures of subclinical atherosclerosis). During a median follow-up of 8.4 years, 650 cardiovascular events (coronary heart disease, stroke, heart failure, and peripheral artery disease) occurred (236 events in subjects with CKD). In Cox proportional hazards models adjusted for Framingham predictors, each subclinical measure was independently associated with cardiovascular outcomes, with larger adjusted hazard ratios (HRs; per 1 SD) for coronary artery calcium score than carotid intima-media thickness or ankle-brachial index in subjects without and with CKD (HR, 1.69; 95% confidence interval [95% CI], 1.45 to 1.97 versus HR, 1.12; 95% CI, 1.00 to 1.25 and HR, 1.20; 95% CI, 1.08 to 1.32, respectively). Compared with inclusion of carotid intima-media thickness or ankle-brachial index, inclusion of the coronary artery calcium score led to greater increases in C statistic for predicting cardiovascular disease and net reclassification improvement. Coronary artery calcium score performed best for the prediction of coronary heart disease and heart failure, regardless of CKD status. In conclusion, each measure improved cardiovascular risk prediction in subjects with CKD, with the greatest improvement observed with coronary artery calcium score. PMID:25145930

Matsushita, Kunihiro; Sang, Yingying; Ballew, Shoshana H; Shlipak, Michael; Katz, Ronit; Rosas, Sylvia E; Peralta, Carmen A; Woodward, Mark; Kramer, Holly J; Jacobs, David R; Sarnak, Mark J; Coresh, Josef

2015-02-01

252

Genetic predisposition to obesity and risk of subclinical atherosclerosis.  

PubMed

Obesity has been associated with increased common carotid artery (CCA) intima-media thickness (IMT), a measure of subclinical atherosclerosis. We assessed the association between genetic predisposition to obesity and CCA IMT. The study included 428 young Chinese adults with CCA IMT measured using a high-resolution B-mode tomographic ultrasound system. We created a genetic risk score (GRS) by summing the risk alleles of 6 obesity-associated genetic variants confirmed in our previous analyses. The GRS was significantly associated with greater CCA IMT (p<0.001) after adjustment for age and gender. Per 2 alleles of the GRS was related to 0.023 mm increment in IMT. The association was attenuated by one half with additional adjustment for obesity status, but remained significant (p=0.009). In addition, we found that blood pressure significantly modified the association between the GRS and CCA IMT (p for interaction=0.001). The associations between the GRS and CCA IMT were stronger in participants with systolic blood pressure (SBP) ?120 mmHg and/or diastolic blood pressure (DBP) ?80 mmHg (per 2 allele increment of the GRS relating to 0.028 mm greater CCA IMT, p for trend<0.001) than those with SBP<120 mmHg and DBP<80 mmHg (per 2 allele increment of the GRS relating to 0.001 smaller CCA IMT, p for trend=0.930). Our data provides suggestive evidence supporting the potential causal relation between obesity and development of subclinical atherosclerosis. Elevated blood pressure might amplify the adverse effect of obesity on cardiovascular risk. PMID:25064489

Shi, Juan; Hong, Jie; Qi, Lu; Cui, Bin; Gu, Weiqiong; Zhang, Yifei; Li, Lijuan; Miao, Lin; Wang, Rui; Wang, Weiqing; Ning, Guang

2014-10-10

253

A historical perspective towards a non-invasive treatment for patients with atherosclerosis  

PubMed Central

The history of atherosclerosis and cardiovascular disease dates back to ancient times. From the teachings of Galen to the response-to-injury hypothesis of Russel Ross, we have now arrived at the concept of the vulnerable plaque. Next to the development of new treatment options for patients with atherosclerosis, also novel diagnostic imaging techniques have been developed to visualise the arterial wall and to characterise plaque composition. In this article the historical context of atherosclerosis and the attempts towards a noninvasive therapy for patients with atherosclerotic diseases are described. (Neth Heart J 2009;17:140-4.19421359) PMID:19421359

Slijkhuis, W.; Mali, W.; Appelman, Y.

2009-01-01

254

Significantly increased risk of carotid atherosclerosis with arsenic exposure and polymorphisms in arsenic metabolism genes  

SciTech Connect

Individual susceptibility to arsenic-induced carotid atherosclerosis might be associated with genetic variations in arsenic metabolism. The purpose of this study is to explore the interaction effect on risk of carotid atherosclerosis between arsenic exposure and risk genotypes of purine nucleoside phosphorylase (PNP), arsenic (+3) methyltransferase (As3MT), and glutathione S-transferase omega 1 (GSTO1) and omega 2 (GSTO2). A community-based case-control study was conducted in northeastern Taiwan to investigate the arsenic metabolic-related genetic susceptibility to carotid atherosclerosis. In total, 863 subjects, who had been genotyped and for whom the severity of carotid atherosclerosis had been determined, were included in the present study. Individual well water was collected and arsenic concentration determined using hydride generation combined with flame atomic absorption spectrometry. The result showed that a significant dose-response trend (P=0.04) of carotid atherosclerosis risk associated with increasing arsenic concentration. Non-significant association between genetic polymorphisms of PNP Gly51Ser, Pro57Pro, As3MT Met287Thr, GSTO1 Ala140Asp, and GSTO2 A-183G and the risk for development of carotid atherosclerosis were observed. However, the significant interaction effect on carotid atherosclerosis risk was found for arsenic exposure (>50 {mu}g/l) and the haplotypes of PNP (p=0.0115). A marked elevated risk of carotid atherosclerosis was observed in subjects with arsenic exposure of >50 {mu}g/l in drinking water and those who carried the PNP A-T haplotype and at least either of the As3MT risk polymorphism or GSTO risk haplotypes (OR, 6.43; 95% CI, 1.79-23.19). In conclusion, arsenic metabolic genes, PNP, As3MT, and GSTO, may exacerbate the formation of atherosclerosis in individuals with high levels of arsenic concentration in well water (>50 {mu}g/l). - Highlights: {yields}Arsenic metabolic genes might be associated with carotid atherosclerosis. {yields} A case-control study was conducted to investigate the arsenic metabolic-related genetic susceptibility to carotid atherosclerosis. {yields} Arsenic metabolic genes, PNP, As3MT, and GSTO, may exacerbate atherosclerosis risk in individuals with high levels of arsenic in well water.

Hsieh, Yi-Chen [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China)] [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Lien, Li-Ming [Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China) [Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); School of Medicine, Taipei Medical University, Taipei, Taiwan (China); Department of Neurology, Shin Kong WHS Memorial Hospital, Taipei, Taiwan (China); Chung, Wen-Ting [Department of Neurology, Wanfang Hospital, Taipei Medical University, Taipei, Taiwan (China) [Department of Neurology, Wanfang Hospital, Taipei Medical University, Taipei, Taiwan (China); Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan (China); Hsieh, Fang-I; Hsieh, Pei-Fan [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China)] [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Wu, Meei-Maan [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China) [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Graduate Institute of Basic Medicine, College of Medicine, Fu-Jen Catholic University, Taipei, Taiwan (China); Tseng, Hung-Pin [Department of Neurology, Lotung Poh-Ai Hospital, I-Lan, Taiwan (China)] [Department of Neurology, Lotung Poh-Ai Hospital, I-Lan, Taiwan (China); Chiou, Hung-Yi, E-mail: hychiou@tmu.edu.tw [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China)] [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Chen, Chien-Jen [Genomics Research Center, Academia Sinica, Taipei, Taiwan (China)] [Genomics Research Center, Academia Sinica, Taipei, Taiwan (China)

2011-08-15

255

Piperlongumine inhibits atherosclerotic plaque formation and vascular smooth muscle cell proliferation by suppressing PDGF receptor signaling  

SciTech Connect

Highlights: Black-Right-Pointing-Pointer Anti-atherogenic effect of PL was examined using partial carotid ligation model in ApoE KO mice. Black-Right-Pointing-Pointer PL prevented atherosclerotic plaque development, VSMCs proliferation, and NF-{kappa}B activation. Black-Right-Pointing-Pointer Piperlongumine reduced vascular smooth muscle cell activation through PDGF-R{beta} and NF-{kappa}B-signaling. Black-Right-Pointing-Pointer PL may serve as a new therapeutic molecule for atherosclerosis treatment. -- Abstract: Piperlongumine (piplartine, PL) is an alkaloid found in the long pepper (Piper longum L.) and has well-documented anti-platelet aggregation, anti-inflammatory, and anti-cancer properties; however, the role of PL in prevention of atherosclerosis is unknown. We evaluated the anti-atherosclerotic potential of PL in an in vivo murine model of accelerated atherosclerosis and defined its mechanism of action in aortic vascular smooth muscle cells (VSMCs) in vitro. Local treatment with PL significantly reduced atherosclerotic plaque formation as well as proliferation and nuclear factor-kappa B (NF-{kappa}B) activation in an in vivo setting. PL treatment in VSMCs in vitro showed inhibition of migration and platelet-derived growth factor BB (PDGF-BB)-induced proliferation to the in vivo findings. We further identified that PL inhibited PDGF-BB-induced PDGF receptor beta activation and suppressed downstream signaling molecules such as phospholipase C{gamma}1, extracellular signal-regulated kinases 1 and 2 and Akt. Lastly, PL significantly attenuated activation of NF-{kappa}B-a downstream transcriptional regulator in PDGF receptor signaling, in response to PDGF-BB stimulation. In conclusion, our findings demonstrate a novel, therapeutic mechanism by which PL suppresses atherosclerosis plaque formation in vivo.

Son, Dong Ju [Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (United States) [Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (United States); Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA (United States); Kim, Soo Yeon [Division of Life Science, Korea Basic Science Institute, Daejeon (Korea, Republic of)] [Division of Life Science, Korea Basic Science Institute, Daejeon (Korea, Republic of); Han, Seong Su [University of Iowa Carver College of Medicine, Department of Pathology, Iowa City, IA (United States)] [University of Iowa Carver College of Medicine, Department of Pathology, Iowa City, IA (United States); Kim, Chan Woo [Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (United States) [Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (United States); Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA (United States); Department of Bioinspired Science, Ehwa Womans University, Seoul (Korea, Republic of); Kumar, Sandeep [Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (United States) [Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (United States); Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA (United States); Park, Byeoung Soo [Nanotoxtech Co., Ansan (Korea, Republic of)] [Nanotoxtech Co., Ansan (Korea, Republic of); Lee, Sung Eun [Division of Applied Biology and Chemistry, Kyungpook National University, Daegu (Korea, Republic of)] [Division of Applied Biology and Chemistry, Kyungpook National University, Daegu (Korea, Republic of); Yun, Yeo Pyo [College of Pharmacy, Chungbuk National University, Cheongju (Korea, Republic of)] [College of Pharmacy, Chungbuk National University, Cheongju (Korea, Republic of); Jo, Hanjoong, E-mail: hjo@emory.edu [Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (United States) [Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (United States); Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA (United States); Department of Bioinspired Science, Ehwa Womans University, Seoul (Korea, Republic of); Park, Young Hyun, E-mail: pyh012@sch.ac.kr [Department of Food Science and Nutrition, College of Natural Sciences, Soonchunhyang University, Asan (Korea, Republic of)

2012-10-19

256

Promotion of atherosclerosis by Helicobacter cinaedi infection that involves macrophage-driven proinflammatory responses.  

PubMed

Helicobacter cinaedi is the most common enterohepatic Helicobacter species that causes bacteremia in humans, but its pathogenicity is unclear. Here, we investigated the possible association of H. cinaedi with atherosclerosis in vivo and in vitro. We found that H. cinaedi infection significantly enhanced atherosclerosis in hyperlipidaemic mice. Aortic root lesions in infected mice showed increased accumulation of neutrophils and F4/80(+) foam cells, which was due, at least partly, to bacteria-mediated increased expression of proinflammatory genes. Although infection was asymptomatic, detection of cytolethal distending toxin RNA of H. cinaedi indicated aorta infection. H. cinaedi infection altered expression of cholesterol receptors and transporters in cultured macrophages and caused foam cell formation. Also, infection induced differentiation of THP-1 monocytes. These data provide the first evidence of a pathogenic role of H. cinaedi in atherosclerosis in experimental models, thereby justifying additional investigations of the possible role of enterohepatic Helicobacter spp. in atherosclerosis and cardiovascular disease. PMID:24732347

Khan, Shahzada; Rahman, H N Ashiqur; Okamoto, Tatsuya; Matsunaga, Tetsuro; Fujiwara, Yukio; Sawa, Tomohiro; Yoshitake, Jun; Ono, Katsuhiko; Ahmed, Khandaker Ahtesham; Rahaman, Md Mizanur; Oyama, Kohta; Takeya, Motohiro; Ida, Tomoaki; Kawamura, Yoshiaki; Fujii, Shigemoto; Akaike, Takaaki

2014-01-01

257

78 FR 77138 - Proposed Collection; 60-day Comment Request: The Atherosclerosis Risk in Communities Study (ARIC)  

Federal Register 2010, 2011, 2012, 2013

...contributing to the occurrence of and the trends for cardiovascular diseases among men, women, African Americans and white...associated with both atherosclerosis and clinical cardiovascular diseases and (2) measure occurrence of and trend...

2013-12-20

258

75 FR 46945 - Proposed Collection; Comment Request; Multi-Ethnic Study of Atherosclerosis (MESA) Event...  

Federal Register 2010, 2011, 2012, 2013

...with the presence and progression of subclinical cardiovascular disease (CVD)-- that is, atherosclerosis and other...instruments, contact Dr. Diane Bild, Division of Cardiovascular Sciences, NHLBI, NIH, II Rockledge...

2010-08-04

259

The renal artery ostium flow diverter: structure and potential role in atherosclerosis  

PubMed Central

Initiation of renal atherosclerosis occurs primarily at the caudal region of the renal artery ostium. To date, no mechanism for initiation of atherosclerosis at this site has been substantiated. Herein, we identify a renal artery flow diverter on the caudal wall of the renal artery ostium that directs flow into the renal artery and selectively retains LDL, an initial step in atherosclerosis. High resolution ultrasound revealed the generation of flow eddies by the caudal diverter in vivo, consistent with a role in directing aortic flow to the renal artery. Two photon excitation en face microscopy of the diverter revealed a substantial reduction in the elastic lamina exposing potential retention sites for LDL. Fluorescent LDL was selectively retained by the renal artery diverter, consistent with its molecular structure. We propose that the rigid macromolecular structure of the renal artery ostium diverter is required for its vascular function and contributes to the initiation of renal atherosclerosis by the retention of LDL. PMID:20149375

Neufeld, Edward B.; Yu, Zu-Xi; Springer, Danielle; Yu, Qing; Balaban, Robert S.

2010-01-01

260

Approach to a successful selection of antihypertensive drugs for the patient with atherosclerosis.  

PubMed

Coronary heart disease has become a medical and public health issue associated with multiple risk factors such as age, diet, and sedentary life style. Associations between hypertension and atherosclerosis have been extensively studied, and several trials have demonstrated antiatherosclerotic properties in some of the most widely used antihypertensive agents. Hence, calcium channel blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers have been the target for a number of controlled randomized trials studying its effect on atherosclerosis progression. Carotid intima-media thickness measurement by ultrasound is used as surrogate of atherosclerosis in most of these controlled trials. This review of the literature aims to summarize the most significant controlled trials involving antihypertensive therapy and atherosclerosis regression based on the carotid intima-media thickness measurement. PMID:23018585

Velasco, Manuel; Rojas, Edward; Pirela, Valmore B

2013-01-01

261

Engineering Atherosclerosis is the leading cause of death, both above and  

E-print Network

channel or knocking down its expression significantly reduces the apparent hydraulic conductivity Lp with atherosclerosis. We also consider manipulation of aquaporin numbers as a strategy to affect disease progression

262

ABCA1 gene expression in peripheral blood lymphocytes and macrophages in patients with atherosclerosis  

Microsoft Academic Search

ABCA1 transporter is known to play an important role in cholesterol transport from peripheral tissues. However, its contribution\\u000a to atherosclerosis development remains obscure. Using Real Time PCR, we detected a significant reduction of ABCA1 mRNA level in leukocytes of patients with atherosclerosis compared to control. Mean ABCA1 expression levels in leukocytes from the group of patients and from the control

E. P. Demina; V. V. Miroshnikova; T. I. Rodygina; P. S. Kurianov; A. G. Vinogradov; A. D. Denisenko; A. L. Schwarzman

2011-01-01

263

Expression of Apolipoprotein AI in Rabbit Carotid Endothelium Protects Against Atherosclerosis  

Microsoft Academic Search

Expression of atheroprotective genes in the blood vessel wall is potentially an effective means of preventing or reversing atherosclerosis. Development of this approach has been hampered by lack of a suitable gene-transfer vector. We used a helper-dependent adenoviral (HDAd) vector to test whether expression of apolipoprotein A-I (apoA-I) in the artery wall could retard the development of atherosclerosis in hyperlipidemic

Rowan Flynn; Kun Qian; Chongren Tang; Nagadhara Dronadula; Joshua M Buckler; Bo Jiang; Shan Wen; Helén L Dichek; David A Dichek

2011-01-01

264

BAS\\/BSCR27 Diesel exhaust particles promote atherosclerosis in apolipoprotein E-deficient mice  

Microsoft Academic Search

Air pollution has been linked to the development of atherosclerosis and cardiovascular disease. Diesel exhaust particulate (DEP) accounts for a substantial proportion of urban air pollution but its effects on atherogenesis are unknown. We hypothesised that DEP will exacerbate plaque formation in a murine model of atherosclerosis.Apolipoprotein E knockout (ApoE) mice (10–12 weeks; n=16) were fed a ‘Western diet’ (21%

M. R. Miller; S. G. McLean; R. Duffin; C. A. Shaw; N. L. Mills; K. Donaldson; D. E. Newby; P. W. F. Hadoke

2010-01-01

265

Preventing diabetes and atherosclerosis in sub-Saharan Africa: Should the metabolic syndrome have a role?  

Microsoft Academic Search

Obesity, hypertension, atherosclerosis, and type 2 diabetes mellitus are increasing in all regions of sub-Saharan Africa.\\u000a The metabolic syndrome is a valuable tool in predicting atherosclerosis and type 2 diabetes in populations in Europe and North\\u000a America. However, the applicability of the metabolic syndrome to African populations has not been studied. Prior to investing\\u000a scarce funds into diagnosing and treating

Omoye E. Imoisili; Anne E. Sumner

2009-01-01

266

New therapy via targeting androgen receptor in monocytes/macrophages to battle atherosclerosis.  

PubMed

The male sex has a higher risk to develop coronary artery diseases, including atherosclerosis. The androgen receptor (AR) is expressed in several atherosclerosis-associated cell types, including monocytes/macrophages, endothelial cells (ECs), and smooth muscle cells (SMCs), but its pathophysiological role in each cell type during the development of atherosclerotic lesions remains unclear. Using the Cre-loxP system, we selectively knocked out AR in these 3 cell types and the resultant AR knockout (ARKO) mice, monocyte/macrophage ARKO, EC-ARKO, and SMC-ARKO, were then crossed with the low-density lipoprotein receptor (LDLR) deficient (LDLR(-/-)) mice to develop monocyte/macrophage ARKO-LDLR(-/-), EC-ARKO-LDLR(-/-), and SMC-ARKO-LDLR(-/-) mice for the study of atherosclerosis. The results showed that the monocyte/macrophage ARKO-LDLR(-/-) mice had reduced atherosclerosis compared with the wild-type-LDLR(-/-) control mice. However, no significant difference was detected in EC-ARKO-LDLR(-/-) and SMC-ARKO-LDLR(-/-) mice compared with wild-type-LDLR(-/-) mice, suggesting that the AR in monocytes/macrophages, and not in ECs and SMCs, plays a major role to promote atherosclerosis. Molecular mechanism dissection suggested that AR in monocytes/macrophages upregulated the tumor necrosis factor-?, integrin ?2, and lectin-type oxidized LDL receptor 1 molecules that are involved in 3 major inflammation-related processes in atherosclerosis, including monocytes/macrophages migration and adhesion to human umbilical vein ECs, and subsequent foam cell formation. Targeting AR via the AR degradation enhancer, ASC-J9, in wild-type-LDLR(-/-) mice showed similar effects as seen in monocyte/macrophage ARKO-LDLR(-/-) mice with little influence on lipid profile. In conclusion, the AR in monocytes/macrophages plays key roles in atherosclerosis and targeting AR with ASC-J9 may represent a new potential therapeutic approach to battle atherosclerosis. PMID:24688120

Huang, Chiung-Kuei; Pang, Haiyan; Wang, Lin; Niu, Yuanjie; Luo, Jie; Chang, Eugene; Sparks, Janet D; Lee, Soo Ok; Chang, Chawnshang

2014-06-01

267

Relation between Birth Weight, Growth, and Subclinical Atherosclerosis in Adulthood  

PubMed Central

Background and Objectives. Adverse conditions in the prenatal environment and in the first years of life are independently associated with increased risk for cardiovascular disease. This paper aims to study the relation between birthweight, growth in the first year of life, and subclinical atherosclerosis in adults. Methods. 88 adults aged between 20 and 31 were submitted to sociodemographic qualities, anthropometric data, blood pressure measurements, metabolic profile, and evaluation of subclinical atherosclerosis. Results. Birthweight <2,500 grams (g) was negatively correlated with (a) increased waist-to-hip ratio (WHR), according to regression coefficient (RC) equal to ?0.323, 95% CI [?0.571, ?0.075] P < 0.05; (b) diastolic blood pressure (RC = ?4.744, 95% CI [?9.017, ?0.470] P < 0.05); (c) low HDL-cholesterol (RC = ?0.272, 95% CI [?0.516, ?0.029] P < 0.05); (d) frequency of intima-media thickness (IMT) of left carotid >75th percentile (RC = ?0.242, 95% CI [?0.476, ?0.008] P < 0.05). Birthweight >3,500?g was associated with (a) BMI >25.0?kg/m2, (RC = 0.317, 95% CI [0.782, 0.557] P < 0.05); (b) increased waist circumference (RC = 0.284, 95% CI [0.054, 0.513] P < 0.05); (c) elevated WHR (RC = 0.280, 95% CI [0.054, 0.505] P < 0.05); (d) minimum subcutaneous adipose tissue (SAT) (RC = 4.354, 95% CI [0.821, 7.888] P < 0.05); (e) maximum SAT (RC = 7.095, 95% CI [0.608, 13.583] P < 0.05); (f) right lobe of the liver side (RC = 6.896, 95% CI [1.946, 11.847] P < 0.001); (g) frequency's right lobe of the liver >75th percentile (RC = 0.361, 95% CI [0.169, 0.552] P < 0.001). Weight gain in the first year of life was inversely correlated with (a) mean IMT of left carotid (RC = ?0.046, 95% CI [?0.086, ?0.006] P < 0.05; (b) frequency IMT of left carotid >75th percentile (RC = ?0.253, 95% CI [?0.487, ?0.018] P < 0.05); (c) mean IMT (RC = ?0.038, 95% CI [0.073, ?0.002] P < 0.05); (d) the frequency of the mean IMT >75th percentile (RC = ?0.241, 95% CI [?0.442, ?0.041] P < 0.05). Conclusions. Adults birthweight <2,500?g and >3,500?g and with insufficient weight gain in the first year of life have showed different metabolic phenotypes, but all of them were related to subclinical atherosclerosis. PMID:25648854

Valente, Maria Helena; Gomes, Filumena Maria da Silva; Benseñor, Isabela Judith Martins; Brentani, Alexandra Valéria Maria; Escobar, Ana Maria de Ulhôa; Grisi, Sandra J. F. E.

2015-01-01

268

Relation between Birth Weight, Growth, and Subclinical Atherosclerosis in Adulthood.  

PubMed

Background and Objectives. Adverse conditions in the prenatal environment and in the first years of life are independently associated with increased risk for cardiovascular disease. This paper aims to study the relation between birthweight, growth in the first year of life, and subclinical atherosclerosis in adults. Methods. 88 adults aged between 20 and 31 were submitted to sociodemographic qualities, anthropometric data, blood pressure measurements, metabolic profile, and evaluation of subclinical atherosclerosis. Results. Birthweight <2,500 grams (g) was negatively correlated with (a) increased waist-to-hip ratio (WHR), according to regression coefficient (RC) equal to -0.323, 95% CI [-0.571, -0.075] P < 0.05; (b) diastolic blood pressure (RC = -4.744, 95% CI [-9.017, -0.470] P < 0.05); (c) low HDL-cholesterol (RC = -0.272, 95% CI [-0.516, -0.029] P < 0.05); (d) frequency of intima-media thickness (IMT) of left carotid >75th percentile (RC = -0.242, 95% CI [-0.476, -0.008] P < 0.05). Birthweight >3,500?g was associated with (a) BMI >25.0?kg/m(2), (RC = 0.317, 95% CI [0.782, 0.557] P < 0.05); (b) increased waist circumference (RC = 0.284, 95% CI [0.054, 0.513] P < 0.05); (c) elevated WHR (RC = 0.280, 95% CI [0.054, 0.505] P < 0.05); (d) minimum subcutaneous adipose tissue (SAT) (RC = 4.354, 95% CI [0.821, 7.888] P < 0.05); (e) maximum SAT (RC = 7.095, 95% CI [0.608, 13.583] P < 0.05); (f) right lobe of the liver side (RC = 6.896, 95% CI [1.946, 11.847] P < 0.001); (g) frequency's right lobe of the liver >75th percentile (RC = 0.361, 95% CI [0.169, 0.552] P < 0.001). Weight gain in the first year of life was inversely correlated with (a) mean IMT of left carotid (RC = -0.046, 95% CI [-0.086, -0.006] P < 0.05; (b) frequency IMT of left carotid >75th percentile (RC = -0.253, 95% CI [-0.487, -0.018] P < 0.05); (c) mean IMT (RC = -0.038, 95% CI [0.073, -0.002] P < 0.05); (d) the frequency of the mean IMT >75th percentile (RC = -0.241, 95% CI [-0.442, -0.041] P < 0.05). Conclusions. Adults birthweight <2,500?g and >3,500?g and with insufficient weight gain in the first year of life have showed different metabolic phenotypes, but all of them were related to subclinical atherosclerosis. PMID:25648854

Valente, Maria Helena; Gomes, Filumena Maria da Silva; Benseñor, Isabela Judith Martins; Brentani, Alexandra Valéria Maria; Escobar, Ana Maria de Ulhôa; Grisi, Sandra J F E

2015-01-01

269

Disentangling charmonium suppression  

NASA Astrophysics Data System (ADS)

Charmonium suppression has been postulated as a unique signature for the creation of hot dense nuclear matter. \\textit{J}/\\psi meson yields, for instance, are predicted to be anomalously suppressed through interactions with the hot and dense medium as well as the disappearance of feed-down channels from more massive charmonium states, when compared to the yields expected from cold nuclear matter (CNM). In both hot and cold nuclear matter the suppression is evaluated by comparing to an expected yield from a participant scaled proton-proton (p+p) baseline. We will discuss the different aspects of \\textit{J}/\\psi suppression and the most recent results from the PHENIX experiment at the RHIC.

Linden Levy, L. A.; PHENIX Collaboration

2009-06-01

270

Depletion of FOXP3+ regulatory T cells promotes hypercholesterolemia and atherosclerosis  

PubMed Central

Atherosclerosis is a chronic inflammatory disease promoted by hyperlipidemia. Several studies support FOXP3-positive regulatory T cells (Tregs) as inhibitors of atherosclerosis; however, the mechanism underlying this protection remains elusive. To define the role of FOXP3-expressing Tregs in atherosclerosis, we used the DEREG mouse, which expresses the diphtheria toxin (DT) receptor under control of the Treg-specific Foxp3 promoter, allowing for specific ablation of FOXP3+ Tregs. Lethally irradiated, atherosclerosis-prone, low-density lipoprotein receptor–deficient (Ldlr–/–) mice received DEREG bone marrow and were injected with DT to eliminate FOXP3+ Tregs. Depletion of Tregs caused a 2.1-fold increase in atherosclerosis without a concomitant increase in vascular inflammation. These mice also exhibited a 1.7-fold increase in plasma cholesterol and an atherogenic lipoprotein profile with increased levels of VLDL. Clearance of VLDL and chylomicron remnants was hampered, leading to accumulation of cholesterol-rich particles in the circulation. Functional and protein analyses complemented by gene expression array identified reduced protein expression of sortilin-1 in liver and increased plasma enzyme activity of lipoprotein lipase, hepatic lipase, and phospholipid transfer protein as mediators of the altered lipid phenotype. These results demonstrate that FOXP3+ Tregs inhibit atherosclerosis by modulating lipoprotein metabolism. PMID:23426179

Klingenberg, Roland; Gerdes, Norbert; Badeau, Robert M.; Gisterå, Anton; Strodthoff, Daniela; Ketelhuth, Daniel F.J.; Lundberg, Anna M.; Rudling, Mats; Nilsson, Stefan K.; Olivecrona, Gunilla; Zoller, Stefan; Lohmann, Christine; Lüscher, Thomas F.; Jauhiainen, Matti; Sparwasser, Tim; Hansson, Göran K.

2013-01-01

271

ADMA/SDMA in elderly subjects with asymptomatic carotid atherosclerosis: values and site-specific association.  

PubMed

Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide synthase (NOS) inhibitor known as a mediator of endothelial dysfunction and atherosclerosis. Circulating ADMA levels are correlated with cardiovascular risk factors such as hypercholesterolemia, arterial hypertension, diabetes mellitus, hyperhomocysteinemia, age and smoking. We assessed the relationship between ADMA values and site-specific association of asymptomatic carotid atherosclerosis (intima-media thickness (CIMT) and plaque) in elderly subjects. One hundred and eighty subjects underwent a complete history and physical examination, determination of serum chemistries and ADMA levels, and carotid ultrasound investigation (CUI). All subjects had no acute or chronic symptoms of carotid atherosclerosis. Statistical analyses showed that high plasma levels of ADMA/SDMA were positively correlated to carotid atherosclerosis (CIMT and plaque) (p<0.001), with significant site-specific association. Total cholesterol, low density lipoprotein cholesterol, triglycerides and C-reactive protein plasma concentrations were significantly associated with asymptomatic carotid atherosclerosis (p<0.001). High serum concentrations of ADMA and SDMA were associated with carotid atherosclerotic lesions as measured by CIMT ad plaque and may represent a new marker of asymptomatic carotid atherosclerosis in elderly subjects. PMID:24739810

Riccioni, Graziano; Scotti, Luca; D'Orazio, Nicolantonio; Gallina, Sabina; Speziale, Giuseppe; Speranza, Lorenza; Bucciarelli, Tonino

2014-01-01

272

Progression and regression of atherosclerosis in APOE3-Leiden transgenic mice: an immunohistochemical study.  

PubMed

Apolipoprotein E3-Leiden (APOE3-Leiden) transgenic mice develop hyperlipidemia and are highly susceptible to diet-induced atherosclerosis. We have studied the progression and regression of atherosclerosis using immunohistochemistry. Female transgenic mice were fed a moderate fat diet to study atherosclerosis over a longer time period. Fatty streaks arose in the intima and consisted of lipid filled macrophages which differed in origin. All macrophages expressed the macrophage scavenger receptor while two thirds expressed sialoadhesin and were positive for an antibody recognizing marginal zone macrophages (MOMA-1). All macrophages were negative for the scavenger receptor MARCO and 50% were positive for CD4. Small fatty streaks contained CD-3 positive T-lymphocytes which were for more than 70% CD4-positive. ICAM-1 was positive both in atherosclerotic and control mice. In early plaques, fibrosis was observed on the luminal and medial site of the foam cells while smooth muscle cells were only observed in the fibrous cap. To study regression, we used a high fat, high cholesterol diet to rapidly induce atherosclerosis (14 weeks). The animals were then fed normal chow. Subsequently, atherosclerosis was assayed over time (4, 8, 16 weeks). Cholesterol levels dropped in 4 weeks to control levels. The animals did not show a significantly decrease in plaque size over time. but the percentage macrophages was significantly smaller in the animals after 4 weeks. In conclusion, the APOE3-Leiden mouse is a useful model to study the progression and regression of atherosclerosis. PMID:10208477

Gijbels, M J; van der Cammen, M; van der Laan, L J; Emeis, J J; Havekes, L M; Hofker, M H; Kraal, G

1999-03-01

273

An accelerated mouse model for atherosclerosis and adipose tissue inflammation  

PubMed Central

Background Obesity and particularly the metabolic syndrome, which is often associated with obesity, combine a major risk for type 2 diabetes and cardiovascular disease. Emerging evidence indicate obesity-associated subclinical inflammation primarily originating from adipose tissue as a common cause for type 2 diabetes and cardiovascular disease. However, a suitable and well-characterized mouse model to simultaneously study obesity-associated metabolic disorders and atherosclerosis is not available yet. Here we established and characterized a murine model combining diet-induced obesity and associated adipose tissue inflammation and metabolic deteriorations as well as atherosclerosis, hence reflecting the human situation of cardio-metabolic disease. Methods We compared a common high-fat diet with 0.15% cholesterol (HFC), and a high-fat, high-sucrose diet with 0.15% cholesterol (HFSC) fed to LDL receptor-deficient (LDLR-/-) mice. Insulin resistance, glucose tolerance, atherosclerotic lesion formation, hepatic lipid accumulation, and inflammatory gene expression in adipose tissue and liver were assessed. Results After 12–16 weeks, LDLR-/- mice fed HFSC or HFC developed significant diet-induced obesity, adipose tissue inflammation, insulin resistance, and impaired glucose tolerance compared to lean controls. Notably, HFSC-fed mice developed significantly higher adipose tissue inflammation in parallel with significantly elevated atherosclerotic lesion area compared to those on HFC. Moreover, LDLR-/- mice on HFSC showed increased insulin resistance and impaired glucose tolerance relative to those on HFC. After prolonged feeding (20 weeks), however, no significant differences in inflammatory and metabolic parameters as well as atherosclerotic lesion formation were detectable any more between LDLR-/- mice fed HFSC or HFC. Conclusion The use of high sucrose rather than more complex carbohydrates in high-fat diets significantly accelerates development of obesity-driven metabolic complications and atherosclerotic plaque formation parallel to obesity-induced adipose tissue inflammation in LDLR-/- mice. Hence LDLR-/- mice fed high-fat high-sucrose cholesterol-enriched diet appear to be a suitable and time-saving animal model for cardio-metabolic disease. Moreover our results support the suggested interrelation between adipose tissue inflammation and atherosclerotic plaque formation. PMID:24438079

2014-01-01

274

Pulp Stone, Haemodialysis, End-stage Renal Disease, Carotid Atherosclerosis  

PubMed Central

Objectives: The aim of this study was to determine the relationship between the presence of pulp calcification and carotid artery calcification on the dental panoramic radiographs in End Stage Renal Disease (ESRD) patients who were on haemodialysis. Methods: A total of 112 End Stage Renal Disease (ESRD) patients on who were haemodialysis participated in this study. The periapical and the panoramic radiographs for all the patients were evaluated for the presence or absence of the narrowing of the dental pulps and for pulp stones in the pulp chambers and the pulp canals. The panoramic radiographs were also evaluated to determine the carotid calcification. Results: Carotid calcifications were detected in none of the patients. 84 (74.99%) patients had dental pulp narrowing, and 38 (33.92%) patients had pulp stones. There was no statistical correlation between pulp narrowing and Carotid Artery Calcification (CAC) in the haemodialysis patient group. There was also no statistical correlation between pulp stones and CAC in the haemodialysis patients. Conclusion: However, the incidental finding of CAC on a panoramic radiograph can provide life-saving information for the vascular disease patients, but in the present study, no significant relationship was found between the presence of the pulpal calcification and CAC in the ESRD patients who were on haemodialysis. Therefore, the presence of pulp calcification does not seem to serve as a diagnostic marker for carotid atherosclerosis. PMID:23905147

Patil, Santosh; Sinha, Nidhi

2013-01-01

275

Vascular health late after Kawasaki disease: implications for accelerated atherosclerosis  

PubMed Central

Kawasaki disease (KD), an acute vasculitis that primarily affects young children, is the most common acquired paediatric cardiovascular disease in developed countries. While sequelae of arterial inflammation in the acute phase of KD are well documented, its late effects on vascular health are increasingly unveiled. Late vascular dysfunction is characterized by structural alterations and functional impairment in term of arterial stiffening and endothelial dysfunction and shown to involve both coronary and systemic arteries. Further evidence suggests that continuous low grade inflammation and ongoing active remodeling of coronary arterial lesions occur late after acute illness and may play a role in structural and functional alterations of the arteries. Potential importance of genetic modulation on vascular health late after KD is implicated by associations between mannose binding lectin and inflammatory gene polymorphisms with severity of peripheral arterial stiffening and carotid intima-media thickening. The changes in cholesterol and lipoproteins levels late after KD further appear similar to those proposed to be atherogenic. While data on adverse vascular health are less controversial in patients with persistent or regressed coronary arterial aneurysms, data appear conflicting in individuals with no coronary arterial involvements or only transient coronary ectasia. Notwithstanding, concerns have been raised with regard to predisposition of KD in childhood to accelerated atherosclerosis in adulthood. Until further evidence-based data are available, however, it remains important to assess and monitor cardiovascular risk factors and to promote cardiovascular health in children with a history of KD in the long term. PMID:25550701

2014-01-01

276

Biomechanical factors in atherosclerosis: mechanisms and clinical implications.  

PubMed

Blood vessels are exposed to multiple mechanical forces that are exerted on the vessel wall (radial, circumferential and longitudinal forces) or on the endothelial surface (shear stress). The stresses and strains experienced by arteries influence the initiation of atherosclerotic lesions, which develop at regions of arteries that are exposed to complex blood flow. In addition, plaque progression and eventually plaque rupture is influenced by a complex interaction between biological and mechanical factors-mechanical forces regulate the cellular and molecular composition of plaques and, conversely, the composition of plaques determines their ability to withstand mechanical load. A deeper understanding of these interactions is essential for designing new therapeutic strategies to prevent lesion development and promote plaque stabilization. Moreover, integrating clinical imaging techniques with finite element modelling techniques allows for detailed examination of local morphological and biomechanical characteristics of atherosclerotic lesions that may be of help in prediction of future events. In this ESC Position Paper on biomechanical factors in atherosclerosis, we summarize the current 'state of the art' on the interface between mechanical forces and atherosclerotic plaque biology and identify potential clinical applications and key questions for future research. PMID:25230814

Kwak, Brenda R; Bäck, Magnus; Bochaton-Piallat, Marie-Luce; Caligiuri, Giuseppina; Daemen, Mat J A P; Davies, Peter F; Hoefer, Imo E; Holvoet, Paul; Jo, Hanjoong; Krams, Rob; Lehoux, Stephanie; Monaco, Claudia; Steffens, Sabine; Virmani, Renu; Weber, Christian; Wentzel, Jolanda J; Evans, Paul C

2014-11-14

277

Vascular health late after Kawasaki disease: implications for accelerated atherosclerosis.  

PubMed

Kawasaki disease (KD), an acute vasculitis that primarily affects young children, is the most common acquired paediatric cardiovascular disease in developed countries. While sequelae of arterial inflammation in the acute phase of KD are well documented, its late effects on vascular health are increasingly unveiled. Late vascular dysfunction is characterized by structural alterations and functional impairment in term of arterial stiffening and endothelial dysfunction and shown to involve both coronary and systemic arteries. Further evidence suggests that continuous low grade inflammation and ongoing active remodeling of coronary arterial lesions occur late after acute illness and may play a role in structural and functional alterations of the arteries. Potential importance of genetic modulation on vascular health late after KD is implicated by associations between mannose binding lectin and inflammatory gene polymorphisms with severity of peripheral arterial stiffening and carotid intima-media thickening. The changes in cholesterol and lipoproteins levels late after KD further appear similar to those proposed to be atherogenic. While data on adverse vascular health are less controversial in patients with persistent or regressed coronary arterial aneurysms, data appear conflicting in individuals with no coronary arterial involvements or only transient coronary ectasia. Notwithstanding, concerns have been raised with regard to predisposition of KD in childhood to accelerated atherosclerosis in adulthood. Until further evidence-based data are available, however, it remains important to assess and monitor cardiovascular risk factors and to promote cardiovascular health in children with a history of KD in the long term. PMID:25550701

Cheung, Yiu-Fai

2014-11-01

278

Novel therapeutic strategies targeting vascular redox in human atherosclerosis.  

PubMed

It is now widely accepted that redox signaling is a key feature in vascular homeostasis. Reactive oxygen species are generated by a wide range of enzymatic systems located in both vascular endothelium and vascular wall. Further, to their role as cytotoxic molecules produced by immune system, free radicals play critical signaling roles in the vascular wall. By regulating several redox-sensitive transcription pathways, free radicals play a key role in the synthesis of inflammatory mediators in both vascular endothelium and vascular wall, with important role in the overall vascular dysfunction. The well-established role of redox state in vascular disease mandates that development of newer therapeutic strategies should be able to alter redox-sensitive intracellular signaling events. Widely used cardiovascular agents like statins or angiotensin receptor blockers have well documented beneficial effects on vascular redox state, reflected also in clinical outcome improvement. Newer promising strategies along with recent patented inventions may also include thiazolidinediones, folates, tetrahydrobiopterin, cyclopentone prostaglandins and aldose reductase inhibitors with well known effects on vascular redox, but with still unclear results on clinical outcome. Better understanding of redox-sensitive intracellular signaling pathways could indicate the critical steps to intervene with newer agents to reverse vascular dysfunction, inhibiting atherosclerosis progression and potentially improve clinical outcome. PMID:19519550

Antonopoulos, Alexis S; Antoniades, Charalambos; Tousoulis, Dimitris; Bakogiannis, Constantinos; Demosthenous, Michael; Psarros, Costas; Stefanadis, Christodoulos

2009-06-01

279

Atherosclerosis: A Link Between Lipid Intake and Protein Tyrosine Nitration  

PubMed Central

Atherosclerosis, a disease characterized by plaque formation in the arterial wall that can lead to heart attack and stroke, is a principal cause of death in the world. Since the 1990’s, protein nitrotyrosine formation has been known to occur in the atherosclerotic plaque. This potentially damaging reaction occurs as a result of tyrosine modification by reactive nitrogen species, such as nitrogen dioxide radical, which forms upon peroxynitrite decomposition or nitrite oxidation by hydrogen peroxide-activated peroxidase enzymes. The presence of protein-bound nitrotyrosine can be considered an indicator of a loss in the natural balance of oxidants and antioxidants, and as such, there is an emerging view that protein-bound nitrotyrosine may be a risk factor for cardiovascular disease. This review brings together evidence that the accumulation of protein nitrotyrosine during atherogenesis is more widespread than initially thought (as its presence can be detected not only in the lesion but also in the blood stream and other organs) and is closely linked to lipid intake. PMID:20157638

Upmacis, Rita K.

2009-01-01

280

Nuclear microscopy investigations into the role of iron in atherosclerosis  

NASA Astrophysics Data System (ADS)

Using nuclear microscopy we have investigated elemental distributions and concentrations in aortic arch tissue sections from three groups of rabbits: (a) rabbits on normal diet (normal group), (b) rabbits on a high-cholesterol diet (control group), and (c) rabbits on a high-cholesterol diet and depleted in iron by weekly bleeding (test group). Rabbits in each group were sacrificed at 4-week time intervals, at 4, 8, 12 and 16 weeks. As early as 4 weeks, the aortic arches of control rabbits showed signs of fatty streaks and lesions, with a 2-fold average increase of iron concentration in the artery wall of cholesterol fed rabbits compared to the normal group. At 12 and 16 weeks the control group exhibited well-developed atherosclerotic lesions with an accompanying 3-fold increase in iron. The test group showed a significant reduction of lesion formation compared to the controls, and only after 12 weeks was an increase in iron concentration in the aortic arch observed. These findings show that controlled blood letting results in reduced uptake of iron by the artery wall and delayed atherosclerotic lesion formation. This correlation strongly suggests that iron has an important role in the aetiology of atherosclerosis.

Makjanic, Jagoda; Ponraj, D.; Tan, B. K. H.; Watt, F.

1999-10-01

281

Human sLZIP promotes atherosclerosis via MMP-9 transcription and vascular smooth muscle cell migration.  

PubMed

Atherosclerosis is a chronic inflammatory response of the vascular wall, and immune responses are involved in every phase of atherosclerosis, from initiation, to progression, and finally to plaque rupture. Cytokines are the major atherogenic mediators that promote plaque formation and progression by activation of inflammatory cells. They induce expressions of matrix metalloproteinases (MMPs), leading to vascular smooth muscle cell (VSMC) migration in atherosclerotic lesions. Although chronic inflammatory mediators, including tumor necrosis factor ? (TNF-?) and MMPs, exacerbate atherosclerosis, the molecular mechanism of atherogenesis remains unclear. In this study we investigated the role of a novel transcription factor the human small leucine zipper protein (sLZIP) in TNF-?-induced MMP expression, VSMC migration, and atherosclerosis progression. The proinflammatory cytokine TNF-? enhanced sLZIP expression by 3-fold via activation of NF-?B signaling. sLZIP induced MMP-9 transcription and the proteolytic activity of MMP-9 by 2.8- and 3.2-fold (P< 0.05), respectively, in macrophages, leading to enhancement of VSMC migration by 2.7-fold (P<0.005). sLZIP(OE/+) (sLZIP transgenic); LDLR(-/-) mice fed a high-cholesterol diet exhibited enhanced arterial plaque formation and increased VSMC migration from the media into the intima by 2.8- and 2.6-fold (P<0.01), respectively, compared with atherosclerosis-prone LDLR(-/-) mice. These results indicate that human sLZIP plays a critical role in development of atherosclerosis and can be used as a therapeutic target molecule for treatment of atherosclerosis. PMID:25077563

Kim, Jeonghan; Ko, Jesang

2014-11-01

282

CETP gene polymorphisms and risk of coronary atherosclerosis in a Chinese population  

PubMed Central

Background Coronary atherosclerosis, the most common form of coronary artery disease (CAD), is characterized by accumulation of lipid in the walls of coronary arteries. Recent data from clinical trials have showed that high-density lipoprotein cholesterol (HDL-C) has causal role in the pathogenesis and development of coronary atherosclerosis. Cholesteryl ester transfer protein (CETP) is an important regulator of plasma HDL-C. Several genetic mutations in the CETP gene were found to be associated with HDL-C levels. The aim of the present study is to evaluate the association of HDL-C-related CETP polymorphisms and risk of coronary atherosclerosis. Methods We investigated the association of seven single nucleotide polymorphisms (SNP) (rs1800775, rs708272, rs5882, rs1532624, rs1864163, rs7499892, and rs9989419) in the CETP gene with the risk of coronary atherosclerosis and levels of HDL-C in a case–control study in China. Included in the study were 420 patients with coronary atherosclerosis and 424 healthy controls. SNP genotyping was performed by TaqMan allelic discrimination assay and serum lipid levels were measured by standard laboratory methods. Results Carriers of the AA and GA?+?AA genotypes of rs708272 had significant lower risks of coronary atherosclerosis (OR?=?0.55, 95% CI: 0.36-0.85, p?=?0.003; OR?=?0.67, 95% CI: 0.50-0.90, p?=?0.007, respectively) compared to those with GG genotype. These relations remained significant after adjustment for confounding effects of age, smoking, diabetes and hypertension. The rs1800775 polymorphism was significantly associated with serum levels of HDL-C in healthy controls (p?=?0.04). Besides, rs708272 was in close linkage disequilibrium (LD) with rs1800775 in this study. Conclusions Our findings indicated that CETP rs708272 may be associated with the risk of coronary atherosclerosis and rs1800775 may influence serum HDL-C levels in healthy controls in Chinese. PMID:24283500

2013-01-01

283

Explosion suppression system  

DOEpatents

An explosion suppression system and triggering apparatus therefor are provided for quenching gas and dust explosions. An electrically actuated suppression mechanism which dispenses an extinguishing agent into the path ahead of the propagating flame is actuated by a triggering device which is light powered. This triggering device is located upstream of the propagating flame and converts light from the flame to an electrical actuation signal. A pressure arming device electrically connects the triggering device to the suppression device only when the explosion is sensed by a further characteristic thereof beside the flame such as the pioneer pressure wave. The light powered triggering device includes a solar panel which is disposed in the path of the explosion and oriented between horizontally downward and vertical. Testing mechanisms are also preferably provided to test the operation of the solar panel and detonator as well as the pressure arming mechanism.

Sapko, Michael J. (Finleyville, PA); Cortese, Robert A. (Pittsburgh, PA)

1992-01-01

284

High glucose downregulates the number of caveolae in monocytes through oxidative stress from NADPH oxidase: implications for atherosclerosis.  

PubMed

Atherosclerosis, an inflammatory disease, is closely associated with hyperglycemia, major sign of diabetes mellitus. Caveolae are vesicular invaginations of the plasma membrane that mediate the intracellular transport of lipids such as cholesterol. We evaluated the relationship between the expression of caveolin-1 and the number of caveolae in macrophages under conditions of high glucose concentration. Increased superoxide production, induction of inducible nitric oxide synthase (iNOS), and decreased caveolin-1 were observed in a concentration-dependent manner in THP-1 derived macrophages with high glucose concentrations. Mannitol, used as an osmotic control, showed no effects. Furthermore, co-localization of the NADPH oxidase component, p47(phox), and caveolin was confirmed by confocal microscopy. An atomic force microscopy (AFM) study showed that high glucose concentrations reduced the number and size of the caveolae. The percentage of cells with fragmented DNA was increased in cells grown in hyperglycemic media. Taken together, high glucose concentrations suppress the levels of caveolin-1 expression and reduce the number of caveolae. This might be due to the actions of superoxide via the activation of NADPH oxidase by translocation of its component and uncoupling of induced iNOS in macrophages. Furthermore, the apoptosis of macrophages might occur with high glucose concentrations, leading to the spreading of lipids from macrophages into intracellular spaces in the vessel wall. PMID:17240121

Hayashi, Toshio; Juliet, Packiasamy A R; Miyazaki, Asaka; Ignarro, Louis J; Iguchi, Akihisa

2007-03-01

285

Roles of human epicardial adipose tissue in coronary artery atherosclerosis.  

PubMed

This study examined the adipocytokine-vascular interactions and link between epicardial adipose tissue and coronary artery atherosclerosis. Thirty-four patients undergoing open heart surgery were chosen randomly, and divided into group I (non-coronary artery disease group) and group II (coronary artery disease group). Blood samples were taken through peripheral vein prior to surgery. Plasma levels of a panel of proteins (adiponectin, IL-10, TNF-?) were detected by using ELISA. Epicardial adipose tissue was taken near the proximal tract of the right coronary artery and subcutaneous adipose was taken from the leg before cardiopulmonary bypassing, adiponectin and CD68 + were detected by using RT-PCR and immunohistochemistry. Our results showed that plasma adiponectin level was significantly lower in the group II as compared with group I (P<0.05). There were no differences in plasma concentration (IL-10, TNF-?, tatal-chol, HDL-chol, LDL-chol) between group I and group II. The number of CD68+ cells in epicardial adipose tissue of group II was significantly higher than that in subcutaneous adipose tissue. Adiponectin mRNA expression was 6 fold higher in subcutaneous adipose tissue than in epicardial adipose tissue of group II (P<0.01). Furthermore, the level of adiponectin mRNA in the epicardial adipose tissue in group II was also significantly lower than in group I (P<0.05). We are led to conclude that inflammation that occurs locally in epicardial adipose tissue of CAD contributes to the pathogenesis of coronary artery disease. PMID:21063839

Chen, Xinzhong; Jiao, Zhouyang; Wang, Lei; Sun, Zongquan; Wei, Yutao; Wang, Xianguo; Xia, Dongsheng

2010-10-01

286

Atherosclerosis diagnostic imaging by optical spectroscopy and optical coherence tomography  

NASA Astrophysics Data System (ADS)

Atherosclerosis is traditionally viewed as a disease of uncontrolled plaque growth leading to arterial occlusion. More recently, however, occlusion of the arterial lumen is being viewed as an acute event triggered by plaque rupture and thrombosis. An atheromatous plaque becomes vulnerable to sudden activation and/or rupture when a constellation of processes are activated by various trigger mechanisms. There is growing evidence that the vulnerability (i.e. susceptibility to rupture) and thrombogenic nature of the plaque need to be taken into account in the planning and treatment of the disease. X-ray fluoroscopy and intravascular ultrasound, the current clinical diagnostic tools are not capable of the providing a complete histological picture of the plaque region. Intravascular diagnostic imaging of coronary atherosclerotic plaques by optical means to assess plaque, patient risk and assist in planning treatment strategies represents the future in angioplasty treatment by interventional cardiologists. The techniques which will enable a clinically acceptable and reliable intravascular diagnostic platform are currently being investigated and compared to the clinical standard of histology. Currently, we are investigating the use of a number of optical and imaging techniques for biochemical analysis of arterial tissue including Raman, near infrared and fluorescence spectroscopies. Biochemical imaging will provide compositional information on collagen, elastin, lipid and thrombogenic by-products as well as gauging inflammation and tissue remodeling activity levels. To complement the functional biochemical imaging, optical coherence tomography will be provide structural morphological imaging. The synergistic combination of functional and structural imagery will provide the interventional cardiologist with a complete clinical picture of the atherosclerotic plaque region. The clinician can use this diagnostic information to plan a personalized treatment procedure based on the entire clinical presentation.

Hewko, M. D.; Choo-Smith, L. P.; Ko, A. C. T.; Smith, M. S. D.; Kohlenberg, E. M.; Bock, E. R.; Leonardi, L.; Sowa, M. G.

2006-02-01

287

Urotensin II Promotes Atherosclerosis in Cholesterol-Fed Rabbits  

PubMed Central

Urotensin II (UII) is a vasoactive peptide composed of 11 amino acids that has been implicated to contribute to the development of cardiovascular disease. The purpose of this study was to investigate whether UII affects the development of atherosclerosis in cholesterol-fed rabbits. UII was infused for 16 weeks through an osmotic mini-pump into male Japanese White rabbits fed on a high-cholesterol diet. Plasma lipids and body weight were measured every 4 weeks. Aortic atherosclerotic lesions along with cellular components, collagen fibers, matrix metalloproteinase-1 and -9 were examined. Moreover, vulnerability index of atherosclerotic plaques was evaluated. UII infusion significantly increased atherosclerotic lesions within the entire aorta by 21% over the control (P?=?0.013). Atherosclerotic lesions were increased by 24% in the aortic arch (P?=?0.005), 11% in the thoracic aorta (P?=?0.054) and 18% in the abdominal aorta (P?=?0.035). These increases occurred without changes in plasma levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides or body weight. Immunohistochemical staining revealed that macrophages and matrix metalloproteinase-9 were significantly enhanced by 2.2-fold and 1.6-fold in UII group. In vitro studies demonstrated that UII up-regulated the expression of vascular cell adhesion protein-1 and intercellular adhesion molecule-1 in human umbilical vein endothelial cells, which was inhibited by the UII receptor antagonist urantide. In conclusion, our results showed that UII promotes the development of atherosclerotic lesions and destabilizes atherosclerotic plaques in cholesterol-fed rabbits. PMID:24747943

Li, Yafeng; Zhao, Sihai; Wang, Yanli; Chen, Yulong; Lin, Yan; Zhu, Ninghong; Zheng, Huadong; Wu, Min; Cheng, Daxing; Li, Yandong; Bai, Liang; Fan, Jianglin; Liu, Enqi

2014-01-01

288

Lipoprotein(a), atherosclerosis, and apolipoprotein(a) gene polymorphism.  

PubMed

High plasma lipoprotein(a) [Lp(a)] levels have been implicated as an independent risk factor for coronary artery disease in Caucasians, Chinese, Africans, and Indians. Apo(a) that evolved from a duplicated plasminogen gene during recent primate evolution is responsible for the concentration of Lp(a) in the artery wall leading to atherosclerosis, by virtue of its ability to bind to the extracellular matrix and its role in stimulating the proliferation and migration of human smooth muscle cells. Several types of polymorphisms, size as well as sequence changes both in the coding and regulatory sequences, have been reported to influence the variability of Lp(a) concentration. Apo(a) exhibits genetic size polymorphism varying between 300 and 800 kDa that could be attributed to the number of k-4 VNTR (variable number of transcribed kringle-4 repeats). An inverse relationship between Lp(a) level and apo(a) allele sizes is a general trend in all ethnic populations although apo(a) allele size distribution could be significantly variable in ethnic types. A negative correlation between the number of pentanucleotide TTTTA(n) repeat (PNR) sequences in the regulatory region of the apo(a) gene and Lp(a) level has also been observed in Caucasians and Indians, but not in African Americans. However, a significant linkage disequilibrium was noted between the PNR number and k-4 VNTR. In order to correlate the role of apo(a) gene polymorphisms to apo(a) gene regulation, we have proposed that liver-specific transcriptional activators and repressors might contribute to the differential expression of apo(a) gene, in an individual-specific manner. PMID:11001801

Pati, U; Pati, N

2000-01-01

289

Treg/Th17 balance in stable CAD patients with different stages of coronary atherosclerosis.  

PubMed

Objective. Immune processes play a significant role in atherosclerosis plaque progression. Regulatory T cells and T helpers 17 were shown to possess anti- and pro-atherogenic activity, respectively. We aimed to investigate the balance of circulating Treg and Th17 in stable angina patients with different stages of coronary atherosclerosis. Methods. Treg, Th17 and Th1 cell frequencies were studied in 117 patients via direct immunofluorescence staining and flow cytometry. Group 1 had intact coronary arteries. Group 2 and Group 3 had undergone previous coronary stenting; in Group 2 no coronary atherosclerosis progression was found, in Group 3 patients had disease progression in non-invaded coronary arteries. Group 4 had severe coronary atherosclerosis. Results. The frequencies of CD4+CD25highCD127low, CD4+foxp3+, and CD4+IL10 + T cells were decreased, and CD4+IL17 + T cells frequencies were increased in group 4 vs. 1. Treg/Th17 ratios were declined in groups 3 and 4 vs. groups 1 and 2. IL-10 level was lower while hsCRP and sCD25 levels were higher in group 4 vs. 1. Conclusion. We assume that the imbalance in pro- and anti-inflammatory/atherogenic lymphocyte subpopulations is associated with atherosclerosis progression. PMID:25461734

Potekhina, Alexandra V; Pylaeva, Ekaterina; Provatorov, Sergey; Ruleva, Natalya; Masenko, Valery; Noeva, Elena; Krasnikova, Tatiana; Arefieva, Tatiana

2015-01-01

290

A brief elevation of serum amyloid A is sufficient to increase atherosclerosis.  

PubMed

Serum amyloid A (SAA) has a number of proatherogenic effects including induction of vascular proteoglycans. Chronically elevated SAA was recently shown to increase atherosclerosis in mice. The purpose of this study was to determine whether a brief increase in SAA similarly increased atherosclerosis in a murine model. The recombination activating gene 1-deficient (rag1(-/-)) × apolipoprotein E-deficient (apoe(-/-)) and apoe(-/-) male mice were injected, multiple times or just once respectively, with an adenoviral vector encoding human SAA1 (ad-SAA); the injected mice and controls were maintained on chow for 12-16 weeks. Mice receiving multiple injections of ad-SAA, in which SAA elevation was sustained, had increased atherosclerosis compared with controls. Strikingly, mice receiving only a single injection of ad-SAA, in which SAA was only briefly elevated, also had increased atherosclerosis compared with controls. Using in vitro studies, we demonstrate that SAA treatment leads to increased LDL retention, and that prevention of transforming growth factor beta (TGF-?) signaling prevents SAA-induced increases in LDL retention and SAA-induced increases in vascular biglycan content. We propose that SAA increases atherosclerosis development via induction of TGF-?, increased vascular biglycan content, and increased LDL retention. These data suggest that even short-term inflammation with concomitant increase in SAA may increase the risk of developing CVD. PMID:25429103

Thompson, Joel C; Jayne, Colton; Thompson, Jennifer; Wilson, Patricia G; Yoder, Meghan H; Webb, Nancy; Tannock, Lisa R

2015-02-01

291

Association of circulating leukocyte count with coronary atherosclerosis regression after pravastatin treatment.  

PubMed

Epidemiological studies have demonstrated that the peripheral blood leukocyte count could be used as a marker of the progression of atherosclerosis. Few data exist regarding the relationship between inhibition of the progression of coronary atherosclerosis and the anti-inflammatory effects of statins, especially the drugs' effects on the leukocyte count in patients with coronary artery disease. A 6-month prospective study was, therefore, conducted in 50 patients treated with pravastatin. The plaque volume, as assessed by volumetric analysis using intravascular ultrasound, reduced significantly by 14% (p<0.0001, vs. baseline) following the treatment, furthermore, a corresponding decrease of the leukocyte count (8.9%, p<0.01, vs. baseline) was also seen. No correlation was found between the change in the leukocyte count and any of the changes in the lipid levels; changes in either of these are known to be associated with the rate of progression of atherosclerosis. A multivariate regression analysis using other traditional risk factors and medications as covariates revealed that the decrease in the leukocyte count was an independent predictor of inhibition of the progression of coronary atherosclerosis. In conclusion, a reduction of the leukocyte count as one of the non-lipid-lowering effects of pravastatin may be a novel marker of regression of coronary atherosclerosis. PMID:18374337

Tani, Shigemasa; Nagao, Ken; Anazawa, Takeo; Kawamata, Hirofumi; Iida, Kiyoshi; Matsumoto, Michiaki; Sato, Yuichi; Hirayama, Atsushi

2008-06-01

292

Potential Mechanisms Linking Atherosclerosis and Increased Cardiovascular Risk in COPD: Focus On Sirtuins  

PubMed Central

The development of atherosclerosis is a multi-step process, at least in part controlled by the vascular endothelium function. Observations in humans and experimental models of atherosclerosis have identified monocyte recruitment as an early event in atherogenesis. Chronic inflammation is associated with ageing and its related diseases (e.g., atherosclerosis and chronic obstructive pulmonary disease). Recently it has been discovered that Sirtuins (NAD+-dependent deacetylases) represent a pivotal regulator of longevity and health. They appear to have a prominent role in vascular biology and regulate aspects of age-dependent atherosclerosis. Many studies demonstrate that SIRT1 exhibits anti-inflammatory properties in vitro (e.g., fatty acid-induced inflammation), in vivo (e.g., atherosclerosis, sustainment of normal immune function in knock-out mice) and in clinical studies (e.g., patients with chronic obstructive pulmonary disease). Because of a significant reduction of SIRT1 in rodent lungs exposed to cigarette smoke and in lungs of patients with chronic obstructive pulmonary disease (COPD), activation of SIRT1 may be a potential target for chronic obstructive pulmonary disease therapy. We review the inflammatory mechanisms involved in COPD-CVD coexistence and the potential role of SIRT1 in the regulation of these systems. PMID:23774840

Corbi, Graziamaria; Bianco, Andrea; Turchiarelli, Viviana; Cellurale, Michele; Fatica, Federica; Daniele, Aurora; Mazzarella, Gennaro; Ferrara, Nicola

2013-01-01

293

Hydrogen sulfide in the pathogenesis of atherosclerosis and its therapeutic potential.  

PubMed

Hydrogen sulfide (H(2)S) was the third gaseous transmitter to be discovered, along with nitric oxide and carbon monoxide, and has been proposed to be involved in numerous physiological processes and pathology of various diseases. Hyperhomocysteinemia is an independent risk factor for cardiovascular disease, including atherosclerosis. Atherosclerosis is characterized by multiple key events including endothelial dysfunction, monocyte infiltration and their differentiation into macrophages, conversion of lesion-resident macrophages into foam cells, and smooth muscle cell proliferation. Increasing evidence has indicated that H(2)S plays a potentially significant role in all of these biological processes and that malfunction of H(2)S homeostasis may contribute to the pathogenesis of atherosclerosis. Experiments have demonstrated that H(2)S supplementation ameliorated many of these atherogenic processes and hence, such supplementation potentially may prove to be of therapeutic benefit in the prevention or treatment of atherosclerosis. H(2)S levels may be induced by the administration of H(2)S or H(2)S donors, or alternatively be reduced by the administration of specific cystathionine ?-synthase or cystathionine ?-lyase inhibitors. However, issues remain with the potential use of currently available H(2)S-modulating agents in a clinical setting. This review will provide a description of the current literature on the involvement of H(2)S in these key aspects of vascular biology that contribute to the development of atherosclerosis, as well as the therapeutic potential of currently available H(2)S-modulating agents. PMID:22115351

Lynn, Edward G; Austin, Richard C

2011-01-01

294

Anti-inflammatory effects of vinpocetine in atherosclerosis and ischemic stroke: a review of the literature.  

PubMed

Immune responses play an important role in the pathophysiology of atherosclerosis and ischemic stroke. Atherosclerosis is a common condition that increases the risk of stroke. Hyperlipidemia damages endothelial cells, thus initiating chemokine pathways and the release of inflammatory cytokines-this represents the first step in the inflammatory response to atherosclerosis. Blocking blood flow in the brain leads to ischemic stroke, and deprives neurons of oxygen and energy. Damaged neurons release danger-associated molecular patterns, which promote the activation of innate immune cells and the release of inflammatory cytokines. The nuclear factor ?-light-chain-enhancer of activated B cells ?B (NF-?B) pathway plays a key role in the pathogenesis of atherosclerosis and ischemic stroke. Vinpocetine is believed to be a potent anti-inflammatory agent and has been used to treat cerebrovascular disorders. Vinpocetine improves neuronal plasticity and reduces the release of inflammatory cytokines and chemokines from endothelial cells, vascular smooth muscle cells, macrophages, and microglia, by inhibiting the inhibitor of the NF-?B pathway. This review clarifies the anti-inflammatory role of vinpocetine in atherosclerosis and ischemic stroke. PMID:25549058

Zhang, Linjie; Yang, Li

2015-01-01

295

A comparison of postmortem coronary atherosclerosis findings in general aviation pilot fatalities.  

PubMed

The autopsy reports of 710 pilots involved in fatal general aviation accidents were received by the FAA for the years 1980-82; they were reviewed to appraise the age-specific prevalence of coronary atherosclerosis among the autopsied group and to compare findings with those of an earlier study. Of the autopsies on pilots killed in aircraft accidents, 69% indicated some degree of coronary atherosclerosis, ranging from minimal to severe. This finding is higher than for a similar group of pilots studied for the years 1975-77. However, only about 2.5% of the 1980-82 study group were found to have severe coronary atherosclerosis, compared with 5% in the previous study. Prevalence of severe coronary atherosclerosis increased with age from 5.8 per 1,000 for ages less than 40 years to 73.9 for age 50 years and above, also reflecting lower age-specific rates for severe coronary atherosclerosis than were found in the previous study. PMID:3579814

Booze, C F; Staggs, C M

1987-04-01

296

Effect of snake venom of Agkistrodon halys on atherosclerosis and blood characteristics in Japanese quail.  

PubMed

Extracts of snake venom have been widely used for the treatment of vascular thrombotic diseases, yet the therapeutic mechanism is not clear. The effect of snake venom fractions on atherosclerosis in Japanese quail was studied. The venom of Agkistrodon halys was fractionated by DEAE-cellulose chromatography and the pooled protein fractions that resulted were injected intravenously into the quail with aortic atherosclerosis induced by dietary cholesterol. After 7 weeks of injections on every other day, the quail were killed, blood clotting times and serum cholesterol levels were determined, and aortic atherosclerosis and fatty liver were scored. The results showed that while no regression of atherosclerosis was observed, the lowering of serum cholesterol, prolonged blood clotting time and reduced fatty liver were significantly affected by the injection of one of the pooled protein fractions. This venom fraction contained two major protein components, one of which had arginine esterase activity. From this study we conclude that snake venom has little effect on the regression of atherosclerosis, but it prolongs blood clotting and lowers serum cholesterol. PMID:2282093

Sun, L G; Hao, W X; Shih, J C

1990-10-01

297

Old and new risk factors for atherosclerosis and development of treatment recommendations.  

PubMed

1. The development of atherosclerosis, including the role of the classical and new risk factors, is briefly reviewed an emphasis on the links between some of these risk factors and atherogenesis. 2. While genetic factors are doubtlessly important, they contribute (from the population point of view) little to the overall burden of atherosclerosis. 3. Our studies on the relationship between abdominal obesity and metabolic risk factors in two ethnic groups, namely individuals of Cantonese and European background, suggest that different ranges for at least some of the risk factors should be established for specific ethnic groups (e.g. waist circumference for individuals of Chinese and European background). 4. Using the example of differences between Cantonese heterozygotes for familial hypercholesterolaemia living in Vancouver, Canada, and Canton, China, we demonstrate how the environment can modify a genetic predisposition for atherosclerosis. 5. Gender differences are illustrated by a study of serum lipoprotein (a) as a risk factor in men and women. 6. The principles of current Canadian recommendations for the assessment and treatment of atherosclerosis are outlined; they are based on knowledge gained from both basic and clinical research of atherosclerosis. PMID:12165052

Frohlich, Jiri; Lear, Scott A

2002-09-01

298

Early Onset Intrauterine Growth Restriction in a Mouse Model of Gestational Hypercholesterolemia and Atherosclerosis  

PubMed Central

The susceptibility to develop atherosclerosis is increased by intrauterine growth restriction and prenatal exposure to maternal hypercholesterolemia. Here, we studied whether mouse gestational hypercholesterolemia and atherosclerosis affected fetal development and growth at different stages of gestation. Female LDLR KO mice fed a proatherogenic, high cholesterol (HC) diet for 3 weeks before conception and during pregnancy exhibited a significant increase in non-HDL cholesterol and developed atherosclerosis. At embryonic days 12.5 (E12.5), E15.5, and E18.5, maternal gestational hypercholesterolemia and atherosclerosis were associated to a 22–24% reduction in male and female fetal weight without alterations in fetal number/litter or morphology nor placental weight or structure. Feeding the HC diet exclusively at the periconceptional period did not alter fetal growth, suggesting that maternal hypercholesterolemia affected fetal weight only after implantation. Vitamin E supplementation (1,000?UI of ?-tocopherol/kg) of HC-fed females did not change the mean weight of E18.5 fetuses but reduced the percentage of fetuses exhibiting body weights below the 10th percentile of weight (HC: 90% vs. HC/VitE: 68%). In conclusion, our results showed that maternal gestational hypercholesterolemia and atherosclerosis in mice were associated to early onset fetal growth restriction and that dietary vitamin E supplementation had a beneficial impact on this condition. PMID:25295255

Busso, Dolores; Mascareño, Lilian; Salas, Francisca; Berkowitz, Loni; Santander, Nicolás; Quiroz, Alonso; Amigo, Ludwig; Valdés, Gloria; Rigotti, Attilio

2014-01-01

299

Heat Shock Proteins: Pathogenic Role in Atherosclerosis and Potential Therapeutic Implications  

PubMed Central

Heat shock proteins (HSPs) are a highly conserved group of proteins that are constitutively expressed and function as molecular chaperones, aiding in protein folding and preventing the accumulation of misfolded proteins. In the arterial wall, HSPs have a protective role under normal physiologic conditions. In disease states, however, HSPs expressed on the vascular endothelial cell surface can act as targets for detrimental autoimmunity due to their highly conserved sequences. Developing therapeutic strategies for atherosclerosis based on HSPs is challenged by the need to balance such physiologic and pathologic roles of these proteins. This paper summarizes the role of HSPs in normal vascular wall processes as well as in the development and progression of atherosclerosis. The potential implications of HSPs in clinical therapies for atherosclerosis are also discussed. PMID:23304456

Kilic, Arman; Mandal, Kaushik

2012-01-01

300

Iron and atherosclerosis: nailing down a novel target with magnetic resonance.  

PubMed

Iron is an essential mineral in many proteins and enzymes in human physiology, with limited means of iron elimination to maintain iron balance. Iron accrual incurs various pathological mechanisms linked to cardiovascular disease. In atherosclerosis, iron catalyzes the creation of reactive oxygen free radicals that contribute to lipid modification, which is essential to atheroma formation. Inflammation further fuels iron-related pathologic processes associated with plaque progression. Given iron's role in atherosclerosis development, in vivo detection techniques sensitive iron are needed for translational studies targeting iron for earlier diagnosis and treatment. Magnetic resonance imaging is uniquely able to quantify iron in human tissues noninvasively and without ionizing radiation, offering appealing for longitudinal and interventional studies. Particularly intriguing is iron's complementary biology vs. calcium, which is readily detectable by computed tomography. This review summarizes the role of iron in atherosclerosis with considerable implications for novel diagnostic and therapeutic approaches. PMID:24590608

Sharkey-Toppen, Travis P; Tewari, Arun K; Raman, Subha V

2014-07-01

301

[Phenotypes of dendritic cells in central lymph of healthy rabbits and during correction of experimental atherosclerosis].  

PubMed

Dendritic cells of central lymph of rabbits have been identified according to the form of the cell body, characteristics of formation and branchiness of its processes in health, in atherosclerosis, its correction with radon, polyphenol preparations made of Sanguisorba officinalis and in combination of the latter. Two main types of dendritic cells have been distinguished. Type I is characterized by a rounded body with clear outlines, protrusions and one compact process. Such cells are often found in lymph of intact animals. Type II has a cell body of various forms with two and more compact or branching processes. This type is mainly detected in atherosclerosis and its correction. The prevalence of the above phenotypes of dendritic cells is attributed to the response of the immune system to atherosclerosis and its correction. PMID:1477343

Kuznetsov, A V

1992-09-01

302

Echium Oil Reduces Atherosclerosis in apoB100-only LDLrKO Mice  

PubMed Central

Introduction The anti-atherogenic and hypotriglyceridemic properties of fish oil are attributed to its enrichment in eicosapentaenoic acid (EPA; 20:5, n-3) and docosahexaenoic acid (DHA; 22:6, n-3). Echium oil contains stearidonic acid (SDA; 18:4, n-3), which is metabolized to EPA in humans and mice, resulting in decreased plasma triglycerides. Objective We used apoB100 only, LDLrKO mice to investigate whether echium oil reduces atherosclerosis. Methods Mice were fed palm, echium, or fish oil-containing diets for 16 weeks and plasma lipids, lipoproteins, and atherosclerosis were measured. Results Compared to palm oil, echium oil feeding resulted in significantly less plasma triglyceride and cholesterol levels, and atherosclerosis, comparable to that of fish oil. Conclusion This is the first report that echium oil is anti-atherogenic, suggesting that it may be a botanical alternative to fish oil for atheroprotection. PMID:22100249

Forrest, Lolita M.; Boudyguina, Elena; Wilson, Martha D.; Parks, John S.

2012-01-01

303

Future non-invasive imaging to detect vascular plaque instability and subclinical non-obstructive atherosclerosis  

PubMed Central

Atherosclerosis underlies the major causes of death in the Western World. Our main goal is to detect early changes of atherosclerosis and to identify subjects at highest cardiovascular risk that may aid in the development of prevention approaches and better management that will decrease cardiovascular morbidity and mortality. The new methods that are of interest include the advanced vascular ultrasound methods, the infra red and near infra red imaging techniques, the EndoPat device that reflects peripheral arterial tone, the electron beam computed tomography, the magnetic resonance imaging, and the molecular imaging techniques. In this review we will focus on the future of advanced imaging techniques that are being developed to detect early (pre-clinical) development of atherosclerosis. PMID:23888178

Blum, Arnon; Nahir, Menachem

2013-01-01

304

Site-Specific Antioxidative Therapy for Prevention of Atherosclerosis and Cardiovascular Disease  

PubMed Central

Oxidative stress has been implicated in pathophysiology of aging and age-associated disease. Antioxidative medicine has become a practice for prevention of atherosclerosis. However, limited success in preventing cardiovascular disease (CVD) in individuals with atherosclerosis using general antioxidants has prompted us to develop a novel antioxidative strategy to prevent atherosclerosis. Reducing visceral adipose tissue by calorie restriction (CR) and regular endurance exercise represents a causative therapy for ameliorating oxidative stress. Some of the recently emerging drugs used for the treatment of CVD may be assigned as site-specific antioxidants. CR and exercise mimetic agents are the choice for individuals who are difficult to continue CR and exercise. Better understanding of molecular and cellular biology of redox signaling will pave the way for more effective antioxidative medicine for prevention of CVD and prolongation of healthy life span. PMID:23738041

Otani, Hajime

2013-01-01

305

Imaging Atherosclerosis with Hybrid Positron Emission Tomography/Magnetic Resonance Imaging  

PubMed Central

Noninvasive imaging of atherosclerosis could potentially move patient management towards individualized triage, treatment, and followup. The newly introduced combined positron emission tomography (PET) and magnetic resonance imaging (MRI) system could emerge as a key player in this context. Both PET and MRI have previously been used for imaging plaque morphology and function: however, the combination of the two methods may offer new synergistic opportunities. Here, we will give a short summary of current relevant clinical applications of PET and MRI in the setting of atherosclerosis. Additionally, our initial experiences with simultaneous PET/MRI for atherosclerosis imaging are presented. Finally, future potential vascular applications exploiting the unique combination of PET and MRI will be discussed.

Kjær, Andreas

2015-01-01

306

Wall Shear Stress Characteristics for the Progression of the Disease, Atherosclerosis  

NASA Astrophysics Data System (ADS)

Wall shear stress (WSS) characteristics of a stenosed artery which are the important physiological parameters for the progression of the arterial diseases atherosclerosis, are studied and compared for different Reynolds numbers and different Womersley numbers. Numerical simulations of physiological pulsatile flow through a model stenotic artery are performed by finite volume method. From this study, it is revealed that the chance of formation of atherosclerosis increases with increase in Reynolds number and decreases with increase in Womersley number. The phenomenon of mass transportation across arterial wall is more in case of increase in Womersley number rather than Reynolds number. The chance of formation of atheromatous plaque will be high with higher Reynolds number and Womersley number. In the low WSS region, high magnitude of Womersley number indicates high chance of progression of the disease atherosclerosis. High magnitude of Womersley number with low Reynolds number is more dangerous for the progression of the disease in the low WSS region.

Goswami, P.; Mandal, D. K.; Manna, N. K.; Chakrabarti, S.

2014-12-01

307

[LOX-1 receptor as a novel target in endothelial dysfunction and atherosclerosis].  

PubMed

Atherosclerosis with its complications like heart attack and stroke, is the most frequent cause of death in the industrialized countries. Oxidized low-density lipoproteins (LDL) play a major role in the pathogenesis of atherosclerosis. Inhibition of cholesterol synthesis by statins has several protective effects but is not sufficient to prevent the uptake of oxidized LDL and the development of atherosclerotic plaques. For this reason a selective pharmacological inhibition of the uptake of oxidized LDL (oxLDL) in endothelial cells is an interesting therapeutic approach. An important novel target molecule is the endothelial lectin-like oxLDL receptor LOX-1. This receptor is able to take up both minimally and highly oxidized LDL. In addition it mediates endothelial phagocytosis of aged and apoptotic cells and plays a role in thrombocyte adhesion and in the interaction between bacterial proteins and endothelial cells in sepsis. LOX-1 is induced by proinflammatory cytokines, oxLDL, angiotensin II, endothelin-1 and arterial hypertension. LOX-1 increases endothelial dysfunction and atherosclerosis by endothelial uptake of oxLDL. This is the reason why LOX-1 has been considered as a novel link between hypertension and atherosclerosis. Transgenic overexpression of the LOX-1 receptor and high-fat diet induces intramyocardial vascular disease and endothelial dysfunction in resistance arteries. In contrast, genetic deletion of the LOX-1 gene reduces the development of atherosclerotic plaques. In the clinical context LOX-1 has been detected in the early phase of endothelial dysfunction and atherosclerosis in arteries of patients with coronary heart disease. Several novel data support a role of LOX-1 in the endothelial dysfunction in diabetic vascular and renal disease, hypercholesterolemia, obesity and preeclampsia. This makes the LOX-1 receptor a novel and interesting target molecule in endothelial dysfunction and atherosclerosis. PMID:20146162

Morawietz, H

2010-02-01

308

11?-hydroxysteroid dehydrogenase type 1 deficiency in bone marrow-derived cells reduces atherosclerosis  

PubMed Central

11?-Hydroxysteroid dehydrogenase type-1 (11?-HSD1) converts inert cortisone into active cortisol, amplifying intracellular glucocorticoid action. 11?-HSD1 deficiency improves cardiovascular risk factors in obesity but exacerbates acute inflammation. To determine the effects of 11?-HSD1 deficiency on atherosclerosis and its inflammation, atherosclerosis-prone apolipoprotein E-knockout (ApoE-KO) mice were treated with a selective 11?-HSD1 inhibitor or crossed with 11?-HSD1-KO mice to generate double knockouts (DKOs) and challenged with an atherogenic Western diet. 11?-HSD1 inhibition or deficiency attenuated atherosclerosis (74–76%) without deleterious effects on plaque structure. This occurred without affecting plasma lipids or glucose, suggesting independence from classical metabolic risk factors. KO plaques were not more inflamed and indeed had 36% less T-cell infiltration, associated with 38% reduced circulating monocyte chemoattractant protein-1 (MCP-1) and 36% lower lesional vascular cell adhesion molecule-1 (VCAM-1). Bone marrow (BM) cells are key to the atheroprotection, since transplantation of DKO BM to irradiated ApoE-KO mice reduced atherosclerosis by 51%. 11?-HSD1-null macrophages show 76% enhanced cholesterol ester export. Thus, 11?-HSD1 deficiency reduces atherosclerosis without exaggerated lesional inflammation independent of metabolic risk factors. Selective 11?-HSD1 inhibitors promise novel antiatherosclerosis effects over and above their benefits for metabolic risk factors via effects on BM cells, plausibly macrophages.—Kipari, T., Hadoke, P. W. F., Iqbal, J., Man, T. Y., Miller, E., Coutinho, A. E., Zhang, Z., Sullivan, K. M., Mitic, T., Livingstone, D. E. W., Schrecker, C., Samuel, K., White, C. I., Bouhlel, M. A., Chinetti-Gbaguidi, G., Staels, B., Andrew, R., Walker, B. R., Savill, J. S., Chapman, K. E., Seckl, J. R. 11?-hydroxysteroid dehydrogenase type 1 deficiency in bone marrow-derived cells reduces atherosclerosis. PMID:23303209

Kipari, Tiina; Hadoke, Patrick W. F.; Iqbal, Javaid; Man, Tak-Yung; Miller, Eileen; Coutinho, Agnes E.; Zhang, Zhenguang; Sullivan, Katie M.; Mitic, Tijana; Livingstone, Dawn E. W.; Schrecker, Christopher; Samuel, Kay; White, Christopher I.; Bouhlel, M. Amine; Chinetti-Gbaguidi, Giulia; Staels, Bart; Andrew, Ruth; Walker, Brian R.; Savill, John S.; Chapman, Karen E.; Seckl, Jonathan R.

2013-01-01

309

Genetic deletion of platelet glycoprotein Ib alpha but not its extracellular domain protects from atherosclerosis.  

PubMed

The pathogenesis of atherosclerosis involves the interplay of haematopoietic, stromal and endothelial cells. Platelet interactions with endothelium and leukocytes are pivotal for atherosclerosis promotion. Glycoprotein (GP) Ib? is the ligand-binding subunit of the platelet GPIb-IX-V receptor complex; its deficiency causes the Bernard-Soulier syndrome (BSS), characterised by absent platelet GPIb-IX-V, macrothrombocytopenia and bleeding. We designed this study to determine the role of platelet GPIb? in the pathogenesis of atherosclerosis using two unique knockout models. Ldlr-/- mice were reconstituted with wild-type (wt), GPIb?-/- (lacks GPIb?) or chimeric IL-4R/GPIb?-Tg (lacks GPIb? extracellular domain) bone marrow and assayed for atherosclerosis development after feeding with pro-atherogenic "western diet". Here, we report that Ldlr-/-mice reconstituted with GPIb?-/- bone marrow developed less atherosclerosis compared to wt controls; accompanied by augmented accumulation of pro-inflammatory CD11b+ and CD11c+ myeloid cells, reduced oxLDL uptake and decreased TNF and IL 12p35 gene expression in the aortas. Flow cytometry and live cell imaging in whole blood-perfused microfluidic chambers revealed reduced platelet-monocyte aggregates in GPIb?-/- mice, which resulted in decreased monocyte activation. Interestingly, Ldlr-/-mice reconstituted with IL-4R/GPIb?-Tg bone marrow, producing less abnormal platelets, showed atherosclerotic lesions similar to wt mice. Platelet interaction with blood monocytes and accumulation of myeloid cells in the aortas were also essentially unaltered. Moreover, only complete GPIb? ablation altered platelet microparticles and CCL5 chemokine production. Thus, atherosclerosis reduction in mice lacking GPIb? may not result from the defective GPIb?-ligand binding, but more likely is a consequence of functional defects of GPIb?-/- platelets and reduced blood platelet counts. PMID:25104056

Koltsova, E K; Sundd, P; Zarpellon, A; Ouyang, H; Mikulski, Z; Zampolli, A; Ruggeri, Z M; Ley, K

2014-12-01

310

Progression of coronary atherosclerosis in African-American patients  

PubMed Central

Background African-Americans with coronary artery disease (CAD) demonstrate worse clinical outcomes than Caucasians. While this is partly due to a lack of accessibility to established therapies, the mechanisms underlying this difference remain to be elucidated. We aimed to characterize the progression of coronary atherosclerosis in African-Americans with CAD. Methods 3,479 patients with CAD underwent serial intravascular ultrasound (IVUS) imaging to evaluate atheroma progression in 7 clinical trials of anti-atherosclerotic therapies. Risk factor control and atheroma progression were compared between African-Americans (n=170) and Caucasians (n=3,309). Results African-Americans were more likely to be female (51.8% vs. 28.1%, P<0.001), have a higher body mass index (32.8±6.0 vs. 31.3±5.8 kg/m2, P=0.002) and greater history of hypertension (85.9% vs. 78.8%, P=0.02), diabetes (41.8% vs. 30.6%, P=0.002) and stroke (12.9% vs. 3.0%, P<0.001). Despite a high use of anti-atherosclerotic medications (93% statin, 89% aspirin, 79% ?-blocker, 52% ACE inhibitor), African-Americans demonstrated higher levels of LDL-C (2.4±0.7 vs. 2.2±0.7 mmol/L, P=0.006), CRP (2.9 vs. 2.0 mg/dL, P<0.001) and systolic blood pressure (133±15 vs. 129±13 mmHg, P<0.001) at follow-up. There was no significant difference in atheroma volume at baseline (189.0±82.2 vs. 191.6±83.3 mm3, P=0.82) between two groups. Serial evaluation demonstrated a greater increase in atheroma volume in African-Americans (0.51±2.1 vs. –3.1±1.7 mm3, P=0.01). This difference persisted with propensity matching accounting for differences in risk factor control (0.1±2.1 vs. –3.7±1.7 mm3, P=0.02). Conclusions African-Americans with CAD achieve less optimal risk factor control and greater atheroma progression. These findings support the need for more intensive risk factor modification in African-Americans. PMID:24282765

Kataoka, Yu; Hsu, Amy; Wolski, Kathy; Uno, Kiyoko; Puri, Rishi; Tuzcu, E. Murat; Nissen, Steven E.

2013-01-01

311

Modulation of paraoxonases during infectious diseases and its potential impact on atherosclerosis  

PubMed Central

The paraoxonase (PON) gene family includes three members, PON1, PON2 and PON3, aligned in tandem on chromosome 7 in humans and on chromosome 6 in mice. All PON proteins share considerable structural homology and have the capacity to protect cells from oxidative stress; therefore, they have been implicated in the pathogenesis of several inflammatory diseases, particularly atherosclerosis. The major goal of this review is to highlight the modulation of each of the PONs by infective (bacterial, viral and parasitic) agents, which may shed a light on the interaction between infectious diseases and PONs activities in order to effectively reduce the risk of developing atherosclerosis. PMID:22824324

2012-01-01

312

LOX-1, oxidant stress, mtDNA damage, autophagy, and immune response in atherosclerosis.  

PubMed

As a major receptor for oxidized low density lipoprotein (ox-LDL), lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is upregulated in many pathophysiological events, including endothelial cell dysfunction and smooth muscle cell growth, as well as monocyte migration and transformation into foam cells, which are present in atherosclerosis and myocardial ischemia. Excessive production of reactive oxygen species (ROS) increases LOX-1 expression, induces mitochondrial DNA damage, and activates autophagy. Damaged mitochondrial DNA that escapes from autophagy induces an inflammatory response. This paper reviews the potential link between LOX-1, mitochondrial DNA damage, autophagy, and immune response in atherosclerosis. PMID:24959993

Ding, Zufeng; Liu, Shijie; Wang, Xianwei; Dai, Yao; Khaidakov, Magomed; Romeo, Francesco; Mehta, Jawahar L

2014-07-01

313

Long Term Follow Up of Celiac Disease—Is Atherosclerosis a Problem?  

PubMed Central

Celiac disease (CD) is a lifelong condition and it often involves impaired nutrition, wide spectrum of symptoms and it requires constant dietetic treatment. The impact of the gluten-free diet on patients’ nutritional status and on the other biochemical parameters is being widely investigated. In this article we looked into particular risk factors that might lead to increased prevalence of atherosclerosis in CD patients, including nutritional status, gluten-free diet, lipids profile and concomitant disease—type 1 diabetes mellitus. Here, we present the current data and research on these risk factors of atherosclerosis with respect to celiac disease. PMID:25050927

Rybak, Anna; Cukrowska, Bo?ena; Socha, Jerzy; Socha, Piotr

2014-01-01

314

Pressure suppression containment system  

DOEpatents

A pressure suppression containment system includes a containment vessel surrounding a reactor pressure vessel and defining a drywell therein containing a non-condensable gas. An enclosed wetwell pool is disposed inside the containment vessel, and a gravity driven cooling system (GDCS) pool is disposed above the wetwell pool in the containment vessel. The wetwell pool includes a plenum for receiving the non-condensable gas carried with steam from the drywell following a loss-of-coolant-accident (LOCA). The wetwell plenum is vented to a plenum above the GDCS pool following the LOCA for suppressing pressure rise within the containment vessel. A method of operation includes channeling steam released into the drywell following the LOCA into the wetwell pool for cooling along with the non-condensable gas carried therewith. The GDCS pool is then drained by gravity, and the wetwell plenum is vented into the GDCS plenum for channeling the non-condensable gas thereto. 6 figures.

Gluntz, D.M.; Townsend, H.E.

1994-03-15

315

Tremor suppression in ECG  

PubMed Central

Background Electrocardiogram recordings are very often contaminated by high-frequency noise usually power-line interference and EMG disturbances (tremor). Specific method for interference cancellation without affecting the proper ECG components, called subtraction procedure, was developed some two decades ago. Filtering out the tremor remains a priori partially successful since it has a relatively wide spectrum, which overlaps the useful ECG frequency band. Method The proposed method for tremor suppression implements the following three procedures. Contaminated ECG signals are subjected to moving averaging (comb filter with linear phase characteristic) with first zero set at 50 Hz to suppress tremor and PL interference simultaneously. The reduced peaks of QRS complexes and other relatively high and steep ECG waves are then restored by an introduced by us procedure called linearly-angular, so that the useful high frequency components are preserved in the range specified by the embedded in the ECG instrument filter, usually up to 125 Hz. Finally, a Savitzky-Golay smoothing filter is applied for supplementary tremor suppression outside the QRS complexes. Results The results obtained show a low level of the residual EMG disturbances together with negligible distortion of the wave shapes regardless of rhythm and morphology changes. PMID:19019218

Dotsinsky, Ivan A; Mihov, Georgy S

2008-01-01

316

Menstrual suppression: current perspectives  

PubMed Central

Menstrual suppression to provide relief of menstrual-related symptoms or to manage medical conditions associated with menstrual morbidity or menstrual exacerbation has been used clinically since the development of steroid hormonal therapies. Options range from the extended or continuous use of combined hormonal oral contraceptives, to the use of combined hormonal patches and rings, progestins given in a variety of formulations from intramuscular injection to oral therapies to intrauterine devices, and other agents such as gonadotropin-releasing hormone (GnRH) antagonists. The agents used for menstrual suppression have variable rates of success in inducing amenorrhea, but typically have increasing rates of amenorrhea over time. Therapy may be limited by side effects, most commonly irregular, unscheduled bleeding. These therapies can benefit women’s quality of life, and by stabilizing the hormonal milieu, potentially improve the course of underlying medical conditions such as diabetes or a seizure disorder. This review addresses situations in which menstrual suppression may be of benefit, and lists options which have been successful in inducing medical amenorrhea. PMID:25018654

Hillard, Paula Adams

2014-01-01

317

Null Association between Abdominal Muscle and Calcified Atherosclerosis in Community-Living Persons Without Clinical Cardiovascular Disease: the Multi-Ethnic Study of Atherosclerosis  

PubMed Central

Objective Detrimental effects of lean muscle loss have been hypothesized to explain J-shaped relationships of body mass index (BMI) with cardiovascular disease (CVD), yet associations of muscle mass with CVD are largely unknown. We hypothesized that low abdominal lean muscle area would be associated with greater calcified atherosclerosis, independent of other CVD risk factors. Materials/Methods We investigated 1020 participants from the Multi-Ethnic Study of Atherosclerosis who were free of clinical CVD. Computed tomography (CT) scans at the 4th and 5th lumbar disk space were used to estimate abdominal lean muscle area. Chest and abdominal CT scans were used to assess coronary artery calcification(CAC), thoracic aortic calcification (TAC), and abdominal aortic calcification (AAC). Results The mean age was 64±10 years, 48% were female, and mean BMI was 28±5 kg/m2. In models adjusted for demographics, physical activity, caloric intake, and traditional CVD risk factors, there was no inverse association of abdominal muscle mass with CAC(Prevalence Ratio [PR] 1.02 [95% CI 0.95,1.10]), TAC (PR 1.13 [95%CI 0.92, 1.39]) or AAC (PR 0.99 [95%CI 0.94, 1.04]) prevalence. Similarly, there was no significant inverse relationship between abdominal lean muscle area and CAC, TAC, and AAC severity. Conclusion In community-living individuals without clinical CVD, greater abdominal lean muscle area is not associated with less calcified atherosclerosis. PMID:23916063

Jensky, Nicole E.; Allison, Matthew A.; Loomba, Rohit; Carnethon, Mercedes R.; de Boer, Ian H.; Budoff, Matthew J.; Burke, Greg L.; Criqui, Michael H.; Ix, Joachim H.

2013-01-01

318

T-Cell Phenotypes, Apoptosis and Inflammation in HIV+ Patients on Virologically Effective cART with Early Atherosclerosis  

PubMed Central

Objective We investigated the potential relationship between T-cell phenotype, inflammation, endotoxemia, and atherosclerosis evaluated by carotid intima-media thickness (IMT) in a cohort of HIV-positive patients undergoing long-term virologically suppressive combination antiretroviral therapy (cART). Design We studied 163 patients receiving virologically suppressive cART. Methods We measured IMT (carotid ultrasound); CD4+/CD8+ T-cell activation (CD38, CD45R0), differentiation (CD127), apoptosis (CD95), and senescence (CD28, CD57) (flow cytometry); plasma sCD14, IL-6, TNF- ?, sVCAM-1, hs-CRP, anti-CMV IgG (ELISA); LPS (LAL). The results were compared by Mann-Whitney, Kruskal-Wallis or Chi-square tests, and factors associated with IMT were evaluated by multivariable logistic regression. Results Of 163 patients, 112 demonstrated normal IMT (nIMT), whereas 51 (31.3%) had pathological IMT (pIMT: ?1 mm). Of the patients with pIMT, 22 demonstrated an increased IMT (iIMT), and 29 were shown to have plaques. These patient groups had comparable nadir and current CD4+, VLs and total length of time on cART. Despite similar proportions of CD38-expressing CD8+ cells (p?=?.95), pIMT patients exhibited higher activated memory CD8+CD38+CD45R0+ cells (p?=?.038) and apoptotic CD4+CD95+ (p?=?.01) and CD8+CD95+ cells (p?=?.003). In comparison to nIMT patients, iIMT patients tended to have lower numbers of early differentiated CD28+CD57? memory CD4+ (p?=?.048) and CD28–CD57?CD8+ cells (p?=?.006), both of which are associated with a higher proliferative potential. Despite no differences in plasma LPS levels, pIMT patients showed significantly higher circulating levels of sCD14 than did nIMT patients (p?=?.046). No differences in anti-CMV IgG was shown. Although circulating levels of sCD14 seemed to be associated with a risk of ATS in an unadjusted analysis, this effect was lost after adjusting for classical cardiovascular predictors. Conclusions Despite the provision of full viral suppression by cART, a hyperactivated, pro-apoptotic T-cell profile characterizes HIV-infected patients with early vascular damage, for whom the potential contribution of subclinical endotoxemia and anti-CMV immunity should be investigated further. PMID:23029393

Suardi, Elisa; Barassi, Alessandra; Cerrone, Maddalena; Martínez, Javier Sánchez; Bai, Francesca; D’Eril, Gian Vico Melzi; Monforte, Antonella D’Arminio; Marchetti, Giulia

2012-01-01

319

Herbal remedy magnolol suppresses IL-6-induced STAT3 activation and gene expression in endothelial cells  

PubMed Central

Magnolol (Mag), an active constituent isolated from the Chinese herb Hou p'u (Magnolia officinalis) has long been used to suppress inflammatory processes. Chronic inflammation is well known to be involved in vascular injuries such as atherosclerosis in which interleukin (IL)-6 may participate. Signal transducer and activator of transcription protein 3 (STAT3), a transcription factor involved in inflammation and the cell cycle, is activated by IL-6. In this study, we evaluated whether Mag can serve as an anti-inflammatory agent during endothelial injuries. The effects of Mag on IL-6-induced STAT3 activation and downstream target gene induction in endothelial cells (ECs) were examined. Pretreatment of ECs with Mag dose dependently inhibited IL-6-induced Tyr705 and Ser727 phosphorylation in STAT3 without affecting the phosphorylation of JAK1, JAK2, and ERK1/2. Mag pretreatment of these ECs dose dependently suppressed IL-6-induced promoter activity of intracellular cell adhesion molecule (ICAM)-1 that contains functional IL-6 response elements (IREs). An electrophoretic mobility shift assay (EMSA) revealed that Mag treatment significantly reduced STAT3 binding to the IRE region. Consistently, Mag treatment markedly inhibited ICAM-1 expression on the endothelial surface. As a result, reduced monocyte adhesion to IL-6-activated ECs was observed. Furthermore, Mag suppressed IL-6-induced promoter activity of cyclin D1 and monocyte chemotactic protein (MCP)-1 for which STAT3 activation plays a role. In conclusion, our results indicate that Mag inhibits IL-6-induced STAT3 activation and subsequently results in the suppression of downstream target gene expression in ECs. These results provide a therapeutic basis for the development of Mag as an anti-inflammatory agent for vascular disorders including atherosclerosis. PMID:16520748

Chen, Shih-Chung; Chang, Ying-Ling; Wang, Danny Ling; Cheng, Jing-Jy

2006-01-01

320

Intimal Hyperplasia of the Infant Parasellar Carotid Artery A Potential Developmental Factor in Atherosclerosis and SIDS  

E-print Network

(pICA) has a high propensity toward atherosclerosis, and lesions at this location frequently cause is caused by the hidden position of the pICA, which prevents the use of modern in vivo techniques of intimal cushions in the parasellar internal carotid artery (pICA) of the human infant. A total of 35

Müller, Gerd B.

321

Coronary arterial calcification in rheumatoid arthritis: comparison with the MultiEthnic Study of Atherosclerosis  

Microsoft Academic Search

INTRODUCTION: Although cardiovascular morbidity and mortality are increased in rheumatoid arthritis, little is known about the burden of subclinical coronary atherosclerosis in these patients. METHODS: Using computed tomography, coronary artery calcification was measured in 195 men and women with rheumatoid arthritis aged 45 to 84 years without clinical cardiovascular disease and compared with 1,073 controls without rheumatoid arthritis enrolled in

Jon T Giles; Moyses Szklo; Wendy Post; Michelle Petri; Roger S Blumenthal; Gordon Lam; Allan C Gelber; Robert Detrano; William W Scott Jr; Richard A Kronmal; Joan M Bathon

2009-01-01

322

Role of Viral Replication, Antiretroviral Therapy, and Immunodeficiency in HIV- Associated Atherosclerosis  

PubMed Central

Objective HIV-seropositive patients are at higher risk for atherosclerosis than HIV-seronegative persons. This has been variably attributed to antiretroviral drug toxicity, immunodeficiency, and/or HIV-associated inflammation. To evaluate the contributions of these factors to HIV-associated atherosclerosis, we assessed carotid artery intima-media thickness (IMT) in a diverse cohort of HIV-seronegative and seropositive adults, including a unique group of HIV-infected patients who were untreated, had undetectable viral loads and had preserved CD4+ T cell counts (HIV controllers). Methods and Results Carotid IMT was measured in 494 subjects, including 33 HIV controllers and 93 HIV-seronegative controls. HIV controllers had higher IMT than seronegative controls even after adjustment for traditional risk factors (p=0.003). IMT in controllers was similar to antiretroviral-untreated patients with detectable viremia. Across all subjects, IMT was strongly associated with the presence of HIV disease rather than viral load or CD4+ T cell count. C-reactive protein was higher in HIV controllers than HIV-seronegative persons. Antiretroviral drug exposure was also associated with higher IMT. Conclusions Increased atherosclerosis with HIV infection can occur in the absence of antiretroviral therapy, detectable viremia, or overt immunodeficiency. Chronic inflammation—which is higher in controllers than in HIV-uninfected persons—may account for early atherosclerosis in these patients. PMID:19390417

Hsue, Priscilla Y.; Hunt, Peter W.; Schnell, Amanda; Kalapus, S. Craig; Hoh, Rebecca; Ganz, Peter; Martin, Jeffrey N.; Deeks, Steven G.

2009-01-01

323

Apolipoprotein E gene polymorphisms and retinal vascular signs: The Atherosclerosis Risk in Communities (ARIC) Study  

Technology Transfer Automated Retrieval System (TEKTRAN)

Our objective was to examine the association between apolipoprotein E (APOE) gene polymorphisms and retinal microvascular signs. We used a population-based, cross-sectional study. Participants from the Atherosclerosis Risk in Communities Study (n=10,036; aged 49-73 years) had retinal photographs tak...

324

Reporting standards for angioplasty and stent-assisted angioplasty for intracranial atherosclerosis  

Microsoft Academic Search

Background and purposeIntracranial cerebral atherosclerosis causes ischemic stroke in a significant number of patients. Technological advances over the past 10 years have enabled endovascular treatment of intracranial atherosclerotic stenosis. The number of patients treated with angioplasty or stent-assisted angioplasty for this condition is increasing. Given the lack of universally accepted definitions, the goal of this document is to provide consensus

H Christian Schumacher; Philip M Meyers; Randall T Higashida; Colin P Derdeyn; Sean D Lavine; Gary M Nesbit; David Sacks; Peter Rasmussen; Lawrence R Wechsler

2010-01-01

325

Imaging atherosclerosis in HIV: carotid intima-media thickness and beyond.  

PubMed

Chronic immune activation and inflammation are associated with an increased risk of atherosclerosis in HIV-infected patients. In this review, we discuss the role of established and novel imaging modalities to define more accurately the structure and function of inflammation-mediated atherosclerosis in the context of HIV. Historically, carotid ultrasound studies were the first to show higher rates of subclinical atherosclerosis in HIV-infected subjects versus uninfected controls. However, computed tomography is the noninvasive gold standard for imaging the coronary arteries, and studies in HIV suggest a higher prevalence of noncalcified plaque. Endothelial dysfunction can be quantified by measuring flow-mediated brachial artery dilation by ultrasound and has been used extensively in antiretroviral switching trials and small pilot trials of therapeutics to assess cardiovascular risk in this population. In the future, novel imaging modalities such as intracoronary optical coherence tomography, positron emission tomography imaging of (18)F-fluorodeoxyglucose uptake, and molecular-targeted magnetic resonance imaging will characterize the burden of vulnerable plaque and other unique features of inflammatory atherosclerosis in HIV. PMID:22340762

Longenecker, Chris T; Hoit, Brian D

2012-03-01

326

Bio390 Atherosclerosis and Resistance thanks to Dr. J.F. Anderson,  

E-print Network

. A consequence of atherosclerosis is elevated blood pressure. High blood pressure, in turn, has many undesirable plaque. If the flow of blood is to continue at its usual rate, a higher pressure is required. Estimate the increase in blood pressure required to maintain normal cardiac output when the radii

Prestwich, Ken

327

Increased Atherosclerosis and Smooth Muscle Cell Hypertrophy in Natriuretic Peptide Receptor A?/? Apolipoprotein E?/? Mice  

PubMed Central

Objective Natriuretic peptide signaling is important in the regulation of blood pressure as well as in the growth of multiple cell types. To examine the role of natriuretic peptide signaling in atherosclerosis, we crossbred mice that lack natriuretic peptide receptor A (NPRA; Npr1?/?) with atherosclerosis-prone mice that lack apolipoprotein E (apoE; Apoe?/?). Methods and Results Doubly deficient Npr1?/? Apoe?/? mice have increased blood pressure relative to Npr1+/+ Apoe?/? mice (118±4 mm Hg compared with 108±2 mm Hg, P<0.05) that is coincident with a 64% greater atherosclerotic lesion size (P<0.005) and more advanced plaque morphology. Additionally, aortic medial thickness is increased by 52% in Npr1?/? Apoe?/? mice relative to Npr1+/+ Apoe?/? mice (P<0.0001). Npr1?/? Apoe?/? mice also have significantly greater cardiac mass (9.0±0.3 mg/g body weight) than either Npr1+/+ Apoe?/? mice (5.8±0.2 mg/g) or Npr1?/? Apoe+/+ mice (7.1±0.2 mg/g), suggesting that the lack of both NPRA and apoE synergistically enhances cardiac hypertrophy. Conclusions These data provide evidence that NPR1 is an atherosclerosis susceptibility locus and represents a potential link between atherosclerosis and cardiac hypertrophy. Our results also suggest roles for Npr1 as well as Apoe in regulation of hypertrophic cell growth. PMID:12702516

Alexander, Matthew R.; Knowles, Joshua W.; Nishikimi, Toshio; Maeda, Nobuyo

2009-01-01

328

Appropriateness of the hamster as a model to study diet-induced atherosclerosis  

Technology Transfer Automated Retrieval System (TEKTRAN)

Golden-Syrian hamsters have been used as an animal model to assess diet-induced atherosclerosis since the early 1980s. Advantages appeared to include a low rate of endogenous cholesterol synthesis, receptor-mediated uptake of LDL cholesterol, cholesteryl ester transfer protein activity, hepatic apo...

329

APOLIPOPROTEIN E GENOTYPE AND INCIDENT ISCHEMIC STROKE: THE ATHEROSCLEROSIS RISK IN COMMUNITY STUDY  

Technology Transfer Automated Retrieval System (TEKTRAN)

BACKGROUND AND PURPOSE: A relationship between the apolipoprotein E (apoE) genotype and ischemic stroke has been inconsistently reported. We explored this relation in the Atherosclerosis Risk in Communities Study (ARIC). METHODS: The ARIC cohort involves 15,792 men and women, aged 45 to 64 years at ...

330

The macrophage-TCR?? is a cholesterol-responsive combinatorial immune receptor and implicated in atherosclerosis.  

PubMed

Recent evidence indicates constitutive expression of a recombinatorial TCR?? immune receptor in mammalian monocytes and macrophages. Here, we demonstrate in vitro that macrophage-TCR? repertoires are modulated by atherogenic low density cholesterol (LDL) and high-density cholesterol (HDL). In vivo, analysis of freshly obtained artery specimens from patients with severe carotid atherosclerosis reveals massive abundance of TCR??(+) macrophages within the atherosclerotic lesions. Experimental atherosclerosis in mouse carotids induces accumulation of TCR bearing macrophages in the vascular wall and TCR deficient rag(-/-) mice have an altered macrophage-dependent inflammatory response. We find that the majority of TCR?? bearing macrophages are localized in the hot spot regions of the atherosclerotic lesions. Advanced carotid artery lesions express highly restricted TCR?? repertoires that are characterized by a striking usage of the V?22 and V?16 chains. This together with a significant degree of interindividual lesion repertoire sharing suggests the existence of atherosclerosis-associated TCR?? signatures. Our results implicate the macrophage-TCR?? combinatorial immunoreceptor in atherosclerosis and thus identify an as yet unknown adaptive component in the innate response-to-injury process that underlies this macrophage-driven disease. PMID:25446098

Fuchs, Tina; Puellmann, Kerstin; Emmert, Alexander; Fleig, Julian; Oniga, Septimia; Laird, Rebecca; Heida, Nana Maria; Schäfer, Katrin; Neumaier, Michael; Beham, Alexander W; Kaminski, Wolfgang E

2015-01-01

331

Population Structure of Hispanics in the United States: The MultiEthnic Study of Atherosclerosis  

Microsoft Academic Search

Using ?60,000 SNPs selected for minimal linkage disequilibrium, we perform population structure analysis of 1,374 unrelated Hispanic individuals from the Multi-Ethnic Study of Atherosclerosis (MESA), with self-identification corresponding to Central America (n = 93), Cuba (n = 50), the Dominican Republic (n = 203), Mexico (n = 708), Puerto Rico (n = 192), and South America (n = 111). By

Ani Manichaikul; Walter Palmas; Carlos J. Rodriguez; Carmen A. Peralta; Jasmin Divers; Xiuqing Guo; Wei-Min Chen; Quenna Wong; Kayleen Williams; Kathleen F. Kerr; Kent D. Taylor; Michael Y. Tsai; Mark O. Goodarzi; Michèle M. Sale; Ana V. Diez-Roux; Stephen S. Rich; Jerome I. Rotter; Josyf C. Mychaleckyj

2012-01-01

332

Dissecting the mechanism of carotid atherosclerosis from the perspective of regulation  

PubMed Central

Carotid atherosclerosis is a chronic inflammatory disease of the arterial wall. The present study aimed to identify changes in the gene expression and regulatory factors for atherosclerotic plaques of carotid atherosclerosis from an early to an advanced stage. The original data were downloaded from the NCBI GEO database under accession no. GSE28829. Differentially expressed genes (DEGs) were detected by the Robust Multiarray Average (RMA). The enriched Gene Ontology (GO) terms and pathways for DEGs using DAVID were subsequently identified. The transcriptional and microRNA (miRNA) regulatory network were constructed for the DEGs. Cis-regulatory signals were also investigated. More genes were activated in the advanced stage compared with the early stage. IGHG1 and SPP1 were upregulated, while MYBL1 and PLD were downregulated. The upregulated genes in the advanced stage were involved in atherosclerosis-related GO terms such as immune, vascular and cell movement homeostasis. The DEGs were significantly enriched in cell adhesion molecules (CAMs) and the focal adhesion pathway. MMP9 and CFL2 played key roles in the transcriptional regulatory network. Moreover, miR-328 was identified as one of the hubs in the miRNA regulatory network. The results may therefore be used to determine the mechanism involved in carotid atherosclerosis. PMID:25318463

LIN, MIN; ZHAO, LIN; ZHAO, WENLONG; WENG, JING

2014-01-01

333

Co-stimulatory molecules in and beyond co-stimulation - tipping the balance in atherosclerosis?  

PubMed

A plethora of basic laboratory and clinical studies has uncovered the chronic inflammatory nature of atherosclerosis. The adaptive immune system with its front-runner, the T cell, drives the atherogenic process at all stages. T cell function is dependent on and controlled by a variety of either co-stimulatory or co-inhibitory signals. In addition, many of these proteins enfold T cell-independent pro-atherogenic functions on a variety of cell types. Accordingly they represent potential targets for immune-modulatory and/or anti-inflammatory therapy of atherosclerosis. This review focuses on the diverse role of co-stimulatory molecules of the B7 and tumour necrosis factor (TNF)-superfamily and their downstream signalling effectors in atherosclerosis. In particular, the contribution of CD28/CD80/CD86/CTLA4, ICOS/ICOSL, PD-1/PDL-1/2, TRAF, CD40/CD154, OX40/OX40L, CD137/CD137L, CD70/CD27, GITR/GITRL, and LIGHT to arterial disease is reviewed. Finally, the potential for a therapeutic exploitation of these molecules in the treatment of atherosclerosis is discussed. PMID:21979444

Gerdes, N; Zirlik, A

2011-11-01

334

Anti-Inflammatory and Immunomodulatory Mechanism of Tanshinone IIA for Atherosclerosis  

PubMed Central

Tanshinone IIA (Tan II A) is widely used in the treatment of cardiovascular diseases as an active component of Salvia miltiorrhiza Bunge. It has been demonstrated to have pleiotropic effects for atherosclerosis. From the anti-inflammatory and immunomodulatory mechanism perspective, this paper reviewed major progresses of Tan IIA in antiatherosclerosis research, including immune cells, antigens, cytokines, and cell signaling pathways. PMID:25525444

Chen, Zhuo

2014-01-01

335

Coronary atherosclerosis is already ongoing in pre-diabetic status: Insight from intravascular imaging modalities  

PubMed Central

Diabetes mellitus is a powerful risk factor of coronary artery disease (CAD), leading to death and disability. In recent years, given the accumulating evidence that prediabetes is also related to increasing risk of CAD including cardiovascular events, a new guideline has been proposed for the treatment of blood cholesterol for primary prevention of cardiovascular events. This guideline recommends aggressive lipid-lowering statin therapy for primary prevention in diabetes and other patients. The ultimate goal of patient management is to inhibit progression of systemic atherosclerosis and prevent fatal cardiovascular events such as acute coronary syndrome (ACS). Because disruption of atherosclerotic coronary plaques is a trigger of ACS, the high-risk atheroma is called a vulnerable plaque. Several types of novel diagnostic imaging technologies have been developed for identifying the characteristics of coronary atherosclerosis before the onset of ACS, especially vulnerable plaques. According to coronary angioscopic evaluation, atherosclerosis severity and plaque vulnerability were more advanced in prediabetic than in nondiabetic patients and comparable to that in diabetic patients. In addition, pharmacological intervention by statin therapy changed plaque color and complexity, and the dynamic changes in plaque features are considered plaque stabilization. In this article, we review the findings of atherosclerosis in prediabetes, detected by intravascular imaging modalities, and the therapeutic implications.

Kurihara, Osamu; Takano, Masamichi; Seino, Yoshihiko; Shimizu, Wataru; Mizuno, Kyoichi

2015-01-01

336

Chemokines and atherosclerosis: focus on the CX3CL1/CX3CR1 pathway  

PubMed Central

Atherosclerosis is currently considered an inflammatory disease. Much attention has been focused on the potential role of inflammatory mediators as prognostic/diagnostic markers or therapeutic targets of atherosclerotic cardiovascular disease. CX3CL1 (or fractalkine) is a structurally and functionally unique chemokine with a well documented role in atherosclerosis. In its membrane bound form it promotes the firm adhesion of rolling leucocytes onto the vessel wall, while in its soluble form it serves as a potent chemoattractant for CX3CR1-expressing cells. Additionally, CX3CL1 exerts cytotoxic effects on the endothelium as well as anti-apoptotic and proliferative effects on vascular cells, affecting the context and stability of the atherosclerotic plaque. Studies on animal models have shown that the blockade of the CX3CL1/CX3CR1 pathway ameliorates the severity of atherosclerosis, while genetic epidemiology has confirmed that a genetically-defined less active CX3CL1/CX3CR1 pathway is associated with a reduced risk of atherosclerotic disease in humans. Although several studies support an important pathogenic role of CX3CL1/CX3CR1 in atherogenesis and plaque destabilization, this does not necessarily suggest that this pathway is a suitable therapeutic target or that CX3CL1 can serve as a prognostic/diagnostic biomarker. Further studies on the CX3CL1/CX3CR1 chemokine pathway are clearly warranted to justify the clinical relevance of its role in atherosclerosis. PMID:23974513

Apostolakis, Stavros; Spandidos, Demetrios

2013-01-01

337

LONG-TERM VITAMIN E SUPPLEMENTATION REDUCES ATHEROSCLEROSIS AND MORTALITY IN LDLR-/-MICE  

Technology Transfer Automated Retrieval System (TEKTRAN)

Epidemiological and experimental evidence indicated potential health benefits of vitamin E supplementation (+E) on coronary heart disease (CHD), but recent clinical trials reported no effect. We hypothesized that +E from early age may prevent or retard development and progression of atherosclerosis...

338

An update on the role of markers of inflammation in atherosclerosis.  

PubMed

In recent years, several studies have used the measurement of carotid intima-media thickness (IMT) as a marker of early atherosclerosis: IMT has been shown to correlate significantly with the presence of coronary artery disease (CAD) and to predict fatal and not fatal cerebro- and cardio-vascular events. These findings highlight the importance of recognizing and managing early stages of atherosclerosis for effective cardiovascular prevention. Beyond traditional established cardiovascular risk factors, inflammation has been shown to be crucial throughout atherosclerosis from endothelial dysfunction to plaque rupture and thrombosis. Several studies have shown the existence of a strong relation between CAD and fibrinogen or highly sensitive C-reactive protein (hs-CRP) levels and their predictive role has been examined through stratification or multivariable statistical analyses: levels of these markers of inflammation have been independently associated with the incidence of coronary events after adjusting for traditional cardiovascular risk factors. Recent studies have further addressed the importance of therapeutical modulation of hs-CRP levels in high-risk patients for the prevention of vascular events. The strong relationship between hs-CRP and IMT may potentially account for the complex role of hs-CRP and IMT in the pathogenesis of cardiovascular events. However, beyond the utility of measuring markers of inflammation to assess patients with subclinical carotid atherosclerosis at higher risk of vascular events, further studies are needed to evaluate the therapeutic implications in this category of patients. PMID:20032572

Corrado, Egle; Rizzo, Manfredi; Coppola, Giuseppe; Fattouch, Khalil; Novo, Giuseppina; Marturana, Ilenia; Ferrara, Filippo; Novo, Salvatore

2010-02-01

339

Acculturation and Subclinical Atherosclerosis among U.S. South Asians: Findings from the MASALA study  

PubMed Central

Objective Longer duration of residence among immigrants to the United States, a proxy measure of acculturation, has been associated with higher subclinical atherosclerosis. South Asian immigrants are the second fastest growing immigrant group in the U.S. but little is known about the effects of acculturation with atherosclerosis in this high cardiovascular risk population. Methods We conducted a cross-sectional analysis using data from a community-based cohort called the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study. Participants (n=900) were between ages of 40–84 years and had no existing cardiovascular disease. We developed a multi-dimensional measure of acculturation in South Asians, called traditional cultural beliefs, and measured other proxy measures of acculturation to determine whether they were associated with higher levels of subclinical atherosclerosis after controlling for socioeconomic, behavior/lifestyle, and cardiovascular risk factors. Results Mean duration of residence in the U.S. was 27±11 years and tertiles of strength of traditional cultural beliefs were examined. Longer duration of U.S. residence was associated with higher levels of coronary artery calcium even after adjustment for covariates and lifestyle mediators. The novel measure of strength of traditional cultural beliefs was associated with lower common carotid intima media thickness among those with moderate traditional beliefs only. Conclusions These findings support the need for better conceptualization and measurement of how migration influences cultural beliefs and practices, and their subsequent influence on health behaviors and cardiovascular disease risk. PMID:25568891

Kanaya, AM; Ewing, SK; Vittinghoff, E; Herrington, D; Tegeler, C; Mills, C; Kandula, NR

2014-01-01

340

Gender differences in the development of hyperlipemia and atherosclerosis in hybrid hamsters  

Microsoft Academic Search

In response to a diet enriched in saturated fat and cholesterol (CH), male Syrian hamsters develop hyperlipemia and changes of early atherosclerosis. However, it has not been determined if female hamsters are equally susceptible to an atherogenic diet. Male and female hamsters of the F1B hybrid strain (Bio Breeders, Fitchburg, MA) were fed either a chow diet or this diet

Sander J. Robins; Joan M. Fasulo; George M. Patton; Ernst J. Schaefer; Donald E. Smith; Jose M. Ordovas

1995-01-01

341

IL-17 and Th17 Cells in Atherosclerosis: Subtle and Contextual Roles.  

PubMed

Atherosclerosis is a chronic inflammatory arterial disease driven by both innate and adaptive immune responses to modified lipoproteins and components of the injured vascular wall. Specific T lymphocyte responses driven by T helper-1 or T regulatory cells play distinct and opposing roles in atherosclerosis. More recently, T helper-17 cells, which produce the prototype cytokine interleukin-17, have been characterized and shown to be critical in mucosal host defense against microbial and fungal pathogens. Sustained production of interleukin-17 in an inflammatory context has been linked to the pathology of several autoimmune and inflammatory diseases. However, regulatory and protective roles have also been reported in selective disease settings. Studies in atherosclerosis led to conflicting results on the roles of interleukin-17 and T helper-17 cells in disease development and plaque stability. The present review provides a summary of the available evidence and putative mechanisms linking this pathway to atherosclerosis, as well as a perspective on the risks and benefits of interleukin-17-targeted cytokine therapy in patients at high cardiovascular risk. PMID:25234818

Taleb, Soraya; Tedgui, Alain; Mallat, Ziad

2015-02-01

342

Association Between Apolipoprotein E Polymorphism and Subclinic Atherosclerosis in Patients with Type 1 Diabetes Mellitus  

PubMed Central

Objective The most important cause of morbidity and mortality in type 1 diabetes mellitus (DM) is atherosclerosis. Apolipoprotein E (Apo E) polymorphism is accused of being the genetic risk factor for atherosclerosis. The aim of the present study was to determine which Apo E polymorphism was related to atherosclerosis in patients with type 1 DM. Methods: Seventy-four patients with type 1 DM were enrolled in the study. Age, diabetes duration, daily insulin dose, microalbuminuria, and major cardiovascular risk factors including anthropometric and metabolic parameters were assessed in each patient. Non-invasive ultrasonographic measurements were also performed. For determination of Apo E genotype, DNA was extracted from venous blood from all subjects using standard methods. Apo E genotyping was performed using a PCR–restriction fragment-length polymorphism assay. Results: Systolic blood pressure and carotid artery intima-media thickness (CA-IMT) were increased in subjects with E4/E4 polymorphism. According to univariate analysis, when adjusted for all risk factors, genotypes did not differ for total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and triglycerides (p>0.05). However, E3/E3, E3/E4 and E4/E4 genotypes were found to be associated with an increase in CA-IMT (p<0.001). Conclusions: Our results suggest that the polymorphism associated with atherosclerosis in type1 DM is Apo E4/E4. Conflict of interest:None declared. PMID:22394699

Atabek, Mehmet Emre; Özkul, Yusuf; Kurto?lu, Selim; Baykara, Murat

2012-01-01

343

CYCLOOXYGENASE POLYMORPHISMS AND RISK OF CARDIOVASCULAR EVENTS: THE ATHEROSCLEROSIS RISK IN COMMUNITIES (ARIC) STUDY  

Technology Transfer Automated Retrieval System (TEKTRAN)

Cyclooxygenase-derived prostaglandins modulate cardiovascular disease risk. We genotyped 2212 Atherosclerosis Risk in Communities study participants (1,023 incident coronary heart disease (CHD) cases; 270 incident ischemic stroke cases; 919 non-cases) with available DNA for polymorphisms in PTGS1 an...

344

Coronary atherosclerosis is already ongoing in pre-diabetic status: Insight from intravascular imaging modalities.  

PubMed

Diabetes mellitus is a powerful risk factor of coronary artery disease (CAD), leading to death and disability. In recent years, given the accumulating evidence that prediabetes is also related to increasing risk of CAD including cardiovascular events, a new guideline has been proposed for the treatment of blood cholesterol for primary prevention of cardiovascular events. This guideline recommends aggressive lipid-lowering statin therapy for primary prevention in diabetes and other patients. The ultimate goal of patient management is to inhibit progression of systemic atherosclerosis and prevent fatal cardiovascular events such as acute coronary syndrome (ACS). Because disruption of atherosclerotic coronary plaques is a trigger of ACS, the high-risk atheroma is called a vulnerable plaque. Several types of novel diagnostic imaging technologies have been developed for identifying the characteristics of coronary atherosclerosis before the onset of ACS, especially vulnerable plaques. According to coronary angioscopic evaluation, atherosclerosis severity and plaque vulnerability were more advanced in prediabetic than in nondiabetic patients and comparable to that in diabetic patients. In addition, pharmacological intervention by statin therapy changed plaque color and complexity, and the dynamic changes in plaque features are considered plaque stabilization. In this article, we review the findings of atherosclerosis in prediabetes, detected by intravascular imaging modalities, and the therapeutic implications. PMID:25685289

Kurihara, Osamu; Takano, Masamichi; Seino, Yoshihiko; Shimizu, Wataru; Mizuno, Kyoichi

2015-02-15

345

Atherosclerosis 161 (2002) 4554 Anti-atherogenic effects of the acyl-CoA:cholesterol acyltransferase  

E-print Network

Atherosclerosis 161 (2002) 45­54 Anti-atherogenic effects of the acyl-CoA:cholesterol; accepted 5 June 2001 Abstract Acyl-CoA:cholesterol acyltransferase (ACAT) inhibitors have been shown of the ACAT inhibitor, avasimibe (CI-1011), during foam cell formation and during cholesterol efflux from

Terasaki, Mark

346

Animal, In Vitro, and Ex Vivo Models of Flow-Dependent Atherosclerosis: Role of Oxidative Stress  

PubMed Central

Abstract Atherosclerosis is an inflammatory disease preferentially occurring in curved or branched arterial regions, whereas straight parts of the arteries are protected, suggesting a close relationship between flow and atherosclerosis. However, evidence directly linking disturbed flow to atherogenesis is just emerging, thanks to the recent development of suitable animal models. In this article, we review the status of various animal, in vitro, and ex vivo models that have been used to study flow-dependent vascular biology and atherosclerosis. For animal models, naturally flow-disturbed regions such as branched or curved arterial regions as well as surgically created models, including arterio-venous fistulas, vascular grafts, perivascular cuffs, and complete, incomplete, or partial ligation of arteries, are used. Although in vivo models provide the environment needed to mimic the complex pathophysiological processes, in vitro models provide simple conditions that allow the study of isolated factors. Typical in vitro models use cultured endothelial cells exposed to various flow conditions, using devices such as cone-and-plate and parallel-plate chambers. Ex vivo models using isolated vessels have been used to bridge the gap between complex in vivo models and simple in vitro systems. Here, we review these flow models in the context of the role of oxidative stress in flow-dependent inflammation, a critical proatherogenic step, and atherosclerosis. Antioxid. Redox Signal. 15, 1433–1448. PMID:20712399

Rezvan, Amir; Ni, Chih-Wen; Alberts-Grill, Noah

2011-01-01

347

GENETIC VARIATION AND DECREASED RISK FOR OBESITY IN THE ATHEROSCLEROSIS RISK IN COMMUNITIES STUDY  

Technology Transfer Automated Retrieval System (TEKTRAN)

Our objective was to investigate the effects of variation in the leptin [LEP (19A>G)] and melanocortin-4 receptor [MC4R (V103I)] genes on obesity-related traits in 13 405 African-American (AA) and white participants from the Atherosclerosis Risk in Communities (ARIC) Study. We tested the association...

348

Monocyte-Targeting Supramolecular Micellar Assemblies: A Molecular Diagnostic Tool for Atherosclerosis.  

PubMed

Atherosclerosis is a multifactorial inflammatory disease that can progress silently for decades and result in myocardial infarction, stroke, and death. Diagnostic imaging technologies have made great strides to define the degree of atherosclerotic plaque burden through the severity of arterial stenosis. However, current technologies cannot differentiate more lethal "vulnerable plaques," and are not sensitive enough for preventive medicine. Imaging early molecular markers and quantifying the extent of disease progression continues to be a major challenge in the field. To this end, monocyte-targeting, peptide amphiphile micelles (PAMs) are engineered through the incorporation of the chemokine receptor CCR2-binding motif of monocyte chemoattractant protein-1 (MCP-1) and MCP-1 PAMs are evaluated preclinically as diagnostic tools for atherosclerosis. Monocyte-targeting is desirable as the influx of monocytes is a marker of early lesions, accumulation of monocytes is linked to atherosclerosis progression, and rupture-prone plaques have higher numbers of monocytes. MCP-1 PAMs bind to monocytes in vitro, and MCP-1 PAMs detect and discriminate between early- and late-stage atherosclerotic aortas. Moreover, MCP-1 PAMs are found to be eliminated via renal clearance and the mononuclear phagocyte system (MPS) without adverse side effects. Thus, MCP-1 PAMs are a promising new class of diagnostic agents capable of monitoring the progression of atherosclerosis. PMID:25156590

Chung, Eun Ji; Mlinar, Laurie B; Nord, Kathryn; Sugimoto, Matthew J; Wonder, Emily; Alenghat, Francis J; Fang, Yun; Tirrell, Matthew

2014-08-22

349

Clinical correlation between N-terminal pro-b-type natriuretic peptide and angiographic coronary atherosclerosis  

PubMed Central

OBJECTIVES: This study aimed to investigate the clinical correlation between angiographic coronary atherosclerosis and N-terminal pro-B-type natriuretic peptide along with other known correlated factors. METHODS: In total, 153 patients with a diagnostic hypothesis of stable angina, unstable angina or acute myocardial infarction were classified as group A (patients with angiographically normal coronary arteries) or group B (patients with angiographic coronary atherosclerosis). The two groups were analyzed with respect to the following factors: gender, age, body mass index, abdominal circumference, smoking, diabetes mellitus, arterial hypertension, early family history of atherosclerosis, statin use, the presence of metabolic syndrome, clinical presentation and biochemical factors, including cholesterol, creatinine and fibrinogen plasma concentrations, monocyte counts and N-terminal pro-B-type natriuretic peptide. RESULTS: Univariate analyses comparing the two groups revealed that group B patients more frequently had diabetes, used statins and had systolic dysfunction, N-terminal pro-B-type natriuretic peptide levels ?250 pg/mL, fibrinogen levels >500 mg/dL and ?501 monocytes/mm3 compared with group A patients (p<0.05). Nevertheless, multivariate logistic regression analysis demonstrated that the independent predictors of angiographic coronary atherosclerosis were an N-terminal pro-B-type natriuretic peptide level ?250 pg/mL, diabetes mellitus and increased monocyte numbers and fibrinogen plasma concentration, regardless of the creatinine level or the presence of systolic dysfunction. CONCLUSIONS: An N-terminal pro-B-type natriuretic peptide plasma concentration of ?250 pg/mL is an independent predictor of angiographic coronary atherosclerosis. PMID:24964305

Ribeiro, Demóstenes G. L.; Silva, Ricardo P.; Barboza, Daniella R. M. M.; Lima-Júnior, Roberto C. P.; Ribeiro, Ronaldo A.

2014-01-01

350

Ursolic Acid Protects Diabetic Mice Against Monocyte Dysfunction and Accelerated Atherosclerosis  

PubMed Central

Aims Accelerated atherosclerosis is a major diabetic complication initiated by the enhanced recruitment of monocytes into the vasculature. In this study, we examined the therapeutic potential of the phytonutrients ursolic acid (UA) and resveratrol (RES) in preventing monocyte recruitment and accelerated atherosclerosis. Methods and Results Dietary supplementation with either RES or UA (0.2%) protected against accelerated atherosclerosis induced by streptozotocin in high-fat diet-fed LDL receptor-deficient mice. However, mice that received dietary UA for 11 weeks were significantly better protected and showed a 53% reduction in lesion formation while mice fed a RES-supplemented diet showed only a 31% reduction in lesion size. Importantly, UA was also significantly more effective in preventing the appearance of proinflammatory GR-1high monocytes induced by these diabetic conditions and reducing monocyte recruitment into MCP-1-loaded Matrigel plugs implanted into these diabetic mice. Oxidatively-stressed THP-1 monocytes mimicked the behavior of blood monocytes in diabetic mice and showed enhanced responsiveness to monocyte chemoattractant protein-1 (MCP-1) without changing MCP-1 receptor (CCR2) surface expression. Pretreatment of THP-1 monocytes with RES or UA (0.3 – 10 ?M) for 15 h resulted in the dose-dependent inhibition of H2O2-accelerated chemotaxis in response to MCP-1, but with an IC50 of 0.4 ?M, UA was 2.7-fold more potent than RES. Conclusion Dietary UA is a potent inhibitor of monocyte dysfunction and accelerated atherosclerosis induced by diabetes. These studies identify ursolic acid as a potential therapeutic agent for the treatment of diabetic complications, including accelerated atherosclerosis, and provide a novel mechanism for the anti-atherogenic properties of ursolic acid. PMID:21752377

Ullevig, Sarah L.; Zhao, Qingwei; Zamora, Debora; Asmis, Reto

2011-01-01

351

[Calcium, magnesium, copper and zinc in blood serum in men with femoral atherosclerosis].  

PubMed

Calcium, magnesium, copper and zinc were determined in serum in men with femoral atherosclerosis. Also total cholesterol, HDL- and LDL-cholesterol were estimated. Subjects in control group were in the same range of age. The present study compares two methods of preparing serum for the flame atomic absorption spectrometry. In the first method (I), serum was diluted by the demineralized water. In the second method (II), serum protein was precipitated by trichloracetic acid (TCA). We found that the first method (I) was simpler and more precise than the other. The optimal proportions of serum and water amounted to 1 + 62 for calcium and magnesium and the coefficient of variation (C.V.) was 2.8%. For copper and zinc, the optimal dilution was 1 + 3 (C.V. = 1%). Total cholesterol was significantly higher (p < 0.05) and HDL-cholesterol was lower (p < 0.05) in subjects with femoral atherosclerosis as compared with controls. There was no difference in LDL-cholesterol. Subjects with femoral atherosclerosis had significantly higher level of all micro- and macroelements determined, then those of the control group (p < 0.05). However, higher serum copper does not necessary mean higher copper body status. It is possible that higher serum copper in femoral atherosclerosis reflects the transfer of copper from the tissue to the ceruloplasmin, as an acute phase reaction. On the other hand, the differences in serum magnesium, calcium, copper and zinc concentrations, may indicate the possible involvement of these elements in the disorder of total and HDL-cholesterol in femoral atherosclerosis. PMID:7481505

Mielcarz, G; Majewski, W; Patelski, J; Uryszek, W

1995-01-01

352

A CYP26B1 Polymorphism Enhances Retinoic Acid Catabolism and May Aggravate Atherosclerosis  

PubMed Central

All-trans retinoic acid, controlled by cytochrome P450, family 26 (CYP26) enzymes, potentially has beneficial effects in atherosclerosis treatment. This study investigates CYP26 subfamily B, polypeptide 1 (CYP26B1) in atherosclerosis and the effects of a genetic polymorphism in CYP26B1 on retinoid catabolism. We found that CYP26B1 mRNA was induced by retinoic acid in human atherosclerotic arteries, and CYP26B1 and the macrophage marker CD68 were colocalized in human atherosclerotic lesions. In mice, Cyp26B1 mRNA was higher in atherosclerotic arteries than in normal arteries. Databases were queried for nonsynonymous CYP26B1 single nucleotide polymorphisms (SNPs) and rs2241057 selected for further studies. Constructs of the CYP26B1 variants were created and used for production of purified proteins and transfection of macrophagelike cells. The minor variant catabolized retinoic acid with significantly higher efficiency, indicating that rs2241057 is functional and suggesting reduced retinoid availability in tissues with the minor variant. rs2241057 was investigated in a Stockholm Coronary Atherosclerosis Risk Factor (SCARF) subgroup. The minor allele was associated with slightly larger lesions, as determined by angiography. In summary, this study identifies the first CYP26B1 polymorphism that alters CYP26B1 capacity to metabolize retinoic acid. CYP26B1 was expressed in macrophage-rich areas of human atherosclerotic lesions, induced by retinoic acid and increased in murine atherosclerosis. Taken together, the results indicate that CYP26B1 capacity is genetically regulated and suggest that local CYP26B1 activity may influence atherosclerosis. PMID:22415012

Krivospitskaya, Olesya; Elmabsout, Ali Ateia; Sundman, Eva; Söderström, Leif Å; Ovchinnikova, Olga; Gidlöf, Andreas C; Scherbak, Nikolai; Norata, Giuseppe Danilo; Samnegård, Ann; Törmä, Hans; Abdel-Halim, Samy M; Jansson, Jan-Håkan; Eriksson, Per; Sirsjö, Allan; Olofsson, Peder S

2012-01-01

353

Myeloid-Specific I?B Kinase ? Deficiency Decreases Atherosclerosis in Low-Density Lipoprotein Receptor–Deficient Mice  

PubMed Central

Objective Inflammatory responses are the driving force of atherosclerosis development. I?B kinase ? (IKK?), a central coordinator in inflammation through regulation of nuclear factor-?B, has been implicated in the pathogenesis of atherosclerosis. Macrophages play an essential role in the initiation and progression of atherosclerosis, yet the role of macrophage IKK? in atherosclerosis remains elusive and controversial. This study aims to investigate the impact of IKK? expression on macrophage functions and to assess the effect of myeloid-specific IKK? deletion on atherosclerosis development. Methods and Results To explore the issue of macrophage IKK? involvement of atherogenesis, we generated myeloid-specific IKK?-deficient low-density lipoprotein receptor–deficient mice (IKK??MyeLDLR?/?). Deficiency of IKK? in myeloid cells did not affect plasma lipid levels but significantly decreased diet-induced atherosclerotic lesion areas in the aortic root, brachiocephalic artery, and aortic arch of low-density lipoprotein receptor–deficient mice. Ablation of myeloid IKK? attenuated macrophage inflammatory responses and decreased atherosclerotic lesional inflammation. Furthermore, deficiency of IKK? decreased adhesion, migration, and lipid uptake in macrophages. Conclusion The present study demonstrates a pivotal role for myeloid IKK? expression in atherosclerosis by modulating macrophage functions involved in atherogenesis. These results suggest that inhibiting nuclear factor-?B activation in macrophages may represent a feasible approach to combat atherosclerosis. PMID:23023371

Park, Se-Hyung; Sui, Yipeng; Gizard, Florence; Xu, Jinxian; Rios-Pilier, Jennifer; Helsley, Robert N.; Han, Seong-Su; Zhou, Changcheng

2014-01-01

354

Protective Role for TLR4 Signaling in Atherosclerosis Progression as Revealed by Infection with a Common Oral Pathogen  

PubMed Central

Clinical and epidemiological studies have implicated chronic infections in the development of atherosclerosis. It has been proposed that common mechanisms of signaling via TLRs link stimulation by multiple pathogens to atherosclerosis. However, how pathogen-specific stimulation of TLR4 contributes to atherosclerosis progression remains poorly understood. In this study, atherosclerosis-prone apolipoprotein-E null (ApoE?/?) and TLR4-deficient (ApoE?/?TLR4?/?) mice were orally infected with the periodontal pathogen Porphyromonas gingivalis. ApoE?/?TLR4?/? mice were markedly more susceptible to atherosclerosis after oral infection with P. gingivalis. Using live animal imaging, we demonstrate that enhanced lesion progression occurs progressively and was increasingly evident with advancing age. Immunohistochemical analysis of lesions from ApoE?/?TLR4?/? mice revealed an increased inflammatory cell infiltrate composed primarily of macrophages and IL-17 effector T cells (Th17), a subset linked with chronic inflammation. Furthermore, enhanced atherosclerosis in TLR4-deficient mice was associated with impaired development of Th1 immunity and regulatory T cell infiltration. In vitro studies suggest that the mechanism of TLR4-mediated protective immunity may be orchestrated by dendritic cell IL-12 and IL-10, which are prototypic Th1 and regulatory T cell polarizing cytokines. We demonstrate an atheroprotective role for TLR4 in response to infection with the oral pathogen P. gingivalis. Our results point to a role for pathogen-specific TLR signaling in chronic inflammation and atherosclerosis. PMID:22956579

Hayashi, Chie; Papadopoulos, George; Gudino, Cynthia V.; Weinberg, Ellen O.; Barth, Kenneth R.; Madrigal, Andrés G.; Chen, Yang; Ning, Hua; LaValley, Michael; Gibson, Frank C.; Hamilton, James A.

2012-01-01

355

Unihemispheric Burst Suppression  

PubMed Central

Burst suppression (BS) consists of bursts of high-voltage slow and sharp wave activity alternating with periods of background suppression in the electroencephalogram (EEG). When induced by deep anesthesia or encephalopathy, BS is bihemispheric and is often viewed as a non-epileptic phenomenon. In contrast, unihemispheric BS is rare and its clinical significance is poorly understood. We describe here two cases of unihemispheric BS. The first patient is a 56-year-old woman with a left temporoparietal tumor who presented in convulsive status epilepticus. EEG showed left hemispheric BS after clinical seizure termination with lorazepam and propofol. The second patient is a 39-year-old woman with multiple medical problems and a vague history of seizures. After abdominal surgery, she experienced a convulsive seizure prompting treatment with propofol. Her EEG also showed left hemispheric BS. In both cases, increasing the propofol infusion rate resulted in disappearance of unihemispheric BS and clinical improvement. The prevailing view that typical bihemispheric BS is non-epileptic should not be extrapolated automatically to unihemispheric BS. The fact that unihemispheric BS was associated with clinical seizure and resolved with propofol suggests that, in both cases, an epileptic mechanism was responsible for unihemispheric BS. PMID:25309713

Villemarette-Pittman, Nicole R.; Rogers, Cornel T.; Torres-Delgado, Frank; Olejniczak, Piotr W.; England, John D.

2014-01-01

356

Correlation study on adiponectin gene SNP45 and long-term oxidative stress in patients with diabetes and carotid atherosclerosis  

PubMed Central

The aim of the present study was to investigate the correlation between the adiponectin gene single nucleotide polymorphism (SNP)45 T/G and long-term oxidative stress in type II diabetes mellitus (T2DM) patients with carotid atherosclerosis. Patients with T2DM were divided into non-carotid atherosclerosis and carotid atherosclerosis groups, which were then subsequently divided into TT and TG + GG groups according to the adiponectin SNP45 T/G genotypes. Enzyme-linked immunosorbent assay, TaqMan probe quantitative polymerase chain reaction (PCR), PCR-TaqMan, color Doppler and other methods were used to determine the adiponectin levels, gene polymorphisms, acquired mitochondrial DNA (mtDNA) A3243G somatic cell mutation rates and the carotid intima-media thickness. The somatic cell mutation rate of acquired mtDNA A3243A/G in the T2DM carotid atherosclerosis group was significantly higher compared with the group without carotid atherosclerosis. In addition, the acquired mtDNA A3243A/G somatic cell mutation rate in the T2DM carotid atherosclerosis group with the adiponectin gene SNP45 TT genotype was significantly lower compared with the SNP45 TG/GG genotype group. T2DM combined with carotid atherosclerosis was associated with long-term oxidative stress. In addition, adiponectin gene SNP45 T/G was associated with increased mtDNA A3243A/G somatic mutation rates in T2DM patients with carotid atherosclerosis. Therefore, adiponectin gene polymorphisms may lead to diabetes atherosclerosis through oxidative stress. PMID:25120586

PIAO, LIANSHAN; HAN, YANHUA; LI, DAN

2014-01-01

357

Overexpression of YKL-40 Predicts Plaque Instability in Carotid Atherosclerosis with CagA-Positive Helicobacter Pylori Infection  

PubMed Central

Objectives YKL-40 has been demonstrated to be related to atherosclerosis, but its role in predicting plaque status and the outcome of carotid atherosclerosis (CAS) caused by CagA-positive helicobacter pylori remains unclear. This study was aimed to investigate the role of YKL-40 in predicting the outcome of carotid atherosclerosis with CagA-positive Helicobacter pylori infection. Methods The serum concentrations of YKL-40, C-reaction protein in 310 patients undergoing color Duplex assessment of carotid atherosclerosis were recorded and divided into 3 groups according to the infectious statuses of helicobacter pylori. We also examined serum YKL-40, C-reaction protein and the plaque morphology in animal model of carotid atherosclerosis with different types of helicobacter pylori infection. Results Overexpression of YKL-40 was only found in carotid atherosclerosis group with CagA-positive helicobacter pylori infection; C-reaction protein failed to distinguish different infectious statuses of helicobacter pylori infection. In patients with CagA-positive helicobacter pylori infection, elevated YKL-40 expression was accompanied by more severe clinical symptoms. We also confirmed similar findings in rabbit model of carotid atherosclerosis with CagA-positive helicobacter pylori infection. We found that in 7 rabbits treated with anti-helicobacter pylori therapy, the serum YKL-40 level decreased and the plaque became more stable. Conclusion Our findings suggested that increased serum YKL-40 level indicates plaque instability and more severe clinical symptoms of carotid atherosclerosis with CagA-positive helicobacter pylori infection. Compared with C-reaction protein, YKL-40 seems to be a more specific predictor of plaque status and outcome of carotid atherosclerosis with CagA-positive helicobacter pylori infection. PMID:23573226

Jia, Qingshuai; Bai, Jun; Zhi, Kangkang; Qu, Lefeng

2013-01-01

358

Risk of carotid atherosclerosis associated with genetic polymorphisms of apolipoprotein E and inflammatory genes among arsenic exposed residents in Taiwan  

SciTech Connect

Arsenic had been reported to be associated with carotid atherosclerosis. However, there were few studies to evaluate the association between the susceptible gene of lipid metabolism and inflammation and carotid atherosclerosis among arsenic exposure residents. The aim of the study was to investigate the associations between the genetic polymorphisms of APOE and MCP-1 and the risk of carotid atherosclerosis among residents of Lanyang Basin in Taiwan which was a newly confirmed arsenic-endemic area. In total, 479 residents who had been genotyped of these two genes and examined the severity of carotid atherosclerosis were included in this study. The study subjects with carotid intima media thickness (IMT) {>=} 1.0 mm or with the observable plaque in the extracranial carotid artery were diagnosed as carotid atherosclerosis. A significantly age- and gender-adjusted odds ratio of 2.0 for the development of carotid atherosclerosis was observed in study subjects with {epsilon}4 allele of APOE than those without {epsilon}4 allele. Compared with study subjects who carried wild genotypes of APOE and MCP-1, those with both risk genotypes of APOE and MCP-1 had 2.5-fold risk of carotid atherosclerosis after adjustment for age and gender, revealing a significant dose-response relationship between number of risk genotypes of these genes and risk of carotid atherosclerosis. Additionally, study subjects with two risk genotypes of APOE and MCP-1 and either had ingested well water contained arsenic level > 10 {mu}g/L or had arsenic exposure > 0.22 mg/L-year would have strikingly highest risk of 10.3-fold and 15.7-fold, respectively, for the development carotid atherosclerosis, showing significant joint effect of arsenic exposure and risk genotypes of APOE and MCP-1.

Hsieh, Y.-C.; Hsieh, F.-I [School of Public Health, Taipei Medical University, Taipei, Taiwan (China); Lien, L.-M. [Department of Neurology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan (China); Chou, Y.-L. [School of Public Health, Taipei Medical University, Taipei, Taiwan (China); Chiou, H.-Y. [School of Public Health, Taipei Medical University, Taipei, Taiwan (China); Topnotch Stroke Center, Taipei Medical University, Taipei, Taiwan (China)], E-mail: hychiou@tmu.edu.tw; Chen, C.-J. [Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei, Taiwan (China)

2008-02-15

359

The Immunologic Injury Composite with Balloon Injury Leads to Dyslipidemia: A Robust Rabbit Model of Human Atherosclerosis and Vulnerable Plaque  

PubMed Central

Atherosclerosis is a condition in which a lipid deposition, thrombus formation, immune cell infiltration, and a chronic inflammatory response, but its systemic study has been hampered by the lack of suitable animal models, especially in herbalism fields. We have tried to perform a perfect animal model that completely replicates the stages of human atherosclerosis. This is the first combined study about the immunologic injury and balloon injury based on the cholesterol diet. In this study, we developed a modified protocol of the white rabbit model that could represent a novel approach to studying human atherosclerosis and vulnerable plaque. PMID:22988422

Zhang, Guangyin; Li, Ming; Li, Liangjun; Xu, Yingzhi; Li, Peng; Yang, Cui; Zhou, Yanan; Zhang, Junping

2012-01-01

360

Pressure suppression system  

DOEpatents

A pressure suppression system includes a containment vessel surrounding a reactor pressure vessel and defining a drywell therein containing a non-condensable gas. An enclosed wetwell pool is disposed inside the containment vessel, and an enclosed gravity driven cooling system (GDCS) pool is disposed above the wetwell pool in the containment vessel. The GDCS pool includes a plenum for receiving through an inlet the non-condensable gas carried with steam from the drywell following a loss-of-coolant accident (LOCA). A condenser is disposed in the GDCS plenum for condensing the steam channeled therein and to trap the non-condensable gas therein. A method of operation includes draining the GDCS pool following the LOCA and channeling steam released into the drywell following the LOCA into the GDCS plenum for cooling along with the non-condensable gas carried therewith for trapping the gas therein.

Gluntz, Douglas M. (San Jose, CA)

1994-01-01

361

Pressure suppression system  

DOEpatents

A pressure suppression system includes a containment vessel surrounding a reactor pressure vessel and defining a drywell therein containing a non-condensable gas. An enclosed wetwell pool is disposed inside the containment vessel, and an enclosed gravity driven cooling system (GDCS) pool is disposed above the wetwell pool in the containment vessel. The GDCS pool includes a plenum for receiving through an inlet the non-condensable gas carried with steam from the drywell following a loss-of-coolant accident (LOCA). A condenser is disposed in the GDCS plenum for condensing the steam channeled therein and to trap the non-condensable gas therein. A method of operation includes draining the GDCS pool following the LOCA and channeling steam released into the drywell following the LOCA into the GDCS plenum for cooling along with the non-condensable gas carried therewith for trapping the gas therein. 3 figs.

Gluntz, D.M.

1994-10-04

362

Interference suppression of SRS  

SciTech Connect

The theory of three-wave SRS is developed, which takes into account nonlinear dispersion of a medium for arbitrary phases of the pump waves at the input to the medium. The effect of interference suppression of SRS is predicted for values of the total phase of the three-wave pump (2n+1){pi} (n=0, {+-}1, {+-}2...), the effect being caused by the destructive interference of polarisations of the nonresonant dipole-allowed transitions. The relation between the contributions of the linear and nonlinear dispersions to the SRS is found. It is shown that at a sufficiently large wave detuning, the anti-Stokes wave amplitude experiences spatial oscillations. (nonlinear-optics phenomena)

Kochanov, V P [V.E. Zuev Institute of Atmospheric Optics, Siberian Branch, Russian Academy of Sciences, Tomsk (Russian Federation)

2011-01-24

363

Understanding Premature Atherosclerosis in Pediatric SLE: Risk Factors of Increased Carotid Intima Medial Thickness (CIMT) in the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) Cohort  

PubMed Central

Objective To evaluate risk factors of sub-clinical atherosclerosis in a pediatric SLE population. Methods A prospective multicenter cohort of 221 patients underwent baseline measurements of carotid intima medial thickening (CIMT) as part of the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) trial. SLE disease measures, medications, and traditional risk factors for atherosclerosis were assessed. A standardized protocol was used to assess thickness of the bilateral common carotids and mean maximal IMT of 12 segments. Univariable analysis identified potential associations with CIMT that were examined in multivariable linear regression modeling. Results Based on mean-mean common or mean-max CIMT as the dependent variable, univariable analysis showed significant associations with increased CIMT: increasing age, longer SLE duration, minority status, higher BMI, male sex, increased creatinine clearance, higher Lp(a), proteinuria, azathioprine use, and prednisone dose. Azathioprine use (P=0.005 for mean-mean common; P=0.102 for mean-max model) and male sex (P< 0.001) were both associated with increases in mean-max CIMT. Moderate dose prednisone (0.15–0.4 mg/kg/day) was associated with decreases in mean-max CIMT (P=0.024) while high or low dose prednisone was associated with mean-mean common CIMT (P=0.021) or mean-max CIMT (P=0.064), respectively. BMI (P<0.001) and creatinine clearance (P=0.031), remained associated with increased mean-mean common CIMT, while increasing age (P<0.001) and increasing Lp(a) (P=0.005) were associated with increased mean-max CIMT. Conclusion Traditional as well as non-traditional risk factors are associated with increased CIMT in pediatric SLE patients in this cohort. Azathioprine treatment was associated with increased CIMT. The relationship of CIMT with prednisone dose may not be linear. PMID:19404953

Schanberg, Laura E.; Sandborg, Christy; Barnhart, Huiman X.; Ardoin, Stacy P.; Yow, Eric; Evans, Gregory W.; Mieszkalski, Kelly L.; Ilowite, Norman T.; Eberhard, Anne; Levy, Deborah M.; Kimura, Yukiko; von Scheven, Emily; Silverman, Earl; Bowyer, Suzanne L.; Punaro, Lynn; Singer, Nora G.; Sherry, David D.; McCurdy, Deborah; Klein-Gitelman, Marissa; Wallace, Carol; Silver, Richard; Wagner-Weiner, Linda; Higgins, Gloria C.; Brunner, Hermine I.; Jung, Lawrence; Soep, Jennifer B.; Reed, Ann

2009-01-01

364

Epidemiological Aspects of Atherosclerosis in Patients Treated for Acute Atherothrombosis of Extremity Arteries  

PubMed Central

ABSTRACT Introduction: Risk factors for development of extremity artery atherosclerosis are the same as for coronary and cerebrovascular atherosclerosis namely, diabetes mellitus, hyperlipidemia, arterial hypertension, age and smoking. Atherosclerosis is polyarterial disease that clinically manifests itself most frequently in the form coronary, cerebrovascular or peripheral arterial disease (PAD). All of them have common, ominous and final pathologic step – atherosclerotic plaque rupture that might eventually lead to atherothrombosis and signs of ischemia. There are few studies of risk factor for peripheral artery disease (PAD). Aim of study: To identify prevalence of known risk factors for atherosclerosis in patients treated for acute atherothrombosis of extremity arteries. Patients and methods: Eighty patient were analyzed with regard to the prevalence of five risk factors for atherosclerosis (diabetes mellitus, smoking, hypertension, hyperlipidemia and age). 80 patients were divided into two groups (Group A and B) depending on country i.e. hospital where they received treatment for acute atherothrombosis of extremity artery. Group A consisted of patients treated at Clinic for vascular surgery in Sarajevo, while patients in Group B were treated in Trollhattan in Sweden at NAL hospital. This study was clinical, comparative, retrospective-prospective. Results: In group A, 20% of patients had diabetes mellitus while in group B prevalence of diabetics was lower (12,5%) but difference was not statistically significant p>0.05. Sixty percent of patients (60%) in group A were smokers. In Sweden, habit of smoking is not as common as in Balkan countries and consequently only 22,5% of patients were smokers in Group l, difference was statistically significant, p<0.05. In patients assigned to group A, 42.5% of them had diagnosis of hypertension while in Group B, 35% of patients were hypertensive. Difference was not statistically significant, p>0.05. 37.5% of patients in group A and 20% of patients in group B had hyperlipidemia. Difference was not statistically significant, p>0.05. In Group A mean age of patients was 67.85 years while mean age in Group B was 73.63. Age difference was statistically significant, p<0.05. Conclusion: Prevalence of risk factors of atherosclerosis in peripheral artery disease were evaluated in this study. Significant difference in prevalence of two risk factors were determined namely, smoking and mean age of occurrence of atherothrombosis. Quiting smoking and adopting healthier life habits may lead to reduction of prevalence PAD in younger patients in Bosnia and Herzegovina. PMID:25568565

Rustempasic, Nedzad; Totic, Dragan; Djedovic, Muhamed; Rustempasic, Medzida; Malesic, Nada

2014-01-01

365

Neighborhood health-promoting resources and obesity risk (the Multi-Ethnic Study of Atherosclerosis). — Measures of the Food Environment  

Cancer.gov

Auchincloss AH, Mujahid MS, Shen M, Michos ED, Whitt-Glover MC, Diez Roux AV. Neighborhood health-promoting resources and obesity risk (the Multi-Ethnic Study of Atherosclerosis). Obesity (Silver Spring) 2012 Apr 19.

366

75 FR 63488 - Submission for OMB Review; Comment Request; Multi-Ethnic Study of Atherosclerosis (MESA) Event...  

Federal Register 2010, 2011, 2012, 2013

...with the presence and progression of subclinical cardiovascular disease (CVD)-- that is, atherosclerosis and other...instruments, contact: Dr. Diane Bild, Division of Cardiovascular Sciences, NHLBI, NIH, II Rockledge...

2010-10-15

367

COMPLIANCE WITH EXPERT POPULATION-BASED DIETARY GUIDELINES AND LOWER ODDS OF CAROTID ATHEROSCLEROSIS IN WOMEN: THE FRAMINGHAM NUTRITION STUDIES  

Technology Transfer Automated Retrieval System (TEKTRAN)

Carotid stenosis, an indicator of subclinical atherosclerosis, predicts future coronary artery disease (CAD) and stroke and provides a noninvasive method to identify candidates for primary prevention. The relation between diet and stenosis is relatively unexplored, particularly in women. We evaluate...

368

Genomic analyses of induced hypercholesterolemia and atherosclerosis in a mixed breed colony of dogs and developmental abnormalities in the Havanese  

E-print Network

). For these reasons, research into risk factors, disease progression, and treatment protocols for atherosclerosis is important. In humans, an excess of low-density lipoprotein (LDL) circulating in the plasma causes macrophages to express scavenger receptors... to atherosclerosis development in the liver. Cells containing multiple values represent fold changes calculated for several probes from a specific gene. (*) indicates a significant P- values (Acid Regulation Organic...

Starr, Alison Nicole

2009-05-15

369

Intakes of long-chain n-3 polyunsaturated fatty acids and fish in relation to measurements of subclinical atherosclerosis  

PubMed Central

Background Data on the relations of different types of fish meals and long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) with measures of atherosclerosis are sparse. Objective We examined intakes of long-chain n-3 PUFAs and fish in relation to clinical measures of subclinical atherosclerosis. Design A cross-sectional study was conducted in 5,488 multiethnic adults aged 45–84 years and free of clinical cardiovascular disease. Diet was assessed using self-administered food frequency questionnaires. Subclinical atherosclerosis was determined by common carotid intima-media thickness (cCIMT, >80th percentile), internal CIMT (iCIMT, >80th percentile), coronary artery calcium score (CAC, >0) or ankle-brachial index (ABI, <0.90), respectively. Results After adjustment for potential confounders, intakes of long-chain n-3 PUFAs and non-fried (broiled, steamed, baked or raw) fish were inversely related to subclinical atherosclerosis determined by cCIMT but not iCIMT, CAC or ABI. The multivariable odds ratio comparing the highest to the lowest quartile of dietary exposures in relation to subclinical atherosclerosis determined by cCIMT was 0.69 (95% CI: 0.55, 0.86; p for trend<0.01) for n-3 PUFA intake, 0.80 (95% CI: 0.64, 1.01; p=0.054) for non-fried fish and 0.90 (95% CI: 0.73, 1.10; p=0.33) for fried fish consumption. Conclusions This study indicates that dietary intake of long-chain n-3 PUFAs or non-fried fish is associated with lower prevalence of subclinical atherosclerosis classified by cCIMT although significant changes in iCIMT, CAC and ABI were not observed. Our findings also suggest that the association of fish and atherosclerosis may vary depending on the type of fish meal consumed and the measures of atherosclerosis. PMID:18842801

He, Ka; Liu, Kiang; Daviglus, Martha L.; Mayer-Davis, Elisabeth; Jenny, Nancy Swords; Jiang, Rui; Ouyang, Pamela; Steffen, Lyn M.; Siscovick, David; Wu, Colin; Barr, R. Graham; Tsai, Michael; Burke, Gregory L.

2014-01-01

370

Subclinical atherosclerosis in patients with rheumatoid arthritis by utilizing carotid intima-media thickness as a surrogate marker  

PubMed Central

Background & objectives: Patients with rheumatoid arthritis (RA) are more prone for accelerated atherosclerosis and Asian Indians as an ethnic group are predisposed to a high risk of premature atherosclerosis. However, sparse data are available regarding the burden of atherosclerosis among asymptomatic adult patients with RA in south India. We studied the burden of asymptomatic atherosclerosis in adult south Indian patients with RA at Tirupati, Andhra Pradesh, India, utilizing carotid intima-media thickness (CIMT) as a surrogate marker. Methods: Ultrasound examination of the carotids and CIMT measurement (mm) were carried out in 32 patients with RA, 32 age- and gender-matched normal controls, and 32 patients with atherosclerosis and angiographically proven coronary artery disease. The CIMT values in patients with CAD and normal controls were used to derive the appropriate cut-off value of CIMT for defining atherosclerosis that would be applicable for the ethnic population studied. Results: Patients with RA had a higher mean CIMT (mm) compared with normal control subjects (0.598 ± 0.131 vs 0.501 ± 0.081; P = 0.001). Carotid plaque was found more frequently among the cases compared with normal controls [5/32 (15.6%) vs 0/32 (0%), P=0.020]. Using this cut-off value derived by the receiver operator characteristic curve method (? 0.57 mm; sensitivity 84.4; specificity 90.6%) and the 75th percentile value among normal controls (? 0.55 mm) as surrogate markers, the presence of subclinical atherosclerosis was significantly more among asymptomatic patients with RA compared with normal controls [(59.3 vs 12.5%; P<0.001) and (62.5 vs 25%; P<0.001) respectively]. Interpretation & conclusions: Based on the present findings CIMT appears to be a useful surrogate marker for detecting subclinical atherosclerosis in adult Indian patients with RA. PMID:25366205

Mohan, Alladi; Sada, Sujay; Kumar, B. Siddhartha; Sarma, K.V.S.; Devi, B. Vijayalakshmi; Rao, P.V.L.N. Srinivasa; Rajasekhar, D.; Katyarmal, D.T.

2014-01-01

371

Comparison of intima-media thickness and ophthalmic artery resistance index for assessing subclinical atherosclerosis in HIV1-infected patients  

Microsoft Academic Search

Background  Human immunodeficiency virus (HIV) infection and antiretroviral treatment are associated with metabolic and cardiovascular\\u000a complications that potentially increase the risk of atherosclerosis and cardiovascular disease in this population. Measurement\\u000a of arterial wall thickness has been used as a surrogate of extent, severity and progression of atherosclerosis. A cross-sectional\\u000a cohort study was performed to compare the validity of two non-invasive arterial

Pierfrancesco Grima; Marcello Guido; Roberto Chiavaroli; Antonella De Donno; Mariangela Tana; Antonella Zizza

2011-01-01

372

STRV CRYOCOOLER TIP MOTION SUPPRESSION  

Microsoft Academic Search

The Space Technology Research Vehicle (STRV- lb) scheduled to fly at the beginning of June 1994, has a cryocooler vibration suppression experiment aboard doing motion suppression of the tip of the coldfinger. STRV-lb is a bread box sized satellite to be launched on the next flight of the Ariane-4. To meet stringent power, weight, and space constraints, the experiment uses

R. Glascr; R. G. Ross

373

STRV Cryocooler Tip Motion Suppression  

NASA Technical Reports Server (NTRS)

The Space Technology Research Vehicle (STRV-1b) scheduled to fly at the beginning of June 1994, has a cryocooler vibration suppression experiment aboard doing motion suppression of the tip of the coldfinger. STRV-1b is a bread box sized satellite to be launched on the next flight of the Ariane-4.

Glaser, R.; Ross, R. G., Jr.; Johnson, D. L.

1994-01-01

374

An Alternative to Thought Suppression?  

ERIC Educational Resources Information Center

Comments on the original article, "Setting free the bears: Escape from thought suppression," by D. M. Wegner (see record 2011-25622-008). While Wegner supposed that we might have to learn to live with bad thoughts, the present author discusses the use of imagination and guided imagery as an alternative to forced thought suppression.

Boice, Robert

2012-01-01

375

One-pot synthesis of magnetic nanoclusters enabling atherosclerosis-targeted magnetic resonance imaging  

PubMed Central

In this study, dextran-encrusted magnetic nanoclusters (DMNCs) were synthesized using a one-pot solution phase method for detection of atherosclerosis by magnetic resonance imaging. Pyrenyl dextran was used as a surfactant because of its electron-stabilizing effect and its amphiphilic nature, rendering the DMNCs stable and water-dispersible. The DMNCs were 65.6±4.3 nm, had a narrow size distribution, and were superparamagnetic with a high magnetization value of 60.1 emu/g. Further, they showed biocompatibility and high cellular uptake efficiency, as indicated by a strong interaction between dextran and macrophages. In vivo magnetic resonance imaging demonstrated the ability of DMNCs to act as an efficient magnetic resonance imaging contrast agent capable of targeted detection of atherosclerosis. In view of these findings, it is concluded that DMNCs can be used as magnetic resonance imaging contrast agents to detect inflammatory disease. PMID:24904209

Kukreja, Aastha; Lim, Eun-Kyung; Kang, Byunghoon; Choi, Yuna; Lee, Taeksu; Suh, Jin-Suck; Huh, Yong-Min; Haam, Seungjoo

2014-01-01

376

Role of Endoplasmic Reticulum Stress in Atherosclerosis and Diabetic Macrovascular Complications  

PubMed Central

Age-related changes in endoplasmic reticulum (ER) are associated with stress of this cell organelle. Unfolded protein response (UPR) is a normal physiological reaction of a cell in order to prevent accumulation of unfolded and misfolded proteins in the ER and improve the normal ER function. However, in pathologic conditions such as atherosclerosis, obesity, and diabetes, ER function becomes impaired, leading to the development of ER stress. In chronic ER stress, defective posttranslational protein folding results in deposits of aberrantly folded proteins in the ER and the induction of cell apoptosis mediated by UPR sensors C/EBP?-homologous protein (CHOP) and inositol requiring protein-1 (IRE1). Since ER stress and ER-induced cell death play a nonredundant role in the pathogenesis of atherosclerosis and diabetic macrovascular complications, pharmaceutical targeting of ER stress components and pathways may be beneficial in the treatment and prevention of cardiovascular pathology. PMID:25061609

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

2014-01-01

377

Liver X Receptors as Therapeutic Targets for Managing Cholesterol: Implications for Atherosclerosis and Other Inflammatory Conditions  

PubMed Central

Summary Atherosclerosis is a disease characterized by excess cholesterol and inflammation in the blood vessels. The liver X receptors (alpha and beta) are members of the nuclear hormone receptor family that are activated by endogenous cholesterol metabolites. These receptors are widely expressed with a tissue distribution that includes the liver, intestine and macrophage. Upon activation, these receptors have been shown to increase reverse cholesterol transport from the macrophage back to the liver to aid in the removal of excess cholesterol. More recently, they have also been shown to inhibit the inflammatory response in macrophages. These functions are accomplished through direct regulation of gene transcription. Herein, we will describe the key benefits and potential risks of targeting the LXRs for the treatment of atherosclerosis. PMID:20852746

Zhang, Yuan; Chan, Jessica F.; Cummins, Carolyn L.

2010-01-01

378

Regulation of Atherosclerosis and Associated Risk Factors by Adenosine and Adenosine Receptors  

PubMed Central

Adenosine is an endogenous metabolite that has an anti-inflammatory effect across the vasculature. Extracellular adenosine activates four G-protein coupled receptors (A1, A3, A2A, and A2B) whose expression varies in different cells and tissues, including the vasculature and blood cells. Higher levels of adenosine are generated during stress, inflammation, and upon tissue damage. Some of the adenosine receptors (AR), such as the A2BAR, are further upregulated following such stresses. This review will discuss the role of adenosine and adenosine receptors in the development of atherosclerosis and some of the risk factors associated with this pathology. These include adenosine receptor-regulated changes in atherosclerosis, blood pressure, thrombosis, and myocardial infarction. PMID:22850979

Koupenova, Milka; Johnston-Cox, Hillary; Ravid, Katya

2013-01-01

379

Matrix metalloproteinases, atherosclerosis, proteinuria and kidney disease: Linkage–based approaches  

PubMed Central

Matrix metalloproteinases (MMPs) are important enzymes of extracellular matrix (ECM) degradation for creating the cellular environments required during development and morphogenesis. MMPs, collectively called matrixins, regulate also the biological activity of non matrix substrates such as cytokines, chemokines, receptors, growth factors and cell adhesion molecules. Enzymatic activity is regulated at multiple levels. Endogenous specific inhibitors of metalloproteinases (TIMPs) participate in controlling the local activities of MMPs in tissues. The pathological effects of MMPs and TIMPs are involved in cardiovascular disease (CVD) processes, including atherosclerosis and in a number of renal pathophysiologic alterations, both acute and chronic, linking them to acute kidney injury, glomerulosclerosis and tubulointerstitial fibrosis. This review presents an overview of the place of MMPs in atherosclerosis, proteinuria and kidney disease as a subject of considerable interest, given the differentiated and ambiguous role of MMPs in the progression of these diseases. PMID:25031504

Dimas, G; Iliadis, F; Grekas, D

2013-01-01

380

Targeting B cells in atherosclerosis: closing the gap from bench to bedside.  

PubMed

Atherosclerotic plaque formation is strongly influenced by different arms of the immune system, including B lymphocytes. B cells are divided into 2 main families: the B1 and the B2 cells. B1 cells are atheroprotective mainly via the production of natural IgM antibodies that bind oxidized low-density lipoprotein and apoptotic cells. B2 cells, which include follicular and marginal zone B cells, are suggested to be proatherogenic. Antibody-mediated depletion of B cells has become a valuable treatment option for certain autoimmune diseases, such as systemic lupus erythematosus and rheumatoid arthritis that are also characterized by the development of premature atherosclerosis. Thus, B cells represent a novel interesting target for therapeutic modulation of the atherosclerotic disease process. Here, we discuss the effect of different of B-cell subsets in experimental atherosclerosis, their mechanism of action as well as potential ways to exploit these findings for the treatment of human disease. PMID:25359862

Tsiantoulas, Dimitrios; Sage, Andrew P; Mallat, Ziad; Binder, Christoph J

2015-02-01

381

Adventitial fibroblasts are activated in the early stages of atherosclerosis in the apolipoprotein E knockout mouse  

SciTech Connect

The role of the adventitia in vascular function and vascular lesion formation has been largely ignored. This study observed the activation of the adventitia and specifically the fibroblasts in the development of atherosclerosis in the apoE(-/-) mouse. The results showed a gradual increase in expression of collagen types I and III after 2, 4, and 8 weeks of hyperlipidic diet. The earliest expression of monocyte chemoattractant protein-1 (MCP-1) protein and mRNA was detected in the adventitial fibroblast before the formation of intimal lesions. Proliferation, too, was first found in the adventitial fibroblasts. We hypothesize that the adventitial fibroblast is activated in the early stage of atherosclerosis. Adventitial inflammation may be an early event in the development of atherosclerotic lesions.

Xu Fang [Department of Pathophysiology, School of Medicine, Shandong University, Jinan 250012, Shandong (China); Ji Jian [Department of Pathophysiology, School of Medicine, Shandong University, Jinan 250012, Shandong (China); Li Li [Department of Pathophysiology, School of Medicine, Shandong University, Jinan 250012, Shandong (China); Chen Rong [Department of Pathophysiology, School of Medicine, Shandong University, Jinan 250012, Shandong (China); Hu Weicheng [Department of Pathophysiology, School of Medicine, Shandong University, Jinan 250012, Shandong (China)]. E-mail: huweicheng@sdu.edu.cn

2007-01-19

382

Reduced endothelial progenitor cells in European and South Asian men with atherosclerosis  

PubMed Central

Background Circulating endothelial progenitor cells (EPCs) play a role in the repair and regeneration of the endothelium and may represent a novel cardiovascular risk factor. South Asian subjects have an increased risk of cardiovascular disease which is not fully explained by known risk factors. This study examined associations of EPCs with atherosclerosis and possible ethnic differences in EPCs. Materials and methods A population sample of 58 European and South Asian adult men was enriched with the recruitment of an additional 59 European and South Asian men with known coronary disease. The coronary artery calcification score was measured by multi-slice computerized tomography (CT), carotid and femoral intima-media thickness (IMT), and femoral plaques were measured by ultrasound. The subjects were further subdivided into three categories of coronary artery disease on the basis of coronary artery calcification score and clinical history. Total EPCs and non-senescent EPCs (ns-EPCs) were quantified after 5 days cell culture and the number of late outgrowth colonies was measured over a 6-week test period. Circulating CD34+ haematopoietic precursor cells were measured by flow cytometry. Results Individuals with femoral plaques had reduced total and ns-EPCs. The number of ns-EPCs were reduced in individuals with the most coronary atheroma and were inversely related to the coronary calcification score and femoral IMT. These relationships persisted after multivariate adjustment for other risk factors. The numbers of late outgrowth colonies or circulating CD34+ cells were unrelated to the presence of atherosclerosis. There were no differences in the number of EPCs between European and South Asian subjects. Conclusion The number of EPCs are reduced in subjects with atherosclerosis independent of other risk factors. Reduction in EPC numbers may be an independent risk factor for atherosclerosis but does not explain ethnic differences in cardiovascular risk. PMID:17181565

Hughes, A. D.; Coady, E.; Raynor, S.; Mayet, J.; Wright, A. R.; Shore, A. C.; Kooner, J. S.; Thom, S. A. McG.; Chaturvedi, N.

2007-01-01

383

Biological Gradient Between Long-Term Arsenic Exposure and Carotid Atherosclerosis  

Microsoft Academic Search

Background—Long-term exposure to ingested arsenic has been documented to induce peripheral vascular disease, ischemic heart disease, and cerebral infarction in a dose-response relationship. This study further examined the biological gradient between ingested inorganic arsenic and carotid atherosclerosis. Methods and Results—We studied 199 male and 264 female adult residents from the southwestern area of endemic arseniasis in Taiwan. The extent of

Chih-Hao Wang; Jiann-Shing Jeng; Ping-Keung Yip; Chi-Ling Chen; Lin-I Hsu; Yu-Mei Hsueh; Hung-Yi Chiou; Meei-Mann Wu; Chien-Jen Chen

384

Chronic Hypoxia Accelerates the Progression of Atherosclerosis in Apolipoprotein E-Knockout Mice  

Microsoft Academic Search

The aim of this study was to investigate the effect of chronic hypoxia on the development and progression of atherosclerosis in apolipoprotein E-knockout (apoE-KO) mice. Male and female apoE-KO mice (6 weeks old) and age- and sex-matched wild-type mice were kept under hypoxic conditions (10.0±0.5% O2) in a gas chamber or in room air for 3 weeks. Aortic atherosclerotic plaque

Daisuke Nakano; Tetsuya Hayashi; Naoko Tazawa; Chika Yamashita; Sakiko Inamoto; Nobuaki Okuda; Tatsuhiko Mori; Koichi Sohmiya; Yasushi Kitaura; Yoshikatsu Okada; Yasuo Matsumura

2005-01-01

385

Matrix Metalloproteinase 7 Is Associated with Symptomatic Lesions and Adverse Events in Patients with Carotid Atherosclerosis  

PubMed Central

Background Atherosclerosis is a major cause of cerebrovascular disease. Matrix metalloproteinases (MMPs) play an important role in matrix degradation within the atherosclerotic lesion leading to plaque destabilization and ischemic stroke. We hypothesized that MMP-7 could be involved in this process. Methods Plasma levels of MMP-7 were measured in 182 consecutive patients with moderate (50–69%) or severe (?70%) internal carotid artery stenosis, and in 23 healthy controls. The mRNA levels of MMP-7 were measured in atherosclerotic carotid plaques with different symptomatology, and based on its localization to macrophages, the in vitro regulation of MMP-7 in primary monocytes was examined. Results Our major findings were (i) Patients with carotid atherosclerosis had markedly increased plasma levels of MMP-7 compared to healthy controls, with particularly high levels in patients with recent symptoms (i.e., within the last 2 months). (ii) A similar pattern was found within carotid plaques with markedly higher mRNA levels of MMP-7 than in non-atherosclerotic vessels. Particularly high protein levels of MMP-7 levels were found in those with the most recent symptoms. (iii) Immunhistochemistry showed that MMP-7 was localized to macrophages, and in vitro studies in primary monocytes showed that the inflammatory cytokine tumor necrosis factor-? in combination with hypoxia and oxidized LDL markedly increased MMP-7 expression. (iv) During the follow-up of patients with carotid atherosclerosis, high plasma levels of MMP-7 were independently associated with total mortality. Conclusion Our findings suggest that MMP-7 could contribute to plaque instability in carotid atherosclerosis, potentially involving macrophage-related mechanisms. PMID:24400123

Abbas, Azhar; Aukrust, Pål; Russell, David; Krohg-Sørensen, Kirsten; Almås, Trine; Bundgaard, Dorte; Bjerkeli, Vigdis; Sagen, Ellen Lund; Michelsen, Annika E.; Dahl, Tuva B.; Holm, Sverre; Ueland, Thor

2014-01-01

386

Cholesterol-Induced Non-Alcoholic Fatty Liver Disease and Atherosclerosis Aggravated by Systemic Inflammation  

PubMed Central

Although triglyceride accumulation in the liver causes non-alcoholic fatty liver disease (NAFLD), hypercholesterolemia is also a main cause of NAFLD as well as atherosclerosis. However, NAFLD and atherosclerosis have not been investigated simultaneously in animal models fed a high-cholesterol diet. Moreover, it is unclear whether systemic inflammation can exacerbate both pathologies in the same model. Accordingly, this study investigated the effect of additional systemic inflammation on NAFLD and atherosclerosis induced by cholesterol overload in wild animals. New Zealand white rabbits were divided into 4 groups: groups I (control) and II received normal chow, and groups III and IV received a 1% cholesterol diet. To induce inflammation via toll-like receptor (TLR)-4 signaling, groups II and IV received subcutaneous injections of 0.5 mL of 1% carrageenan every 3 weeks. After 3 months, total cholesterol markedly increased in groups III and IV, and the serum expressions of systemic inflammatory markers were elevated in the groups II–IV. Early NAFLD lesions (e.g., mild fatty changes in the liver with sporadic fibrosis) and atherosclerosis (e.g., intimal hyperplasia composed of foam cells) were observed in both the liver and aorta specimens from group III, and advanced lesions were observed in group IV. The expressions of inflammatory cellular receptors, TLR-2 and TLR-4, in the aorta gradually increased from group I to IV but were similar in the liver in groups II–IV. Cholesteryl ester (CE) levels were higher in group IV than in group III, although the difference was not significant. CE levels in the aorta were similar between groups III and IV. Systemic inflammation can simultaneously exacerbate existing early lesions due to cholesterol overload in both the liver and aorta of rabbits. However, the cellular response of inflammatory receptors and expression of cholesterol metabolites differ between these organs. PMID:24901254

Seo, Hong Seog; Lee, Yong Jik; Kim, Hyun Hee; Son, Hyun-Hwa; Choi, Man Ho

2014-01-01

387

Independent associations between metabolic syndrome, diabetes mellitus and atherosclerosis: observations from the Dallas Heart Study  

Microsoft Academic Search

Diabetes mellitus (DM) has been termed a “coronary disease equivalent”, yet data suggest that only those DM subjects with metabolic syndrome (MetS) are at increased coronary risk.Using data from the Dallas Heart Study, a large, probability-based population study, we assessed the individual and joint associations between MetS, DM and atherosclerosis, defined as coronary artery calcium (CAC) detected by electron-beam computerised

Karen Chen; Jason B Lindsey; Amit Khera; James A. De Lemos; Colby R Ayers; Abhinav Goyal; Gloria L Vega; Sabina A Murphy; Scott M Grundy; Darren K Mcguire

2008-01-01

388

Agonistic antibody to angiotensin II type 1 receptor accelerates atherosclerosis in ApoE-/- mice  

PubMed Central

This study aimed to investigate the effects of agonistic antibody to angiotensin II type 1 receptor (AT1-AA) on atherosclerosis in male ApoE-/- mice which were employed to establish the animal models of AT1-AA in two ways. In the first group, mice were injected subcutaneously with conjugated AT1 peptide at multiple sites; in the second group, mice were infused with AT1-AA prepared from rabbits that were treated with AT1 peptide intraperitoneally. Mice in each group were further randomly divided into five subgroups and treated with AT1 peptide/AT1-AA, AT1 peptide/AT1-AA plus valsartan, AT1 peptide/AT1-AA plus fenofibrate, AT1 peptide/ AT1-AA plus pyrrolidine dithiocarbamate (PDTC) and control vehicle, respectively. Antibodies were detected in mice (except for mice in control group). Aortic atherosclerotic lesions were assessed by oil red O staining, while plasma CRP, TNF-?, nuclear factor-kappa B (NF-?B) and H2O2 were determined by ELISA. CCR2 (the receptor of MCP-1), macrophages, and smooth muscle cells were detected by immunohistochemistry. P47phox, MCP-1 and eNOS were detected by RT-PCR, while P47phox, NF-?B and MCP-1 were detected by Western blot assay. The aortic atherosclerotic lesions were significantly increased in AT1 peptide/AT1-AA treated mice, along with simultaneous increases in inflammatory parameters. However, mice treated with valsartan, fenofibrate or PDTC showed alleviated progression of atherosclerosis and reductions in inflammatory parameters. Thus, AT1-AA may accelerate aortic atherosclerosis in ApoE-/- mice, which is mediated, at least in part, by the inflammatory reaction involving nicotinamide-adenine dinucleotide phosphate oxidase, reactive oxygen species, and NF-?B. In addition, valsartan, fenofibrate and PDTC may inhibit the AT1-AA induced atherosclerosis.

Li, Weijuan; Chen, Yaoqi; Li, Songhai; Guo, Xiaopeng; Zhou, Wenping; Zeng, Qiutang; Liao, Yuhua; Wei, Yumiao

2014-01-01

389

Autoantibodies against MDA-LDL in subjects with severe and minor atherosclerosis and healthy population controls  

Microsoft Academic Search

Autoantibodies against oxidized low-density lipoprotein (LDL) have been reported to be associated with atherosclerosis. However, data are not consistent.We compared the titres of autoantibodies to malondialdehyde-modified LDL in three groups, a case group with angiographically documented severe coronary stenosis (>80% stenosis in at least 1 vessel, n = 47), a hospital control group with minor stenosis on the coronary angiography

Roland Steyger; Geert van Poppel; Jolanda M. A. Boer; Dick A. C. M. Kruijssen; Jacob C. Seidell; Hans M. G. Princen

1996-01-01

390

Emerging role of FDG-PET\\/CT in assessing atherosclerosis in large arteries  

Microsoft Academic Search

Atherosclerosis is a dynamic inflammatory disorder. The biological composition and inflammatory state of an atherosclerotic\\u000a plaque, rather than the degree of stenosis or its size are the major determinants of acute clinical events. A noninvasive\\u000a technique to detect vulnerable atherosclerotic plaque is critically needed. FDG-PET\\/CT, a combined functional and structural\\u000a whole-body imaging modality, holds great potential for this purpose. FDG

Wengen Chen; Gonca G. Bural; Drew A. Torigian; Daniel J. Rader; Abass Alavi

2009-01-01

391

Polymorphic variants in tenascin-C ( TNC ) are associated with atherosclerosis and coronary artery disease  

Microsoft Academic Search

Tenascin-C (TNC) is an extracellular matrix protein implicated in biological processes important for atherosclerotic plaque development and\\u000a progression, including smooth muscle cell migration and proliferation. Previously, we observed differential expression of\\u000a TNC in atherosclerotic aortas compared with healthy aortas. The goal of this study was to investigate whether common genetic\\u000a variation within TNC is associated with risk of atherosclerosis and

Mollie A. Minear; David R. Crosslin; Beth S. Sutton; Jessica J. Connelly; Sarah C. Nelson; Shera Gadson-Watson; Tianyuan Wang; David Seo; Jeffrey M. Vance; Michael H. Sketch; Carol Haynes; Pascal J. Goldschmidt-Clermont; Svati H. Shah; William E. Kraus; Elizabeth R. Hauser; Simon G. Gregory

2011-01-01

392

Effect of crude extract of Bombyx mori coccoons in hyperlipidemia and atherosclerosis  

PubMed Central

The silkworm is the larva or caterpillar of the domesticated silkmoth, Bombyx mori and being a primary producer of silk is an economically important insect. These days the silk is emerging as a resource for solving a broad range of biological problems. The silk (Abresham) is popularly known as Abresham muqriz (muqriz means cut) in Unani medicine. Its cocoons are extensively used as an ingredient of various Unani formulations like Khameer-E- Abresham Sada, Khameere Abresham Hakeem Arshad Wala, Khameere Abresham Ood Mastagi Wala etc. and are used to treat many cardiac and nervous disorders. The hypolipidemic activity of this drug, along with Nepata Hindostana (Badranjboya) and Terminalia Arjuna (Arjan) has been documented. But action of extract of Bombyx mori cocoons as a single drug is not documented. That's why; it was decided to study its effect on hyperlipidemia and atherosclerosis. The Male New Zealand White rabbits all of 1.5kgs were selected for the study. After stabilization period (2 weeks) the rabbits were divided into 3 groups (Group I - Control, Group II Lesion Control and Group III treated with extract of Bombyx mori silk cocoon). Hyperlipidemia and atherosclerosis were induced with 1% cholesterol diet. After induction of hyperlipidemia and atherosclerosis for twelve weeks, Group III rabbits were treated with Bombyx mori for 6 weeks (45 days). A significant decrease in hyperlipidemia was seen within 4 weeks of treatment. Histopathologically, the atherosclerotic plaques showed reduction in size. The third group showed a significant increase in the body weight and also an increase in the HDL cholesterol levels. The study concludes that extract of Bombyx mori cocoons has a significant effect on hypercholesterolemia and atherosclerosis probably because of its antioxidant and hypolipidemic effect. PMID:21760692

Ali, Mir Mahdi; Arumugam, Sarasa Bharati A.

2011-01-01

393

Importance of intra-abdominal visceral fat accumulation to coronary atherosclerosis in heterozygous familial hypercholesterolaemia  

Microsoft Academic Search

OBJECTIVES: Hyper-low-density lipoprotein (LDL)-cholesterolaemia is a potent risk factor for coronary atherosclerosis. We have recently demonstrated that a cluster of risk factors including insulin resistance, glucose intolerance, hypertriglyceridaemia, and hypertension based on intra-abdominal visceral fat accumulation are closely related to coronary artery disease. In the current study, we evaluated the relationship between visceral fat accumulation and the severity and distribution

T Nakamura; H Kobayashi; K Yanagi; T Nakagawa; M Nishida; S Kihara; H Hiraoka; S Nozaki; T Funahashi; S Yamashita; K Kameda-Takemura; Y Matsuzawa

1997-01-01

394

Does Early Mismatched Nutrition Predispose to Hypertension and Atherosclerosis, in Male Mice?  

Microsoft Academic Search

BackgroundA link between early mismatched nutritional environment and development of components of the metabolic syndrome later in life has been shown in epidemiological and animal data. The aim of this study was to investigate whether an early mismatched nutrition produced by catch-up growth after fetal protein restriction could induce the appearance of hypertension and\\/or atherosclerosis in adult male mice.Methodology\\/Principal FindingsWild-type

Vanesa Bol; Fanny Desjardins; Brigitte Reusens; Jen-Luc Balligand; Claude Remacle; Carlo Polidori

2010-01-01

395

HIV protein Nef causes dyslipidemia and formation of foam cells in mouse models of atherosclerosis.  

PubMed

Patients with HIV are at an increased risk of cardiovascular disease. In this study we investigated the effect of Nef, a secreted HIV protein responsible for the impairment of cholesterol efflux, on the development of atherosclerosis in two animal models. ApoE(-/-) mice fed a high-fat diet and C57BL/6 mice fed a high-fat, high-cholesterol diet were injected with recombinant Nef (40 ng/injection) or vehicle, and the effects of Nef on development of atherosclerosis, inflammation, and dyslipidemia were assessed. In apoE(-/-) mice, Nef significantly increased the size of atherosclerotic lesions and caused vessel remodeling. Nef caused elevation of total cholesterol and triglyceride levels in the plasma while reducing high-density lipoprotein cholesterol levels. These changes were accompanied by a reduction of ABCA1 abundance in the liver, but not in the vessels. In C57BL/6 mice, Nef caused a significant number of lipid-laden macrophages presented in adventitia of the vessels; these cells were absent from the vessels of control mice. Nef caused sharp elevations of plasma triglyceride levels and body weight. Taken together, our findings suggest that Nef causes dyslipidemia and accumulation of cholesterol in macrophages within the vessel wall, supporting the role of Nef in pathogenesis of atherosclerosis in HIV-infected patients.-Cui, H. L., Ditiatkovski, M., Kesani, R., Bobryshev, Y. V., Liu, Y., Geyer, M., Mukhamedova, N., Bukrinsky, M., Sviridov, D. HIV protein Nef causes dyslipidemia and formation of foam cells in mouse models of atherosclerosis. PMID:24642731

Cui, Huanhuan L; Ditiatkovski, Michael; Kesani, Rajitha; Bobryshev, Yuri V; Liu, Yingying; Geyer, Matthias; Mukhamedova, Nigora; Bukrinsky, Michael; Sviridov, Dmitri

2014-07-01

396

Beijing ambient particle exposure accelerates atherosclerosis in ApoE knockout mice by upregulating visfatin expression.  

PubMed

Ambient particulate matter (PM) exposure has been associated with atherosclerosis. However, research on the effect of real-world exposure to ambient PM in regulating visfatin expression in an animal model is very limited. The objective is to investigate whether Beijing ambient PM exposure could accelerate atherosclerosis in ApoE knockout (ApoE(-/-)) mice by upregulating visfatin expression. Forty male ApoE(-/-) mice were exposed to untreated ambient air (PM group, n = 20) or filtered air (FA group, n = 20), 24 h/day, 7 days/week, for 2 months. During the exposure, the mass concentrations of PM2.5 and PM10 in the two groups were continuously monitored. Moreover, a receptor source apportionment model was applied to apportion sources of PM2.5. At the end of the exposure, visfatin in plasma and aorta, biomarkers of inflammation, oxidative stress and lipid metabolism in blood samples, and bronchoalveolar lavage fluid (BALF) were determined, and the plaque area of the atherosclerosis lesions was quantified. PM-exposed mice were significantly higher than FA-exposed mice in terms of plasma visfatin, OxLDL, MDA, serum TC, LDL, TNF-? as well as IL-6, TNF-?, OxLDL, and MDA in BALF, while SOD and GSH-Px activities in plasma and BALF were reduced in PM-exposed mice. Pathological analysis of the aorta demonstrated that the plaque area and visfatin protein in the PM group increased significantly compared to the FA group. Our findings indicate that ambient PM exposure could accelerate atherosclerosis, which is related to visfatin upregulation, as well as the activation of inflammation and oxidative stress. PMID:24523034

Wan, Qiang; Cui, Xiaobing; Shao, Jiman; Zhou, Fenghua; Jia, Yuhua; Sun, Xuegang; Zhao, Xiaoshan; Chen, Yuyao; Diao, Jianxin; Zhang, Lei

2014-09-01

397

Leonardo da Vinci on atherosclerosis and the function of the sinuses of Valsalva  

Microsoft Academic Search

lthough well studied by a medical scholar like Kenneth D. Keele, 1 Leonardo da Vinci’s elaborate study of the heart is not generally known. This article focuses on two of Leonardo’s achievements concerning atherosclerosis and the sinuses of Valsalva. 2 The first is his post-mortem observation on the degeneration of the vascular system in an old man, an early case

B. Boon

398

Atherosclerosis and liver inflammation induced by increased dietary cholesterol intake: a combined transcriptomics and metabolomics analysis  

PubMed Central

Background Increased dietary cholesterol intake is associated with atherosclerosis. Atherosclerosis development requires a lipid and an inflammatory component. It is unclear where and how the inflammatory component develops. To assess the role of the liver in the evolution of inflammation, we treated ApoE*3Leiden mice with cholesterol-free (Con), low (LC; 0.25%) and high (HC; 1%) cholesterol diets, scored early atherosclerosis and profiled the (patho)physiological state of the liver using novel whole-genome and metabolome technologies. Results Whereas the Con diet did not induce early atherosclerosis, the LC diet did so but only mildly, and the HC diet induced it very strongly. With increasing dietary cholesterol intake, the liver switches from a resilient, adaptive state to an inflammatory, pro-atherosclerotic state. The liver absorbs moderate cholesterol stress (LC) mainly by adjusting metabolic and transport processes. This hepatic resilience is predominantly controlled by SREBP-1/-2, SP-1, RXR and PPAR?. A further increase of dietary cholesterol stress (HC) additionally induces pro-inflammatory gene expression, including pro-atherosclerotic candidate genes. These HC-evoked changes occur via specific pro-inflammatory pathways involving specific transcriptional master regulators, some of which are established, others newly identified. Notably, several of these regulators control both lipid metabolism and inflammation, and thereby link the two processes. Conclusion With increasing dietary cholesterol intake the liver switches from a mainly resilient (LC) to a predominantly inflammatory (HC) state, which is associated with early lesion formation. Newly developed, functional systems biology tools allowed the identification of novel regulatory pathways and transcriptional regulators controlling both lipid metabolism and inflammatory responses, thereby providing a rationale for an interrelationship between the two processes. PMID:17892536

Kleemann, Robert; Verschuren, Lars; van Erk, Marjan J; Nikolsky, Yuri; Cnubben, Nicole HP; Verheij, Elwin R; Smilde, Age K; Hendriks, Henk FJ; Zadelaar, Susanne; Smith, Graham J; Kaznacheev, Valery; Nikolskaya, Tatiana; Melnikov, Anton; Hurt-Camejo, Eva; van der Greef, Jan; van Ommen, Ben; Kooistra, Teake

2007-01-01

399

Reflection magnitude as a predictor of mortality: the Multi-Ethnic Study of Atherosclerosis.  

PubMed

Arterial wave reflections have been associated with mortality in an ethnically homogenous Asian population. It is unknown whether this association is present in a multiethnic population or whether it is independent of subclinical atherosclerosis. We hypothesized that reflection magnitude (defined as the ratio of the amplitude of the backward wave [Pb] to that of the forward wave [Pf]) is associated with all-cause mortality in a large multiethnic adult community-based sample. We studied 5984 participants enrolled in the Multi-Ethnic Study of Atherosclerosis who had analyzable arterial tonometry waveforms. During 9.8±1.7 years of follow-up, 617 deaths occurred, of which 134 (22%) were adjudicated cardiovascular deaths. In Cox proportional hazards models, each 10% increase in reflection magnitude was associated with a 31% increased risk for all-cause mortality (hazard ratio [HR]=1.31; 95% confidence interval [CI]=1.11-1.55; P=0.001). This relationship persisted after adjustment for various confounders and for markers of subclinical atherosclerosis (HR=1.23; 95% CI=1.01-1.51; P=0.04), including the coronary calcium score, ankle-brachial index, common carotid intima-media thickness, and ascending thoracic aortic Agatston score. Pb was independently associated with all-cause mortality in a similarly adjusted model (HR per 10 mm Hg increase in P(b)=2.18; 95% CI=1.21-3.92; P=0.009). Reflection magnitude (HR=1.71; 95% CI=1.06-2.77; P=0.03) and P(b) (HR=5.02; 95% CI=1.29-19.42; P=0.02) were mainly associated with cardiovascular mortality. In conclusion, reflection magnitude is independently associated with all-cause mortality in a multiethnic population initially free of clinically evident cardiovascular disease. This relationship persists after adjustment for a comprehensive set of markers of subclinical atherosclerosis. PMID:25259746

Zamani, Payman; Jacobs, David R; Segers, Patrick; Duprez, Daniel A; Brumback, Lyndia; Kronmal, Richard A; Lilly, Scott M; Townsend, Raymond R; Budoff, Matthew; Lima, Joao A; Hannan, Peter; Chirinos, Julio A

2014-11-01

400

Leonardo da Vinci on atherosclerosis and the function of the sinuses of Valsalva  

Microsoft Academic Search

\\u000a Abstract  Although well studied by a medical scholar like Kenneth D. Keele, Leonardo da Vinci’s elaborate study of the heart is not\\u000a generally known. This article focuses on two of Leonardo’s achievements concerning atherosclerosis and the sinuses of Valsalva.\\u000a The first is his post-mortem observation on the degeneration of the vascular system in an old man, an early case history.

B. Boon

2009-01-01

401

Atherosclerosis associated with vasculopathic lesions in a golden retriever with hypercholesterolemia  

PubMed Central

A 2-year-old neutered male golden retriever dog presented for lameness secondary to ulcerations of multiple digital paw pads was diagnosed with vasculitis and hypercholesterolemia. Despite treatment, ischemic necrosis progressed to include all distal extremities and the dog eventually expired due to myocardial infarction secondary to severe atherosclerosis. The rapid demise and the dermatologic lesions may have been secondary to cholesterol embolism syndrome which has never before been reported in a dog. PMID:24790237

Boynosky, Nicole A.; Stokking, Laura

2014-01-01

402

Gender Differences in the Association between Socioeconomic Status and Subclinical Atherosclerosis  

PubMed Central

Objectives This study explored the pattern of associations between socioeconomic status (SES) and atherosclerosis progression (as indicated by carotid intima media thickness, CIMT) across gender. Design Cross-sectional analysis of a sample of 5474 older persons (mean age 73 years) recruited between 1999 and 2001 in the 3C study (France). We fitted linear regression models including neighborhood SES, individual SES and cardiovascular risk factors. Results CIMT was on average 24 µm higher in men (95% CI: 17 to 31). Neighborhood SES was inversely associated with CIMT in women only (highest versus lowest tertiles: ?12.2 µm, 95%CI ?22 to ?2.4). This association persisted when individual SES and risk factors were accounted for. High individual education was associated with lower CIMT in men (?21.4 µm 95%CI ?37.5 to ?5.3) whereas high professional status was linked to lower CIMT among women (?15.7 µm 95%CI: ?29.2 to ?2.2). Adjustment for cardiovascular risk factors resulted in a slightly more pronounced reduction of the individual SES-CIMT association observed in men than in women. Conclusion In this sample, neighborhood and individual SES displayed different patterns of associations with subclinical atherosclerosis across gender. This suggests that the causal pathways leading to SES variations in atherosclerosis may differ among men and women. PMID:24282522

Grimaud, Olivier; Lapostolle, Annabelle; Berr, Claudine; Helmer, Catherine; Dufouil, Carole; Kihal, Wahida; Alpérovitch, Annick; Chauvin, Pierre

2013-01-01

403

Role of the Vasa Vasorum and Vascular Resident Stem Cells in Atherosclerosis  

PubMed Central

Atherosclerosis is considered an “inside-out” response, that begins with the dysfunction of intimal endothelial cells and leads to neointimal plaque formation. The adventitia of large blood vessels has been recognized as an active part of the vessel wall that is involved in the process of atherosclerosis. There are characteristic changes in the adventitial vasa vasorum that are associated with the development of atheromatous plaques. However, whether vasa vasorum plays a causative or merely reactive role in the atherosclerotic process is not completely clear. Recent studies report that the vascular wall contains a number of stem/progenitor cells that may contribute to vascular remodeling. Microvessels serve as the vascular niche that maintains the resident stem/progenitor cells of the tissue. Therefore, the vasa vasorum may contribute to vascular remodeling through not only its conventional function as a blood conducting tube, but also its new conceptual function as a stem cell reservoir. This brief review highlights the recent advances contributing to our understanding of the role of the adventitial vasa vasorum in the atherosclerosis and discusses new concept that involves vascular-resident factors, the vasa vasorum and its associated vascular-resident stem cells, in the atherosclerotic process. PMID:24724094

Hasebe, Naoyuki

2014-01-01

404

Hepatocyte-specific IKK? expression aggravates atherosclerosis development in APOE*3-Leiden mice  

PubMed Central

Objective The liver is the key organ involved in systemic inflammation, but the relation between hepatic inflammation and atherogenesis is poorly understood. Since nuclear factor-?B (NF-?B) is a central regulator of inflammatory processes, we hypothesized that chronically enhanced hepatic NF-?B activation, through hepatocyte-specific expression of I?B kinase-? (IKK?) (LIKK), will aggravate atherosclerosis development in APOE*3-Leiden (E3L) mice. Methods and Results E3L.LIKK and E3L control littermates were fed a Western-type diet for 24 weeks. E3L.LIKK mice showed a 2.3-fold increased atherosclerotic lesion area and more advanced atherosclerosis in the aortic root with less segments without atherosclerotic lesions (11 vs. 42%), and more segments with mild (63% vs. 44%) and severe (26% vs. 14 %) lesions. Expression of LIKK did not affect basal levels of inflammatory parameters, but plasma cytokine levels tended to be higher in E3L.LIKK mice after lipopolysaccharide (LPS) administration. E3L.LIKK mice showed transiently increased plasma cholesterol levels, confined to (V)LDL. This transient character resulted in a mild (+17%) increased cumulative plasma cholesterol exposure. Conclusion We conclude that selective activation of NF-?B in hepatocytes considerably promotes atherosclerosis development which is (at least partly) explained by an increased sensitivity to proinflammatory triggers and transiently increased plasma cholesterol levels. PMID:21798539

Wong, Man C.; van Diepen, Janna A.; Hu, Lihui; Guigas, Bruno; de Boer, Hetty C.; van Puijvelde, Gijs H.; Kuiper, Johan; van Zonneveld, Anton J.; Shoelson, Steven E.; Voshol, Peter J.; Romijn, Johannes A.; Hav