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1

Irbesartan but Not Amlodipine Suppresses Diabetes-Associated Atherosclerosis  

Microsoft Academic Search

Background—It remains controversial whether specific blockade of the renin-angiotensin system confers superior antiatherosclerotic effects over other antihypertensive agents in diabetes. Therefore, the aim of this study was to compare equihypotensive doses of the angiotensin II subtype 1 (AT1) receptor blocker irbesartan with the calcium antagonist amlodipine on diabetes-induced plaque formation in the apolipoprotein E (apoE)-null mouse and to explore molecular

Riccardo Candido; Terri J. Allen; Markus Lassila; Zemin Cao; Vicki Thallas; Mark E. Cooper; Karin A. Jandeleit-Dahm

2010-01-01

2

Irbesartan inhibits human T-lymphocyte activation through downregulation of activator protein-1  

PubMed Central

Irbesartan is a promising antihypertensive drug with beneficial effects on atherosclerotic processes. In the progression of atherosclerosis, human T-lymphocytes play an important role, but it is not yet known how irbesartan modulates human T-lymphocytes activation. To gain insight into the mechanisms by which irbesartan acts, we investigated its effects on human T-lymphocytes. Primary human T-lymphocytes were isolated from whole blood. Cytokines were determined by ELISA. Activator protein-1 (AP-1) and related protein activities were determined by electrophoretic mobility shift assays, kinase assays, Western blotting and transfection assays. Irbesartan inhibited the production of both tumor necrosis factor-alpha and interferon-gamma by activated T-cells, especially at therapeutic concentrations. Further investigation at the molecular level indicated that the inhibition of activated human T-lymphocytes specifically correlated with the downregulation of AP-1 DNA-binding activity. In the Jurkat T-cell line, irbesartan also inhibited AP-1 transcriptional activity. Finally, we revealed that irbesartan is unique in its ability to inhibit the activation of both c-Jun NH2-terminal protein kinase and p38 MAPK. Our studies show that irbesartan may modulate inflammation-based atherosclerotic diseases through a cell-mediated mechanism involving suppression of human T-lymphocytes activation via downregulation of AP-1 activity.

Cheng, Shu-Meng; Yang, Shih-Ping; Ho, Ling-Jun; Tsao, Tien-Ping; Chang, Deh-Ming; Lai, Jenn-Haung

2004-01-01

3

Effects of diltiazem on suppression and regression of experimental atherosclerosis.  

PubMed Central

The effects of diltiazem (a calcium antagonist) on the suppression and regression of atherosclerosis were studied. Thirty-one rabbits were fed a 1% cholesterol (atherogenic) diet together with saline (n = 22) or diltiazem (n = 9) injections. After 10 weeks, seven rabbits that received saline and nine rabbits that received diltiazem were killed. The remaining 15 saline-treated rabbits were then put on a standard (regression) diet for the next 15 weeks with saline (n = 7) or diltiazem (n = 8) injections. Sixteen rabbits given a standard diet were used as controls. At 5 and 10 weeks, the plasma LDL cholesterol level in rabbits on the atherogenic diet with diltiazem was significantly lower than in those on the atherogenic diet with saline. The aortic total cholesterol, esterified cholesterol and calcium contents were also significantly lower in rabbits on the atherogenic diet with diltiazem. After 25 weeks (15 weeks on the regression diet), the differences in aortic total cholesterol and calcium contents between the two groups on the regression diet were not significant; however, the aortic esterified cholesterol content was significantly lower in the regression diet with diltiazem. The results suggest that diltiazem has a favourable effect both on regression and on suppression of atherosclerosis.

Sugano, M.; Nakashima, Y.; Tasaki, H.; Takasugi, M.; Kuroiwa, A.; Koide, O.

1988-01-01

4

Atherosclerosis  

MedlinePLUS

Atherosclerosis is a disease in which plaque builds up inside your arteries. Plaque is a sticky substance ... flow of oxygen-rich blood to your body. Atherosclerosis can lead to serious problems, including Coronary artery ...

5

PPARdelta regulates multiple proinflammatory pathways to suppress atherosclerosis  

Microsoft Academic Search

Lipid homeostasis and inflammation are key determinants in atherogenesis, exemplified by the requirement of lipid-laden, foam cell macrophages for atherosclerotic lesion formation. Although the nuclear receptor PPARdelta has been implicated in both systemic lipid metabolism and macrophage inflammation, its role as a therapeutic target in vascular disease is unclear. We show here that orally active PPARdelta agonists significantly reduce atherosclerosis

Grant D. Barish; Annette R. Atkins; Michael Downes; Peter Olson; Ling-Wa Chong; Mike Nelson; Yuhua Zou; Hoosang Hwang; Heonjoong Kang; Linda Curtiss; Ronald M. Evans; Chih-Hao Lee

2008-01-01

6

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

7

Effects of Ang II Receptor Blocker Irbesartan on Adipose Tissue Function in Mice with Metabolic Disorders  

PubMed Central

Recent studies indicate that the functional renin-angiotensin system (RAS) exists in the adipose tissue. The adipose tissue RAS is proposed in the pathophysiology of metabolic disorders. In the present study, we examined therapeutic effects of irbesartan, an angiotensin II (Ang II) type 1 receptor (AT1R)-specific blocker, in genetically obese diabetic KKAy mice, a model of human metabolic disorders without any dietary loading, with our focus on the analysis on possible effect of irbesartan on the adipose tissue. The treatment with irbesartan significantly lowered systolic blood pressure with a concomitant decrease in body weight in KKAy mice. In addition, irbesartan significantly decreased the adipose leptin mRNA expression and tended to decrease IL-6 mRNA expression in the adipose tissue of KKAy mice. Furthermore irbesartan preserved the adipose gene expression of AT1R-associated protein (ATRAP), an endogenous inhibitory molecule of tissue AT1R signaling, with a concomitant tendency of up-regulation of adipose tissue ATRAP/AT1R ratio. Collectively, these results suggest that the irbesartan-induced beneficial suppressive effect on the leptin-IL-6 axis in the adipose tissue in KKAy mice is partly mediated by a trend of up-regulation of the adipose ATRAP/AT1R ratio as one of pleiotropic effects of irbesartan.

Maeda, Akinobu; Tamura, Kouichi; Wakui, Hiromichi; Ohsawa, Masato; Azushima, Kengo; Uneda, Kazushi; Kobayashi, Ryu; Tsurumi-Ikeya, Yuko; Kanaoka, Tomohiko; Dejima, Toru; Ohki, Koji; Haku, Sona; Yamashita, Akio; Umemura, Satoshi

2014-01-01

8

Effects of Ang II Receptor Blocker Irbesartan on Adipose Tissue Function in Mice with Metabolic Disorders.  

PubMed

Recent studies indicate that the functional renin-angiotensin system (RAS) exists in the adipose tissue. The adipose tissue RAS is proposed in the pathophysiology of metabolic disorders. In the present study, we examined therapeutic effects of irbesartan, an angiotensin II (Ang II) type 1 receptor (AT1R)-specific blocker, in genetically obese diabetic KKAy mice, a model of human metabolic disorders without any dietary loading, with our focus on the analysis on possible effect of irbesartan on the adipose tissue. The treatment with irbesartan significantly lowered systolic blood pressure with a concomitant decrease in body weight in KKAy mice. In addition, irbesartan significantly decreased the adipose leptin mRNA expression and tended to decrease IL-6 mRNA expression in the adipose tissue of KKAy mice. Furthermore irbesartan preserved the adipose gene expression of AT1R-associated protein (ATRAP), an endogenous inhibitory molecule of tissue AT1R signaling, with a concomitant tendency of up-regulation of adipose tissue ATRAP/AT1R ratio. Collectively, these results suggest that the irbesartan-induced beneficial suppressive effect on the leptin-IL-6 axis in the adipose tissue in KKAy mice is partly mediated by a trend of up-regulation of the adipose ATRAP/AT1R ratio as one of pleiotropic effects of irbesartan. PMID:24834011

Maeda, Akinobu; Tamura, Kouichi; Wakui, Hiromichi; Ohsawa, Masato; Azushima, Kengo; Uneda, Kazushi; Kobayashi, Ryu; Tsurumi-Ikeya, Yuko; Kanaoka, Tomohiko; Dejima, Toru; Ohki, Koji; Haku, Sona; Yamashita, Akio; Umemura, Satoshi

2014-01-01

9

Suppression of experimental atherosclerosis by the Ca++-antagonist lanthanum. Possible role of calcium in atherogenesis.  

PubMed Central

Agents inhibiting calcium deposition into arteries are known to suppress atherosclerosis in animals. However, the precise role of calcium in atherogenesis is unknown. In this study, the specific Ca2+-antagonist lanthanum was used to attempt suppression of experimental atherosclerosis and to gain more insight into the possible effects of calcium on atherogenesis. Rabbits were fed an atherogenic diet with and without increasing doses of LaCl3. All cholesterol-fed rabbits showed marked increases in serum cholesterol and ca2+. Untreated atherogenic animals revealed pronounced gross and microscopic atherosclerosis and striking increases in the aortic content of cholesterol, collagen, "elastin," and calcium as well as of elastin calcium, polar amino acids, and cholesterol. With increasing LaCl3 dosage these abnormalities progressively decreased and were completely abolished at the highest dose. The ingested La3+ was absorbed only in small quantities and had no discernible effect on the calcium and connective tissue content of bone, skin, lung, heart, and skeletal muscle nor on myocardial function (left ventricle pressure and left ventricle dp/dt) or myocardial and muscle content in ATP and creatine phosphate. The data suggest that shifts in arterial Ca2+-distribution may play a decisive part in atherogenesis, and provision of arterial calcium homeostasis by La3+ a pivotal role in its prevention, despite hypercholesteremia. Other inhibitors of calcium deposition into arteries may exert their protective effect by similar mechanisms. However, a direct inhibition of atherogenesis by La3+ cannot entirely be ruled out in this study, although no direct effects of La3+ on tissue metabolism have as yet been reported. Images

Kramsch, D M; Aspen, A J; Apstein, C S

1980-01-01

10

Atherosclerosis as a microvascular disease: impaired angiogenesis mediated by suppressed basic fibroblast growth factor expression.  

PubMed

We present evidence that hypercholesterolemia and oxidized low-density lipoprotein (ox-LDL) impair endothelial cell growth by suppressing basic fibroblast growth factor (bFGF) expression. Background studies show that diet-induced hypercholesterolemia in rabbits impairs hyperplastic lumen-expanding remodeling of the carotid artery in response to a chronic flow load. Hypercholesterolemia also markedly impairs compensatory macrovascular and microvascular growth in rabbit ears with surgical restriction of arterial supply. In an in vitro model of angiogenesis, arterial explants cultured in a three-dimensional collagen gel exhibited organized endothelial cell growth with formation of capillary-like microtubes (CLM). CLM growth was sensitive to inhibition by neutralizing antibodies against bFGF. With explants excised from both the aorta of hypercholesterolemic rabbits and from coronary arteries of patients with coronary arteriosclerosis, CLM growth and release of immunoassayable bFGF to the culture medium were suppressed. Growth suppression was reversed partially by exogenous bFGF. In control explants, ox-LDL produced a suppression of CLM growth that could be reversed by exogenous bFGF. In endothelial cells in culture, ox-LDL suppressed bFGF expression and DNA synthesis in a dose-dependent manner. We conclude that atherosclerosis is associated with impaired bFGF-dependent endothelial cell growth manifested by impaired adaptive growth responses of large arteries and microvessels. PMID:9220533

Chen, C H; Henry, P D

1997-07-01

11

A glucagon-like peptide-1 analog liraglutide suppresses macrophage foam cell formation and atherosclerosis.  

PubMed

Macrophage foam cell formation, characterized by cholesterol ester accumulation catalyzed by acyl-CoA:cholesterol acyltransferase 1 (ACAT1), is the hallmark of early atherogenesis. We previously demonstrated the suppressive effects of incretins, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), on the development of atherosclerotic lesions in apolipoprotein E-deficient (apoE(-/-)) mice. The present study was performed to evaluate the suppressive effects of these incretins and GLP-1 analogs, such as exendin-4 and liraglutide, on human macrophage foam cell formation in vitro and those of liraglutide on atherosclerotic lesion development in apoE(-/-) mice. We investigated the suppressive effects of GLP-1, GIP, exendin-4, and liraglutide against oxidized low-density lipoprotein (oxLDL)-induced foam cell formation in primary cultured human monocyte-derived macrophages. Seventeen-week-old apoE(-/-) mice were administered a long-acting GLP-1 analog liraglutide by osmotic mini-pumps for 4 weeks. Aortic atherosclerosis, oxLDL-induced foam cell formation, and related gene expression in exudate peritoneal macrophages were determined in vivo and ex vivo. Receptors for GLP-1 and GIP were expressed at high levels in human aortic smooth muscle cells and monocytes, but at relatively low levels in human macrophages and foam cells. GLP-1, GIP, exendin-4, and liraglutide significantly suppressed oxLDL-induced foam cell formation mainly associated with ACAT1 down-regulation in human monocyte-derived macrophages. The infusion of liraglutide into apoE(-/-) mice significantly retarded atherosclerotic lesions with monocyte/macrophage infiltration in the aortic wall and suppressed foam cell formation and ACAT1 expression in macrophages. These findings indicate that liraglutide could prevent the development of atherosclerotic lesions by suppressing macrophage foam cell formation mainly associated with ACAT1 down-regulation. PMID:24418070

Tashiro, Yuko; Sato, Kengo; Watanabe, Takuya; Nohtomi, Kyoko; Terasaki, Michishige; Nagashima, Masaharu; Hirano, Tsutomu

2014-04-01

12

HMG-CoA reductase inhibitors suppress maturation of human dendritic cells: new implications for atherosclerosis  

Microsoft Academic Search

The beneficial effects of statins in atherosclerosis have been partly attributed to their immunomodulating functions. Dendritic cells (DC), which are “professional” antigen-presenting cells, were recently detected in atherosclerotic plaques. It is assumed that DC play a critical role in the immunological processes related to atherosclerosis. Thus, we investigated the effects of statins on maturation and antigen-presenting function of DC. Human

Atilla Yilmaz; Christine Reiss; Omeima Tantawi; Alexander Weng; Christian Stumpf; Dorette Raaz; Josef Ludwig; Thomas Berger; Alexander Steinkasserer; Werner G. Daniel; Christoph D. Garlichs

2004-01-01

13

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.

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

2013-01-01

14

Effect of lovastatin on suppression and regression of atherosclerosis in lipid-fed rabbits.  

PubMed

The present study was designed to evaluate the effects of lovastatin on suppression and regression of atherosclerosis in the lipid-fed rabbit. Fifty-seven New Zealand rabbits in six groups were fed a 0.3% cholesterol diet for 10 weeks. In the progression phase of the study, group C10 served as a control and received 1 ml of DMSO daily by gavage. Two other groups, L10 and H10, received low (L)-dose (10 mg/day) or high (H)-dose (20 mg/day) lovastatin dissolved in 1 ml of DMSO for 10 weeks. In the regression phase of the study, three groups of rabbits received the high lipid diet for 10 weeks and were then shifted to a normal diet for the second 10 weeks. During the second 10 weeks, the control group C20 received 1 ml of DMSO daily, and groups L20 and H20 received 10 and 20 mg/day of lovastatin by gavage, respectively. In the progression phase of the study, lovastatin significantly attenuated the percent of aortic lesions in groups L10 (8 +/- 7%) and H10 (9 +/- 14%) vs. the control group C10 (31 +/- 17%; p less than 0.01). There was a similar reduction in pulmonary lesions in groups L10 (10 +/- 6%) and H10 (4 +/- 5%) compared to the control group C10 (30 +/- 16%; p less than 0.01). There was also a reduction in plaque thickness in both the aorta and pulmonary artery, and hence an even greater reduction in estimated plaque volume. In the regression phase of the study, lovastatin also significantly reduced the percent of aortic lesions (groups L20 and H20 vs. C20: 27 +/- 18 and 22 +/- 7% vs. 40 +/- 17%; p less than 0.05) and pulmonary lesions (21 +/- 10 and 17 +/- 6% vs. 26 +/- 9%; p greater than 0.05 and p less than 0.05, respectively); the average maximum plaque thickness of aorta (0.24 and 0.26 mm vs. 0.49 mm; p less than 0.01); and the standardized plaque volume per unit area of aorta (4.5 and 3.4 vs. 12.1 mm-%; p less than 0.05 and p less than 0.01, respectively). However, there was no significant difference in the percent of aortic lesions between groups L20 and H20 and group C10 (27 +/- 18 and 22 +/- 7 vs. 31 +/- 17%; p greater than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS) PMID:1376794

Zhu, B Q; Sievers, R E; Sun, Y P; Isenberg, W M; Parmley, W W

1992-02-01

15

MicroRNA-126-5p promotes endothelial proliferation and limits atherosclerosis by suppressing Dlk1.  

PubMed

Atherosclerosis, a hyperlipidemia-induced chronic inflammatory process of the arterial wall, develops preferentially at sites where disturbed laminar flow compromises endothelial cell (EC) function. Here we show that endothelial miR-126-5p maintains a proliferative reserve in ECs through suppression of the Notch1 inhibitor delta-like 1 homolog (Dlk1) and thereby prevents atherosclerotic lesion formation. Endothelial recovery after denudation was impaired in Mir126(-/-) mice because lack of miR-126-5p, but not miR-126-3p, reduced EC proliferation by derepressing Dlk1. At nonpredilection sites, high miR-126-5p levels in endothelial cells confer a proliferative reserve that compensates for the antiproliferative effects of hyperlipidemia, such that atherosclerosis was exacerbated in Mir126(-/-) mice. In contrast, downregulation of miR-126-5p by disturbed flow abrogated EC proliferation at predilection sites in response to hyperlipidemic stress through upregulation of Dlk1 expression. Administration of miR-126-5p rescued EC proliferation at predilection sites and limited atherosclerosis, introducing a potential therapeutic approach. PMID:24584117

Schober, Andreas; Nazari-Jahantigh, Maliheh; Wei, Yuanyuan; Bidzhekov, Kiril; Gremse, Felix; Grommes, Jochen; Megens, Remco T A; Heyll, Kathrin; Noels, Heidi; Hristov, Michael; Wang, Shusheng; Kiessling, Fabian; Olson, Eric N; Weber, Christian

2014-04-01

16

Irbesartan administration therapeutically influences circulating endothelial progenitor cell and microparticle mobilization by involvement of pro-inflammatory cytokines.  

PubMed

Circulating microparticles (MPs) and endothelial progenitor cells (EPCs) correlate with endothelial dysfunction and contribute to the pathogenesis of atherosclerosis. In this context, we explored whether the angiotensin II type I receptor antagonist, irbesartan, exerts a pharmacological control in the atherosclerotic process by the improvement of EPC mobilization and inhibitory effects on MP release and VEGF and SDF-1? levels in the hypertensive-hypercholesterolemic (HH) hamster model. The HH hamsters were treated with irbesartan (50mg/kg b.w/day administered by gavage) for 4 month (HHI). We analyzed MP/EPC infiltration in vascular wall before and after irbesartan administration as well as the endothelial function and expression of VEGF/SDF-1? in plasma and tissue and of molecular pathways activated by them. The results showed that treatment with irbesartan significantly increased EPC infiltration and decreased MP infiltration. The mechanisms underlying this response include the reduction/increase of a number of specific membrane receptors exposed by MPs (TF, P-Selectin, E-Selectin, PSGL-1, Rantes), respectively, by EPCs (?2-Integrins, ?4?1-integrin), the augmentation of endothelium-mediated vasodilation and the reduction of protein expression of VEGF/SDF-1? followed by: (1) the diminishment of pro-inflammatory endothelial cytokines: VEGFR1, VEGFR2, CXCR4, Tie2, PIGF with role in EPC homing to sites of damaged endothelium; and (2) the increase of protein expression of COX-2, PGI2 synthase molecules with role in the improvement of arterial wall vasodilatation. In conclusion, the study underlines that irbesartan administration therapeutically improves/reduces EPC, respectively, MP mobilization and this action may be of salutary relevance contributing to its beneficial cardiovascular effects. PMID:23639758

Georgescu, Adriana; Alexandru, Nicoleta; Nemecz, Miruna; Titorencu, Irina; Popov, Doina

2013-07-01

17

Silence of NLRP3 Suppresses Atherosclerosis and Stabilizes Plaques in Apolipoprotein E-Deficient Mice  

PubMed Central

Objectives. The role of the NLRP3 inflammasome in atherosclerosis remains controversial. The aim of this study was to determine whether inhibition of NLRP3 signaling by lentivirus-mediated RNA interference could reduce atherosclerosis and stabilizes plaques. We also tried to explore the mechanisms of the impact of NLRP3 inflammasome on atherosclerosis. Methods. Apolipoprotein E-deficient mice aged 8 weeks were fed a high-fat diet and were injected with NLRP3 interfering or mock viral suspension after 4 weeks. Lentivirus transfer was repeated in 2 weeks. Four weeks after the first lentivirus injection, we evaluated the effects of NLRP3 gene silencing on plaque composition and stability and on cholesterol efflux and collagen metabolism, by histopathologic analyses and real-time PCR. Results. Gene silence of NLRP3 prevented plaques progression and inhibited inductions of proinflammatory cytokines. Moreover, this RNA interference reduced plaque content of macrophages and lipid, and increased plaque content of smooth muscle cells and collagen, leading to the stabilizing of atherosclerotic plaques. Conclusions. NLRP3 inflammasomes may play a vital role in atherosclerosis, and lentivirus-mediated NLRP3 silencing would be a new strategy to inhibit plaques progression and to reduce local inflammation.

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

2014-01-01

18

Comprehensive overview: efficacy, tolerability, and cost-effectiveness of irbesartan  

PubMed Central

Background Hypertension represents a major health problem, affecting more than one billion adults worldwide. Irbesartan, an angiotensin II receptor blocker, is considered to be a highly effective treatment in the management of hypertension. The purpose of this review is to evaluate the efficacy, safety and tolerability profile , and cost-effectiveness of treatment with irbesartan in hypertension. Methods A review of the literature was conducted using the electronic PubMed and Cochrane Library databases and the Health Economic Evaluations Database of search terms relating to irbesartan efficacy, tolerability, and cost-effectiveness, and the results were utilized. Results Findings from the present analysis show that irbesartan either as monotherapy or in combination with other antihypertensive agents can achieve significant reductions in blood pressure, both systolic and diastolic, compared with alternative treatment options. Irbesartan was also found to have a renoprotective effect independent of its blood pressure-lowering in patients with type 2 diabetes and nephropathy. Furthermore, irbesartan demonstrated an excellent safety and tolerability profile , with either lower or equal adverse events compared with placebo and other alternative treatments. In terms of economic analyses, compared with other antihypertensive therapy alternatives, irbesartan was found to be a preferred option, that is less costly and more effective. Conclusion The evidence indicates that treating patients with hypertension alone or with type 2 diabetes and nephropathy using irbesartan can control hypertension, prolong life, and reduce costs in relation to existing alternatives.

Gialama, Fotini; Maniadakis, Nikos

2013-01-01

19

Inhibition of Nuclear Factor of Activated T-Cells (NFAT) Suppresses Accelerated Atherosclerosis in Diabetic Mice  

PubMed Central

Objective of the Study Diabetic patients have a much more widespread and aggressive form of atherosclerosis and therefore, higher risk for myocardial infarction, peripheral vascular disease and stroke, but the molecular mechanisms leading to accelerated damage are still unclear. Recently, we showed that hyperglycemia activates the transcription factor NFAT in the arterial wall, inducing the expression of the pro-atherosclerotic protein osteopontin. Here we investigate whether NFAT activation may be a link between diabetes and atherogenesis. Methodology and Principal Findings Streptozotocin (STZ)-induced diabetes in apolipoprotein E?/? mice resulted in 2.2 fold increased aortic atherosclerosis and enhanced pro-inflammatory burden, as evidenced by elevated blood monocytes, endothelial activation- and inflammatory markers in aorta, and pro-inflammatory cytokines in plasma. In vivo treatment with the NFAT blocker A-285222 for 4 weeks completely inhibited the diabetes-induced aggravation of atherosclerosis, having no effect in non-diabetic mice. STZ-treated mice exhibited hyperglycemia and higher plasma cholesterol and triglycerides, but these were unaffected by A-285222. NFAT-dependent transcriptional activity was examined in aorta, spleen, thymus, brain, heart, liver and kidney, but only augmented in the aorta of diabetic mice. A-285222 completely blocked this diabetes-driven NFAT activation, but had no impact on the other organs or on splenocyte proliferation or cytokine secretion, ruling out systemic immunosuppression as the mechanism behind reduced atherosclerosis. Instead, NFAT inhibition effectively reduced IL-6, osteopontin, monocyte chemotactic protein 1, intercellular adhesion molecule 1, CD68 and tissue factor expression in the arterial wall and lowered plasma IL-6 in diabetic mice. Conclusions Targeting NFAT signaling may be a novel and attractive approach for the treatment of diabetic macrovascular complications.

Zetterqvist, Anna V.; Berglund, Lisa M.; Blanco, Fabiana; Garcia-Vaz, Eliana; Wigren, Maria; Duner, Pontus; Andersson, Anna-Maria Dutius; To, Fong; Spegel, Peter; Nilsson, Jan; Bengtsson, Eva; Gomez, Maria F.

2013-01-01

20

HMG-CoA reductase inhibitors suppress maturation of human dendritic cells: new implications for atherosclerosis.  

PubMed

The beneficial effects of statins in atherosclerosis have been partly attributed to their immunomodulating functions. Dendritic cells (DC), which are "professional" antigen-presenting cells, were recently detected in atherosclerotic plaques. It is assumed that DC play a critical role in the immunological processes related to atherosclerosis. Thus, we investigated the effects of statins on maturation and antigen-presenting function of DC. Human monocyte-derived DC were incubated with simvastatin or atorvastatin (1-10microM) for different periods (1-48h), and were subsequently stimulated with a cytokine cocktail (1.25ng/ml TNF-alpha, 1ng/ml Il-1beta, and 0.5microg/ml prostaglandin E(2)) to induce maturation. In contrast to untreated DC, statin-preincubated DC exhibited an immature phenotype and a significantly lower expression of the maturation-associated markers CD83, CD40, CD86, HLA-DR, and CCR7. The inhibitory statin effect was completely reversed by mevalonate or geranylgeranyl pyrophosphate. In addition, preincubation with statins significantly reduced the ability of cytokine-stimulated DC to induce T cell proliferation. In the present study, we have shown that statins inhibit the maturation and antigen-presenting function of human myeloid dendritic cells, thus maybe contributing to their beneficial effects in atherosclerosis. Therefore, the use of statins as immunomodulators might also provide a new therapeutic approach to other immunological disorders. PMID:14709361

Yilmaz, Atilla; Reiss, Christine; Tantawi, Omeima; Weng, Alexander; Stumpf, Christian; Raaz, Dorette; Ludwig, Josef; Berger, Thomas; Steinkasserer, Alexander; Daniel, Werner G; Garlichs, Christoph D

2004-01-01

21

Suppressive effects of cacao polyphenols on the development of atherosclerosis in apolipoprotein E-deficient mice.  

PubMed

Previous studies in humans have shown that the cacao polyphenols, (-)-epicatechin and its oligomers, prevent in vitro and ex vivo low-density lipoprotein oxidation mediated by free radical generators and metal ions and also reduce plasma LDL-cholesterol levels. The aim of this study was to examine the effects of cacao polyphenols on the development of atherosclerosis in apolipoprotein E-deficient (-/-) mice. Mice aged 8 weeks (n = 90) were randomized into three groups, and fed either normal mouse chow (controls) or chow supplemented with 0.25 or 0.40 % cacao polyphenols for 16 weeks. The mean plaque area in cross-sections of the brachiocephalic trunk was measured and found to be lower in the 0.25 % cacao polyphenol group than in the control group (p < 0.05). Pathological observations showed that accumulation of cholesterol crystals in the plaque area was greater in the control group compared with the 0.40 % cacao polyphenol group (p < 0.05). Immunochemical staining in the 0.25 and 0.40 % groups showed that expression of the cell adhesion molecules (VCAM-1 and ICAM-1) and production of oxidative stress markers (4-hydroxynonenal, hexanoyl-lysine, and dityrosine) were reduced in cross-sections of the brachiocephalic trunk. These results suggest that cacao polyphenols inhibit the development of atherosclerosis in apolipoprotein E-deficient (-/-) mice by reducing oxidative stress and inflammatory responses. PMID:24374929

Natsume, Midori; Baba, Seigo

2014-01-01

22

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.

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

2012-01-01

23

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

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

24

Endothelial effects of antihypertensive treatment: focus on irbesartan  

PubMed Central

The endothelium is characterized by a wide range of important homeostatic functions. It participates in the control of hemostasis, blood coagulation and fibrinolysis, platelet and leukocyte interactions with the vessel wall, regulation of vascular tone, and of blood pressure. Many crucial vasoactive endogenous compounds are produced by the endothelial cells to control the functions of vascular smooth muscle cells and of circulating blood cells. These complex systems determine a fine equilibrium which regulates the vascular tone. Impairments in endothelium-dependent vasodilation lead to the so called endothelial dysfunction. Endothelial dysfunction is then characterized by unbalanced concentrations of vasodilating and vasoconstricting factors, the most important being represented by nitric oxide (NO) and angiotensin II (AT II). High angiotensin-converting enzyme (ACE) activity leads to increased AT II generation, reduced NO levels with subsequent vasoconstriction. The net acute effect results in contraction of vascular smooth muscle cells and reduced lumen diameter. Furthermore, when increased ACE activity is chronically sustained, increase in growth, proliferation and differentiation of the vascular smooth muscle cells takes place; at the same time, a decrease in the anti-proliferative action by NO, a decrease in fibinolysis and an increase in platelets aggregation may be observed. AT II is then involved not only in the regulation of blood pressure, but also in vascular inflammation, permeability, smooth muscle cells remodelling, and oxidative stress which in turn lead to atherosclerosis and increased cardiovascular risk. Given the pivotal role exerted by AT II in contributing to alteration of endothelial function, treatment with ACE inhibitors or angiotensin receptor blockers (ARBs) may be of particular interest to restore a physiological activity of endothelial cells. In this view, the blockade of the renin-angiotensin system (RAS), has been shown to positively affect the endothelial function, beyond the antihypertensive action displayed by these compounds. In this review, attention has been specifically focused on an ARB, irbesartan, to examine its effects on endothelial function.

Negro, Roberto

2008-01-01

25

Pioglitazone Suppresses Inflammation In Vivo In Murine Carotid Atherosclerosis: Novel Detection by Dual-Target Fluorescence Molecular Imaging  

PubMed Central

Objective Anti-inflammatory actions of peroxisome proliferator-activated receptor (PPAR)-? agonists such as pioglitazone (PIO) may underlie their reported but incompletely understood repression of atherosclerosis. This molecular imaging study investigated the effects of pioglitazone on plaque matrix metalloproteinase (MMP) and macrophage responses in vivo. Methods and Results In vitro, pioglitazone suppressed MMP-9 mRNA expression in murine peritoneal macrophages (P<0.05). To assess pioglitazone's effects on plaque inflammation, nondiabetic apoE?/? mice on high-cholesterol diet (HCD) received a MMP-activatable fluorescence imaging agent and a spectrally-distinct macrophage-avid fluorescent nanoparticle. After 24 hours, mice underwent survival dual-target intravital fluorescence microscopy (IVFM) of carotid arterial plaques. These mice were then randomized to HCD or HCD+PIO 0.012% for 8 weeks, followed by a second IVFM study of the same carotid plaque. In the HCD group, in vivo MMP and macrophage target-to-background ratios (TBRs) increased similarly (P<0.01 vs. baseline). In contrast, pioglitazone reduced MMP and macrophage TBRs (P<0.01 vs. HCD). Changes in MMP and macrophage signals correlated strongly (r-values?0.75). Microscopy demonstrated MMP and macrophage reductions in pioglitazone-treated mice, as well as a PIO-modulated increase in plaque collagen. Conclusions Serial optical molecular imaging demonstrates that plaque MMP and macrophage activity in vivo intensify with hypercholesterolemia and are reduced by pioglitazone therapy.

Chang, Kiyuk; Francis, Sanjeev A; Aikawa, Elena; Figueiredo, Jose-Luiz; Kohler, Rainer H; McCarthy, Jason R; Weissleder, Ralph; Plutzky, Jorge; Jaffer, Farouc A

2010-01-01

26

Resveratrol, Wine, and Atherosclerosis  

PubMed Central

This review emphasizes the effects of resveratrol on factors involved in the mechanism of atherosclerosis and risk factors for atherosclerosis. The effects of wine and resveratrol on atherosclerosis are also discussed. Resveratrol is a potent antioxidant and an anti-inflammatory agent. It reduces the expression of cell adhesion molecules, monocyte colony stimulating factors, matrix metalloproteinases, and growth factors; and inhibits platelet aggregation and vascular smooth muscle cell proliferation. It reduces the serum levels of total cholesterol, triglycerides (TG), and raises high-density lipoprotein cholesterol, inhibits expression of C-reactive protein and lowers the levels of advanced glycation end products and its receptor in the vascular tissue. It lowers the risk factors for plaque rupture. Epidemiological data show that moderate consumption of alcohol has an inverse association with carotid atherosclerosis while high consumption has a positive association with carotid atherosclerosis. Wine reduces the extent of atherosclerosis in animal model. The antiatherosclerotic effect of wine is mainly due to it resveratrol content. Resveratrol reduces the extent of atherosclerosis in animal model of atherosclerosis (apolipoprotein [Apo] E-deficient and Apo E?/?/low-density lipoprotein receptor-deficient mice and macrophage). In rabbit model of atherosclerosis, both reduction and acceleration of atherosclerosis have been reported with resveratrol. There are no data for regression and slowing of progression of atherosclerosis. Robust clinical trials for suppression of atherosclerosis are lacking. In conclusion, resveratrol has potential but experimental studies in depth and robust clinical trials are lacking for this agent to be of any value in the primary and secondary prevention of coronary and peripheral artery disease.

Prasad, Kailash

2012-01-01

27

Anti-inflammatory effects of a Chinese herbal medicine in atherosclerosis via estrogen receptor ? mediating nitric oxide production and NF-?B suppression in endothelial cells  

PubMed Central

Bu-Shen-Ning-Xin Decoction (BSNXD) administration has alleviated the early pathologic damage of atherosclerosis by inhibiting the adhesion molecule expression and upregulating the estrogen receptor (ER) ? expression in endothelial cells, and increasing the serum nitric oxide (NO) level without any effect on serum lipid status, endometrium and fat deposition in liver in ovariectomized rabbits. The BSNXD-derived serum increases ER ? expression in the human umbilical vein endothelial cells (HUVECs), and decreases malondialdehyde (MDA) production, and upregulates eNOS expression then increases NO synthesis through ER?-dependent pathway. NO not only suppresses the LPS-induced NF-?B transcription in HUVECs, but also decreases apoptosis of endothelial cells. The BSNXD-derived serum decreases monocyte chemoattractant protein-1 production, and suppresses cell adhesion molecules (ICAM-1, VCAM-1 and E-selectin) expression in HUVECs injured by oxidized low-density lipoproteins (ox-LDL), and these effects can be abolished by ER? antagonist (R,RTHC) and NO synthase inhibitor (L-NAME). The BSNXD-derived serum-treated HUVECs supernatant reduces CCR2, LFA-1 and VLA-4 expression in monocytes cell line U937 cells, which in turn inhibits adherence of U937 to injured endothelial cells. NO synthesis increases, and MDA production decreases through ER?-mediated pathway that suppresses apoptosis and NF-?B activity in endothelial cells that downregulates adhesion molecules expression on endothelial cells via ER?/NO/NF-?B pathway, and in turn leukocyte adhesion, which suggests BSNXD potential value in prophylaxis atherosclerosis.

Wang, L; Qiu, X-M; Hao, Q; Li, D-J

2013-01-01

28

Stimulation of ?7 nicotinic acetylcholine receptor by AR-R17779 suppresses atherosclerosis and aortic aneurysm formation in apolipoprotein E-deficient mice.  

PubMed

Atherosclerosis is a chronic inflammatory disease. It has been appreciated that vagus nerve inhibits macrophage activation via ?7 nicotinic acetylcholine receptor (nAChR), termed the cholinergic anti-inflammatory pathway. We explored the effects of AR-R17779, a selective ?7nAChR agonist, on atherosclerosis and aneurysm formation in apolipoprotein E (ApoE)-deficient mice. ApoE-deficient mice were fed a high-fat diet (HFD) and angiotensin II (Ang II) was infused by osmotic minipumps from 10-week-old for 4weeks. AR-R17779 was given in drinking water ad libitum. Oil red O staining of the aorta showed that combined loading of HFD and Ang II induced marked atherosclerosis compared with control mice fed a normal chow. Treatment with AR-R17779 significantly reduced atherosclerotic plaque area and improved survival of mice. Treatment with AR-R17779 also suppressed abdominal aortic aneurysm formation. Quantitative RT-PCR of the aorta revealed that mRNA expression levels of interleukin-1?, interleukin-6 and NOX2 were significantly decreased in AR-R17779-treated mice compared with Ang II+HFD mice. AR-R17779 treatment also reduced blood pressure and serum lipid levels. In conclusion, ?7nAChR activation attenuates atherogenesis and aortic abdominal aneurysm formation in ApoE-deficient mice possibly through an anti-inflammatory effect and reduction of blood pressure and lipid levels. Pharmacological activation of ?7nAChR may have a therapeutic potential against atherosclerotic vascular diseases through multiple mechanisms. PMID:24685818

Hashimoto, Toru; Ichiki, Toshihiro; Watanabe, Aya; Hurt-Camejo, Eva; Michaëlsson, Erik; Ikeda, Jiro; Inoue, Eriko; Matsuura, Hirohide; Tokunou, Tomotake; Kitamoto, Shiro; Sunagawa, Kenji

2014-01-01

29

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.

30

The effects of age and gender on the pharmacokinetics of irbesartan  

PubMed Central

Aims Single dose pharmacokinetics and safety of irbesartan, an angiotensin II receptor antagonist, were evaluated in healthy young and elderly male and female subjects. Methods Irbesartan was administered as two 25 mg capsules after a 10 h fast to 12 young men, 12 young women, 12 elderly men and 12 elderly women. Serial blood and urine sample were collected up to 96 h after the dose. Plasma and urine samples were analysed for irbesartan by h.p.l.c./fluorescence methods. Results No statistically significant gender effects were observed in peak plasma concentration (Cmax), area under the curve (AUC), and terminal elimination half-life (t1/2) of irbesartan. The geometric mean AUC and Cmax increased by about 43% and 49%, respectively, in the elderly subjects. Also the time to peak was significantly shorter in the elderly subjects compared with that observed in the young subjects. Renal clearance of irbesartan was significantly reduced in the elderly females but this reduction is not likely to be of any clinical relevance since less than 3% of the administered dose of irbesartan is excreted unchanged in the urine. Conclusions Although there was an effect of age on the pharmacokinetics of irbesartan, based on the safety and efficacy profile, no adjustment in irbesartan dosage is necessary with respect to age or gender.

Vachharajani, Nimish N; Shyu, Wen Chyi; Smith, Robert A; Greene, Douglas S

1998-01-01

31

A Deficiency of Herp, an Endoplasmic Reticulum Stress Protein, Suppresses Atherosclerosis in ApoE Knockout Mice by Attenuating Inflammatory Responses  

PubMed Central

Herp was originally identified as an endoplasmic reticulum (ER) stress protein in vascular endothelial cells. ER stress is induced in atherosclerotic lesions, but it is not known whether Herp plays any role in the development of atherosclerosis. To address this question, we generated Herp- and apolipoprotein E (apoE)-deficient mice (Herp?/?; apoE?/? mice) by crossbreeding Herp?/? mice and apoE?/? mice. Herp was expressed in the endothelial cells and medial smooth muscle cells of the aorta, as well as in a subset of macrophages in the atherosclerotic lesions in apoE?/? mice, while there was no expression of Herp in the Herp?/?; apoE?/? mice. The doubly deficient mice developed significantly fewer atherosclerotic lesions than the apoE?/? mice at 36 and 72 weeks of age, whereas the plasma levels of cholesterol and triglycerides were not significantly different between the strains. The plasma levels of non-esterified fatty acids were significantly lower in the Herp?/?; apoE?/? mice when they were eight and 16 weeks old. The gene expression levels of ER stress response proteins (GRP78 and CHOP) and inflammatory cytokines (IL-1?, IL-6, TNF-? and MCP-1) in the aorta were significantly lower in Herp?/?; apoE?/? mice than in apoE?/? mice, suggesting that Herp mediated ER stress-induced inflammation. In fact, peritoneal macrophages isolated from Herp-deficient mice and RAW264.7 macrophages in which Herp was eliminated with a siRNA expressed lower levels of mRNA for inflammatory cytokines when they were treated with tunicamycin. Herp deficiency affected the major mediators of the unfolded protein response, including IRE1 and PERK, but not ATF6. These findings suggest that a deficiency of Herp suppressed the development of atherosclerosis by attenuating the ER stress-induced inflammatory reactions.

Shinozaki, Shohei; Chiba, Tsuyoshi; Kokame, Koichi; Miyata, Toshiyuki; Kaneko, Eiji; Shimokado, Kentaro

2013-01-01

32

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

33

Quantitation of irbesartan and major proteins in human plasma by mass spectrometry with time-of-flight analyzer  

Microsoft Academic Search

A simple matrix-assisted laser desorption\\/ionization time-of-flight mass spectrometry (MALDI-TOF MS) method was developed to analyze irbesartan in human plasma. Irbesartan is a kind of angiotensin II receptor blocker (ARB) and is used as an antihypertensive drug. MALDI-TOF MS is a rare application for clinical drug analysis in human plasma. After simple micro-liquid–liquid extraction, irbesartan-containing supernatant was spotted on a target

Chi-Yu Lu; Chia-Hsien Feng

2011-01-01

34

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.

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

2014-01-01

35

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

36

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

37

Effects of irbesartan on serum uric acid levels in patients with hypertension and diabetes  

PubMed Central

Background Hyperuricemia has been proposed to be a risk factor for cardiovascular disease and chronic kidney disease. Since diabetes is often complicated by hypertension and hyperuricemia, efficient therapeutic strategy against these two complications is very important in diabetic treatment. It has been reported that the antihypertensive drug, irbesartan, inhibits the renal uric acid reabsorptive transporters, URAT1 and GLUT9; this result suggests that irbesartan decreases serum uric acid level (SUA). Subjects and methods A retrospective study of 107 patients with hypertension and diabetes was performed to analyze the effects of irbesartan on blood pressure, estimated glomerular filtration rate (eGFR), and SUA. The follow-up period was 6–12 months. Seventy percent of the patients were diagnosed with diabetic nephropathy stage II–IV. We excluded patients treated with drugs that influenced SUA. The multiple logistic regression analysis was introduced to identify the relative factors for SUA decline. The time-dependent SUA changes were examined in a mixed-linear model. Results Irbesartan reduced blood pressure significantly after 1, 6, and 12 months’ treatment. No subject showed significant change in eGFR from baseline level throughout the period. The multiple logistic regression analysis revealed that SUA baseline significantly influenced SUA decline after 6–12 months. In patients whose SUA baseline was ?5.9 mg/dL, the SUA was significantly decreased from 6.6±0.16 mg/dL to 6.2±0.16 mg/dL (P=0.010), after 12 months’ irbesartan treatment. In the SUA baseline <5.9 mg/dL group, the SUA did not show significant change over the monitoring period. Conclusion Our results demonstrate that irbesartan reduces the risk of hyperuricemia. No decline in renal function was observed after the initiation of irbesartan treatment. The present report determines the criteria of SUA baseline for introducing an antihyperuricemic effect using irbesartan. Its antihypertensive effect coupled with SUA decline would be effective for the treatment of hypertension complicated by hyperuricemia.

Nakamura, Makiko; Sasai, Nobuo; Hisatome, Ichiro; Ichida, Kimiyoshi

2014-01-01

38

Effects of emodin and irbesartan on ventricular fibrosis in Goldblatt hypertensive rats.  

PubMed

Left ventricular (LV) fibrosis is one of the most prominent pathophysiological results of hypertension. We initiated this study to investigate the effects and mechanisms of emodin and its combination with irbesartan on LV fibrosis in Goldblatt (2K1C) hypertensive rats. Goldblatt hypertension rats were prepared by two kidney one clip (2K1C) operations and then treated with either emodin, irbesartan or their combination. As a result, the systolic blood pressure (SBP) and the left ventricular mass index (LVMI) increased significantly (P < or = 0.05) in all 2K1C rats. After drugs treatment, irbesartan and the drug combination remarkably decreased SBP, LVMI, contents of angiotensinII (AngII), hydroxyproline and collagen, the mRNA and protein expression levels of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) (P < or = 0.05). As for the emodin, LVMI, contents of hydroxyproline and collagen, and MMP-2 and TIMP-2 expression were found to decrease significantly; however, the SBP and AngII contents stayed stable within certain extent. Therefore, emodin, irbesartan or two drugs together can potentially inhibit the ventricular fibrosis in Goldblatt hypertensive rats by reducing MMP-2 and TIMP-2 expression. Furthermore, the combination of these two drugs may provide a better anti-fibrosis effect than the single application. PMID:24855831

Chen, Qiang; Pang, Lingpin; Huang, Shian; Lei, Wei; Huang, Dangsheng

2014-05-01

39

An economic evaluation of the Irbesartan in Diabetic Nephropathy Trial (IDNT) in a UK setting  

Microsoft Academic Search

There are substantial healthcare costs associated with the provision of renal replacement therapy. Patients with diabetes mellitus are the largest and fastest growing group developing end-stage renal disease (ESRD) in the United Kingdom (UK). Treatment leading to a slowing of progression to ESRD in diabetic patients could lead to considerable cost savings. Using treatment-specific probabilities derived from the Irbesartan in

A J Palmer; L Annemans; S Roze; M Lamotte; R A Rodby; R W Bilous

2004-01-01

40

Regulatory T cells and Atherosclerosis  

PubMed Central

Atherosclerosis is a chronic autoimmune inflammatory disease. The involvement of both innate and adaptive immune responses in the pathogenesis of the disease has been well recognized. Tregs are an essential part of the immune system and have indispensable functions in maintaining immune system homeostasis, mediating peripheral tolerance, preventing autoimmune diseases, and suppressing inflammatory and proatherogenic immune response. Tregs carry out their immunosuppressive functions via several mechansims. One of the well-documented suppressive mechanisms of Tregs is the secretion of anti-inflammatory cytokines including IL-10, TGF-?, and IL-35. Studies have found that IL-10 and TGF-? have atheroprotective properties. In addition, Tregs can suppress the activity of proatherogenic effector T cells, suggesting an atheroprotective role. In fact, fewer Tregs are found in atherogenic ApoE?/? mice comparing to wild-type mice, suggesting an uncontrolled balance between weakened Tregs and effector T cells in atherogenesis. Some clinical studies of autoimmune diseases also suggest that decreased Tregs numbers are associated with increased disease activity. The importance of Tregs in many autoimmune diseases and experimental atherosclerosis has been established in in vivo and in vitro studies. However, the roles of Tregs in atherosclerosis in the clinical setting remains to be further characterized.

Pastrana, Jahaira Lopez; Sha, Xiaojin; Virtue, Anthony; Mai, Jietang; Cueto, Ramon; Lee, In Ae; Wang, Hong; Yang, Xiao-feng

2013-01-01

41

Atherosclerosis Prevention in Youth  

PubMed Central

Atherosclerosis-associated circulatory disturbance is one of the most important global issues. In patients with atherosclerosis, eccentric intimal thickening and lipid deposition progress over a long period (at least 20 to 30 years). On the other hand, in patients with atherosclerosis-associated circulatory disturbance represented by myocardial infarction, the direct cause of death is thrombus formation rather than marked stenosis; wall destruction may lead to a fatal outcome. In the future, atherosclerosis susceptibility, that is, intrinsic genes, should be investigated.

2012-01-01

42

Atherosclerosis and Physical Activity  

PubMed Central

Atherosclerosis and coronary heart disease have been considered as major health problem worldwide. Abnormalities in lipids and lipoprotein metabolism and impairment of endothelial function have been implicated as the main contributing factors in atherosclerosis and its progression. Physical activity has been recognized as a preventive measure for atherosclerosis.

Al-Mamari, Ali

2009-01-01

43

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

44

[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

45

Dendritic cells in atherosclerosis  

PubMed Central

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.

Tabas, Ira

2013-01-01

46

Atherosclerosis in transplant heart.  

PubMed

Graft atherosclerosis in the transplant heart is essentially asymptomatic due to denervation of the transplant heart and also is rapidly progressive. After one year it is the major cause of transplant rejection. Histopathologically, graft atherosclerosis differs from the conventional atherosclerosis. Intra-vascular ultrasound and repeated coronary angiography help in its early diagnosis. Angioplasty and bypass graft surgery are not of much help. Preventive measures through dietary means to keep triglycerides under control and prophylactic use of calcium channel blocker, diltiazem are rewarding. Many patients with graft coronary atherosclerosis end up with retransplant. PMID:9251401

Sharada, B; Wasir, H S

1996-04-01

47

WIP-ing out atherosclerosis with autophagy.  

PubMed

Atherosclerosis commonly causes coronary and cerebrovascular diseases, which are major morbidities worldwide. Controlling these conditions remains a challenge owing to an incomplete understanding of underlying molecular mechanisms. We have recently shown that PPM1D/WIP1 phosphatase plays a crucial role in regulating atherosclerosis in mice. Deletion of Ppm1d results in the suppression of lipid droplet accumulation in macrophages, which prevents the formation of foam cells, and ultimately the development of atherosclerotic plaques. This process is controlled by the ATM-MTOR pathway and depends on the activation of selective autophagy to regulate cholesterol efflux from macrophage foam cells. Our data suggest that modulating autophagy through the PPM1D-ATM-MTOR pathway may be beneficial at both early and advanced stages of atherosclerosis. PMID:22895013

Brichkina, Anna; Bulavin, Dmitry V

2012-10-01

48

Irbesartan Ameliorates Diabetic Nephropathy by Reducing the Expression of Connective Tissue Growth Factor and Alpha-Smooth-Muscle Actin in the Tubulointerstitium of Diabetic Rats  

Microsoft Academic Search

The effect of irbesartan on the expression of connective tissue growth factor (CTGF) and ?-smooth-muscle actin (?-SMA) in the renal tubulointerstitium of diabetic rats was investigated in our study. Diabetes was induced in male Wistar rats by intraperitoneal administration of streptozotocin (STZ), 60 mg·kg–1 body weight. The rats were then randomized to a diabetic group (DM) and an irbesartan therapy

Xiaojun Ren; Guangju Guan; Gang Liu; Gaohong Liu

2009-01-01

49

Individual and joint association of ?1A-adrenergic receptor Arg347Cys polymorphism and plasma irbesartan concentration with blood pressure therapeutic response in Chinese hypertensive subjects  

Microsoft Academic Search

Background: Individual variability in the therapeutic response to an antihypertensive drug could have a genetic basis. We investigated whether the ?1A-adrenergic receptor (?1A-AR) Arg347Cys polymorphism is associated with the blood pressure (BP) therapeutic response to irbesartan and whether the association could be altered by the plasma irbesartan level.Methods: A total of 696 hypertensive subjects were treated with a daily oral

Shanqun Jiang; Guangyun Mao; Shanchun Zhang; Xiumei Hong; Genfu Tang; Zhiping Li; Xue Liu; Yan Zhang; Binyan Wang; Xiping Xu; Xiaobin Wang

2005-01-01

50

Renal Effects of Aliskiren Compared With and in Combination With Irbesartan in Patients With Type 2 Diabetes, Hypertension, and Albuminuria  

PubMed Central

OBJECTIVE We investigated whether the antiproteinuric effect of the direct renin inhibitor aliskiren is comparable to that of irbesartan and the effect of the combination. RESEARCH DESIGN AND METHODS This was a double-blind, randomized, crossover trial. After a 1-month washout period, 26 patients with type 2 diabetes, hypertension, and albuminuria (>100 mg/day) were randomly assigned to four 2-month treatment periods in random order with placebo, 300 mg aliskiren once daily, 300 mg irbesartan once daily, or the combination using identical doses. Patients received furosemide in a stable dose throughout the study. The primary end point was a change in albuminuria. Secondary measures included change in 24-h blood pressure and glomerular filtration rate (GFR). RESULTS Placebo geometric mean albuminuria was 258 mg/day (range 84–2,361), mean ± SD 24-h blood pressure was 140/73 ± 15/8 mmHg, and GFR was 89 ± 27 ml/min per 1.73 m2. Aliskiren treatment reduced albuminuria by 48% (95% CI 27–62) compared with placebo (P < 0.001), not significantly different from the 58% (42–79) reduction with irbesartan treatment (P < 0.001 vs. placebo). Combination treatment reduced albuminuria by 71% (59–79), more than either monotherapy (P < 0.001 and P = 0.028). Fractional clearances of albumin were significantly reduced (46, 56, and 67% reduction vs. placebo). Twenty-four-hour blood pressure was reduced 3/4 mmHg by aliskiren (NS/P = 0.009), 12/5 mmHg by irbesartan (P < 0.001/P = 0.002), and 10/6 mmHg by the combination (P = 0.001/P < 0.001). GFR was significantly reduced 4.6 (95% CI 0.3–8.8) ml/min per 1.73 m2 by aliskiren, 8.0 (3.6–12.3) ml/min per 1.73 m2 by irbesartan, and 11.7 (7.4–15.9) ml/min per 1.73 m2 by the combination. CONCLUSIONS The combination of aliskiren and irbesartan is more antiproteinuric in type 2 diabetic patients with albuminuria than monotherapy.

Persson, Frederik; Rossing, Peter; Reinhard, Henrik; Juhl, Tina; Stehouwer, Coen D.A.; Schalkwijk, Casper; Danser, A.H. Jan; Boomsma, Frans; Frandsen, Erik; Parving, Hans-Henrik

2009-01-01

51

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.

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

2014-01-01

52

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

53

CYP2C9*3 allelic variant is associated with metabolism of irbesartan in Chinese population  

Microsoft Academic Search

Objective  There is considerable variability in the individual pharmaceutical dosages required to achieve optimal therapeutic effects,\\u000a which may be due to environmental or genetic factors. The objective of this study was to test the presence of the CYP2C9*3 allelic variant in the Chinese population and to investigate the association of this variant with both metabolism and therapeutic\\u000a efficacy of irbesartan on

Xiumei Hong; Shanchun Zhang; Guangyun Mao; Shanqun Jiang; Yan Zhang; Yunxian Yu; Genfu Tang; Houxun Xing; Xiping Xu

2005-01-01

54

Chitinase Inhibition Promotes Atherosclerosis in Hyperlipidemic Mice  

PubMed Central

Chitinase 1 (CHIT1) is secreted by activated macrophages. Chitinase activity is raised in atherosclerotic patient sera and is present in atherosclerotic plaque. However, the role of CHIT1 in atherosclerosis is unknown. Preliminary studies of atherosclerosis in cynomolgous monkeys revealed CHIT1 to be closely correlated with areas of macrophage infiltration. Thus, we investigated the effects of a chitinase inhibitor, allosamidin, on macrophage function in vitro and on atherosclerotic development in vivo. In RAW264.7 cells, allosamidin elevated monocyte chemoattractant protein 1 and tumor necrosis factor alpha expression, and increased activator protein 1 and nuclear factor-?B transcriptional activity. Although inducible nitric oxide synthase, IL-6, and IL-1? expression were increased, Arg1 expression was decreased by chitinase inhibition, suggesting that suppression of CHIT1 activity polarizes macrophages into a M1 phenotype. Allosamidin decreased scavenger receptor AI, CD36, ABCA1, and ABCG1 expression which led to suppression of cholesterol uptake and apolipoprotein AI-mediated cholesterol efflux in macrophages. These effects were confirmed with CHIT1 siRNA transfection and CHIT1 plasmid transfection experiments in primary macrophages. Apolipoprotein E-deficient hyperlipidemic mice treated for 6 weeks with constant administration of allosamidin and fed an atherogenic diet showed aggravated atherosclerotic lesion formation. These data suggest that CHIT1 exerts protective effects against atherosclerosis by suppressing inflammatory responses and polarizing macrophages toward an M2 phenotype, and promoting lipid uptake and cholesterol efflux in macrophages.

Kitamoto, Shiro; Egashira, Kensuke; Ichiki, Toshihiro; Han, Xinbing; McCurdy, Sara; Sakuda, Shohei; Sunagawa, Kenji; Boisvert, William A.

2014-01-01

55

Who Is at Risk for Atherosclerosis?  

MedlinePLUS

... NHLBI on Twitter. Who Is at Risk for Atherosclerosis? Coronary heart disease (atherosclerosis of the coronary arteries) ... role in atherosclerosis risk. Other Factors That Affect Atherosclerosis Other factors also may raise your risk for ...

56

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.

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

2013-01-01

57

The UPR in atherosclerosis  

PubMed Central

Multiple systemic factors and local stressors in the arterial wall can disturb the functions of endoplasmic reticulum (ER), causing ER stress in endothelial cells (ECs), smooth muscle cells (SMCs), and macrophages during the initiation and progression of atherosclerosis. As a protective response to restore ER homeostasis, the unfolded protein response (UPR) is initiated by three major ER sensors: protein kinase RNA-like ER kinase (PERK), inositol-requiring protein 1? (IRE1?), and activating transcription factor 6 (ATF6). The activation of the various UPR signaling pathways displays a temporal pattern of activation at different stages of the disease. The ATF6 and IRE1? pathways that promote the expression of protein chaperones in ER are activated in ECs in athero-susceptible regions of prelesional arteries and before the appearance of foam cells. The PERK pathway that reduces ER protein client load by blocking protein translation is activated in SMCs and macrophages in early lesions. The activation of these UPR signaling pathways aims to cope with the ER stress and plays a pro-survival role in the early stage of atherosclerosis. However, with the progression of atherosclerosis, the extended duration and increased intensity of ER stress in lesions lead to prolonged and enhanced UPR signaling. Under this circumstance, the PERK pathway induces expression of death effectors, and possibly IRE1? activates apoptosis signaling pathways, leading to apoptosis of macrophages and SMCs in advanced lesions. Importantly, UPR-mediated cell death is associated with plaque instability and the clinical progression of atherosclerosis. Moreover, UPR signaling is linked to inflammation and possibly to macrophage differentiation in lesions. Therapeutic approaches targeting the UPR may have promise in the prevention and/or regression of atherosclerosis. However, more progress is needed to fully understand all of the roles of the UPR in atherosclerosis and to harness this information for therapeutic advances.

Zhou, Alex X.; Tabas, Ira

2014-01-01

58

Imaging of Atherosclerosis  

PubMed Central

It is now well recognized that the atherosclerotic plaques responsible for thrombus formation are not necessarily those that impinge most on the lumen of the vessel. Nevertheless, clinical investigations for atherosclerosis still focus on quantifying the degree of stenosis caused by plaques. Many of the features associated with a high-risk plaque, including a thin fibrous cap, large necrotic core, macrophage infiltration, neovascularization, and intraplaque hemorrhage, can now be probed by novel imaging techniques. Each technique has its own strengths and drawbacks. In this article, we review the various imaging modalities used for the evaluation and quantification of atherosclerosis.

Owen, D.R.J.; Lindsay, A.C.; Choudhury, R.P.; Fayad, Z.A.

2014-01-01

59

Insulin resistance and atherosclerosis  

PubMed Central

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.

Semenkovich, Clay F.

2006-01-01

60

Wip1-dependent regulation of autophagy, obesity, and atherosclerosis.  

PubMed

Obesity and atherosclerosis-related diseases account for over one-third of deaths in the western world. Controlling these conditions remains a major challenge due to an incomplete understanding of the molecular pathways involved. Here, we show that Wip1 phosphatase, a known negative regulator of Atm-dependent signaling, plays a major role in controlling fat accumulation and atherosclerosis in mice; specifically, Wip1 deficiency prevents both conditions. In the course of atherosclerosis, deletion of Wip1 results in suppression of macrophage conversion into foam cells, thus preventing the formation of atherosclerotic plaques. This process appears to be independent of p53 but rely on a noncanonical Atm-mTOR signaling pathway and on selective autophagy in regulation of cholesterol efflux. We propose that the Wip1-dependent control of autophagy and cholesterol efflux may provide avenues for treating obesity and atherosclerosis. PMID:22768840

Le Guezennec, Xavier; Brichkina, Anna; Huang, Yi-Fu; Kostromina, Elena; Han, Weiping; Bulavin, Dmitry V

2012-07-01

61

Inulin and poly(acrylic acid) grafted inulin for dissolution enhancement and preliminary controlled release of poorly water-soluble Irbesartan drug.  

PubMed

In this article, inulin and poly(acrylic acid) grafted inulin copolymer were used to enhance the dissolution of poorly water-soluble Irbesartan drug and to control its drug release rate, respectively. Topological structure of inulin showed sleazy separable flower-like platelets and granules accumulated above each other, which adapt it to physically bind Irbesartan drug and enhance its dissolution. Consequently, the increase of inulin content in the polymeric matrix was found to increase the drug dissolution gradually until it reaches its maximum (?90%) within the first 60 min. The release rate had followed zero-order transport mechanism. On the other hand, the poly(acrylic acid) grafted inulin copolymer, characterized using (1)H NMR, FTIR, TGA, and SEM techniques, was found to form highly consistent amorphous systems of two-dimensional surfaces with some voids topology. Such features adapted it to control Irbesartan drug dissolution (?33%) and show Fickian diffusion mechanism. PMID:21421037

Fares, Mohammad M; Salem, Mu'taz Sheikh; Khanfar, Mai

2011-05-30

62

Non-coronary atherosclerosis.  

PubMed

During the last decades, the clinical and research interest in atherosclerosis has been mostly focused on coronary arteries. After the publications of the European Society Guidelines and AHA/ACC Guidelines on Peripheral artery diseases, and of the Registry REduction in Atherothrombosis for Continued Health Registry, there has been an increased interest in atherosclerosis of the lower extremity arteries and its presence in multifocal disease. However, awareness in the general population and the medical community of non-coronary artery diseases, and of its major prognostic implications remain relatively low. The aim of this general review stemming out of an ESC Working Group on Peripheral Circulation meeting in 2011 is to enhance awareness of this complex disease highlighting the importance of the involvement of atherosclerosis at different levels with respect to clinical presentation, diagnosis, and co-existence of the disease in the distinct arterial territories. We also emphasize the need of an interdisciplinary approach to face the broad and complex spectrum of multifocal disease, and try to propose a series of tentative recommendations and measures to be implemented in non-coronary atherosclerosis. PMID:24595865

Gallino, Augusto; Aboyans, Victor; Diehm, Curt; Cosentino, Francesco; Stricker, Hans; Falk, Erling; Schouten, Olaf; Lekakis, John; Amann-Vesti, Beatrice; Siclari, Francesco; Poredos, Pavel; Novo, Salvatore; Brodmann, Marianne; Schulte, Karl-Ludwig; Vlachopoulos, Charalambos; De Caterina, Raffaele; Libby, Peter; Baumgartner, Iris

2014-05-01

63

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); Pierre Fontana (University of Geneva); Anne Angelillo-Scherrer (University of Lausanne)

2009-02-01

64

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

65

Soy, Isoflavones and Atherosclerosis  

Microsoft Academic Search

Consumption of soy protein is associated with a lower risk of cardiovascular disease in man, and reduced atherosclerosis in a variety of experimental animals. Although a portion of the cardiovascular protective effects appears to be due to reductions in plasma lipoprotein concentration, in most people the magnitude of this effect is relatively small. In many, but not all studies using

R. Clair; M. Anthony

66

Pharmacokinetics and bioequivalence study of irbesartan tablets after a single oral dose of 300 mg in healthy Thai volunteers.  

PubMed

Objective: Pharmacokinetics and bioequivalence of 300 mg irbesartan tablets were studied in 26 healthy Thai male volunteers. Methods: A single oral dose of one 300 mg tablet of the test product and the reference product was given to each volunteer according to a randomized two-way crossover design with 1-week wash out period. Blood samples were collected at predetermined time intervals until 72 hours post dose and irbesartan concentration was quantified with a validated HPLC method. Individual plasma irbesartan concentration-time profile was analyzed for pharmacokinetic parameters. Results: Maximum plasma concentrations (Cmax) of 3,617.19 and 3,295.77 ng/mL for test and reference, respectively, were achieved. Areas under the plasma concentration-time curve; AUC0-t and AUC0-? were 15,304.65 and 15,638.90 ng×h/mL for test and 15,389.21 and 15,730.34 ng×h/mL for reference. The median tmax was 1.50 hours and 1.25 hours for test and reference, respectively. Plasma elimination half-lives (t1/2) were 7.35 hours and 8.09 hours for test and reference, respectively. Primary pharmacokinetic parameters Cmax, AUC0-t, and AUC0-? were tested parametrically by analysis of variance (ANOVA), and it revealed no statistically significant difference (defined as p < 0.05) between the corresponding Cmax, AUC0-t, and AUC0-? with respect to sequence, volunteers, period and formulation. The 90% confidence intervals for the ratio of test and reference product of the parameters Cmax, AUC0-t, and AUC0-? were within 80 - 125% (100.13 - 121.40% for Cmax, 90.83 - 106.86% for AUC0-t and 91.11 - 106.55% for AUC0-?). Conclusion: The two products were bioequivalent in terms of both rate and extent of drug absorption into systemic circulation. PMID:24725445

Wittayalertpanya, Supeecha; Chariyavilaskul, Pajaree; Prompila, Nantaporn; Sayankuldilok, Nonlanee; Eiamart, Wanna

2014-05-01

67

Macrophage death and defective inflammation resolution in atherosclerosis  

Microsoft Academic Search

A key event in atherosclerosis is a maladaptive inflammatory response to subendothelial lipoproteins. A crucial aspect of this response is a failure to resolve inflammation, which normally involves the suppression of inflammatory cell influx, effective clearance of apoptotic cells and promotion of inflammatory cell egress. Defects in these processes promote the progression of atherosclerotic lesions into dangerous plaques, which can

Ira Tabas

2009-01-01

68

Myocardial infarction accelerates atherosclerosis  

PubMed Central

SUMMARY During progression of atherosclerosis, myeloid cells destabilize lipid-rich plaque in the arterial wall and cause its rupture, thus triggering myocardial infarction and stroke. Survivors of acute coronary syndromes have a high risk of recurrent events for unknown reasons. Here we show that the systemic response to ischemic injury aggravates chronic atherosclerosis. After myocardial infarction or stroke, apoE?/? mice developed larger atherosclerotic lesions with a more advanced morphology. This disease acceleration persisted over many weeks and was associated with markedly increased monocyte recruitment. When seeking the source of surplus monocytes in plaque, we found that myocardial infarction liberated hematopoietic stem and progenitor cells from bone marrow niches via sympathetic nervous system signaling. The progenitors then seeded the spleen yielding a sustained boost in monocyte production. These observations provide new mechanistic insight into atherogenesis and provide a novel therapeutic opportunity to mitigate disease progression.

Dutta, Partha; Courties, Gabriel; Wei, Ying; Leuschner, Florian; Gorbatov, Rostic; Robbins, Clinton; Iwamoto, Yoshiko; Thompson, Brian; Carlson, Alicia L.; Heidt, Timo; Majmudar, Maulik D.; Lasitschka, Felix; Etzrodt, Martin; Waterman, Peter; Waring, Michael T.; Chicoine, Adam T.; van der Laan, Anja M.; Niessen, Hans W.M.; Piek, Jan J.; Rubin, Barry B.; Butany, Jagdish; Stone, James; Katus, Hugo A.; Murphy, Sabina A.; Morrow, David A.; Sabatine, Marc S.; Vinegoni, Claudio; Moskowitz, Michael A.; Pittet, Mikael J.; Libby, Peter; Lin, Charles P.; Swirski, Filip K.; Weissleder, Ralph; Nahrendorf, Matthias

2012-01-01

69

Genetic Susceptibility to Atherosclerosis  

PubMed Central

Atherosclerosis is a complex multifocal arterial disease involving interactions of multiple genetic and environmental factors. Advances in techniques of molecular genetics have revealed that genetic ground significantly influences susceptibility to atherosclerotic vascular diseases. Besides further investigations of monogenetic diseases, candidate genes, genetic polymorphisms, and susceptibility loci associated with atherosclerotic diseases have been identified in recent years, and their number is rapidly increasing. This paper discusses main genetic investigations fields associated with human atherosclerotic vascular diseases. The paper concludes with a discussion of the directions and implications of future genetic research in arteriosclerosis with an emphasis on prospective prediction from an early age of individuals who are predisposed to develop premature atherosclerosis as well as to facilitate the discovery of novel drug targets.

Kovacic, Sanja; Bakran, Mirjana

2012-01-01

70

Shear Stress and Atherosclerosis  

PubMed Central

Hemodynamic shear stress, the frictional force acting on vascular endothelial cells, is crucial for endothelial homeostasis under normal physiological conditions. When discussing blood flow effects on various forms of endothelial (dys)function, one considers two flow patterns: steady laminar flow and disturbed flow because endothelial cells respond differently to these flow types both in vivo and in vitro. Laminar flow which exerts steady laminar shear stress is atheroprotective while disturbed flow creates an atheroprone environment. Emerging evidence has provided new insights into the cellular mechanisms of flow-dependent regulation of vascular function that leads to cardiovascular events such as atherosclerosis, atherothrombosis, and myocardial infarction. In order to study effects of shear stress and different types of flow, various models have been used. In this review, we will summarize our current views on how disturbed flow-mediated signaling pathways are involved in the development of atherosclerosis.

Heo, Kyung-Sun; Fujiwara, Keigi; Abe, Jun-ichi

2014-01-01

71

Myocardial infarction accelerates atherosclerosis.  

PubMed

During progression of atherosclerosis, myeloid cells destabilize lipid-rich plaques in the arterial wall and cause their rupture, thus triggering myocardial infarction and stroke. Survivors of acute coronary syndromes have a high risk of recurrent events for unknown reasons. Here we show that the systemic response to ischaemic injury aggravates chronic atherosclerosis. After myocardial infarction or stroke, Apoe-/- mice developed larger atherosclerotic lesions with a more advanced morphology. This disease acceleration persisted over many weeks and was associated with markedly increased monocyte recruitment. Seeking the source of surplus monocytes in plaques, we found that myocardial infarction liberated haematopoietic stem and progenitor cells from bone marrow niches via sympathetic nervous system signalling. The progenitors then seeded the spleen, yielding a sustained boost in monocyte production. These observations provide new mechanistic insight into atherogenesis and provide a novel therapeutic opportunity to mitigate disease progression. PMID:22763456

Dutta, Partha; Courties, Gabriel; Wei, Ying; Leuschner, Florian; Gorbatov, Rostic; Robbins, Clinton S; Iwamoto, Yoshiko; Thompson, Brian; Carlson, Alicia L; Heidt, Timo; Majmudar, Maulik D; Lasitschka, Felix; Etzrodt, Martin; Waterman, Peter; Waring, Michael T; Chicoine, Adam T; van der Laan, Anja M; Niessen, Hans W M; Piek, Jan J; Rubin, Barry B; Butany, Jagdish; Stone, James R; Katus, Hugo A; Murphy, Sabina A; Morrow, David A; Sabatine, Marc S; Vinegoni, Claudio; Moskowitz, Michael A; Pittet, Mikael J; Libby, Peter; Lin, Charles P; Swirski, Filip K; Weissleder, Ralph; Nahrendorf, Matthias

2012-07-19

72

Cardiac and Renal Protective Effects of Irbesartan via Peroxisome Proliferator-Activated Receptor?-Hepatocyte Growth Factor Pathway Independent of Angiotensin II Type 1a Receptor Blockade in Mouse Model of Salt-Sensitive Hypertension  

PubMed Central

Background “Aldosterone breakthrough” observed in patients receiving long?term treatment with angiotensin blockade is strongly associated with increased risk of left ventricular hypertrophy, poor exercise capacity, refractory proteinuria, and declining glomerular filtration rate through the profibrotic actions of aldosterone. To overcome aldosterone breakthrough, we examined the additional organ?protective actions of irbesartan, because irbesartan is an angiotensin II type 1 receptor (AT1R) blocker (ARB) with peroxisome proliferator?activated receptor (PPAR)? agonistic effects, which mediate organ?protective effects independent of AT1R blockade. In this study, we examined the organ?protective effects of irbesartan in a salt?sensitive hypertension model using AT1aR knockout mice. Methods and Results Aldosterone and 1% NaCl treatment resulted in a significant increase in severe cardiac and renal fibrosis. Irbesartan, but not losartan, significantly reduced renal fibrosis, glomerular injury through inhibition of macrophage infiltration, epithelial–mesenchymal transition, and oxidative stress. Similarly, cardiac fibrosis and myocyte hypertrophy were decreased by irbesartan, but not losartan, treatment, associated with a significant reduction in oxidative stress. Importantly, anti–hepatocyte growth factor (HGF) neutralizing antibody and a PPAR? antagonist (GW9662) attenuated these organ?protective effects of irbesartan. HGF protein level was increased by irbesartan, especially in the kidney and heart, while GW9662 treatment inhibited the increase in HGF level. Conclusions In this study, we showed that irbesartan, which has not only AT1aR?blocking effects, but also PPAR? agonistic effects accompanied by HGF expression, inhibited organ damage by aldosterone and salt treatment. Second?generation ARBs such as irbesartan, which has the dual actions of AT1R blockade and PPAR? activation, may have clinical value for the treatment of hypertensive patients with aldosterone breakthrough.

Kusunoki, Hiroshi; Taniyama, Yoshiaki; Rakugi, Hiromi; Morishita, Ryuichi

2013-01-01

73

Immunization for atherosclerosis  

Microsoft Academic Search

This review summarizes experimental findings that highlight the complex roles of the immune system in atherogenesis. Immune\\u000a activation can have either proatherogenic or atheroprotective effects. Immune-modulation therapy via an active or passive\\u000a immunization strategy aims to exploit the atheroprotective aspects of the immune system to modulate atherosclerosis. Several\\u000a experimental studies have demonstrated that such an approach is feasible and effective,

Kuang-Yuh Chyu; Jan Nilsson; Prediman K. Shah

2007-01-01

74

Atherosclerosis induced by arsenic in drinking water in rats through altering lipid metabolism  

SciTech Connect

Arsenic in drinking water is a global environmental health problem, and the exposure may increase cardiovascular and cerebrovascular diseases mortalities, most likely through causing atherosclerosis. However, the mechanism of atherosclerosis formation after arsenic exposure is still unclear. To study the mechanism of atherosclerosis formation after arsenic exposure and explore the role of high cholesterol diet (HCD) in this process, we fed spontaneous hypertensive rats and Wistar Kyoto rats with basal diet or HCD and provided with them drinking water containing arsenic at different ages and orders for 20 consecutive weeks. We measured high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), total cholesterol, triglycerides, heat shock protein 70 (HSP 70), and high sensitive C-reactive protein (hs-CRP) at predetermined intervals and determined expressions of cholesteryl ester transfer protein-1 (CETP-1) and liver X receptor {beta} (LXR{beta}) in the liver. Atherosclerosis was determined by examining the aorta with hematoxylin and eosin stain. After 20 weeks, we found arsenic, alone or combined with HCD, may promote atherosclerosis formation with transient increases in HSP 70 and hs-CRP. Early combination exposure decreased the HDL-C/LDL-C ratio without changing the levels of total cholesterol and triglyceride until 30 weeks old. Both CETP-1 and LXR{beta} activities were suppressed, most significantly in early combination exposure. In conclusion, arsenic exposure may induce atherosclerosis through modifying reverse cholesterol transport in cholesterol metabolism and suppressing LXR{beta} and CEPT-1 expressions. For decreasing atherosclerosis related mortality associated with arsenic, preventing exposure from environmental sources in early life is an important element. - Highlights: > Arsenic causes cardiovascular and cerebrovascular diseases through atherosclerosis. > Arsenic may promote atherosclerosis with transient increase in HSP 70 and hs-CRP. > Arsenic exposure and high cholesterol diet early in life suppress CEPT-1 and LXR? > Arsenic may induce atherosclerosis by modifying reverse cholesterol transport. > Prevent arsenic exposure in early life is important to decreasing atherosclerosis.

Cheng, Tain-Junn [Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 704, Taiwan (China); Department of Neurology, Chi Mei Medical Center, 901 Chung-Hwa Road, Tainan 710, Taiwan (China); Department of Occupational Medicine, Chi Mei Medical Center, 901 Chung-Hwa Road, Yongkang, Tainan 710, Taiwan (China); Department of Occupational Safety, College of Environment, Chia Nan University of Pharmacy and Science, 60, Sec. 1, Erh-Jen Road, Jen-Te, Tainan 711, Taiwan (China); Chuu, Jiunn-Jye [Department of Biotechnology, Southern Taiwan University, 1 Nan-Tai Street, Yongkang, Tainan 710, Taiwan (China); Chang, Chia-Yu [Department of Neurology, Chi Mei Medical Center, 901 Chung-Hwa Road, Tainan 710, Taiwan (China); Department of Biotechnology, Southern Taiwan University, 1 Nan-Tai Street, Yongkang, Tainan 710, Taiwan (China); Tsai, Wan-Chen; Chen, Kuan-Jung [Department of Biotechnology, Southern Taiwan University, 1 Nan-Tai Street, Yongkang, Tainan 710, Taiwan (China); Guo, How-Ran, E-mail: hrguo@mail.ncku.edu.tw [Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 704, Taiwan (China); Department of Occupational and Environmental Medicine, National Cheng Kung University Hospital, 138 Sheng-Li Road, Tainan 704, Taiwan (China); Sustainable Environment Research Center, National Cheng Kung University, 138 Sheng-Li Road, Tainan 704, Taiwan (China); Center for Occupational and Environmental Health and Preventive Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 704, Taiwan (China)

2011-10-15

75

Telmisartan and Irbesartan Therapy in Type 2 Diabetic Patients Treated with Rosiglitazone: Effects on Insulin-Resistance, Leptin and Tumor Necrosis Factor-?  

Microsoft Academic Search

The aim of our study was to investigate the metabolic effect of telmisartan and irbesartan in subjects treated with rosiglitazone, a well-known insulin-sensitizing drug, in order to clarify the direct metabolic effects of the two former drugs. Patients were enrolled, evaluated, and followed at 3 Italian centers. We evaluated 188 type 2 diabetic patients with metabolic syndrome (94 males and

Giuseppe Derosa; Arrigo F. G. CICERO; Angela D'angelo; Pietro D. RAGONESI; Leonardina Ciccarelli; Mario N. PICCINNI; Fabio Pricolo; Sibilla A. T. SALVADEO; Ilaria Ferrari; Alessia Gravina; Roberto Fogari

2006-01-01

76

Identification and characterization of degradation products of irbesartan using LC–MS\\/TOF, MS n , on-line H\\/D exchange and LC–NMR  

Microsoft Academic Search

Irbesartan was subjected to hydrolytic, oxidative, photolytic and thermal stress, according to ICH guideline Q1A (R2). The drug showed degradation only in acidic, basic and photoacidic conditions, while it was stable to other stress conditions. A total of three degradation products were formed, which were separated on a C-8 column employing a gradient HPLC method. Initially, a complete mass fragmentation

Ravi P. Shah; Archana Sahu; Saranjit Singh

2010-01-01

77

The genetic basis of atherosclerosis  

Microsoft Academic Search

Atherogenesis is a complex process that involves the contributions of several pathophysiological subsystems. The dissection\\u000a of the genetic component of atherosclerosis has become possible using current molecular technologies and analytical methods.\\u000a Genetic factors are considered to determine the limits under which atherosclerosis develops and environmental factors are\\u000a considered to position an individual’s risk within these limits. Atherosclerosis proceeds through a

R. A. Hegele

1997-01-01

78

Macrophages, inflammation, and atherosclerosis.  

PubMed

The macrophage plays a diverse array of roles in atherogenesis and lipoprotein metabolism. The macrophage functions as a scavenger cell, an immune mediator cell, and as a source of chemotactic molecules and cytokines. Chemokines have been implicated in promoting migration of monocytes into the arterial intima. Monocyte chemoattractant protein-1 (MCP-1) attracts monocytes bearing the chemokine receptor CCR-2. Macrophage expression of cyclooxygenase-2, a key enzyme in inflammation, promotes atherosclerotic lesion formation in low-density lipoprotein receptor (LDLR)-deficient mice. In the arterial intima, monocytes differentiate into macrophages, which accumulate cholesterol esters to form lipid-laden foam cells. Foam cell formation can be viewed as an imbalance in cholesterol homeostasis. The uptake of atherogenic lipoproteins is mediated by scavenger receptors, including SR-A and CD36. In the macrophage, ACAT-1 is responsible for esterifying free cholesterol with fatty acids to form cholesterol esters. Surprisingly, deficiency of macrophage ACAT-1 promotes atherosclerosis in LDLR-deficient mice. A number of proteins have been implicated in the process of promoting the efflux of free cholesterol from the macrophage, including apoE, ABCA1, and SRB-1. Macrophage-derived foam cells express the adipocyte fatty acid-binding protein (FABP), aP2, a cytoplasmic FABP that plays an important role in regulating systemic insulin resistance in the setting of obesity. ApoE-deficient mice null for macrophage aP2 expression develop significantly less atherosclerosis than controls wild type for macrophage aP2 expression. These results demonstrate a significant role for macrophage aP2 in the formation of atherosclerotic lesions independent of its role in systemic glucose and lipid metabolism. Furthermore, macrophages deficient in aP2 display alterations in inflammatory cytokine production. Through its distinct actions in adipocytes and macrophages, aP2 links features of the metabolic syndrome including insulin resistance, obesity, inflammation, and atherosclerosis. PMID:14704742

Linton, MacRae F; Fazio, Sergio

2003-12-01

79

The immune system in atherosclerosis  

Microsoft Academic Search

Cardiovascular disease, a leading cause of mortality worldwide, is caused mainly by atherosclerosis, a chronic inflammatory disease of blood vessels. Lesions of atherosclerosis contain macrophages, T cells and other cells of the immune response, together with cholesterol that infiltrates from the blood. Targeted deletion of genes encoding costimulatory factors and proinflammatory cytokines results in less disease in mouse models, whereas

Andreas Hermansson; Göran K Hansson

2011-01-01

80

B Cell Subsets in Atherosclerosis  

PubMed Central

Atherosclerosis, the underlying cause of heart attacks and strokes, is a chronic inflammatory disease of the artery wall. Immune cells, including lymphocytes modulate atherosclerotic lesion development through interconnected mechanisms. Elegant studies over the past decades have begun to unravel a role for B cells in atherosclerosis. Recent findings provide evidence that B cell effects on atherosclerosis may be subset-dependent. B-1a B cells have been reported to protect from atherosclerosis by secretion of natural IgM antibodies. Conventional B-2 B cells can promote atherosclerosis through less clearly defined mechanism that may involve CD4 T cells. Yet, there may be other populations of B cells within these subsets with different phenotypes altering their impact on atherosclerosis. Additionally, the role of B cell subsets in atherosclerosis may depend on their environmental niche and/or the stage of atherogenesis. This review will highlight key findings in the evolving field of B cells and atherosclerosis and touch on the potential and importance of translating these findings to human disease.

Perry, Heather M.; Bender, Timothy P.; McNamara, Coleen A.

2012-01-01

81

Xanthine oxidase inhibition by febuxostat attenuates experimental atherosclerosis in mice.  

PubMed

Atherosclerosis is a chronic inflammatory disease due to lipid deposition in the arterial wall. Multiple mechanisms participate in the inflammatory process, including oxidative stress. Xanthine oxidase (XO) is a major source of reactive oxygen species (ROS) and has been linked to the pathogenesis of atherosclerosis, but the underlying mechanisms remain unclear. Here, we show enhanced XO expression in macrophages in the atherosclerotic plaque and in aortic endothelial cells in ApoE(-/-) mice, and that febuxostat, a highly potent XO inhibitor, suppressed plaque formation, reduced arterial ROS levels and improved endothelial dysfunction in ApoE(-/-) mice without affecting plasma cholesterol levels. In vitro, febuxostat inhibited cholesterol crystal-induced ROS formation and inflammatory cytokine release in murine macrophages. These results demonstrate that in the atherosclerotic plaque, XO-mediated ROS formation is pro-inflammatory and XO-inhibition by febuxostat is a potential therapy for atherosclerosis. PMID:24686534

Nomura, Johji; Busso, Nathalie; Ives, Annette; Matsui, Chieko; Tsujimoto, Syunsuke; Shirakura, Takashi; Tamura, Mizuho; Kobayashi, Tsunefumi; So, Alexander; Yamanaka, Yoshihiro

2014-01-01

82

Efficacy and safety of early versus late titration of fixed-dose irbesartan/hydrochlorothiazide: ACTUAL study.  

PubMed

Hypertension management guidelines recommend titrating antihypertensive drugs stepwise every 4-6 weeks.We compared efficacy and safety of early versus late titration after 10 weeks' treatment with irbesartan/hydrochlorothiazide. Hypertensive patients uncontrolled on monotherapy were randomized into two groups. In the early titration group (E), patients received irbesartan/hydrochlorothiazide 150/12.5 mg for 2 weeks; uncontrolled patients were up-titrated to 300/25 mg at weeks 2 and 6. In the late titration group (L), patients received 150/12.5 mg for 6 weeks; uncontrolled patients were up-titrated to 300/25 mg at week 6 (W6). The change of mean systolic (SBP) and diastolic blood pressure (DBP) from baseline to week 10 (W10) were studied using a covariance analysis model. The percentage of controlled patients at W10 was compared between groups using Fisher's exact test. Of 833 patients enrolled from 14 countries, the intent-to-treat (ITT) population included 795 (mean age 58 +/- 12 years, female 60%, obesity 38%, diabetes 22%). AtW6, mean SBP decrease was: E - 28.8 mmHg vs L - 26.3 mmHg (p = 0.02). At W10, there was similar mean SBP decrease: E - 29.5 mmHg vs L- 31.0 mmHg (p = 0.14). The control rate at W10 was 58% (E) and 64% (L), p = 0.06. Serious adverse events were more frequent in E (2.5% vs 0.7%, p= 0.044). Both early and late titration regimens provide similar BP decrease and control rate. PMID:22352122

Girerd, Xavier; Rosenbaum, David; Aoun, Joseph

2011-12-01

83

[Major pathogenic links of atherosclerosis].  

PubMed

The experimental and clinical data concerning pathogenesis of the atherosclerosis are summarized and analyzed in this article. Major concepts that explain initiation and progressive growth of atherosclerosis such as lipid infiltrations, response to disturbing factors, "response on the keeping of particles" and inflammatory processes are discussed. These concepts are considered as base for integral theory of atherosclerosis according which the inflammatory process in atherosclerosis are the result of the universal response reaction of endothelium to the various disturbing risk factors. Chronic inflammation leads to complex cellular and molecular interactions among cells derived from the endothelium, smooth muscle and several blood cell components and causes oxidative stress, proliferation of smooth muscle cells, oxidative modification of LDL, uptake and macrophage foam cell formation, endothelium dysfunction. Major pathogenic links of atherosclerosis, such as inflammation, oxidative stress, oxidative modification of LDL, lipid infiltration, endothelial dysfunction closely interact, forming close vicious circles which leads to metabolic and morphological disturbances, re-modulation of blood vessels, cardiovascular diseases and such complication as cardiac infarction and stroke. Pathogenic peculiarities of atherosclerosis are the theoretic base to the elaboration of therapeutic strategy. Endothelium may be discussed as a new therapeutic target in atherosclerosis. So far as the leukotrienes play an important role in inflammatory processes, it is suggested that the leukotrienes may be as a potential therapeutic target in cardiovascular diseases. PMID:16369071

Antelava, N A; Pachkoriia, K Z; Kezeli, T D; Nikuradze, N S; Shamkulashvili, G G

2005-11-01

84

Hyperhomocysteinemia and atherosclerosis.  

PubMed

Arteriosclerosis and its complications, such as heart attack and stroke, are the major causes of death in developed countries. It was believed that age, hyperlipidemia, hypertension, diabetes and smoking are common risk factors for cardiovascular disease. In addition, overwhelming clinical and epidemiological studies have identified homocysteine (Hcy) as a significant and independent risk factor for cardiovascular disease. In healthy individuals, plasma Hcy is between 5 and 10 micromol/L. One cause of severe hypehomocys- teinemia (HHcy) is the deficiency of cystathionine beta-synthase (CBS), which converts Hcy to cystathionine. CBS homozygous deficiency results in severe HHcy with Hcy levels up to 100 to 500 micromol/L. Patients with severe HHcy usually present with neurological abnormalities, premature arteriosclerosis. It has been reported that lowering plasma Hcy improved endothelial dysfunction and reduced incidence of major adverse events after percutaneous coronary intervention. The mechanisms by which Hcy induces atherosclerosis are largely unknown. Several biological mechanisms have been proposed to explain cardiovascular pathological changes associated with HHcy. These include: (1) endothelial cell damage and impaired endothelial function; (2) dysregulation of cholesterol and triglyceride biosynthesis; (3) stimulation of vascular smooth muscle cell proliferation; (4) thrombosis activation and (5) activation of monocytes. Four major biochemical mechanisms have been proposed to explain the vascular pathology of Hcy. These include: (1) autooxidation through the production of reactive oxygen species; (2) hypomethylation by forming SAH, a potent inhibitor of biological transmethylations; (3) nitrosylation by binding to nitric oxide or (4) protein homocysteinylation by incorporating into protein. In summary, our studies, as well as data from other laboratories support the concept that Hcy is causally linked to atherosclerosis, and is not merely associated with the disease. Although folic acid, vitamin B12 and B6 can lower plasma Hcy levels, the long-term effects on cardiovascular disease risk are still unknown and judgments about therapeutic benefits await the findings of ongoing clinical trials. PMID:15830093

Yang, Fan; Tan, Hong-Mei; Wang, Hong

2005-04-25

85

"In vivo" imaging of atherosclerosis.  

PubMed

Atherosclerosis is a systemic and multifocal disease, which starts early in life, and that usually takes decades before overt disease eventually appears as a consequence of progressive obstruction or abrupt thrombotic occlusion. This silent course makes necessary to develop predictors of disease long before symptomatic lesions develop. Besides several classical risk factors and new emerging humoral risk predictors, imaging may constitute a formidable diagnostic and prognostic tool in order to identify presence, extension, progression (or regression) of disease as well as vulnerability of atherosclerotic lesions. This review summarizes the rapidly growing clinical and research field in imaging atherosclerosis from different perspectives opening important opportunities for timely detection and treatment of atherosclerosis. PMID:22682779

Gallino, Augusto; Stuber, Matthias; Crea, Filippo; Falk, Erling; Corti, Roberto; Lekakis, John; Schwitter, Jürg; Camici, Paolo; Gaemperli, Oliver; Di Valentino, Marcello; Prior, John; Garcia-Garcia, Hector M; Vlachopoulos, Charalambos; Cosentino, Francesco; Windecker, Stephan; Pedrazzini, Giovanni; Conti, Richard; Mach, François; De Caterina, Raffaele; Libby, Peter

2012-09-01

86

Use of irbesartan to maintain sinus rhythm in patients with long-lasting persistent atrial fibrillation. A prospective and randomized study  

Microsoft Academic Search

Background—Data from studies of angiotensin-converting enzyme inhibitors provide evidence that the renin-angioten- sin-aldosterone system plays a role as a mediator of atrial remodeling in atrial fibrillation. The present study has evaluated the effect of treatment with the angiotensin I type 1 receptor blocker irbesartan on maintaining sinus rhythm after conversion from persistent atrial fibrillation. Methods and Results—To be included in

Antonio H. Madrid; Manuel G. Bueno; Jose M. G. Rebollo

2002-01-01

87

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

88

Chronic Intermittent Hypoxia Induces Atherosclerosis  

Microsoft Academic Search

Rationale:Obstructivesleep apnea, acondition leadingtochronicinter- mittent hypoxia (CIH), is associated with hyperlipidemia, atherosclero- sis, and a high cardiovascular risk. A causal link between obstructive sleep apnea and atherosclerosis has not been established. Objectives: The objective of the present study was to examine whether CIH may induce atherosclerosis in C57BL\\/6J mice. Methods: Forty male C57BL\\/6J mice, 8 weeks of age, were fed

Vladimir Savransky; Ashika Nanayakkara; Jianguo Li; Shannon Bevans; Philip L. Smith; Annabelle Rodriguez; Vsevolod Y. Polotsky

2007-01-01

89

Atherosclerosis imaging and heart failure  

Microsoft Academic Search

Coronary atherosclerosis is the most important primary etiologic factor predisposing to the development of heart failure.\\u000a The mechanisms by which coronary atherosclerosis lead to heart failure likely involve the initial development of regional\\u000a myocardial dysfunction, later progressing to global ventricular failure and symptomatic congestive disease. A variety of imaging\\u000a strategies have been investigated for their value in identifying and characterizing

Verônica Rolim S. Fernandes; Susan Cheng; João A. C. Lima

2006-01-01

90

Carotenoids and asymptomatic carotid atherosclerosis.  

PubMed

High plasma concentrations of lycopene and beta-carotene have been associated with reduced prevalence of cardiovascular disease. The aim of this study is to compare plasma concentrations of these carotenoids in subjects with or without ultrasonic evidence of asymptomatic carotid atherosclerosis. One hundred and sixty-five subjects underwent physical examination and ultrasonic measurement of common carotid artery intima-media thickness. Analysis of variance and logistic regression methods were used to determine whether differences existed between participants with or without ultrasonic evidence of asymptomatic carotid atherosclerosis. Of the 165 participants, 80 exhibited evidence of carotid atherosclerosis (carotid intima-media thickness>0.8 mm), while 85 did not (carotid intima-media thickness>0.8 mm), while 85 did not (carotid intima-media thickness<0.8 mm). Participants with ultrasonic evidence of carotid atherosclerosis exhibited significantly greater body mass index, significantly higher serum concentrations of total cholesterol, LDL-associated cholesterol and triglycerides, and significantly higher plasma concentrations of uric acid, C-reactive protein and fibrinogen. In contrast, participants with ultrasonic evidence of carotid atherosclerosis exhibited significantly lower plasma concentrations of lycopene and beta-carotene. These results suggest that lycopene and beta-carotene may play important roles in delaying the development of the early asymptomatic stage of carotid atherosclerosis. Encouraging adequate intakes of antioxidant carotenoids may provide an important public health service. PMID:21122284

Riccioni, G; D'Orazio, N; Speranza, L; Di Ilio, E; Glade, M; Bucciarelli, V; Scotti, L; Martini, F; Pennelli, A; Bucciarelli, T

2010-01-01

91

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

92

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 until ... concentrating. Rate This Content: Featured Video What is atherosclerosis? Atherosclerosis Clinical Trials Clinical trials are research studies ...

93

Inhibition of NADPH Oxidase by Apocynin Attenuates Progression of Atherosclerosis  

PubMed Central

Of the multiple sources of reactive oxygen species (ROS) in the blood vessel, NADPH oxidases are the primary source. Whereas several studies have implicated NADPH oxidases in the initiation of atherosclerosis, their roles in disease progression are incompletely understood. Our objective was to determine the potential clinical relevance of inhibiting NADPH oxidase in established atherosclerosis. Using a hypercholesteremic murine model of atherosclerosis (ApoE?/?/LDLR?/? (AS) mice on normal chow diet), we first established a time-dependent relationship between superoxide levels and lesion size in AS mice. Next, we identified NADPH oxidase as the primary source of ROS in atherosclerotic lesions. Treatment of aortic segments from AS mice with apocynin, which interferes with NADPH oxidase activation in part by preventing translocation of the subunit p47phox, significantly reduced superoxide levels. Moreover, addition of apocynin to the drinking water of AS mice produced a decrease in lesion size as compared to untreated AS mice, with the effect most pronounced in the thoracoabdominal aorta but absent from the aortic arch. Granulocyte function in AS+apocynin mice was suppressed, confirming efficacy of apocynin treatment. We conclude that apocynin attenuates the progression of atherosclerosis in hypercholesterolemic mice, potentially by its ability to inhibit generation of superoxide by NADPH oxidase.

Kinkade, Kara; Streeter, Jennifer; Miller, Francis J.

2013-01-01

94

Oxidative Stress, AntioxidantVitamins, and Atherosclerosis  

Microsoft Academic Search

Oxidative stress is involved in the pathogenesis of atherosclerosis, while a variety of antioxidants has been used in clinical studies, during the past few years, for the prevention and treatment of atherosclerosis. In small clinical studies it was found that both vitamins C and E may improve endothelial function in patients with risk factors for atherosclerosis such as diabetes mellitus,

Charalambos Antoniades; Dimitris Tousoulis; Costas Tentolouris; Pavlos Toutouzas; Christodoulos Stefanadis

2003-01-01

95

Chylomicronemia Elicits Atherosclerosis in Mice  

PubMed Central

Objective The risk of atherosclerosis in the setting of chylomicronemia has been a topic of debate. In this study, we examined susceptibility to atherosclerosis in Gpihbp1-deficient mice (Gpihbp1?/?), which manifest severe chylomicronemia as a result of defective lipolysis. Methods and Results Gpihbp1?/? mice on a chow diet have plasma triglyceride and cholesterol levels of 2812 ± 209 and 319 ± 27 mg/dl, respectively. Even though nearly all of the lipids were contained in large lipoproteins (50–135 nm), the mice developed progressive aortic atherosclerosis. In other experiments, we found that both Gpihbp1-deficient “apo-B48–only” mice and Gpihbp1-deficient “apo-B100–only” mice manifest severe chylomicronemia. Thus, GPIHBP1 is required for the processing of both apo-B48– and apo-B100–containing lipoproteins. Conclusions Chylomicronemia causes atherosclerosis in mice. Also, we found that GPIHBP1 is required for the lipolytic processing of both apo-B48– and apo-B100–containing lipoproteins.

Weinstein, Michael M.; Yin, Liya; Tu, Yiping; Wang, Xuping; Wu, Xiaohui; Castellani, Lawrence W.; Walzem, Rosemary L.; Lusis, Aldons J.; Fong, Loren G.; Beigneux, Anne P.; Young, Stephen G.

2009-01-01

96

PPAR? in atherosclerosis and inflammation  

PubMed Central

Summary Peroxisome proliferators-activated receptor (PPAR)? is a nuclear receptor activated by natural ligands such as fatty acids as well as by synthetic ligands such as fibrates currently used to treat dyslipidemia. PPAR? regulates the expression of genes encoding proteins that are involved in lipid metabolism, fatty acid oxidation and glucose homeostasis, thereby improving markers for atherosclerosis and insulin resistance. In addition, PPAR? exerts anti-inflammatory effects both in the vascular wall and the liver. Here we provide an overview of the mechanisms through which PPAR? affects the initiation and progression of atherosclerosis, with emphasis on the modulation of atherosclerosis-associated inflammatory responses. PPAR? activation interferes with early steps in angiogenesis by reducing leukocyte adhesion to activated endothelial cells of the arterial vessel wall and inhibiting subsequent transendothelial leukocyte migration. In later stages of atherosclerosis, evidence suggests activation of PPAR? inhibits the formation of macrophage foam cells by regulating expression of genes involved in reverse cholesterol transport, formation of reactive oxygen species (ROS), and associated lipoprotein oxidative modification among others. Furthermore, PPAR? may increase the stability of atherosclerotic plaques and limit plaque thrombogenicity. These various effects may be linked to the generation of PPAR? ligands by endogenous mechanisms of lipoprotein metabolism. In spite of this dataset, other reports implicate PPAR? in responses such as hypertension and diabetic cardiomyopathy. Although some clinical trials data with fibrates suggest that fibrates may decrease cardiovascular events, other studies have been less clear, at least in the presence of concomitant statin therapy. Independent of the clinical effects of currently used purported PPAR? agonists, extensive data establishes the importance of PPAR? in the transcriptional regulation of lipid metabolism, atherosclerosis and inflammation.

Zandbergen, Fokko; Plutzky, Jorge

2007-01-01

97

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

98

Complex Regulation and Function of the Inflammatory Smooth Muscle Cell Phenotype in Atherosclerosis  

Microsoft Academic Search

Vascular smooth muscle cell (SMC) phenotypic modulation plays a key role in atherosclerosis and is classically defined as a switch from a ‘contractile’ phenotype to a ‘synthetic’ phenotype, whereby genes that define the contractile SMC phenotype are suppressed and proliferation and\\/or migratory mechanisms are induced. There is also evidence that SMCs may take on a ‘proinflammatory’ phenotype, whereby SMCs secrete

Anthony Wayne Orr; Nicole E. Hastings; Brett R. Blackman; Brian R. Wamhoff

2010-01-01

99

Atherosclerosis, inflammation and Chlamydia pneumoniae.  

PubMed

Coronary heart disease is the single most common cause of illness and death in the developed world. Coronary atherosclerosis is by far the most frequent cause of ischemic heart disease, and plaque disruption with superimposed thrombosis is the main cause of the acute coronary syndromes of unstable angina, myocardial infarction, and sudden death. Atherosclerosis is the result of a complex interaction between blood elements, disturbed flow, and vessel wall abnormality, involving several pathological processes: inflammation, with increased endothelial permeability, endothelial activation, and monocyte recruitment; growth, with smooth muscle cell proliferation, migration, and matrix synthesis; degeneration, with lipid accumulation; necrosis, possibly related to the cytotoxic effect of oxidized lipid; calcification/ossification, which may represent an active rather than a dystrophic process; and thrombosis, with platelet recruitment and fibrin formation. In this review we discuss these processes and the possible pathological effects of Chlamydia infection and the ensuing phlogosis. PMID:21160574

Fazio, Giovanni; Giovino, Maria; Gullotti, Alessandro; Bacarella, Daniela; Novo, Giuseppina; Novo, Salvatore

2009-12-31

100

Atherosclerosis Viewed from the Inside  

Microsoft Academic Search

\\u000a The clinical illness of coronary artery disease is the end-stage of silent long established arterial disease or the rapid\\u000a consecutive events following injury to the vessel wall. The most common form of degenerative arterial disease is atherosclerosis,\\u000a which is a complex process determined by endothelial cell injury, migration, thrombosis and monocytes infiltration. These\\u000a factors are related to the two main

Peter den Heijer

101

Plasmacytoid Dendritic Cells in Atherosclerosis  

PubMed Central

Atherosclerosis, a chronic inflammatory disease of the vessel wall and the underlying cause of cardiovascular disease, is initiated and maintained by innate and adaptive immunity. Accumulating evidence suggests an important contribution of autoimmune responses to this disease. Plasmacytoid dendritic cells (pDCs), a specialized cell type known to produce large amounts of type I interferons (IFNs) in response to bacterial and viral infections, have recently been revealed to play important roles in atherosclerosis. For example, the development of autoimmune complexes consisting of self-DNA and antimicrobial peptides, which trigger chronic type I IFN production by pDCs, promote early atherosclerotic lesion formation. pDCs and pDC-derived type I IFNs can also induce the maturation of conventional DCs and macrophages, and the development of autoreactive B cells and antibody production. These mechanisms, known to play a role in the pathogenesis of other autoimmune diseases such as systemic lupus erythematosus and psoriasis, may also affect the development and progression of atherosclerotic lesion formation. This review discusses emerging evidence showing a contribution of pDCs in the onset and progression of atherosclerosis.

Doring, Yvonne; Zernecke, Alma

2012-01-01

102

Immunity, atherosclerosis and cardiovascular disease  

PubMed Central

Atherosclerosis, the major cause of cardiovascular disease (CVD), is a chronic inflammatory condition with immune competent cells in lesions producing mainly pro-inflammatory cytokines. Dead cells and oxidized forms of low density lipoproteins (oxLDL) are abundant. The major direct cause of CVD appears to be rupture of atherosclerotic plaques. oxLDL has proinflammatory and immune-stimulatory properties, causes cell death at higher concentrations and contains inflammatory phospholipids with phosphorylcholine (PC) as an interesting epitope. Antibodies against PC (anti-PC) may be atheroprotective, one mechanism being anti-inflammatory. Bacteria and virus have been discussed, but it has been difficult to find direct evidence, and antibiotic trials have not been successful. Heat shock proteins could be one major target for atherogenic immune reactions. More direct causes of plaque rupture include pro-inflammatory cytokines, chemokines, and lipid mediators. To prove that inflammation is a cause of atherosclerosis and CVD, clinical studies with anti-inflammatory and/or immune-modulatory treatment are needed. The potential causes of immune reactions and inflammation in atherosclerosis and how inflammation can be targeted therapeutically to provide novel treatments for CVD are reviewed.

2013-01-01

103

Spectroscopic and spectrofluorimetric studies on the interaction of irbesartan with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone and iodine.  

PubMed

Raman, UV-vis, 1H NMR, FT-IR, mass and fluorescence spectral techniques were employed to investigate the mechanism of interaction of irbesartan (IRB) drug with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and iodine. Interaction of IRB with iodine yields triiodide ion and its formation was confirmed by electronic and Raman spectra. The peaks appeared in Raman spectrum of the isolated product at 143, 113 and 76 cm(-1) are assigned to ?as(I-I), ?s(I-I) and ?(I3-) respectively, confirmed the presence of I3- ion. The interaction of DDQ with irbesartan was found to proceed through the formation of outer complex and its conversion to the CT complex. Formation constant (K), molar extinction coefficient (?) and thermodynamic properties ?H#, ?S# and ?G# were determined and discussed. Fluorescence quenching studies indicated that the interaction between the IRB and the acceptors are spontaneous and the IRB-DDQ interaction is found to be stronger than that the other system. Solvent variation studies indicated that the binding constant increased with an increase in polarity of the medium. PMID:21684193

Ganesh, K; Balraj, C; Elango, K P

2011-09-01

104

Spectroscopic and spectrofluorimetric studies on the interaction of irbesartan with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone and iodine  

NASA Astrophysics Data System (ADS)

Raman, UV-vis, 1H NMR, FT-IR, mass and fluorescence spectral techniques were employed to investigate the mechanism of interaction of irbesartan (IRB) drug with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and iodine. Interaction of IRB with iodine yields triiodide ion and its formation was confirmed by electronic and Raman spectra. The peaks appeared in Raman spectrum of the isolated product at 143, 113 and 76 cm -1 are assigned to ?as(I-I), ?s(I-I) and ?(I 3-) respectively, confirmed the presence of I 3- ion. The interaction of DDQ with irbesartan was found to proceed through the formation of outer complex and its conversion to the CT complex. Formation constant ( K), molar extinction coefficient ( ?) and thermodynamic properties ? H#, ? S# and ? G# were determined and discussed. Fluorescence quenching studies indicated that the interaction between the IRB and the acceptors are spontaneous and the IRB-DDQ interaction is found to be stronger than that the other system. Solvent variation studies indicated that the binding constant increased with an increase in polarity of the medium.

Ganesh, K.; Balraj, C.; Elango, K. P.

2011-09-01

105

A validated stability-indicating liquid chromatographic method for determination of process related impurities and degradation behavior of Irbesartan in solid oral dosage.  

PubMed

The present work describes the development and validation of a stability-indicating RP-HPLC method for the estimation of degradation and process related impurities of Irbesartan, namely Impurity-1, Impurity-2, Impurity-3 and Impurity-4. The developed LC method was validated with respect to specificity, limit of detection and quantification, linearity, precision, accuracy and robustness. The chromatographic separation was achieved on Hypersil Octadecylsilyl (4.6 mm × 150 mm, 3 ?m) column by using mobile phase containing a gradient mixture of solvent A (0.55% v/v ortho-phosphoric acid, pH adjusted to 3.2 with triethyl amine) and B (95:5 v/v mixture of acetonitrile and solvent A) at a flow rate of 1.2 mL/min. The detection was carried out at a wavelength of 220 nm. During method validation parameter such as precision, linearity, accuracy, specificity, limit of detection and quantification were evaluated, which remained within acceptable limits. HPLC analytical method is linear, accurate, precise, robust and specific, being able to separate the main drug from its degradation products. The degradation products were well-resolved from the main peak and its impurities, thus proving the stability-indicating power of the method. The method is stability-indicating in nature and can be used for routine analysis of production samples and to check the stability of the Irbesartan HCl tablets. PMID:24695518

Goswami, Nishant

2014-01-01

106

A validated stability-indicating liquid chromatographic method for determination of process related impurities and degradation behavior of Irbesartan in solid oral dosage  

PubMed Central

The present work describes the development and validation of a stability-indicating RP-HPLC method for the estimation of degradation and process related impurities of Irbesartan, namely Impurity-1, Impurity-2, Impurity-3 and Impurity-4. The developed LC method was validated with respect to specificity, limit of detection and quantification, linearity, precision, accuracy and robustness. The chromatographic separation was achieved on Hypersil Octadecylsilyl (4.6 mm × 150 mm, 3 ?m) column by using mobile phase containing a gradient mixture of solvent A (0.55% v/v ortho-phosphoric acid, pH adjusted to 3.2 with triethyl amine) and B (95:5 v/v mixture of acetonitrile and solvent A) at a flow rate of 1.2 mL/min. The detection was carried out at a wavelength of 220 nm. During method validation parameter such as precision, linearity, accuracy, specificity, limit of detection and quantification were evaluated, which remained within acceptable limits. HPLC analytical method is linear, accurate, precise, robust and specific, being able to separate the main drug from its degradation products. The degradation products were well-resolved from the main peak and its impurities, thus proving the stability-indicating power of the method. The method is stability-indicating in nature and can be used for routine analysis of production samples and to check the stability of the Irbesartan HCl tablets.

Goswami, Nishant

2014-01-01

107

Immune Response to Lipoproteins in Atherosclerosis  

PubMed Central

Atherosclerosis, the underlying cause of cardiovascular disease, is characterized by chronic inflammation and altered immune response. Cholesterol is a well-known risk factor associated with the development of cardiovascular diseases. Elevated serum cholesterol is unique because it can lead to development of atherosclerosis in animals and humans even in the absence of other risk factors. Modifications of low-density lipoproteins mediated by oxidation, enzymatic degradation, and aggregation result in changes in their function and activate both innate and adaptive immune system. Oxidized low-density lipoprotein (LDL) has been identified as one of the most important autoantigens in atherosclerosis. This escape from self-tolerance is dependent on the formation of oxidized phospholipids. The emerging understanding of the importance of immune responses against oxidized LDL in atherosclerosis has focused attention on the possibility of development of novel therapy for atherosclerosis. This review provides an overview of immune response to lipoproteins and the fascinating possibility of developing an immunomodulatory therapy for atherosclerosis.

Samson, Sonia; Mundkur, Lakshmi; Kakkar, Vijay V.

2012-01-01

108

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

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

2000-01-01

109

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

110

ABC Transporters, Atherosclerosis and Inflammation  

PubMed Central

Atherosclerosis, driven by inflamed lipid-laden lesions, can occlude the coronary arteries and lead to myocardial infarction. This chronic disease is a major and expensive health burden. However, the body is able to mobilize and excrete cholesterol and other lipids, thus preventing atherosclerosis by a process termed reverse cholesterol transport (RCT). Insight into the mechanism of RCT has been gained by the study of two rare syndromes caused by the mutation of ABC transporter loci. In Tangier Disease, loss of ABCA1 prevents cells from exporting cholesterol and phospholipid, thus resulting in the build-up of cholesterol in the peripheral tissues and a loss of circulating HDL. Consistent with HDL being an athero-protective particle, Tangier patients are more prone to develop atherosclerosis. Likewise, sitosterolemia is another inherited syndrome associated with premature atherosclerosis. Here mutations in either the ABCG5 or G8 loci, prevents hepatocytes and enterocytes from excreting cholesterol and plant sterols, including sitosterol, into the bile and intestinal lumen. Thus, ABCG5 and G8, which from a heterodimer, constitute a transporter that excretes cholesterol and dietary sterols back into the gut, while ABCA1 functions to export excess cell cholesterol and phospholipid during the biogenesis of HDL. Interestingly, a third protein, ABCG1, that has been shown to have anti-atherosclerotic activity in mice, may also act to transfer cholesterol to mature HDL particles. Here we review the relationship between the lipid transport activities of these proteins and their anti-atherosclerotic effect, particularly how they may reduce inflammatory signaling pathways. Of particular interest are recent reports that indicate both ABCA1 and ABCG1 modulate cell surface cholesterol levels and inhibit its partitioning into lipid rafts. Given lipid rafts may provide platforms for innate immune receptors to respond to inflammatory signals, it follows that loss of ABCA1 and ABCG1 by increasing raft content will increase signaling through these receptors, as has been experimentally demonstrated. Moreover, additional reports indicate ABCA1, and possibly SR-BI, another HDL receptor, may directly act as anti-inflammatory receptors independent of their lipid transport activities. Finally, we give an update on the progress and pitfalls of therapeutic approaches that seek to stimulate the flux of lipids through the RCT pathway.

Fitzgerald, Michael L.; Mujawar, Zahedi; Tamehiro, Norimasa

2010-01-01

111

ABC transporters, atherosclerosis and inflammation.  

PubMed

Atherosclerosis, driven by inflamed lipid-laden lesions, can occlude the coronary arteries and lead to myocardial infarction. This chronic disease is a major and expensive health burden. However, the body is able to mobilize and excrete cholesterol and other lipids, thus preventing atherosclerosis by a process termed reverse cholesterol transport (RCT). Insight into the mechanism of RCT has been gained by the study of two rare syndromes caused by the mutation of ABC transporter loci. In Tangier disease, loss of ABCA1 prevents cells from exporting cholesterol and phospholipid, thus resulting in the build-up of cholesterol in the peripheral tissues and a loss of circulating HDL. Consistent with HDL being an athero-protective particle, Tangier patients are more prone to develop atherosclerosis. Likewise, sitosterolemia is another inherited syndrome associated with premature atherosclerosis. Here mutations in either the ABCG5 or G8 loci, prevents hepatocytes and enterocytes from excreting cholesterol and plant sterols, including sitosterol, into the bile and intestinal lumen. Thus, ABCG5 and G8, which from a heterodimer, constitute a transporter that excretes cholesterol and dietary sterols back into the gut, while ABCA1 functions to export excess cell cholesterol and phospholipid during the biogenesis of HDL. Interestingly, a third protein, ABCG1, that has been shown to have anti-atherosclerotic activity in mice, may also act to transfer cholesterol to mature HDL particles. Here we review the relationship between the lipid transport activities of these proteins and their anti-atherosclerotic effect, particularly how they may reduce inflammatory signaling pathways. Of particular interest are recent reports that indicate both ABCA1 and ABCG1 modulate cell surface cholesterol levels and inhibit its partitioning into lipid rafts. Given lipid rafts may provide platforms for innate immune receptors to respond to inflammatory signals, it follows that loss of ABCA1 and ABCG1 by increasing raft content will increase signaling through these receptors, as has been experimentally demonstrated. Moreover, additional reports indicate ABCA1, and possibly SR-BI, another HDL receptor, may directly act as anti-inflammatory receptors independent of their lipid transport activities. Finally, we give an update on the progress and pitfalls of therapeutic approaches that seek to stimulate the flux of lipids through the RCT pathway. PMID:20138281

Fitzgerald, Michael L; Mujawar, Zahedi; Tamehiro, Norimasa

2010-08-01

112

External imaging of human atherosclerosis  

SciTech Connect

Autologous plasma low-density lipoproteins labeled with I-125 were used as a tracer to identify atherosclerotic lesions in the carotid arteries of the neck. Following intravenous injection of I-125-LDL, images were made at intervals from 6 to 36 hr with the gamma camera in three patients with known carotid disease and one control subject. The carotid lesions, confirmed by angiography, were imaged successfully in all three patients, whereas no focal LDL accumulation was visible in the carotid arteries of the control subject. The findings suggest that it may be possible to image atherosclerosis externally and thus to follow the course of the disease.

Lees, R.S.; Lees, A.M.; Strauss, H.W.

1983-02-01

113

External imaging of human atherosclerosis  

SciTech Connect

Autologous plasma low-density lipoproteins labeled with /sup 125/I were used as a tracer to identify atherosclerotic lesions in the carotid arteries of the neck. Following intravenous injection of /sup 125/I-LDL, images were made at intervals from 6 to 36 hr with the gamma camera in three patients with known carotid disease and one control subject. The carotid lesions, confirmed by angiography, were imaged successfully in all three patients, whereas no focal LDL accumulation was visible in the carotid arteries of the control subject. The findings suggest that it may be possible to image atherosclerosis externally and thus to follow the course of the disease.

Lees, R.S.; Lees, A.M.; Strauss, H.W.

1983-02-01

114

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

115

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.

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

2013-01-01

116

From endothelial dysfunction to atherosclerosis.  

PubMed

It has recently emerged that endothelial dysfunction is an early step in the development of atherosclerosis and is mainly characterised by a reduction in the bioavailability of nitric oxide. All of the traditional cardiovascular (CV) risk factors (dyslipidemia, arterial hypertension, hyperglycemia and diabetes) are associated with endothelial dysfunction, and oxidised low-density lipoproteins, the renin-angiotensin axis and insulin resistance play important roles in the pathogenesis of impaired endothelial function. The increased expression of adhesion molecules and pro-inflammatory cytokines leads to abnormal endothelium-dependent vasodilation which could be investigated using vasoreactivity tests such as flow-mediated dilation in the brachial artery. Recently, new evidences showed that the immune system plays an important role in the pathogenesis of endothelial dysfunction and atherosclerosis with a particular regard towards autoimmunity. The high prevalence of the atherosclerotic process in systemic autoimmune diseases supports the hypothesis of the immune pathogenesis. Evaluating coronary microvascular dysfunction by means of transthoracic echocardiography with non-invasive coronary flow reserve assessment is particularly interesting as it could detect preclinical impairment of coronary microvascular function. The discovery that the mechanisms responsible for endothelial damage have a genetic basis could improve the approach to CV diseases. This review summarises the most important aspects of the pathogenesis and development of endothelial dysfunction, with particular attention to the role of traditional CV risk factors, the usefulness of vasoreactivity tests, and the future perspectives opened by genetic studies. PMID:20678595

Sitia, S; Tomasoni, L; Atzeni, F; Ambrosio, G; Cordiano, C; Catapano, A; Tramontana, S; Perticone, F; Naccarato, P; Camici, P; Picano, E; Cortigiani, L; Bevilacqua, M; Milazzo, L; Cusi, D; Barlassina, C; Sarzi-Puttini, P; Turiel, M

2010-10-01

117

Atherosclerosis  

MedlinePLUS

... Your body also gets cholesterol directly from the food you eat (such as eggs, meats and dairy products). There are 2 important types of cholesterol to know about: low-density lipoprotein (LDL), or “bad” cholesterol, and high-density ...

118

Atherosclerosis  

MedlinePLUS

... the damage, fats, cholesterol, platelets, cellular debris and calcium accumulate over time in the artery wall. These substances may stimulate the cells of the artery wall to produce other substances, ...

119

Atherosclerosis  

MedlinePLUS

... hardens and narrows your arteries. This limits the flow of oxygen-rich blood to your organs and other parts ... your neck (the carotid arteries). These arteries supply oxygen-rich blood to your brain. If blood flow to your brain is reduced or blocked, you ...

120

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

121

[The role of adiponectin in atherosclerosis].  

PubMed

Adiponectin is a adipose tissue-derived protein. In the light of current investigations, the role of adiponectin goes far beyond only adipose tissue regulatory factor, being involved in some pathological processes as endothelium damage or atherosclerosis. Unique properties of adiponectin make it a very promising agent that posses ability to slow down the progression of atherosclerosis. In this article, a structure and a function of adiponectin have been reviewed. The special emphasis was put upon the role of adiponectin in atherosclerosis. PMID:16886584

Lewicki, Maciej; Kotyla, Przemys?aw; Jankiewicz-Ziobro, Katarzyna; Kucharz, Eugeniusz Józef

2006-04-01

122

Atherosclerosis: lessons from LXR and the intestine.  

PubMed

Modulation of the cholesterol-sensing liver X receptors (LXRs) and their downstream targets has emerged as promising therapeutic avenues in atherosclerosis. The intestine is important for its unique capabilities to act as a gatekeeper for cholesterol absorption and to participate in the process of cholesterol elimination in the feces and reverse cholesterol transport (RCT). Pharmacological and genetic intestine-specific LXR activation have been shown to protect against atherosclerosis. In this review we discuss the LXR-targeted molecular players in the enterocytes as well as the intestine-driven pathways contributing to cholesterol homeostasis with therapeutic potential as targets in the prevention and treatment of atherosclerosis.. PMID:23158108

Bonamassa, Barbara; Moschetta, Antonio

2013-03-01

123

Matrix study of irbesartan with hydrochlorothiazide in mild-to-moderate hypertension 1 1 This study was sponsored by Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey  

Microsoft Academic Search

The purpose of this study was to assess the safety and antihypertensive dose-response effects of irbesartan and hydrochlorothiazide (HCTZ) in patients with mild-to-moderate hypertension. After a 4- to 5-week single-blind placebo lead-in period, 683 patients with seated diastolic blood pressure (SeDBP) between 95 and110 mm Hg were randomized to receive once-daily dosing with one of 16 different double-blind, fixed combinations

M. Kochar; R. Guthrie; J. Triscari; K. Kassler-Taub; R. A. Reeves

1999-01-01

124

Innate and Adaptive Immunity in Atherosclerosis  

PubMed Central

Atherosclerosis, a chronic inflammatory disorder, involves both the innate and adaptive arms of the immune response that mediate the initiation, progression, and ultimate thrombotic complications of atherosclerosis. Most fatal thromboses, which may manifest as acute myocardial infarction or ischemic stroke, result from frank rupture or superficial erosion of the fibrous cap overlying the atheroma, processes that occur in inflammatorily active, rupture-prone plaques. Appreciation of the inflammatory character of atherosclerosis has led to the application of C-reactive protein as a biomarker of cardiovascular risk, and the characterization of the anti-inflammatory and immunomodulatory actions of the statin class of drugs. An improved understanding of the pathobiology of atherosclerosis and further studies of its immune mechanisms provide avenues for the development of future strategies directed toward better risk stratification of patients as well as the identification of novel anti-inflammatory therapies. This review retraces leukocyte subsets involved in innate and adaptive immunity and their contributions to atherogenesis.

Packard, Rene R. S.; Lichtman, Andrew H.; Libby, Peter

2010-01-01

125

Small Molecules for the Treatment of Atherosclerosis.  

National Technical Information Service (NTIS)

This invention provides novel small molecules that ameliorate one or more symptoms of atherosclerosis. The small molecules are highly stable and readily administered via an oral route. The small molecules are effective to stimulate the formation and cycli...

A. M. Fogelman G. M. Anantharamaiah M. Navab

2005-01-01

126

Atherosclerosis and the internal mammary arteries  

SciTech Connect

One hundred and fifty patients with coronary artery disease (CAD), 14 (9.3%) of whom had coexisting peripheral vascular disease, underwent bilateral internal mammary arteriography to study the incidence and extent of atherosclerosis in these vessels. Significant atherosclerosis of the internal mammary arteries (IMAs) was present in three patients (2%), of whom one had coexisting peripheral vascular disease. Lesions in the IMAs were found either proximally, close to the origin or distally, around the terminal bifurcation. Six of the 14 patients with peripheral vascular disease (4% of total subjects) had significant atherosclerosis of the brachiocephalic arteries. Atherosclerotic involvement of the IMA is very unusual and rarely interferes with the use of these vessels for coronary bypass. More common, however, is atherosclerosis of the subclavian arteries, a contraindication for IMA grafting if the lesion is proximal to the IMA origin.

Singh, R.N.

1983-06-01

127

DNA damage, vascular senescence and atherosclerosis  

Microsoft Academic Search

Atherosclerosis, an intrinsically age-related disease, is attributed to an excessive inflammatory and fibroproliferative process\\u000a that selectively affects arteries. However, premature atherosclerosis is a feature of several human diseases that are known\\u000a to be defective in DNA repair pathways and characterised by predisposition to early onset of age-related diseases. Accordingly,\\u000a there is a growing amount of data demonstrating that oxidative-stress-induced DNA

Maria Grazia Andreassi

2008-01-01

128

Enhanced Macrophage Tribbles-1 Expression in Murine Experimental Atherosclerosis  

PubMed Central

Development of the atherosclerotic plaque involves a complex interplay between a number of cell types and an extensive inter-cellular communication via cell bound as well as soluble mediators. The family of tribbles proteins has recently been identified as novel controllers of pro-inflammatory signal transduction. The objective of this study was to address the expression pattern of all three tribbles proteins in atherosclerotic plaques from a mouse model of atherosclerosis. Each tribbles were expressed in vascular smooth muscle cells, endothelial cells as well as in resident macrophages of mouse atherosclerotic plaques. The role of IL-1 mediated inflammatory events in controlling tribbles expression was also addressed by inducing experimental atherosclerosis in ApoE?/?IL1R1?/? (double knockout) mice. Immunohistochemical analysis of these mice showed a selective decrease in the percentage of trb-1 expressing macrophages, compared to the ApoE?/? cohort (14.7% ± 1.55 vs. 26.3% ± 1.19). The biological significance of this finding was verified in vitro where overexpression of trb-1 in macrophages led to a significant attenuation (~70%) of IL-6 production as well as a suppressed IL-12 expression induced by a proinflammatory stimulus. In this in vitro setting, expression of truncated trb-1 mutants suggests that the kinase domain of this protein is sufficient to exert this inhibitory action.

Sung, Hye Youn; Francis, Sheila E.; Arnold, Nadine D.; Holland, Karen; Ernst, Vanessa; Angyal, Adrienn; Kiss-Toth, Endre

2012-01-01

129

Enhanced macrophage tribbles-1 expression in murine experimental atherosclerosis.  

PubMed

Development of the atherosclerotic plaque involves a complex interplay between a number of cell types and an extensive inter-cellular communication via cell bound as well as soluble mediators. The family of tribbles proteins has recently been identified as novel controllers of pro-inflammatory signal transduction. The objective of this study was to address the expression pattern of all three tribbles proteins in atherosclerotic plaques from a mouse model of atherosclerosis. Each tribbles were expressed in vascular smooth muscle cells, endothelial cells as well as in resident macrophages of mouse atherosclerotic plaques. The role of IL-1 mediated inflammatory events in controlling tribbles expression was also addressed by inducing experimental atherosclerosis in ApoE-/-IL1R1-/- (double knockout) mice. Immunohistochemical analysis of these mice showed a selective decrease in the percentage of trb-1 expressing macrophages, compared to the ApoE-/- cohort (14.7% ± 1.55 vs. 26.3% ± 1.19). The biological significance of this finding was verified in vitro where overexpression of trb-1 in macrophages led to a significant attenuation (~70%) of IL-6 production as well as a suppressed IL-12 expression induced by a proinflammatory stimulus. In this in vitro setting, expression of truncated trb-1 mutants suggests that the kinase domain of this protein is sufficient to exert this inhibitory action. PMID:24832046

Sung, Hye Youn; Francis, Sheila E; Arnold, Nadine D; Holland, Karen; Ernst, Vanessa; Angyal, Adrienn; Kiss-Toth, Endre

2012-01-01

130

The Chylomicron: Relationship to Atherosclerosis  

PubMed Central

The B-containing lipoproteins are the transporters of cholesterol, and the evidence suggests that the apo B48-containing postprandial chylomicron particles and the triglyceride-rich very low density lipoprotein (VLDL) particles play an important part in the development of the plaque both directly and indirectly by their impact on LDL composition. The ratio of dietary to synthesised cholesterol is variable but tightly regulated: hence intervention with diet at best reduces serum cholesterol by <20% andusually <10%. Statins are the mainstay of cholesterol reduction therapy, but they increase cholesterol absorption, an example of the relationship between synthesis and absorption. Inhibition of cholesterol absorption with Ezetimibe, an inhibitor of Niemann Pick C1-like 1 (NPC1-L1), the major regulator of cholesterol absorption, increases cholesterol synthesis and hence the value of adding an inhibitor of cholesterol absorption to an inhibitor of cholesterol synthesis. Apo B48, the structural protein of the chylomicron particle, is synthesised in abundance so that the release of these particles is dependent on the amount of cholesterol and triglyceride available in the intestine. This paper will discuss cholesterol absorption and synthesis, chylomicron formation, and the effect of postprandial lipoproteins on factors involved in atherosclerosis.

Tomkin, Gerald H.; Owens, Daphne

2012-01-01

131

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.

Matthys, K. E.

1997-01-01

132

Superoxide and Peroxynitrite in Atherosclerosis  

NASA Astrophysics Data System (ADS)

The role of reactive oxygen species in the vascular pathology associated with atherosclerosis was examined by testing the hypothesis that impaired vascular reactivity results from the reaction of nitric oxide (^.NO) with superoxide (O^-_2), yielding the oxidant peroxynitrite (ONOO^-). Contractility studies were performed on femoral arteries from rabbits fed a cholesterol-supplemented diet. Cholesterol feeding shifted the EC50 for acetylcholine (ACh)-induced relaxation and impaired the maximal response to ACh. We used pH-sensitive liposomes to deliver CuZn superoxide dismutase (SOD; superoxide:superoxide oxidoreductase, EC 1.15.1.1) to critical sites of ^.NO reaction with O^-_2. Intravenously injected liposomes (3000 units of SOD per ml) augmented ACh-induced relaxation in the cholesterol-fed group to a greater extent than in controls. Quantitative immunocytochemistry demonstrated enhanced distribution of SOD in both endothelial and vascular smooth muscle cells as well as in the extracellular matrix. SOD activity in vessel homogenates of liposome-treated rabbits was also increased. Incubation of ? very low density lipoprotein with ONOO^- resulted in the rapid formation of conjugated dienes and thiobarbituric acid-reactive substances. Our results suggest that the reaction of O^-_2 with ^.NO is involved in the development of atherosclerotic disease by yielding a potent mediator of lipoprotein oxidation, as well as by limiting ^.NO stimulation of vascular smooth muscle guanylate cyclase activity.

White, C. Roger; Brock, Tommy A.; Chang, Ling-Yi; Crapo, James; Briscoe, Page; Ku, David; Bradley, William A.; Gianturco, Sandra H.; Gore, Jeri; Freeman, Bruce A.; Tarpey, Margaret M.

1994-02-01

133

Hyperimmunization of apo-E-deficient mice with homologous malondialdehyde low-density lipoprotein suppresses early atherogenesis  

Microsoft Academic Search

The role of the immune system in modulating atherosclerosis has recently been the subject of intensive research. Several previous authors have put forward a paradigm of the autoimmune process occurring in the vicinity of the plaque. Two recent studies have shown that immunization of rabbits with homologous modified low-density lipoprotein (LDL) led to suppression of atherosclerosis. In the current study

Jacob George; Arnon Afek; Boris Gilburd; Hana Levkovitz; Aviv Shaish; Iris Goldberg; Yuri Kopolovic; Georg Wick; Yehuda Shoenfeld; Dror Harats

1998-01-01

134

Optimal therapeutic strategy for treating patients with hypertension and atherosclerosis: focus on olmesartan medoxomil  

PubMed Central

Cardiovascular (CV) disease is a major factor in mortality rates around the world and contributes to more than one-third of deaths in the US. The underlying cause of CV disease is atherosclerosis, a chronic inflammatory process that is clinically manifested as coronary artery disease, carotid artery disease, or peripheral artery disease. It has been predicted that atherosclerosis will be the primary cause of death in the world by 2020. Consequently, developing a treatment regimen that can slow or even reverse the atherosclerotic process is imperative. Atherogenesis is initiated by endothelial injury due to oxidative stress associated with CV risk factors including diabetes mellitus, hypertension, cigarette smoking, dyslipidemia, obesity, and metabolic syndrome. Since the renin–angiotensin–aldosterone system (RAAS) plays a key role in vascular inflammatory responses, hypertension treatment with RAAS-blocking agents (angiotensin-converting enzyme inhibitors [ACEIs] and angiotensin II receptor blockers [ARBs]) may slow inflammatory processes and disease progression. Reduced nitric oxide (NO) bioavailability has an important role in the process of endothelial dysfunction and hypertension. Therefore, agents that increase NO and decrease oxidative stress, such as ARBs and ACEIs, may interfere with atherosclerosis. Studies show that angiotensin II type 1 receptor antagonism with an ARB improves endothelial function and reduces atherogenesis. In patients with hypertension, the ARB olmesartan medoxomil provides effective blood pressure lowering, with inflammatory marker studies demonstrating significant RAAS suppression. Several prospective, randomized studies show vascular benefits with olmesartan medoxomil: reduced progression of coronary atherosclerosis in patients with stable angina pectoris (OLIVUS); decreased vascular inflammatory markers in patients with hypertension and micro- (pre-clinical) inflammation (EUTOPIA); improved common carotid intima-media thickness and plaque volume in patients with diagnosed atherosclerosis (MORE); and resistance vessel remodeling in patients with stage 1 hypertension (VIOS). Although CV outcomes were not assessed in these studies, the observed benefits in surrogate endpoints of disease suggest that RAAS suppression with olmesartan medoxomil may potentially have beneficial effects on CV outcomes in these patient populations.

Mason, R Preston

2011-01-01

135

EP01 A stinky remedy for atherosclerosis.  

PubMed

Being the last key enzyme of the reverse trans-sulfuration pathway, cystathionine gamma-lyase (CSE) catalyzes the conversion of cystathionine into cysteine, ?-ketobutyrate, and ammonia. It further catalyzes cysteine into a gasotransmitter H2S [1]. CSE-mediated H2S production affects lipid metabolism and cardiovascular health, which is exemplarily manifested in the pathogenesis of atherosclerosis [2]. In order to identify the role of endogenous H2S in the development of atherosclerosis, we tried to feed CSE deficient (CSE-KO) mice with a high fat diet as an atherosclerosis model. The control diet for this treatment is the cysteine-limited casein based rodent diet. With this control diet, CSE-KO mice showed growth retardation, decreased cysteine, H2S, and glutathione levels, and increased plasma homocysteine level. None of the CSE-KO mice survived with the cysteine-limited diet. Supplementation of cysteine, but not NaHS, to the animals sustained their lives [3]. The linkage between cysteine biosynthesis and CSE deficiency for life sustainability is thus established [3,4]. In the following studies, cysteine had been added to control chow or atherogenic paigen-type diet to feed CSE-KO and WT mice for 12weeks. While WT mice and CSE-KO mice did not develop any atherosclerosis with the control chow, CSE-KO mice fed with atherogenic diet developed early fatty streak lesions in the aortic root. We further show that increased atherosclerotic lesion formation in CSE-KO mice was associated with elevated plasma cholesterol and LDL-cholesterol levels, enhanced aortic cell proliferation and oxidative stress as well as increased adhesion molecule expression. Supplementation of NaHS to the animals significantly reversed the atherosclerosis development. The mice with double knockout of CSE and apolipoprotein E (apoE) gene expression exhibited more severe atherosclerosis than CSE or apoE knockout alone [5]. Our results demonstrate that a physiological level of endogenous H2S limits the development of atherosclerosis by reducing vessel intimal proliferation and inhibiting adhesion molecule expression, and that the down-regulation of CSE/H2S system predisposes vascular tissues to vascular remodelling and early development of atherosclerosis. We may now claim that H2S is a stinky remedy for atherosclerosis [2]. PMID:24948232

Wang, Rui

2013-09-01

136

Advances in experimental dyslipidemia and atherosclerosis.  

PubMed

Among the models of dyslipidemia and atherosclerosis, a number of wild-type, naturally defective, and genetically modified animals (rabbits, mice, pigeons, dogs, pigs, and monkeys) have been characterized. In particular, their similarities to and differences from humans in respect to relevant biochemical, physiologic, and pathologic conditions have been evaluated. Features of atherosclerotic lesions and their specific relationship to plasma lipoprotein particles have been critically reviewed and summarized. All animal models studied have limitations: the most significant advantages and disadvantages of using a specific animal species are outlined here. New insights in lipid metabolism and genetic background with regard to variations in pathogenesis of dyslipidemia-associated atherogenesis have also been reviewed. Evidence suggests that among wild-type species, strains of White Carneau pigeons and Watanabe Heritable Hyperlipidemic and St. Thomas's Hospital rabbits are preferable to the cholesterol-fed wild-type animal species in dyslipidemia and atherosclerosis research. Evidence for the usefulness of both wild-type and transgenic animals in studying the involvement of inflammatory pathways and Chlamydia pneumoniae infection in pathogenesis of atherosclerosis has also been summarized. Transgenic mice and rabbits are excellent tools for studying specific gene-related disorders. However, despite these significant achievements in animal experimentation, there are no suitable animal models for several rare types of fatal dyslipidemia-associated disorders such as phytosterolemia and cerebrotendinous xanthomatosis. An excellent model of diabetic atherosclerosis is unavailable. The question of reversibility of atherosclerosis still remains unanswered. Further work is needed to overcome these deficiencies. PMID:11555665

Moghadasian, M H; Frohlich, J J; McManus, B M

2001-09-01

137

[The status of atherosclerosis prevention in Austria].  

PubMed

Although atherosclerosis is today seen as presenting a distinct clinical picture, there are almost no data available about the impact this has on medical practice and about the point at which a patient is considered high-risk. As part of a larger project on the prevention of heart disease and atherosclerosis, "Aktion plus leben", 1,117 physicians were polled in a scientific survey. The study was carried out in some 100 hospitals throughout Austria, above all in departments of internal medicine, but also in neurological departments, and in a number of other units. The results showed that in fact over 90% of those questioned see atherosclerosis as a separate, treatable illness in the context of risk prevention. The most frequent methods of diagnosis were specified as ultrasound and the clarification of symptoms of coronary heart disease. Atherosclerosis prevention is initiated above all in patients with coronary heart disease, myocardial infarction and stroke, but also very frequently in those with diabetes, peripheral vascular occlusive disease, hyperlipidemia and hypertension. Of particular interest to us was the respondents' evaluation of the effect of ramipril, the angiotensin-converting enzyme (ACE) inhibitor used in the HOPE study. The majority of those questioned see a broad range of indications for this ACE inhibitor and ascribe to it a profibrinolytic, antiinflammatory and plaque-stabilising action. Although the survey sought assessment of just one particular medication as a possible treatment option, the study documents the importance of a more inclusive concept of atherosclerosis prevention. PMID:13677258

Schoberberger, Rudolf; Bayer, Peter; Kunze, Michael

2003-01-01

138

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.

Eren, Esin; Yilmaz, Necat; Aydin, Ozgur

2013-01-01

139

The Hemostasis System in Murine Atherosclerosis  

PubMed Central

Atherosclerosis is a self-sustaining inflammatory fibroproliferative disease that progresses in discrete stages and involves a number of cell types and effector molecules. The potential importance of the coagulation, anticoagulation, and fibrinolytic systems in atherosclerosis is based on the observation that fibrin deposits and fibrin degradation products are resident in atherosclerotic plaques. A number of investigations have been conducted to probe the relationships between components of the hemostasis system and atherosclerosis; and these types of studies proliferated after the availability of mice genetically manipulated to emphasize the impact of genes of interest. In order to summarize recent progress in this area, this review is focused on mice lacking individual hemostasis genes and their contributions to steps of the atherosclerotic process.

Iwaki, Takayuki; Ploplis, Victoria A.; Castellino, Francis J.

2013-01-01

140

Toll-Like Receptors in Atherosclerosis  

PubMed Central

Atherosclerosis, the leading cause of cardiovascular disease (CVD), is driven by inflammation. Increasing evidence suggests that toll-like receptors (TLRs) are key orchestrators of the atherosclerotic disease process. Interestingly, a distinct picture is being revealed for individual receptors in atherosclerosis. TLRs exhibit a complex nature enabling the detection of multiple motifs named danger-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs). Activation of these receptors triggers an intracellular signalling cascade mediated through MyD88 or TRIF, leading to the production of pro- and anti-inflammatory cytokines. In this review we explore key novel findings pertaining to TLR signalling in atherosclerosis, including recently described endosomal TLRs and future directions in TLR research.

Falck-Hansen, Mika; Kassiteridi, Christina; Monaco, Claudia

2013-01-01

141

HIV, inflammation, and calcium in atherosclerosis.  

PubMed

Atherosclerosis is consistently higher among the HIV-positive patients, with or without treatment, than among the HIV-negative population. Risk factors linked to atherosclerotic cardiovascular disease in HIV infection are both traditional and HIV specific although the underlying mechanisms are not fully delineated. Three key sequential biological processes are postulated to accelerate progression of atherosclerosis in the context of HIV: (1) inflammation, (2) transformation of monocytes to macrophages and then foam cells, and (3) apoptosis of foam cells leading to plaque development through Ca(2+)-dependent endoplasmic reticulum stress. These proatherogenic mechanisms are further affected when HIV interacts with the genes involved in various phases within this network. PMID:24265418

Shrestha, Sadeep; Irvin, Marguerite R; Grunfeld, Carl; Arnett, Donna K

2014-02-01

142

Impact of Infectious Burden on Progression of Carotid Atherosclerosis  

Microsoft Academic Search

Background and Purpose—Recent findings suggest a causative role of infections in the pathogenesis of atherosclerosis. The extent of atherosclerosis and the prognosis of patients with atherosclerosis seem to be increased by the number of infections to which an individual has been exposed. In a prospective study, we evaluated the effect of 8 pathogens and the aggregate pathogen burden on the

Christine Espinola-Klein; Hans-Jürgen Rupprecht; Stefan Blankenberg; Christoph Bickel; Helmuth Kopp; Anja Victor; Gerd Hafner; Wilfried Prellwitz; Wolfgang Schlumberger; Jürgen Meyer

2010-01-01

143

Aliskiren reduces blood pressure and suppresses plasma renin activity in combination with a thiazide diuretic, an angiotensin-converting enzyme inhibitor, or an angiotensin receptor blocker.  

PubMed

Thiazide diuretics, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers all cause reactive rises in plasma renin activity. We hypothesized that renin inhibition with aliskiren would prevent this reactive rise and also enhance blood pressure lowering. In 3 open-label studies in which blood pressure was assessed with ambulatory measurement, aliskiren was administered to patients with mild-to-moderate hypertension in combination with hydrochlorothiazide (n=23), ramipril (n=21), or irbesartan (n=23). In the diuretic combination study, the addition of 25 mg of hydrochlorothiazide to 150 mg of aliskiren daily for 3 weeks significantly lowered daytime pressure, compared with aliskiren monotherapy (systolic/diastolic mean change from baseline [SEM]: daytime: -18.4 [2.1]/ -10.6 [1.7] versus -10.4 [1.8]/-5.8 [1.4]; nighttime: -15.6 [2.7]/-8.1 [1.8] versus -8.8 [2.9]/-5.0 [2.2]). In the angiotensin-converting enzyme inhibitor combination study, the addition of 75 or 150 mg of aliskiren to 5 mg of ramipril alone for 3 weeks further lowered both daytime and nighttime pressures compared with ramipril monotherapy (daytime: -10.5 [2.9]/-8.1 [2.1] and -14 [3.7]/-8.7 [2.3] versus -6.1 [2.4]/-5.9 [1.5]; nighttime: -8.1 [2.6]/-5.3 [2.4] and -9.6 [3.4]/-5.3 [2.4] versus -2 [2.3]/-0.7 [2.2]). In the angiotensin receptor blocker combination study, the addition of 75 or 150 mg of aliskiren to 150 mg of irbesartan alone, for 3 weeks, resulted in significantly lower nighttime pressures compared with irbesartan monotherapy (daytime: -14.8 [2]/-8.2 [1.3] and -13.3 [1.6]/-6.8 [0.9] versus -11.4 [1.6]/-6.5 [1.1]; nighttime: -16.1 [2.4]/-8.6 [1.7] and -13.2 [2.7]/-7.2 [1.9] versus -9.0 [2.5]/-4.7 [1.9]). Aliskiren (150 mg) alone significantly inhibited plasma renin activity by 65% (P<0.0001). Ramipril and irbesartan monotherapy caused 90% and 175% increases in plasma renin activity, respectively. By contrast, when aliskiren was coadministered with hydrochlorothiazide, ramipril, or irbesartan, plasma renin activity did not increase but remained similar to baseline levels or was decreased (combination therapy versus untreated; median [interquartile range]; aliskiren and hydrochlorothiazide: 0.4 [0.2 to 1.1] versus 0.7 [0.5 to 1.3]; ramipril and aliskiren: 0.5 [0.3 to 0.9] versus 0.6 [0.5 to 0.8]; irbesartan and aliskiren: 0.4 [0.2 to 0.9] versus 0.6 [0.4 to 0.9]). These results suggest that renin inhibition with aliskiren in these combinations increases renin-angiotensin system suppression, improves 24-hour blood pressure control, and may ultimately provide better end-organ protection in patients with hypertension. PMID:17159081

O'Brien, Eoin; Barton, John; Nussberger, Juerg; Mulcahy, David; Jensen, Chris; Dicker, Patrick; Stanton, Alice

2007-02-01

144

A rare case of lack of correlation of carotid atherosclerosis and coronary atherosclerosis.  

PubMed

Signs of plaque inflammation in carotid arteries may serve as a window to the entire cardiovascular system, to identify "vulnerable" patients. Moreover, flow-mediated vasodilation in the brachial artery and intima media thickness (IMT) in the carotid artery could represent a surrogate diagnostic method for assessment of coronary artery disease (CAD) severity. Renal function is an important predictor of the presence and severity of angiographic CAD in patients without severe renal impairment with incremental value over traditional risk factors for CAD and IMT. It has also been reported ,that renal dysfunction may exert differential effects on the development of coronary and peripheral atherosclerosis. An accumulating burden of hypertension, diabetes, and smoking is important in the progression of atherosclerosis from the coronary to the carotid circulation. We present an unusual case of lack of correlation of carotid atherosclerosis and coronary atherosclerosis. PMID:19345427

Dattilo, Giuseppe; Morabito, Gaetano; Cerrito, Marco; Lamari, Annalisa; Tulino, Domenico; Marte, Filippo; Patanè, Salvatore

2011-10-01

145

The role of heat shock protein 90 in migration and proliferation of vascular smooth muscle cells in the development of atherosclerosis.  

PubMed

The molecular chaperone heat shock protein 90 (HSP90) is overexpressed in plaques of atherosclerosis patients, and is associated with plaque instability. However, the role of HSP90 in atherosclerosis remains unclear. The present study investigated the effects of HSP90 inhibition on migration and proliferation of vascular smooth muscle cells (VSMCs) and involvement in atherosclerosis. To examine the role of HSP90 in VSMC migration, VSMCs were treated with the specific HSP90 inhibitors, 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) and STA-9090. Results of a chemotaxis assay showed that the HSP90 inhibitors suppress migration of VSMCs. HSP90 inhibition also prevented invasion and sprout formation of VSMCs via inhibition of matrix metalloproteinase-2 proteolytic activity. Results of a flow cytometric analysis showed that HSP90 inhibition induces cell cycle arrest via regulation of cyclin D3, PCNA and pRb. To investigate the role of HSP90 in the development of atherosclerosis, low-density lipoprotein receptor (LDLR) deficient mice were fed with a high cholesterol diet for 4weeks and treated with 17-AAG for 8weeks. HSP90 inhibition suppressed migration of VSMCs into atherosclerotic plaque lesions in high cholesterol diet-stimulated LDLR(-/-) mice. Inhibition of HSP90 attenuates formation of atherosclerotic plaques via suppression of VSMC migration and proliferation, indicating that HSP90 inhibitors can be used as therapeutic agents for atherosclerosis and in stent restenosis. PMID:24650873

Kim, Jeonghan; Jang, Sung-Wuk; Park, Eunsoo; Oh, Minseok; Park, Sodam; Ko, Jesang

2014-07-01

146

Immune and Inflammatory Mechanisms of Atherosclerosis*  

PubMed Central

Atherosclerosis is an inflammatory disease of the wall of large- and medium-sized arteries that is precipitated by elevated levels of low-density lipoprotein (LDL) cholesterol in the blood. Although dendritic cells (DCs) and lymphocytes are found in the adventitia of normal arteries, their number is greatly expanded and their distribution changed in human and mouse atherosclerotic arteries. Macrophages, DCs, foam cells, lymphocytes, and other inflammatory cells are found in the intimal atherosclerotic lesions. Beneath these lesions, adventitial leukocytes organize in clusters that resemble tertiary lymphoid tissues. Experimental interventions can reduce the number of available blood monocytes, from which macrophages and most DCs and foam cells are derived, and reduce atherosclerotic lesion burden without altering blood lipids. Under proatherogenic conditions, nitric oxide production from endothelial cells is reduced and the burden of reactive oxygen species (ROS) and advanced glycation end products (AGE) is increased. Incapacitating ROS-generating NADPH oxidase or the receptor for AGE (RAGE) has beneficial effects. Targeting inflammatory adhesion molecules also reduces atherosclerosis. Conversely, removing or blocking IL-10 or TGF-? accelerates atherosclerosis. Regulatory T cells and B1 cells secreting natural antibodies are atheroprotective. This review summarizes our current understanding of inflammatory and immune mechanisms in atherosclerosis.

Galkina, Elena; Ley, Klaus

2009-01-01

147

The Insulin Resistance Atherosclerosis Study (IRAS)  

Microsoft Academic Search

The Insulin Resistance Atherosclerosis Study (IRAS) is the first epidemiologic study designed to assess the relationships between insulin resistance, insulinemia, glycemia, other components of the insulin resistance syndrome, and prevalent cardiovascular disease (CVD) in a large multiethnic cohort. Over 1600 men and women were recruited from four geographic areas to represent a range of glucose tolerance (normal, impaired, and diabetic)

Lynne E. Wagenknecht; Elizabeth J. Mayer; Marian Rewers; Steven Haffner; Joseph Selby; Gerald M Borok; Leora Henkin; George Howard; Peter J. Savage; Mohammed F. Saad; Richard N. Bergman; Richard Hamman

1995-01-01

148

Atherosclerosis: current pathogenesis and therapeutic options  

Microsoft Academic Search

Coronary artery disease (CAD) arising from atherosclerosis is a leading cause of death and morbidity worldwide. The underlying pathogenesis involves an imbalanced lipid metabolism and a maladaptive immune response entailing a chronic inflammation of the arterial wall. The disturbed equilibrium of lipid accumulation, immune responses and their clearance is shaped by leukocyte trafficking and homeostasis governed by chemokines and their

Heidi Noels; Christian Weber

2011-01-01

149

Oestrogen, atherosclerosis and cardiovascular disease in women  

PubMed Central

What part menopause and hormone replacement therapy (HRT) play in the risk of cardiovascular disease in women after middle-age is still debated. The associations between menopause, HRT and cardiovascular disease as well as atherosclerosis were examined in a large cohort study. Our results suggest menopause has an unfavorable association with several cardiovascular risk factors, structural characteristics of the large arteries, on atherosclerosis and on coronary heart disease. HRT was shown to protect women from development of atherosclerosis in the lower extremities and in the common carotid artery. This suggests that the mechanisms underlying this protection include inhibition of the atherosclerotic process. Our analyses of a randomised, placebo-controlled study could not confirm the effect on HRT on atherosclerosis of the common carotid artery. As findings from large randomised trials do not confirm the benefit of estrogen therapy for prevention of cardiovascular disease no definite conclusions can be drawn, and HRT should not be recommended for this purpose in clinical practice. ImagesFigure 1Figure 2Figure 3

Westendorp, I.C.D.; Grobbee, D.E.; Witteman, J.C.M.

2001-01-01

150

Is atherosclerosis an immunologically mediated disease?  

Microsoft Academic Search

In contrast to general beliefs, recent data from different laboratories have provided evidence that the first stages of atherosclerosis are of an inflammatory nature. Here, Georg Wick and colleagues suggest that an autoimmune reaction against heat shock protein 60 (Hsp60), expressed by endothelial cells in areas that are subject to increased haemodynamic stress, is the initiating event in atherogenesis. Humoral

Georg Wick; Georg Schett; Albert Amberger; Roman Kleindienst; Qingbo Xu

1995-01-01

151

PPARs and LXRs: atherosclerosis goes nuclear  

Microsoft Academic Search

Atherosclerosis is the leading cause of mortality in the Western world, and new therapeutics to target the metabolic and inflammatory factors that underlie its pathogenesis are needed. Peroxisome proliferator-activated receptors and liver X receptors are lipid-activated nuclear receptors that regulate systemic glucose and lipid metabolism, and modulate inflammation within the vascular wall. New understanding of their functions in physiology and

Grant D. Barish; Ronald M. Evans

2004-01-01

152

Protective Role of Interleukin10 in Atherosclerosis  

Microsoft Academic Search

The potential role of anti-inflammatory cytokines in the modulation of the atherosclerotic process remains unknown. Interleukin (IL)-10 has potent deactivating properties in macrophages and T cells and modulates many cellular processes that may interfere with the development and stability of the atherosclerotic plaque. IL-10 is expressed in human atherosclerosis and is associated with decreased signs of inflammation. In the present

Ziad Mallat; Sandrine Besnard; Micheline Duriez; Virginie Deleuze; Florence Emmanuel; Michel F. Bureau; Fabienne Soubrier; Bruno Esposito; Helene Duez; Catherine Fievet; Bart Staels; Nicolas Duverger; Daniel Scherman; Alain Tedgui

2010-01-01

153

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.

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

2014-01-01

154

Infectious burden and atherosclerosis: A clinical issue.  

PubMed

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

2014-07-16

155

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

156

ATP-Binding Cassette Transporters and HDL Suppress Hematopoietic Stem Cell Proliferation  

PubMed Central

Elevated leukocyte cell numbers (leukocytosis), and monocytes in particular, promote atherosclerosis; however, how they become increased is poorly understood. Mice deficient in the adenosine triphosphate–binding cassette (ABC) transporters ABCA1 and ABCG1, which promote cholesterol efflux from macrophages and suppress atherosclerosis in hypercholesterolemic mice, displayed leukocytosis, a transplantable myeloproliferative disorder, and a dramatic expansion of the stem and progenitor cell population containing Lin? Sca-1+Kit+ (LSK) in the bone marrow. Transplantation of Abca1?/? Abcg1?/? bone marrow into apolipoprotein A-1 transgenic mice with elevated levels of high-density lipoprotein (HDL) suppressed the LSK population, reduced leukocytosis, reversed the myeloproliferative disorder, and accelerated atherosclerosis. The findings indicate that ABCA1, ABCG1, and HDL inhibit the proliferation of hematopoietic stem and multipotential progenitor cells and connect expansion of these populations with leukocytosis and accelerated atherosclerosis.

Yvan-Charvet, Laurent; Pagler, Tamara; Gautier, Emmanuel L.; Avagyan, Serine; Siry, Read L.; Han, Seongah; Welch, Carrie L.; Wang, Nan; Randolph, Gwendalyn J.; Snoeck, Hans W.; Tall, Alan R.

2011-01-01

157

Follow-up of cardiovascular risk markers in hypertensive patients treated with irbesartan: results of the i-SEARCH Plus Registry.  

PubMed

Microalbuminuria (MAU), high-sensitivity C-reactive protein (hsCRP), and N-terminal pro-brain natriuretic peptide (NT-proBNP) are risk markers used to predict the prognosis of hypertensive patients; however, they have not been prospectively evaluated in primary care. An investigation was conducted using i-SEARCH Plus, a registry documenting 1649 patients with hypertension who received irbesartan at office-based cardiologists over 12 months. Mean age at baseline was 61.4±11.3 years, 43.2% were women, and blood pressure was 159.8±20.1/93.4±11.9mm Hg. Median albumin/creatinine ratio (ACR) at baseline was 9.90 (interquartile range [IQR], 5.76--25.52) mg/g, hsCRP 2.46 (IQR, 1.16--5.14) mg/L, and NT-proBNP 89.28 (IQR, 38.63-203.40) pg/mL. In patients with MAU (ACR ?20mg/g), the age-adjusted risk of a combined end point of newly diagnosed coronary artery disease (CAD), myocardial infarction, stroke/transitory ischemic attack, and death at 12-month follow-up was increased (odds ratio [OR], 2.67; 95% confidence interval [CI], 1.49-4.76), as was the incidence of CAD (OR, 3.27; 95%CI, 1.39-7.68) and death (OR, 4.63; 95%CI, 1.44-14.94). No correlations with end points were found for hsCRP or NT-proBNP after adjusting for age and the presence of MAU. MAU is an independent predictor of cardiovascular events in hypertensive patients. These findings confirm previous reports on the prognostic value of MAU and establish its incremental value over hsCRP and NT-proBNP. PMID:21122056

Tebbe, Ulrich; Bramlage, Peter; Lüders, Stephan; Cuneo, Alessandro; Sistig, Peter; de Haan, Fokko; Schmieder, Roland; Böhm, Michael; Paar, W Dieter; Schrader, Jochen

2010-12-01

158

Conjugated Equine Estrogens Inhibit Progression of Atherosclerosis but Have No Effect on Intimal Hyperplasia or Arterial Remodeling Induced by Balloon Catheter Injury in Monkeys  

Microsoft Academic Search

Objectives. This study sought to determine the effects of estro- gen treatment on atherosclerosis progression and the proliferative and structural responses of the atherosclerotic arteries to injury. Background. Estrogen treatment suppresses the intimal re- sponse to arterial injury in nonatherosclerotic rodents and rab- bits and inhibits the in vitro proliferation of smooth muscle cells. However, the effect of estrogen on

RANDOLPH L. GEARY; MICHAEL R. ADAMS; MARSHALL E. BENJAMIN; J. KOUDY WILLIAMS; DVM Winston-Salem

159

Apolipoproteins and amyloid fibril formation in atherosclerosis.  

PubMed

Amyloid fibrils arise from the aggregation of misfolded proteins into highly-ordered structures. The accumulation of these fibrils along with some non-fibrillar constituents within amyloid plaques is associated with the pathogenesis of several human degenerative diseases. A number of plasma apolipoproteins, including apolipoprotein (apo) A-I, apoA-II, apoC-II and apoE are implicated in amyloid formation or influence amyloid formation by other proteins. We review present knowledge of amyloid formation by apolipoproteins in disease, with particular focus on atherosclerosis. Further insights into the molecular mechanisms underlying their amyloidogenic propensity are obtained from in vitro studies which describe factors affecting apolipoprotein amyloid fibril formation and interactions. Additionally, we outline the evidence that amyloid fibril formation by apolipoproteins might play a role in the development and progression of atherosclerosis, and highlight possible molecular mechanisms that could contribute to the pathogenesis of this disease. PMID:21400045

Teoh, Chai Lean; Griffin, Michael D W; Howlett, Geoffrey J

2011-02-01

160

Subclinical atherosclerosis in primary antiphospholipid syndrome.  

PubMed

To test the atherosclerosis hypothesis in primary antiphospholipid syndrome (PAPS) we measured intima media thickness (IMT) of carotid arteries and other cardiovascular risk factors in 44 patients with PAPS (mean age 35 +/- 12 years), in 25 patients with inherited thrombophilia (mean age 40 +/- 10 years), and in 34 normal controls (mean age 38 +/- 11 years). The frequency of smoking, hypertension, and dyslipidemia was similar across groups. IMT was almost similar across groups at age groups below 40 years but IMT was greater in PAPS than controls at the common carotid (P = 0.01), at the bifurcation (P = 0.003), and at the internal carotid (P = 0.005) in the age group over 40 years. Atherosclerosis is a possibility in PAPS patients in their fourth decade of life or older. PMID:17894012

Margarita, Annamaria; Batuca, Joana; Scenna, Giovanna; Alves, Jose' Delgado; Lopez, Louis; Iannaccone, Luigi; Matsuura, Eiji; Ames, Paul R J

2007-06-01

161

Quest for New Biomarkers in Atherosclerosis  

PubMed Central

The Cho and Baldan labs focus their efforts on novel pathways that control atherogenesis. MIF (Macrophage migration inhibitory factor) recruits macrophages to atherosclerotic lesions and activates the production of matrix proteinases, which in turn destabilize atherosclerotic plaques. On the other hand, miR-33 coordinates the expression of several sterol transporters essential for high-density lipoprotein metabolism and bile secretion. Thus, both MIF and miR-33 are promising therapeutic targets to manage patients at risk of developing atherosclerosis.

Cho, Yoonsang; Baldan, Angel

2013-01-01

162

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

163

Genetic markers in atherosclerosis: a review.  

PubMed Central

There is a growing number of lipoprotein markers recognized by immunological, electrophoretic, and other biochemical methods, and a beginning has been made on studying their modes of inheritance and linkage relations. Suggestive but inconclusive evidence of a relation between the cerumen polymorphism and arteriosclerosis has been published. Associations of the ABO blood groups with cardiovascular disease and serum lipid levels have been established, but the exact relation to lipoproteins and atherosclerosis remains to be determined.

Morton, N E

1976-01-01

164

Emerging, noninvasive surrogate markers of atherosclerosis  

Microsoft Academic Search

Noninvasive surrogate markers of atherosclerosis allow the physician to identify subclinical disease before the occurrence\\u000a of adverse cardiovascular events, thereby limiting the need to perform invasive diagnostic procedures. Imaging modalities,\\u000a such as carotid artery ultrasound, two-dimensional echocardiography, coronary artery calcium imaging, cardiac magnetic resonance\\u000a imaging, ankle-brachial indices, brachial artery reactivity testing, and epicardial coronary flow reserve measurements, provide\\u000a information that

Samir N. Patel; Venkataraman Rajaram; Sanjay Pandya; Benjamin M. Fiedler; Charlotte J. Bai; Rachel Neems; Matt Feinstein; Marshall Goldin; Steven B. Feinstein

2004-01-01

165

Bone mineral density and coronary atherosclerosis  

PubMed Central

Background The association between low bone mineral density (BMD) and atherosclerosis is still unknown. In this study BMD assessed in patients with and without coronary artery atherosclerosis is determined by angiography. Methods A total number of 123 consecutive patients referred for coronary angiography were evaluated by dual X-ray absorptiometry. Obstructive CAD was diagnosed when ?50% of lumen was narrowed. Conventional atherosclerosis risk factors were also assessed. Results The mean age of the patients was 59 ± 8 years. There was frequency of 48.7% male. The prevalence of diabetes was 31.2%, hypertension 57%, dyslipoproteinaemia 51%, vitamin D deficiency 50% and history of smoking 80.8%. Coronary angiography was normal in 15 patients (12.6%) while 67 patients (55.5%) had obstructive CAD. DXA scan showed 25 patients (21%) with normal BMD, 39 patients (32.7%) with osteopenia, and 55 others (46.2%) with osteoporosis. Lower BMD results were significantly associated with older age and lower BMI but it was not associated significantly with diabetes, hypertension, lipids levels or smoking. Moreover the prevalence of obstructive CAD and minimal CAD differed between groups with normal and low bone density but this was not significant (p = 0.67 and 0.52, respectively). The mean T score comparison between patients with and without CAD was also not different. Conclusions In patients with and without obstructive CAD the prevalence of low BMD results are not different.

Hajsadeghi, Shokoofeh; Khamseh, Mohamad-Ebrahim; Larijani, Bagher; Abedin, Behzad; Vakili-Zarch, Anoushiravan; Meysamie, Amir-Pasha; Yazdanpanah, Fariba

2011-01-01

166

Increased atherosclerosis in myeloperoxidase-deficient mice  

PubMed Central

Myeloperoxidase (MPO), a heme enzyme secreted by activated phagocytes, generates an array of oxidants proposed to play critical roles in host defense and local tissue damage. Both MPO and its reaction products are present in human atherosclerotic plaque, and it has been proposed that MPO oxidatively modifies targets in the artery wall. We have now generated MPO-deficient mice, and show here that neutrophils from homozygous mutants lack peroxidase and chlorination activity in vitro and fail to generate chlorotyrosine or to kill Candida albicans in vivo. To examine the potential role of MPO in atherosclerosis, we subjected LDL receptor–deficient mice to lethal irradiation, repopulated their marrow with MPO-deficient or wild-type cells, and provided them a high-fat, high-cholesterol diet for 14 weeks. White cell counts and plasma lipoprotein profiles were similar between the two groups at sacrifice. Cross-sectional analysis of the aorta indicated that lesions in MPO-deficient mice were about 50% larger than controls. Similar results were obtained in a genetic cross with LDL receptor–deficient mice. In contrast to advanced human atherosclerotic lesions, the chlorotyrosine content of aortic lesions from wild-type as well as MPO-deficient mice was essentially undetectable. These data suggest an unexpected, protective role for MPO-generated reactive intermediates in murine atherosclerosis. They also identify an important distinction between murine and human atherosclerosis with regard to the potential involvement of MPO in protein oxidation.

Brennan, Marie-Luise; Anderson, Melissa M.; Shih, Diana M.; Qu, Xiao-Dan; Wang, Xuping; Mehta, Asha C.; Lim, Lesley L.; Shi, Weibin; Hazen, Stanley L.; Jacob, Jason S.; Crowley, Jan R.; Heinecke, Jay W.; Lusis, Aldons J.

2001-01-01

167

Fire Suppression  

Microsoft Academic Search

\\u000a Water sprinkler sprays (with relatively large droplet sizes) in residential and commercial structures are probably the most\\u000a well-known application of sprays in fire suppression. In more recent years, water mists (characterized by reduced droplet\\u000a sizes, which may contain additives) have been considered as a replacement for Halon 1301, the most common fire suppressant\\u000a chemical aboard aircraft and ships, but banned

C. Presser; J. C. Yang

168

Atherosclerosis and Atheroma Plaque Rupture: Normal Anatomy of Vasa Vasorum and Their Role Associated with Atherosclerosis  

PubMed Central

Atherosclerosis is primarily a degenerative disorder related to aging with a chronic inflammatory component. There are differences in expression among different vascular beds, inflicting a range of vascular diseases. The majority of studies focus on the inner and medial vascular layers, which are affected at the development of atherosclerosis. Recent evidence shows that the outer layer of blood vessels, composed of the adventitial layer and the vasa vasorum, not only plays a significant role in maintaining vessel integrity, but also reacts to atheroma. What is not clear is the extent of contribution of the outer layer to the process of atherosclerosis. Is it involved in the initiation, progression, and clinical expression of atheroma? Is the inflammation associated with atheroma limited to being merely reactive or is there a proactive element? This paper provides an overview of the normal anatomy of vasa vasorum and potential mechanism of plaque formation due to vascular injury (vasa vasorum) and microhemorrhage.

2014-01-01

169

Deficiency of ABCA1 and ABCG1 in Macrophages Increases Inflammation and Accelerates Atherosclerosis in Mice  

PubMed Central

Rationale Plasma HDL levels are inversely correlated with atherosclerosis. Although it is widely assumed that this is due to the ability of HDL to promote cholesterol efflux from macrophage foam cells, direct experimental support for this hypothesis is lacking. Objective To assess the role of macrophage cholesterol efflux pathways in atherogenesis. Methods and Results We developed MAC-ABCDKO mice with efficient deletion of the ATP Binding Cassette Transporters A1 and G1 (ABCA1 and ABCG1) in macrophages but not in hematopoietic stem or progenitor populations. MAC-ABCDKO bone marrow (BM) was transplanted into Ldlr-/- recipients. On the chow diet, these mice had similar plasma cholesterol and blood monocyte levels but increased atherosclerosis compared to controls. On the Western type diet (WTD), MAC-ABCDKO BM transplanted Ldlr-/- mice had disproportionate atherosclerosis, considering they also had lower VLDL/LDL cholesterol levels than controls. ABCA1/G1 deficient macrophages in lesions showed increased inflammatory gene expression. Unexpectedly, WTD-fed MAC-ABCDKO BM transplanted Ldlr-/- mice displayed monocytosis and neutrophilia in the absence of HSPC proliferation. Mechanistic studies revealed increased expression of M-CSF and G-CSF in splenic macrophage foam cells, driving BM monocyte and neutrophil production. Conclusion These studies 1) show that macrophage deficiency of ABCA1/G1 is pro-atherogenic likely by promoting plaque inflammation and 2) uncover a novel positive feedback loop in which cholesterol-laden splenic macrophages signal BM progenitors to produce monocytes, with suppression by macrophage cholesterol efflux pathways.

Westerterp, Marit; Murphy, Andrew J.; Wang, Mi; Pagler, Tamara A.; Vengrenyuk, Yuliya; Kappus, Mojdeh S.; Gorman, Darren J.; Nagareddy, Prabhakara R.; Zhu, Xuewei; Abramowicz, Sandra; Parks, John S.; Welch, Carrie; Fisher, Edward A.; Wang, Nan; Yvan-Charvet, Laurent; Tall, Alan R.

2013-01-01

170

PPAR? deficiency reduces insulin resistance and atherosclerosis in apoE-null mice  

PubMed Central

PPAR? is a ligand-dependent transcription factor expressed at high levels in the liver. Its activation by the drug gemfibrozil reduces clinical events in humans with established atherosclerosis, but the underlying mechanisms are incompletely defined. To clarify the role of PPAR? in vascular disease, we crossed PPAR?-null mice with apoE-null mice to determine if the genetic absence of PPAR? affects vascular disease in a robust atherosclerosis model. On a high-fat diet, concentrations of atherogenic lipoproteins were higher in PPAR?–/–apoE–/– than in PPAR?+/+apoE–/– mice, due to increased VLDL production. However, en face atherosclerotic lesion areas at the aortic arch, thoracic aorta, and abdominal aorta were less in PPAR?-null animals of both sexes after 6 and 10 weeks of high-fat feeding. Despite gaining as much or more weight than their PPAR?+/+apoE–/– littermates, PPAR?–/–apoE–/– mice had lower fasting levels of glucose and insulin. PPAR?-null animals had greater suppression of endogenous glucose production in hyperinsulinemic clamp experiments, reflecting less insulin resistance in the absence of PPAR?. PPAR?–/–apoE–/– mice also had lower blood pressures than their PPAR?+/+apoE–/– littermates after high-fat feeding. These results suggest that PPAR? may participate in the pathogenesis of diet-induced insulin resistance and atherosclerosis.

Tordjman, Karen; Bernal-Mizrachi, Carlos; Zemany, Laura; Weng, Sherry; Feng, Chu; Zhang, Fengjuan; Leone, Teresa C.; Coleman, Trey; Kelly, Daniel P.; Semenkovich, Clay F.

2001-01-01

171

The role of the vascular dendritic cell network in atherosclerosis  

PubMed Central

A complex role has been described for dendritic cells (DCs) in the potentiation and control of vascular inflammation and atherosclerosis. Resident vascular DCs are found in the intima of atherosclerosis-prone vascular regions exposed to disturbed blood flow patterns. Several phenotypically and functionally distinct vascular DC subsets have been described. The functional heterogeneity of these cells and their contributions to vascular homeostasis, inflammation, and atherosclerosis are only recently beginning to emerge. Here, we review the available literature, characterizing the origin and function of known vascular DC subsets and their important role contributing to the balance of immune activation and immune tolerance governing vascular homeostasis under healthy conditions. We then discuss how homeostatic DC functions are disrupted during atherogenesis, leading to atherosclerosis. The effectiveness of DC-based “atherosclerosis vaccine” therapies in the treatment of atherosclerosis is also reviewed. We further provide suggestions for distinguishing DCs from macrophages and discuss important future directions for the field.

Alberts-Grill, Noah; Denning, Timothy L.; Rezvan, Amir

2013-01-01

172

Oxidized low-density lipoprotein biomarkers in atherosclerosis  

Microsoft Academic Search

The concept that the oxidation of lipoproteins is central in the pathogenesis of atherosclerosis was first reported over 25\\u000a years ago, initially by in vitro studies and subsequently through experimental models of atherosclerosis. The innate immune\\u000a system plays a key role in atherogenesis as manifested by its atherosclerosis-modulating properties, the immunogenicity of\\u000a oxidized low-density lipoprotein (LDL), and the presence of

Sotirios Tsimikas

2006-01-01

173

Advanced atherosclerosis in predialysis patients with chronic renal failure  

Microsoft Academic Search

Advanced atherosclerosis in predialysis patients with chronic renal failure.BackgroundAtherosclerosis is advanced in hemodialysis patients as shown by increased intima-media thickness of carotid arteries (CA-IMT), although it is not established whether the advanced atherosclerosis results from hemodialysis treatment or from chronic renal failure. The purpose of this study was to evaluate the effects of hemodialysis and renal failure on CA-IMT in

Tetsuo Shoji; Masanori Emoto; Tsutomu Tabata; Eiji Kimoto; Kayo Shinohara; Kiyoshi Maekawa; Takahiko Kawagishi; Hideki Tahara; Eiji Ishimura; Yoshiki Nishizawa

2002-01-01

174

Vascular respiratory uncoupling increases blood pressure and atherosclerosis  

Microsoft Academic Search

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

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

2005-01-01

175

Beyond the joint: Subclinical atherosclerosis in rheumatoid arthritis  

PubMed Central

Rheumatoid arthritis is a chronic autoimmune inflammatory disease associated with increased cardiovascular risk and higher mortality in respect to general population. Beyond joint disease, inflammation is the major determinant of accelerated atherosclerosis observed in rheumatoid arthritis. We review the relationship between inflammation, atherosclerosis and cardiovascular risk in rheumatoid arthritis, focusing on the assessment of subclinical atherosclerosis by functional and morphological methods. These tools include flow mediated dilatation, carotid intima-media thickness, ankle/brachial index, coronary calcium content, pulse wave analysis and serum biomarker of subclinical atherosclerosis.

Scarno, Antongiulio; Perrotta, Fabio Massimo; Cardini, Francesca; Carboni, Alessia; Annibali, Gianmarco; Lubrano, Ennio; Spadaro, Antonio

2014-01-01

176

Beyond the joint: Subclinical atherosclerosis in rheumatoid arthritis.  

PubMed

Rheumatoid arthritis is a chronic autoimmune inflammatory disease associated with increased cardiovascular risk and higher mortality in respect to general population. Beyond joint disease, inflammation is the major determinant of accelerated atherosclerosis observed in rheumatoid arthritis. We review the relationship between inflammation, atherosclerosis and cardiovascular risk in rheumatoid arthritis, focusing on the assessment of subclinical atherosclerosis by functional and morphological methods. These tools include flow mediated dilatation, carotid intima-media thickness, ankle/brachial index, coronary calcium content, pulse wave analysis and serum biomarker of subclinical atherosclerosis. PMID:25035836

Scarno, Antongiulio; Perrotta, Fabio Massimo; Cardini, Francesca; Carboni, Alessia; Annibali, Gianmarco; Lubrano, Ennio; Spadaro, Antonio

2014-07-18

177

Simvastatin Treatment Ameliorates Autoimmune Disease Associated with Accelerated Atherosclerosis in a Murine Lupus Model1  

PubMed Central

Patients with systemic lupus erythematosus develop accelerated atherosclerosis independent of traditional risk factors. The 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors are widely prescribed for hyperlipidemia, but they also exhibit anti-inflammatory actions that appear to be independent of their suppressive actions on plasma cholesterol levels. In this study, we analyzed the effect of the HMG-CoA reductase inhibitor simvastatin on disease manifestations in gld.apoE?/? mice that lack functional Fas ligand and apolipoprotein E and exhibit accelerated atherosclerosis and aggravated lupus-like features. Wild-type, gld, apoE?/?, and gld.apoE?/? mice were maintained on a high cholesterol Western diet and received daily simvastatin (0.125 mg/kg) or saline for 12 wk. Serum cholesterol levels were unaffected by simvastatin treatment, but atherosclerotic lesion area was reduced in both apoE?/? and gld.apoE?/? mice treated with simvastatin. Simvastatin also reduced the lymphadenopathy, renal disease, and proinflammatory cytokine production seen in gld.apoE?/?, but not gld, mice. The immunomodulatory effects in gld.apoE?/? mice were associated with enhanced STAT6 and decreased STAT4 induction in submandibular lymph node cells. Along with reductions in serum TNF-? and IFN-? levels, there was also an increase in IL-4 and IL-10 transcript levels in lymph nodes. These data indicate that HMG-CoA reductase inhibitors ameliorate atherosclerosis and lupus-like autoimmunity independent of their cholesterol-lowering effects via a shift from a Th1 to a Th2 phenotype in the gld.apoE?/? model. Thus, the anti-inflammatory activities of statins may have utility for the treatment of both autoimmunity and atherosclerosis in patients with systemic lupus erythematosus.

Aprahamian, Tamar; Bonegio, Ramon; Rizzo, Jennifer; Perlman, Harris; Lefer, David J.; Rifkin, Ian R.; Walsh, Kenneth

2009-01-01

178

Simvastatin treatment ameliorates autoimmune disease associated with accelerated atherosclerosis in a murine lupus model.  

PubMed

Patients with systemic lupus erythematosus develop accelerated atherosclerosis independent of traditional risk factors. The 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors are widely prescribed for hyperlipidemia, but they also exhibit anti-inflammatory actions that appear to be independent of their suppressive actions on plasma cholesterol levels. In this study, we analyzed the effect of the HMG-CoA reductase inhibitor simvastatin on disease manifestations in gld.apoE-/- mice that lack functional Fas ligand and apolipoprotein E and exhibit accelerated atherosclerosis and aggravated lupus-like features. Wild-type, gld, apoE-/-, and gld.apoE-/- mice were maintained on a high cholesterol Western diet and received daily simvastatin (0.125 mg/kg) or saline for 12 wk. Serum cholesterol levels were unaffected by simvastatin treatment, but atherosclerotic lesion area was reduced in both apoE-/- and gld.apoE-/- mice treated with simvastatin. Simvastatin also reduced the lymphadenopathy, renal disease, and proinflammatory cytokine production seen in gld.apoE-/-, but not gld, mice. The immunomodulatory effects in gld.apoE-/- mice were associated with enhanced STAT6 and decreased STAT4 induction in submandibular lymph node cells. Along with reductions in serum TNF-alpha and IFN-gamma levels, there was also an increase in IL-4 and IL-10 transcript levels in lymph nodes. These data indicate that HMG-CoA reductase inhibitors ameliorate atherosclerosis and lupus-like autoimmunity independent of their cholesterol-lowering effects via a shift from a Th1 to a Th2 phenotype in the gld.apoE-/- model. Thus, the anti-inflammatory activities of statins may have utility for the treatment of both autoimmunity and atherosclerosis in patients with systemic lupus erythematosus. PMID:16920939

Aprahamian, Tamar; Bonegio, Ramon; Rizzo, Jennifer; Perlman, Harris; Lefer, David J; Rifkin, Ian R; Walsh, Kenneth

2006-09-01

179

Reversibility of atherosclerosis--evolving perspectives from two arterial imaging clinical trials: the cholesterol lowering atherosclerosis regression study and the monitored atherosclerosis regression study.  

PubMed

The Cholesterol Lowering Atherosclerosis Study (CLAS) and the Monitored Atherosclerosis Regression Study (MARS) are serial arterial imaging clinical trials that have explored the reversibility of atherosclerosis with lipid-lowering therapy in native coronary, carotid, and femoral arterial beds, as well as in coronary artery bypass grafts. Results demonstrate that progression of atherosclerosis can be reduced in all these vascular beds. Evolving data indicate that coronary lesions > or = 50% diameter stenosis (%S) at baseline respond more readily to lipid-lowering therapy than lesions <50%S. In addition, lipoproteins may have a differential effect on coronary lesion progression according to lesion size, with triglyceride-rich lipoproteins playing an important role in the progression of lesions <50%S. Limited data indicate that progression of atherosclerosis in women may be more responsive to lipid-lowering therapy than in men, and that estrogen replacement may enhance the anti-atherosclerosis effects of lipid lowering. Longitudinal measurements of carotid artery far wall intima-media thickness (IMT) with B-mode ultrasonography in CLAS and MARS indicate that carotid atherosclerosis at a stage before lesions intrude into the vessel lumen can be reduced by lipid-lowering therapy. Together, CLAS and MARS data indicate that the spectrum from very early lesions confined to the arterial wall to established lesions late in the atherosclerotic process can be reversed with lipid-lowering therapy. PMID:8907211

Hodis, H N

1995-01-01

180

The Metabolic Syndrome, LDL Particle Size, and Atherosclerosis The Atherosclerosis and Insulin Resistance (AIR) Study  

Microsoft Academic Search

An operative definition of the metabolic syndrome has been suggested by a working group associated with the World Health Organization in 1998. The aim of this study was to examine whether small, low density lipoprotein (LDL) particle size was associated with the metabolic syndrome and with subclinical atherosclerosis as measured by ultrasound in the carotid and femoral arteries. The study

Johannes Hulthe; Lena Bokemark; John Wikstrand; Bjorn Fagerberg

181

Sustained activation of XBP1 splicing leads to endothelial apoptosis and atherosclerosis development in response to disturbed flow  

PubMed Central

X-box binding protein 1 (XBP1) is a key signal transducer in endoplasmic reticulum stress response, and its potential role in the atherosclerosis development is unknown. This study aims to explore the impact of XBP1 on maintaining endothelial integrity related to atherosclerosis and to delineate the underlying mechanism. We found that XBP1 was highly expressed at branch points and areas of atherosclerotic lesions in the arteries of ApoE?/? mice, which was related to the severity of lesion development. In vitro study using human umbilical vein endothelial cells (HUVECs) indicated that disturbed flow increased the activation of XBP1 expression and splicing. Overexpression of spliced XBP1 induced apoptosis of HUVECs and endothelial loss from blood vessels during ex vivo cultures because of caspase activation and down-regulation of VE-cadherin resulting from transcriptional suppression and matrix metalloproteinase-mediated degradation. Reconstitution of VE-cadherin by Ad-VEcad significantly increased Ad-XBP1s-infected HUVEC survival. Importantly, Ad-XBP1s gene transfer to the vessel wall of ApoE?/? mice resulted in development of atherosclerotic lesions after aorta isografting. These results indicate that XBP1 plays an important role in maintaining endothelial integrity and atherosclerosis development, which provides a potential therapeutic target to intervene in atherosclerosis.

Zeng, Lingfang; Zampetaki, Anna; Margariti, Andriana; Pepe, Anna Elena; Alam, Saydul; Martin, Daniel; Xiao, Qingzhong; Wang, Wen; Jin, Zheng-Gen; Cockerill, Gillian; Mori, Kazutoshi; Li, Yi-shuan Julie; Hu, Yanhua; Chien, Shu; Xu, Qingbo

2009-01-01

182

Imaging and nanomedicine in inflammatory atherosclerosis.  

PubMed

Bioengineering provides unique opportunities to better understand and manage atherosclerotic disease. The field is entering a new era that merges the latest biological insights into inflammatory disease processes with targeted imaging and nanomedicine. Preclinical cardiovascular molecular imaging allows the in vivo study of targeted nanotherapeutics specifically directed toward immune system components that drive atherosclerotic plaque development and complication. The first multicenter trials highlight the potential contribution of multimodality imaging to more efficient drug development. This review describes how the integration of engineering, nanotechnology, and cardiovascular immunology may yield precision diagnostics and efficient therapeutics for atherosclerosis and its ischemic complications. PMID:24898749

Mulder, Willem J M; Jaffer, Farouc A; Fayad, Zahi A; Nahrendorf, Matthias

2014-06-01

183

Mechanisms and therapy of atherosclerosis and its clinical complications  

Microsoft Academic Search

In 1913, exactly 100 years ago, Nikolai Nikolaevich Anichkov (1885-1964) and Semen Sergeevich Chalatov (1884-1951) discovered in St. Petersburg, Russia, that atherosclerosis of large arteries is critically dependent on cholesterol. The inflammatory nature of atherosclerosis was first observed and suggested by Rudolf Virchow in 1856. Today, we have orally active drugs at our disposition that not only lower cholesterol levels

M. Barton

2013-01-01

184

Atherosclerosis imaging and calcified plaque: coronary artery disease risk assessment  

Microsoft Academic Search

Over the last decade, there has been increased recognition that atherosclerosis imaging adds greatly to the ability to identify patients at high risk for cardiac events. Technologies such as electron beam computed tomography and carotid intimal media thickness have contributed significantly to our understanding of the prevalence of preclinical atherosclerosis and its consequences. Guidelines and policy toward these modalities have

Matthew J Budoff

2003-01-01

185

Genetic Basis of Atherosclerosis: Insights from Mice and Humans  

PubMed Central

Atherosclerosis is a complex and heritable disease involving multiple cell types and the interactions of many different molecular pathways. The genetic and molecular mechanisms of atherosclerosis have in part been elucidated by mouse models; at least 100 different genes have been shown to influence atherosclerosis in mice. Importantly, unbiased genome-wide association studies have recently identified a number of novel loci robustly associated with atherosclerotic coronary artery disease (CAD). Here we review the genetic data elucidated from mouse models of atherosclerosis, as well as significant associations for human CAD. Furthermore, we discuss in greater detail some of these novel human CAD loci. The combination of mouse and human genetics has the potential to identify and validate novel genes that influence atherosclerosis, some of which may be candidates for new therapeutic approaches.

Stylianou, Ioannis M.; Bauer, Robert C.; Reilly, Muredach P.; Rader, Daniel J.

2012-01-01

186

[Molecular mechanisms of effects of rosuvastatin on systemic oxidative stress and endogenous inflammation in patients with atherosclerosis].  

PubMed

Aim of the study was to investigate peculiarities of effects of rosuvastatin on the state of oxidative stress and endogenous inflammation in patients with extensive atherosclerosis. Patients with extensive atherosclerosis included into the study (n=46, mean age 56.5 +/- 2.2 years) were distributed to 2 equivalent according to clinico-instrumental data groups. To patients of group 1 (n=24) standard therapy was prescribed (antiaggregants, ACE inhibitors, b-adrenoblockers, and nitrates when indicated), patients of group 2 (n=22) in addition to standard therapy took rosuvastatin (10 mg/day). Investigations included measurement of parameters of serum lipid profile, content of thiol groups of blood serum proteins, activity of enzyme glutathione peroxidase, in vivo oxidation of whole blood serum and HDL, concentration of 3-nitrotirosine, high sensitivity C-reactive protein and interleukin-6, activity of type 2IIA secretory phospholipase A2. It was found that level of 3-nitrotirosine and activity of secretory phospholipase A2 together with high sensitivity C-reactive protein appear to be effective markers of systemic oxidative stress and endogenous inflammation in patients with extensive atherosclerosis. Treatment with rosuvastatin in moderate doses significantly suppressed activity of endogenous inflammation and oxidative stress by way of activation of antioxidant system of plasma, decrease of oxidation of fractions of lipoproteins, suppression of " nitrotirosine " stress, as well as partial inhibition of efficacy of action of secretory phospholipase A2, lowering of content of C-reactive protein and interleukin-6. PMID:18789009

Shchukin, Iu V; D'iachkov, V A; Seleznev, E I; Danilova, E A; Pikatova, E A; Medvedeva, E A

2008-01-01

187

Ginseng Extracts Restore High-Glucose Induced Vascular Dysfunctions by Altering Triglyceride Metabolism and Downregulation of Atherosclerosis-Related Genes  

PubMed Central

The king of herbs, Panax ginseng, has been used widely as a therapeutic agent vis-à-vis its active pharmacological and physiological effects. Based on Chinese pharmacopeia Ben Cao Gang Mu and various pieces of literature, Panax ginseng was believed to exert active vascular protective effects through its antiobesity and anti-inflammation properties. We investigated the vascular protective effects of ginseng by administrating ginseng extracts to rats after the induction of diabetes. We found that Panax ginseng can restore diabetes-induced impaired vasorelaxation and can reduce serum triglyceride but not cholesterol level in the diabetic rats. The ginseng extracts also suppressed the expression of atherosclerosis-related genes and altered the expression of lipid-related genes. The results provide evidence that Panax ginseng improves vascular dysfunction induced by diabetes and the protective effects may possibly be due to the downregulation of atherosclerosis-related genes and altered lipid metabolism, which help to restore normal endothelium functions.

Chan, Gabriel Hoi-huen; Law, Betty Yuen-kwan; Chu, John Man-tak; Yue, Kevin Kin-man; Jiang, Zhi-hong; Lau, Chi-wai; Huang, Yu; Chan, Shun-wan; Ying-kit Yue, Patrick; Wong, Ricky Ngok-shun

2013-01-01

188

Life-course socioeconomic positions and subclinical atherosclerosis in the multi-ethnic study of atherosclerosis.  

PubMed

A major limitation of past work on the social patterning of atherosclerosis has been the reliance on measures of neighborhood or individual-level socioeconomic position (SEP) assessed at a single point in time in adulthood. Risk of chronic disease is thought to accumulate throughout the life-course, so the use of a measure for a single point in time may result in inaccurate estimates of the social patterning of subclinical disease. Using data from the US Multi-Ethnic Study of Atherosclerosis (MESA), we examined the relation between childhood SEP [CSEP] (father or caretaker's education), adulthood SEP [ASEP] (a summary score of income, education, and wealth), and 20-year average exposure to neighborhood poverty [NSEP] (residential addresses geocoded and linked to census data) and the prevalence of subclinical atherosclerosis, as assessed by common carotid intimal-medial thickness (IMT) in mid to late adulthood. Participants were 45-84 years of age at baseline and were sampled from six study sites in the United States. After adjustment for age, CSEP and ASEP were both inversely and independently associated with IMT in men. All three indicators CSEP, ASEP, and NSEP were inversely and independently associated with IMT in women. Associations were somewhat reduced after adjustment for cardiovascular risk factors, suggesting that these factors may play a mediating role. There was evidence of heterogeneity in effects of NSEP by gender, and in the effects of ASEP and NSEP by race/ethnicity. Our results contribute to the growing body of work that shows that SEP at multiple points in the life-course, and at the individual and neighborhood level, contributes to the development of atherosclerosis. PMID:19081660

Lemelin, Emily T; Diez Roux, Ana V; Franklin, Tracy G; Carnethon, Mercedes; Lutsey, Pamela L; Ni, Hanyu; O'Meara, Ellen; Shrager, Sandi

2009-02-01

189

Atherosclerosis and Rheumatoid Arthritis: More Than a Simple Association  

PubMed Central

In the last decades a large amount of evidence linked rheumatoid arthritis (RA) to atherosclerosis. In fact, RA patients have an increased risk of cardiovascular events that is not fully explained by other classic cardiovascular risk factors. RA and atherosclerosis may share several common pathomechanisms and inflammation undoubtedly plays a primary role. The proinflammatory cytokines such as tumor necrosis factor alpha and interleukin-6, involved in the pathogenesis of RA, are also independently predictive of subsequent cardiovascular disease (CVD). In RA, inflammation alters HDL constituents and the concentration of LDL and HDL, thus facilitating atherosclerosis and CVD events. On the other hand, also the increase of oxidative processes, frequently observed in RA, induces atherosclerosis. Interestingly, some genetic polymorphisms associated with RA occurrence enhance atherosclerosis, however, other polymorphisms associated with RA susceptibility do not increase CVD risk. Several other mechanisms may influence atherosclerotic processes in RA. Moreover, atherosclerosis may be directly mediated also by underlying autoimmune processes, and indirectly by the occurrence of metabolic syndrome and impaired physical activity. Finally, the effects of RA therapies on cardiovascular system in general and on atherosclerosis in particular are really wide and different. However, the starting point of every RA treatment is that disease control, or better remission, is the best way we have for the reduction of CVD occurrence.

Cavagna, Lorenzo; Boffini, Nicola; Cagnotto, Giovanni; Inverardi, Flora; Grosso, Vittorio; Caporali, Roberto

2012-01-01

190

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.

Koenen, Rory R; Weber, Christian

2011-01-01

191

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

192

High density lipoproteins and atherosclerosis: emerging aspects  

PubMed Central

High density lipoproteins (HDL) promote the efflux of excess cholesterol from peripheral tissues to the liver for excretion. This ability is responsible for the most relevant anti-atherogenic effect of HDL. The ability of HDL to promote cholesterol efflux results also in the modulation of a series of responses in the immune cells involved in atherosclerosis, including monocyte-macrophages, B and T lymphocytes. Furthermore, during inflammation, the composition of this class of lipoproteins varies to a large extent, thus promoting the formation of dysfunctional HDL. The aim of this review is to discuss the emerging role of HDL in modulating the activity of immune cells and immune-inflammatory mediators during atherogenesis.

Sala, Federica; Catapano, Alberico Luigi; Norata, Giuseppe Danilo

2012-01-01

193

The role of triglycerides in atherosclerosis.  

PubMed

Hypertriglyceridemia is a prevalent risk factor for cardiovascular disease (CVD) and increasingly important in the setting of current obesity and insulin resistance epidemics. High triglyceride (TG) levels are markers for several types of atherogenic lipoproteins. Patients who have hypertriglyceridemia may be at significant risk for CVD even if low-density lipoprotein cholesterol levels are at goal, and therefore warrant treatment that optimizes diet, reduces overweight, and promotes regular exercise. High-risk patients with hypertriglyceridemia, such as those with diabetes, CVD, or metabolic syndrome, may benefit from additional drug treatment aside from a statin to address other lipid abnormalities. In this discussion, we review the role of hypertriglyceridemia and its associated atherogenic lipoproteins in the pathogenesis of atherosclerosis, the relevance of a high TG level as a predictor of CVD, the cardiovascular outcomes from TG-lowering intervention trials, and the current guidelines for treating hypertriglyceridemia. PMID:21968696

Talayero, Beatriz G; Sacks, Frank M

2011-12-01

194

Adiponectin and Atherosclerosis in Rheumatoid Arthritis  

PubMed Central

In the present study, we examined the potential impact of adiponectin on carotid ultrasound determined atherosclerosis in 210 (119 black and 91 white) RA patients in mixed regression models. Total adiponectin concentrations were smaller in patients with compared to those without the metabolic syndrome (MetS) defined waist criterion (median (range) = 6.47 (1.23–34.54) versus 8.38 (0.82–85.30)?ng/mL, P = 0.02, resp.); both total and high molecular weight (HMW) adiponectin concentrations were larger in patients with compared to those without joint deformities (7.97 (0.82–85.30) and 3.51 (0.01–35.40) versus 5.36 (1.29–19.49) and 2.34 (0.01–19.49)?ng/mL, P = 0.003 and 0.02, resp.). Total and HMW adiponectin concentrations were associated with carotid artery plaque in patients with MetS waist (odds ratio (95% CI) = 0.87 (0.76–0.99) and 0.92 (0.85–0.99) per 1-standard deviation increment, P = 0.02 for both) and those without joint deformities (odds ratio (95% CI) = 0.94 (0.88–0.99) and 0.94 (0.89–0.99), P = 0.03 for both). Plaque prevalence was lower in patients without compared to those with joint deformities (23.4% versus 42.6, P = 0.004 in multivariable analysis). In RA patients with abdominal obesity or no clinically evident joint damage, adiponectin concentrations are reduced but nevertheless associated with decreased carotid atherosclerosis.

Dessein, Patrick H.; Tsang, Linda; Solomon, Ahmed; Woodiwiss, Angela J.; Millen, Aletta M. E.; Norton, Gavin R.

2014-01-01

195

Heavy Snoring as a Cause of Carotid Artery Atherosclerosis  

PubMed Central

Study Objectives: Previous studies have suggested that snoring and obstructive sleep apnea hypopnea syndrome may be important risk factors for the development of carotid atherosclerosis and stroke. However, it is not clear if snoring per se is independently related to the risk of developing carotid atherosclerotic plaque. Design: Observational cohort study. Setting: Volunteer sample examined in a sleep laboratory. Participants: One hundred ten volunteers (snorers and nonsnorers with only mild, nonhypoxic obstructive sleep apnea hypopnea syndrome) underwent polysomnography with quantification of snoring, bilateral carotid and femoral artery ultrasound with quantification of atherosclerosis, and cardiovascular risk factor assessment. Subjects were categorized into 3 snoring groups: mild (0%–25% night snoring), moderate (> 25%–50% night snoring), and heavy (> 50% night snoring). Interventions: N/A. Measurements and Results: The prevalence of carotid atherosclerosis was 20% with mild snoring, 32% with moderate snoring, and 64% with heavy snoring (P < 0.04, ?2). Logistic regression analysis was used to determine the independent effect of snoring on the prevalence of carotid and femoral atherosclerosis. After adjustment for age, sex, smoking history, and hypertension, heavy snoring was significantly associated with carotid atherosclerosis (odds ratio 10.5; 95% confidence interval 2.1–51.8; P = 0.004) but not with femoral atherosclerosis. Conclusions: Heavy snoring significantly increases the risk of carotid atherosclerosis, and the increase is independent of other risk factors, including measures of nocturnal hypoxia and obstructive sleep apnea severity. Considering the high prevalence of snoring in the community, these findings have substantial public health implications for the management of carotid atherosclerosis and the prevention of stroke. Citation: Lee SA; Amis TC; Byth K; Larcos G; Kairaitis K; RobinsonTD; Wheatley JR. Heavy snoring as a cause of carotid artery atherosclerosis. SLEEP 2008;31(9):1207-1213.

Lee, Sharon A.; Amis, Terence C.; Byth, Karen; Larcos, George; Kairaitis, Kristina; Robinson, Tracey D.; Wheatley, John R.

2008-01-01

196

Lymphocytes and the adventitial immune response in atherosclerosis.  

PubMed

Although much of the research on atherosclerosis has focused on the intimal accumulation of lipids and inflammatory cells, there is an increasing amount of interest in the role of the adventitia in coordinating the immune response in atherosclerosis. In this review of the contributions of the adventitia and adventitial lymphocytes to the development of atherosclerosis, we discuss recent research on the formation and structural nature of adventitial immune aggregates, potential mechanisms of crosstalk between the intima, media, and adventitia, specific contributions of B lymphocytes and T lymphocytes, and the role of the vasa vasorum and surrounding perivascular adipose tissue. Furthermore, we highlight techniques for the imaging of lymphocytes in the vasculature. PMID:22427326

Campbell, Kirsti A; Lipinski, Michael J; Doran, Amanda C; Skaflen, Marcus D; Fuster, Valentin; McNamara, Coleen A

2012-03-16

197

Imaging macrophage development and fate in atherosclerosis and myocardial infarction.  

PubMed

Macrophages are central regulators of disease progression in both atherosclerosis and myocardial infarction (MI). In atherosclerosis, macrophages are the dominant leukocyte population that influences lesional development. In MI, which is caused by atherosclerosis, macrophages accumulate readily and have important roles in inflammation and healing. Molecular imaging has grown considerably as a field and can reveal biological process at the molecular, cellular and tissue levels. Here, we explore how various imaging modalities, from intravital microscopy in mice to organ-level imaging in patients, are contributing to our understanding of macrophages and their progenitors in cardiovascular disease. PMID:23207281

Swirski, Filip K; Nahrendorf, Matthias

2013-04-01

198

Gene Deficiency in Activating Fc? Receptors Influences the Macrophage Phenotypic Balance and Reduces Atherosclerosis in Mice  

PubMed Central

Immunity contributes to arterial inflammation during atherosclerosis. Oxidized low-density lipoproteins induce an autoimmune response characterized by specific antibodies and immune complexes in atherosclerotic patients. We hypothesize that specific Fc? receptors for IgG constant region participate in atherogenesis by regulating the inflammatory state of lesional macrophages. In vivo we examined the role of activating Fc? receptors in atherosclerosis progression using bone marrow transplantation from mice deficient in ?-chain (the common signaling subunit of activating Fc? receptors) to hyperlipidemic mice. Hematopoietic deficiency of Fc? receptors significantly reduced atherosclerotic lesion size, which was associated with decreased number of macrophages and T lymphocytes, and increased T regulatory cell function. Lesions of Fc? receptor deficient mice exhibited increased plaque stability, as evidenced by higher collagen and smooth muscle cell content and decreased apoptosis. These effects were independent of changes in serum lipids and antibody response to oxidized low-density lipoproteins. Activating Fc? receptor deficiency reduced pro-inflammatory gene expression, nuclear factor-?B activity, and M1 macrophages at the lesion site, while increasing anti-inflammatory genes and M2 macrophages. The decreased inflammation in the lesions was mirrored by a reduced number of classical inflammatory monocytes in blood. In vitro, lack of activating Fc? receptors attenuated foam cell formation, oxidative stress and pro-inflammatory gene expression, and increased M2-associated genes in murine macrophages. Our study demonstrates that activating Fc? receptors influence the macrophage phenotypic balance in the artery wall of atherosclerotic mice and suggests that modulation of Fc? receptor-mediated inflammatory responses could effectively suppress atherosclerosis.

Mallavia, Benat; Oguiza, Ainhoa; Lopez-Franco, Oscar; Recio, Carlota; Ortiz-Munoz, Guadalupe; Lazaro, Iolanda; Lopez-Parra, Virginia; Egido, Jesus; Gomez-Guerrero, Carmen

2013-01-01

199

Mild Renal Dysfunction and Metabolites Tied to Low HDL Cholesterol Are Associated With Monocytosis and Atherosclerosis  

PubMed Central

Background The number of circulating blood monocytes impacts atherosclerotic lesion size, and in mouse models, elevated levels of high-density lipoprotein cholesterol suppress blood monocyte counts and atherosclerosis. We hypothesized that individuals with mild renal dysfunction at increased cardiovascular risk would have reduced high-density lipoprotein levels, high blood monocyte counts, and accelerated atherosclerosis. Methods and Results To test whether mild renal dysfunction is associated with an increase in a leukocyte subpopulation rich in monocytes that has a known association with future coronary events, we divided individuals from the Malmö Diet and Cancer study (MDC) into baseline cystatin C quintiles (n=4757). Lower levels of renal function were accompanied by higher monocyte counts, and monocytes were independently associated with carotid bulb intima-media thickness cross-sectionally (P=0.02). Cystatin C levels were positively and plasma high-density lipoprotein cholesterol levels negatively associated with monocyte counts at baseline, after adjustment for traditional risk factors. Several amino acid metabolites tied to low levels of high-density lipoprotein cholesterol and insulin resistance measured in a subset of individuals (n=752) by use of liquid chromatography–mass spectrometry were independently associated with a 22% to 34% increased risk of being in the top quartile of monocytes (P<0.05). Conclusions A low high-density lipoprotein cholesterol, insulin resistance phenotype occurs in subjects with mild renal dysfunction and is associated with elevated monocytes and atherosclerosis. High blood monocyte counts may represent a previously unrecognized mechanism underlying the strong relationship between cystatin C and cardiovascular risk.

Ganda, Anjali; Magnusson, Martin; Yvan-Charvet, Laurent; Hedblad, Bo; Engstrom, Gunnar; Ai, Ding; Wang, Thomas J.; Gerszten, Robert E.; Melander, Olle; Tall, Alan R.

2014-01-01

200

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

201

Oxidized low density lipoprotein, stem cells, and atherosclerosis.  

PubMed

Oxidized low density lipoprotein (ox-LDL), a risk factor of atherosclerosis, facilitates the formation and vulnerability of atherosclerotic plaque, thus contributing to several clinical complications. Stem cells participate in vascular repair after damage and atherosclerosis is a process of inflammation accompanied with vascular injury. Researchers have proposed that stem cells participate in the formation of atherosclerotic plaque. Also, because ox-LDL is capable of inducing toxic effects on stem cells, it is reasonable to postulate that ox-LDL promotes the progress of atherosclerosis via acting on stem cells. In the present article, we review the relationship between ox-LDL, stem cells, and atherosclerosis and a portion of the associated mechanisms. PMID:22747902

Yang, Hui; Mohamed, Ahmed Salah Salem; Zhou, Sheng-Hua

2012-01-01

202

Local Bone Marrow Renin-Angiotensin System and Atherosclerosis  

PubMed Central

Local hematopoietic bone marrow (BM) renin-angiotensin system (RAS) affects the growth, production, proliferation differentiation, and function of hematopoietic cells. Angiotensin II (Ang II), the dominant effector peptide of the RAS, regulates cellular growth in a wide variety of tissues in pathobiological states. RAS, especially Ang II and Ang II type 1 receptor (AT1R), has considerable proinflammatory and proatherogenic effects on the vessel wall, causing progression of atherosclerosis. Recent investigations, by analyzing several BM chimeric mice whose BM cells were positive or negative for AT1R, disclosed that AT1R in BM cells participates in the pathogenesis of atherosclerosis. Therefore, AT1R blocking not only in vascular cells but also in the BM could be an important therapeutic approach to prevent atherosclerosis. The aim of this paper is to review the function of local BM RAS in the pathogenesis of atherosclerosis.

Beyazit, Yavuz; Purnak, Tugrul; Guven, Gulay Sain; Haznedaroglu, Ibrahim C.

2011-01-01

203

Development of Models of Coronary and Aortic Atherosclerosis in Minipigs.  

National Technical Information Service (NTIS)

The objective of this program is to develop 'models' of human atherosclerosis in miniature swine that would be suitable for invasive and non-invasive instrumentation for the diagnosis and evaluation of the atherosclerotic conditions of various vessels. At...

K. T. Lee

1975-01-01

204

Multifactorial Approach to the Primary and Secondary Prevention of Atherosclerosis  

PubMed Central

We review data regarding the importance of various conventional and evolving atherosclerosis risk factors. In addition, we discuss a multifactorial approach to the primary and secondary prevention of major vascular events, including stroke.

Lavie, Carl J.; Milani, Richard V.

2003-01-01

205

Inflammatory and Autoimmune Reactions in Atherosclerosis and Vaccine Design Informatics  

PubMed Central

Atherosclerosis is the leading pathological contributor to cardiovascular morbidity and mortality worldwide. As its complex pathogenesis has been gradually unwoven, the regime of treatments and therapies has increased with still much ground to cover. Active research in the past decade has attempted to develop antiatherosclerosis vaccines with some positive results. Nevertheless, it remains to develop a vaccine against atherosclerosis with high affinity, specificity, efficiency, and minimal undesirable pathology. In this review, we explore vaccine development against atherosclerosis by interpolating a number of novel findings in the fields of vascular biology, immunology, and bioinformatics. With recent technological breakthroughs, vaccine development affords precision in specifying the nature of the desired immune response—useful when addressing a disease as complex as atherosclerosis with a manifold of inflammatory and autoimmune components. Moreover, our exploration of available bioinformatic tools for epitope-based vaccine design provides a method to avoid expenditure of excess time or resources.

Jan, Michael; Meng, Shu; Chen, Natalie C.; Mai, Jietang; Wang, Hong; Yang, Xiao-Feng

2010-01-01

206

Serum sialic acid and sialoglycoproteins in asymptomatic carotid artery atherosclerosis  

Microsoft Academic Search

Serum total sialic acid (S-TSA) is a recently identified risk marker for atherosclerosis and cardiovascular mortality. The purpose of this study was to evaluate the influence of three sialic acid rich glycoproteins (orosomucoid, haptoglobin, and ?1-antitrypsin) on the relationship between S-TSA and carotid atherosclerosis. The mean S-TSA was 0.045 g\\/l higher among cases than controls (P<0.001) in 310 45–64 year-old

Gunnar Lindberg; Lennart Råstam; Peter Nilsson-Ehle; Arne Lundblad; Jonas Ranstam; Aaron R Folsom; Gregory L Burke

1999-01-01

207

Adaptive immunity in atherosclerosis: mechanisms and future therapeutic targets  

Microsoft Academic Search

Chronic inflammation drives the development of atherosclerosis, and adaptive immunity is deeply involved in this process. Initial studies attributed a pathogenic role to T cells in atherosclerosis, mainly owing to the proatherogenic role of the T-helper (TH)-1 cell subset, whereas the influence of TH2 and TH17 subsets is still debated. Today we know that T regulatory cells play a critical

Charlotte Lahoute; Olivier Herbin; Ziad Mallat; Alain Tedgui

2011-01-01

208

A 3 Adenosine Receptors, HIF-1 Modulation and Atherosclerosis  

Microsoft Academic Search

\\u000a Atherosclerosis, a multifactorial disease of the large arteries, is the major cause of heart disease and stroke worldwide.\\u000a Epidemiological studies have discovered several relevant environmental and genetic risk factors associated with this pathology.\\u000a Genomic and proteomic-based strategies in humans and rodent models have been instrumental in discovering genes and proteins\\u000a involved in the initiation and progression of atherosclerosis. Moreover multiple

Stefania Gessi; Stephen MacLennan; Edward Leung; Pier Andrea Borea

209

Atherosclerosis in Autoimmune Rheumatic Diseases—Mechanisms and Clinical Findings  

Microsoft Academic Search

Atherosclerosis is one of the major entities leading to morbidity and mortality in the western world. It is known now that\\u000a atherosclerosis cannot be explained merely by the presence of the Framingham traditional risk factors and that autoimmunity\\u000a takes a significant role in its pathogenesis. It is also known that individuals with autoimmune diseases demonstrate increased\\u000a incidence of cardiovascular manifestations

Hasya Zinger; Yaniv Sherer; Yehuda Shoenfeld

2009-01-01

210

Prevention and Treatment of Atherosclerosis: A Practitioner's Guide for 2008  

Microsoft Academic Search

Atherosclerosis causes nearly 75% of cardiovascular-related deaths and is found in 80% to 90% of adults ?30 years old in the United States. Successful treatment minimizes lifetime chances of cardiovascular events, morbidity, and mortality. Risk factors for atherosclerosis should be monitored, beginning in childhood, even in asymptomatic patients. Modifiable factors (e.g., blood pressure, smoking, serum lipids) and nonmodifiable factors (e.g.,

Sandra J. Lewis

2009-01-01

211

C-Peptide: A New Mediator of Atherosclerosis in Diabetes  

PubMed Central

Diabetes type 2 and insulin resistance are the risk factors for cardiovascular disease. It is already known that atherosclerosis is an inflammatory disease, and a lot of different factors are involved in its onset. C-peptide is a cleavage product of proinsulin, an active substance with a number of effects within different complications of diabetes. In this paper we discuss the role of C-peptide and its effects in the development of atherosclerosis in type 2 diabetic patients.

Vasic, Dusica; Walcher, Daniel

2012-01-01

212

Advance of studies on anti-atherosclerosis mechanism of berberine.  

PubMed

Coptis Chinensis is a traditional Chinese medicine herb that has the effect of clearing heat and drying dampness, purging fire to eliminate toxin. Berberine is the main alkaloid of Coptis Chinensis, and, recent researches showed that berberine had the effect of anti-atherosclerosis. This paper reviewed the anti-atherosclerosis mechanism of berberine, which may be related to regulating lipids, anti-inflammation, decompression, reducing blood sugar, and inhibiting vascular smooth muscle cell proliferation. PMID:20473748

Wu, Min; Wang, Jie; Liu, Long-tao

2010-04-01

213

Abnormal fatty acid composition and human atherosclerosis  

PubMed Central

Eighty patients with aorto-iliac / femoro-popliteal atherosclerosis were collected to examine in detail their plasma cholesteryl ester fatty acid compositions and to compare them with the incidence of ischaemic heart disease through a 4-year follow-up. Various other biochemical and rheological parameters were also measured to see if these might explain any association between the abnormal fatty acid pattern and ischaemic heart disease. The abnormal fatty acid pattern was specifically and generally similar to that found in essential fatty acid (EFA) deficient animals and children as shown by the increase of the specific trienoic acid (C.20: 3?9) by reduced linoleic acid concentrations, and by an increase of C.18 and C.16 monoenoic acids (oleic and palmitoleic), but not of their corresponding saturated forms, stearic and palmitic. The results suggest that the abnormal fatty acid composition resulted from an increased synthesis of monoenoic acids and monounsaturase activity, coupled with a relative inadequacy of linoleic acid. The patients with a reduced concentration of linoleic acid (<35%) subsequently had a higher incidence of myocardial infarction. No significant correlations were found between the fatty acid concentration and various other biochemical or rheological parameters except marginally between linoleic acid and platelet adhesiveness. Only the linoleic acid concentration distinguished between the patients with and without myocardial infarction. A marked inverse correlation was found, however, between the monoenoic and linoleic acid concentration, without parallel changes in other fatty acids. It seems that as in animals, a balance exists between EFA and monoenoic pathways which are known to compete for the same desaturase systems and acyl sites. It appears that human EFA requirements and effects need to be considered not only by their intake and metabolism, but also through individual factors which vary the monoenoic concentrations and monounsaturase activity. Since these factors include several currently associated with human atherosclerosis the question arises of whether the EFA-monoenoic balance is one link between them and the pathology of the arterial occlusions and myocardial infarction.

Kingsbury, K. J.; Brett, C.; Stovold, R.; Chapman, A.; Anderson, J.; Morgan, D. M.

1974-01-01

214

A major role for RCAN1 in atherosclerosis progression.  

PubMed

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

2013-12-01

215

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

PubMed

Intestinal microbiota metabolism of choline and phosphatidylcholine produces trimethylamine (TMA), which is further metabolized to a proatherogenic species, trimethylamine-N-oxide (TMAO). We demonstrate here that metabolism by intestinal microbiota of dietary L-carnitine, a trimethylamine abundant in red meat, also produces TMAO and accelerates atherosclerosis in mice. Omnivorous human subjects produced more TMAO than did vegans or vegetarians following ingestion of L-carnitine through a microbiota-dependent mechanism. The presence of specific bacterial taxa in human feces was associated with both plasma TMAO concentration and dietary status. Plasma L-carnitine levels in subjects undergoing cardiac evaluation (n = 2,595) predicted increased risks for both prevalent cardiovascular disease (CVD) and incident major adverse cardiac events (myocardial infarction, stroke or death), but only among subjects with concurrently high TMAO levels. Chronic dietary L-carnitine supplementation in mice altered cecal microbial composition, markedly enhanced synthesis of TMA and TMAO, and increased atherosclerosis, but this did not occur if intestinal microbiota was concurrently suppressed. In mice with an intact intestinal microbiota, dietary supplementation with TMAO or either carnitine or choline reduced in vivo reverse cholesterol transport. Intestinal microbiota may thus contribute to the well-established link between high levels of 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

2013-05-01

216

Noninvasive indicators of atherosclerosis in subclinical hypothyroidism  

PubMed Central

Introduction: Cardiovascular system is rich in thyroid hormone receptors and is one of the major sites of action for thyroid hormones. However, the effect of subclinical hypothyroidism (SCH) on atherosclerosis has not been cleared yet. Materials and Methods: SCH is defined as high thyroid-stimulating hormone (TSH) levels in the presence of normal serum T4 and T3 levels. A total of 32 patients with SCH and 29 controls were included in the study. Carotid intima-media thickness, flow-mediated dilatation, and aortic distensibility were compared between the groups. Results: FMD was lower in patients with SCH than in controls. GTN-induced vasodilatation was similar in the patients with SCH and controls. There was no statistically significant difference between the patients with SCH and controls with respect to CIMT and aortic distensibility. Conclusion: SCH is associated with endothelial dysfunction as established by FMD. Inconsistent results of CIMT and aortic stiffness can be explained by these parameters being measures of structural changes whereas FMD is a dynamic measure that reflects the impact of both acute and chronic influences on endothelial function.

Kilic, Ismail Dogu; Tanriverdi, Halil; Fenkci, Semin; Akin, Fulya; Uslu, Sukriye; Kaftan, Asuman

2013-01-01

217

Endothelium Preserving Microwave Treatment for Atherosclerosis  

NASA Technical Reports Server (NTRS)

Method and apparatus are provided to treat atherosclerosis wherein the artery is partially closed by dilating the artery while preserving the vital and sensitive endothelial layer thereof. Microwave energy having a frequency from 3 GHz to 300 GHz is propagated into the arterial wall to produce a desired temperature profile therein at tissue depths sufficient for thermally necrosing connective tissue and softening fatty and waxy plaque while limiting heating of surrounding tissues including the endothelial layer and/or other healthy tissue, organs, and blood. The heating period for raising the temperature a potentially desired amount, about 20 C. within the atherosclerotic lesion may be less than about one second. In one embodiment of the invention, a radically beveled waveguide antenna is used to deliver microwave energy at frequencies from 25 GHz or 30 GHz to about 300 GHz and is focused towards a particular radial sector of the artery. Because the atherosclerotic lesions are often asymmetrically disposed, directable or focussed heating preserves healthy sectors or the artery and applies energy to the asymmetrically positioned lesion faster than a non-directed bean. A computer simulation predicts isothermic temperature profiles for the given conditions and may be used in selecting power, pulse duration, beam width, and frequency of operation to maximize energy deposition and control heat rise within the atherosclerotic lesion without harming healthy tissues or the sensitive endothelium cells.

Carl, James R. (Inventor); Arndt, Dickey (Inventor); Fink, Patrick W. (Inventor); Beer, Reginald (Inventor); Henry, Phillip D. (Inventor); Pacifico, Antonio (Inventor); Raffoul, George W. (Inventor)

2002-01-01

218

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

219

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.

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

2013-01-01

220

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.

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

2014-01-01

221

Inhibition of plaque neovascularization reduces macrophage accumulation and progression of advanced atherosclerosis  

PubMed Central

Plaque angiogenesis promotes the growth of atheromas, but the functions of plaque capillaries are not fully determined. Neovascularization may act as a conduit for the entry of leukocytes into sites of chronic inflammation. We observe vasa vasorum density correlates highly with the extent of inflammatory cells, not the size of atheromas in apolipoprotein E-deficient mice. We show atherosclerotic aortas contain activities that promote angiogenesis. The angiogenesis inhibitor angiostatin reduces plaque angiogenesis and inhibits atherosclerosis. Macrophages in the plaque and around vasa vasorum are reduced, but we detect no direct effect of angiostatin on monocytes. After angiogenesis blockade in vivo, the angiogenic potential of atherosclerotic tissue is suppressed. Activated macrophages stimulate angiogenesis that can further recruit inflammatory cells and more angiogenesis. Our findings demonstrate that late-stage inhibition of angiogenesis can interrupt this positive feedback cycle. Inhibition of plaque angiogenesis and the secondary reduction of macrophages may have beneficial effects on plaque stability.

Moulton, Karen S.; Vakili, Khashayar; Zurakowski, David; Soliman, Mohsin; Butterfield, Catherine; Sylvin, Erik; Lo, Kin-Ming; Gillies, Stephen; Javaherian, Kashi; Folkman, Judah

2003-01-01

222

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.

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

2012-01-01

223

Serotonin reuptake inhibitor antidepressants (SSRIs) against atherosclerosis.  

PubMed

Selective serotonin reuptake inhibitors (SSRIs) are a class of drug widely used for treatment of mood disorders, including depression and cardiovascular disease. A search for related articles in the PubMed database was attempted. It covered studies, reports, reviews and editorials of the last 5 years. Pro-inflammatory cytokines, such as TNF-?, IL-1 and IL-6, stimulate central serotonin (5-HT) neurotransmission and are over-expressed in depression, which has been linked with hypothalamic-pituitary-adrenal axis (HPA) hyperactivity. They have also been implicated in the pathogenesis and progression of other stress-induced disorders, like myocardial infarction (MI) and coronary heart disease (CHD), as they seem to modulate cardiovascular function by a variety of mechanisms. Biological mechanisms like these may explain the link between depression and CHD. There are a variety of environmental factors as well as genetic factors that might influence the pharmacogenetics of antidepressant drugs. New generation selective serotonin reuptake inhibitor antidepressants (SSRIs) causing a reduced cardiovascular morbidity and mortality may be related to serotonin platelet abnormalities in depressed patients that are effectively treated by SSRIs. SSRIs such as fluoxetine, paroxetine, sertraline and citalopram are not only considered to be free from the cardiotoxicity of their predecessors but also to function as safe and efficacious agents against depression, platelet activation, atherosclerosis and development and prognosis of coronary heart disease. However, there is a need for more studies in order to establish the exact biochemical mechanisms that are responsible for these diseases and the immunoregulatory effects of chronic use of SSRI medications. PMID:21873959

Wozniak, Greta; Toska, Aikaterini; Saridi, Maria; Mouzas, Odysseas

2011-09-01

224

Lycopene, atherosclerosis, and coronary heart disease.  

PubMed

Diets rich in fruits and vegetables containing carotenoids have been of interest because of their potential health benefit against chronic diseases such as cardiovascular diseases (CVD) and cancer. Interest particularly in lycopene is growing rapidly following the recent publication of epidemiological studies that have associated high lycopene levels with reductions in CVD incidence. Two studies were conducted. In the first one, we examined the role of lycopene as a risk-lowering factor with regard to acute coronary events and stroke in the prospective Kuopio Ischemic Heart Disease Risk Factor (KIHD) Study. The subjects were 725 middle-aged men free of coronary heart disease and stroke at the study baseline. In a Cox's proportional hazards' model adjusting for covariates, men in the lowest quartile of serum levels of lycopene had a 3.3-fold (P < 0.001) risk of the acute coronary event or stroke as compared with others. In the second study, we assessed the association between plasma concentration of lycopene and intima-media thickness of the common carotid artery wall (CCA-IMT) in a cross-sectional analysis of the Antioxidant Supplementation in the Atherosclerosis Prevention (ASAP) study data in 520 asymptomatic men and women. In a covariance analysis adjusting for common cardiovascular risk factors, low plasma levels of lycopene were associated with an 18% increase of IMT in men as compared with men in whom plasma levels were higher than median (P = 0.003 for difference). In women, the difference did not remain significant after the adjustments. On the basis of these works, it is evident that the circulating levels of lycopene play some role with regard to cardiovascular health in Finland, at least in men. We conclude that circulating levels of lycopene, a biomarker of tomato-rich food, may play a role in early stages of atherogenesis and may have clinical and public health relevance. PMID:12424332

Rissanen, Tiina; Voutilainen, Sari; Nyyssönen, Kristiina; Salonen, Jukka T

2002-11-01

225

Heme Oxygenase-1, Oxidation, Inflammation, and Atherosclerosis  

PubMed Central

Atherosclerosis is an inflammatory process of the vascular wall characterized by the infiltration of lipids and inflammatory cells. Oxidative modifications of infiltrating low-density lipoproteins and induction of oxidative stress play a major role in lipid retention in the vascular wall, uptake by macrophages and generation of foam cells, a hallmark of this disorder. The vasculature has a plethora of protective resources against oxidation and inflammation, many of them regulated by the Nrf2 transcription factor. Heme oxygenase-1 (HO-1) is a Nrf2-regulated gene that plays a critical role in the prevention of vascular inflammation. It is the inducible isoform of HO, responsible for the oxidative cleavage of heme groups leading to the generation of biliverdin, carbon monoxide, and release of ferrous iron. HO-1 has important antioxidant, antiinflammatory, antiapoptotic, antiproliferative, and immunomodulatory effects in vascular cells, most of which play a significant role in the protection against atherogenesis. HO-1 may also be an important feature in macrophage differentiation and polarization to certain subtypes. The biological effects of HO-1 are largely attributable to its enzymatic activity, which can be conceived as a system with three arms of action, corresponding to its three enzymatic byproducts. HO-1 mediated vascular protection may be due to a combination of systemic and vascular local effects. It is usually expressed at low levels but can be highly upregulated in the presence of several proatherogenic stimuli. The HO-1 system is amenable for use in the development of new therapies, some of them currently under experimental and clinical trials. Interestingly, in contrast to the HO-1 antiatherogenic actions, the expression of its transcriptional regulator Nrf2 leads to proatherogenic effects instead. This suggests that a potential intervention on HO-1 or its byproducts may need to take into account any potential alteration in the status of Nrf2 activation. This article reviews the available evidence that supports the antiatherogenic role of HO-1 as well as the potential pathways and mechanisms mediating vascular protection.

Araujo, Jesus A.; Zhang, Min; Yin, Fen

2012-01-01

226

Preclinical atherosclerosis in patients with prolactinoma.  

PubMed

Objective: The aim of this study was to evaluate the effect of hyperprolactinemia on body fat, insulin sensitivity, inflammatory markers, and cardiovascular risk in patients with prolactinoma.Methods: The study included 35 untreated hyperprolactinemic patients with pituitary adenomas, and 36 age-, gender-, and body mass index (BMI)-matched healthy controls without any known disease. Serum glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR, lipid profile, high-sensitivity C-reactive protein (hs-CRP), and heart-type fatty acid binding protein (H-FABP) levels were measured. Waist and hip circumference (WC and HC) were measured in all the participants. The body fat percentage was measured, and the visceral fat and abdominal fat percentages were measured via bioelectrical impedance (BIA). In addition, carotid intima media thickness (CIMT) was measured using high-resolution B-mode ultrasound.Results: The serum glucose level, HOMA-IR, triglyceride level, and SC were significantly higher in the patient group than in the control group. The hs-CRP level and CIMT were significantly higher in the hyperprolactinemic patients. Visceral and truncal fat percentages were significantly higher in the patients with prolactinoma. H-FABP levels were similar in the 2 groups, and there was a positive correlation between the prolactin (PRL) and H-FABP protein levels.Conclusions: Based on the present findings, hyperprolactinemia is associated with preclinical atherosclerosis and metabolic abnormalities. Patients with hyperprolactinemia might experience cardiovascular disease in the long term. Metabolic control should be achieved in addition to the control of hyperprolactinemia in the clinical management of patients diagnosed with prolactinoma. PMID:24325995

Arslan, Muyesser Sayki; Topaloglu, Oya; Sahin, Mustafa; Tutal, Esra; Gungunes, Askin; Cakir, Evrim; Ozturk, Ilknur Unsal; Karbek, Basak; Ucan, Bekir; Ginis, Zeynep; Cakal, Erman; Ozbek, Mustafa; Delibasi, Tuncay

2014-05-01

227

Serotonin reuptake inhibitor antidepressants (SSRIs) against atherosclerosis  

PubMed Central

Summary Selective serotonin reuptake inhibitors (SSRIs) are a class of drug widely used for treatment of mood disorders, including depression and cardiovascular disease. A search for related articles in the PubMed database was attempted. It covered studies, reports, reviews and editorials of the last 5 years. Pro-inflammatory cytokines, such as TNF-?, IL-1 and IL-6, stimulate central serotonin (5-HT) neurotransmission and are over-expressed in depression, which has been linked with hypothalamic-pituitary-adrenal axis (HPA) hyperactivity. They have also been implicated in the pathogenesis and progression of other stress-induced disorders, like myocardial infarction (MI) and coronary heart disease (CHD), as they seem to modulate cardiovascular function by a variety of mechanisms. Biological mechanisms like these may explain the link between depression and CHD. There are a variety of environmental factors as well as genetic factors that might influence the pharmacogenetics of antidepressant drugs. New generation selective serotonin reuptake inhibitor antidepressants (SSRIs) causing a reduced cardiovascular morbidity and mortality may be related to serotonin platelet abnormalities in depressed patients that are effectively treated by SSRIs. SSRIs such as fluoxetine, paroxetine, sertraline and citalopram are not only considered to be free from the cardiotoxicity of their predecessors but also to function as safe and efficacious agents against depression, platelet activation, atherosclerosis and development and prognosis of coronary heart disease. However, there is a need for more studies in order to establish the exact biochemical mechanisms that are responsible for these diseases and the immunoregulatory effects of chronic use of SSRI medications.

Wozniak, Greta; Toska, Aikaterini; Saridi, Maria; Mouzas, Odysseas

2011-01-01

228

[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

229

Telomeres, atherosclerosis, and the hemothelium: the longer view.  

PubMed

The model we propose to explain the links between atherosclerosis and telomere dynamics (birth telomere length and its age-dependent shortening) in leukocytes takes cues from three facts: atherosclerosis is a disease of the vascular endothelium; the hematopoietic system and the vascular endothelium share a common embryonic origin; interindividual variation in leukocyte telomere length (LTL) in the general population has a genetic explanation. The model posits that LTL dynamics mirror telomere dynamics in hematopoietic stem cells (HSCs), where telomere length is an index of HSC reserves. Diminished HSC reserves at birth, their accelerated attrition rate afterward, or both are are reflected in shortened LTL during adulthood-a phenomenon that confers increased risk for atherosclerosis. We explain how telomere length in HSCs serves as both a biomarker of atherosclerosis and a determinant of its development. Our model comes down to this proposition: Shortened LTL predicts increased atherosclerotic risk because the injurious component of atherosclerosis exceeds the repair capacity of HSC reserves, which largely depend on HSC telomere length. PMID:22017444

Aviv, Abraham; Levy, Daniel

2012-01-01

230

IL-35: a potential target for the treatment of atherosclerosis.  

PubMed

The imbalance of anti- inflammatory/pro-inflammatory cytokines plays an important role in the process of atherosclerosis. IL-35 is an anti-inflammatory cytokine comprising the p35 subunit of IL-12 and the subunit Epstein-Barr virus (EBV) -induced gene 3(EBI3). Accumulating evidence showed that IL-35 up-regulates the expression of anti-inflammatory cytokines, induces the generation of CD4 + regulatory T cells, inhibits CD4 + effector T cells response and other target cells activity, and reduces the progression of inflammatory and autoimmune diseases. In addition, it has been found that Ebi3 and p35 strongly coexpressed in human advanced lesions. Therefore, we hypothesize that IL-35 may become a novel target for the treatment of atherosclerosis. Further studies are required to investigate the precise effect and the signaling pathway of IL-35 in atherosclerosis process. PMID:24273881

Huang, Ying; Lin, Ying-Zhong; Shi, Ying; Ji, Qing-Wei

2013-10-01

231

Redox balance and blood elemental levels in atherosclerosis  

NASA Astrophysics Data System (ADS)

Oxidation of lipids and proteins represents a causative event for atherogenesis, which can be opposed by antioxidant activity. Elements, such as, Fe, Cu, Zn and Se can be involved in both mechanisms. Thus, evaluation of blood elemental levels, easily detected by PIXE, and of redox parameters may be useful in assessing the risk of atherosclerosis. A group of stable patients suffering from atherosclerosis, was matched with a cohort of normo-tensive and -lipidemic volunteers. Although no major discrepancies were observed for trace elemental levels in blood, increased concentrations of K and Ca were found in atherosclerotic group. Patients presented enhance levels of antioxidant (?-tocopherol) and decreased of protein oxidation (protein carbonyls), while for the lipid oxidation marker (malondialdehyde) no variation was observed. This study contributes to a better understanding of atherosclerosis development and its relationship with blood elemental levels, and set basis for further clinical trials with pathological groups in acute phase.

Napoleão, P.; Lopes, P. A.; Santos, M.; Steghens, J.-P.; Viegas-Crespo, A. M.; Pinheiro, T.

2006-08-01

232

Symptomatic atherosclerosis is associated with an altered gut metagenome  

PubMed Central

Recent findings have implicated the gut microbiota as a contributor of metabolic diseases through the modulation of host metabolism and inflammation. Atherosclerosis is associated with lipid accumulation and inflammation in the arterial wall, and bacteria have been suggested as a causative agent of this disease. Here we use shotgun sequencing of the gut metagenome to demonstrate that the genus Collinsella was enriched in patients with symptomatic atherosclerosis, defined as stenotic atherosclerotic plaques in the carotid artery leading to cerebrovascular events, whereas Roseburia and Eubacterium were enriched in healthy controls. Further characterization of the functional capacity of the metagenomes revealed that patient gut metagenomes were enriched in genes encoding peptidoglycan synthesis and depleted in phytoene dehydrogenase; patients also had reduced serum levels of ?-carotene. Our findings suggest that the gut metagenome is associated with the inflammatory status of the host and patients with symptomatic atherosclerosis harbor characteristic changes in the gut metagenome.

Karlsson, Fredrik H.; Fak, Frida; Nookaew, Intawat; Tremaroli, Valentina; Fagerberg, Bjorn; Petranovic, Dina; Backhed, Fredrik; Nielsen, Jens

2012-01-01

233

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

234

Internal mammary artery atherosclerosis: an ultrastructural study of two cases.  

PubMed

Atherosclerosis of the internal mammary artery (IMA) is generally regarded as a rare (but existent) pathological entity with only a few cases reported in the most recent literature. The only study which to our knowledge has investigated the ultrastructural features of IMA atherosclerosis, demonstrate the presence of endothelial cells loss, defects of internal elastic lamina with no evidence of lipid accumulation. In the present study, we describe two cases of IMA atherosclerosis in which ultrastructural analysis revealed the presence of a typical atherosclerotic plaque morphology with infiltration of inflammatory cells, formation of intraplaque lipid pools, and accumulation of lipid-laden foam cells throughout the thickened intima, never described in this rare lesion before. Microscopically, the lesions were also characterized by intimal thickening, invagination of endothelial cells, migration of smooth muscle cells with splitting, fenestration and/or fragmentation of the elastic sheets. Our observations add new data to the scarce and contradictory literature and to this largely understudied vascular disorder. PMID:24467374

Perrotta, Ida; Sciangula, Alfonso; Concistrè, Giovanni; Mazzulla, Sergio; Aquila, Saveria; Agnino, Alfonso

2014-05-01

235

CXCL5 limits macrophage foam cell formation in atherosclerosis.  

PubMed

The ELR(+)-CXCL chemokines have been described typically as potent chemoattractants and activators of neutrophils during the acute phase of inflammation. Their role in atherosclerosis, a chronic inflammatory vascular disease, has been largely unexplored. Using a mouse model of atherosclerosis, we found that CXCL5 expression was upregulated during disease progression, both locally and systemically, but was not associated with neutrophil infiltration. Unexpectedly, inhibition of CXCL5 was not beneficial but rather induced a significant macrophage foam cell accumulation in murine atherosclerotic plaques. Additionally, we demonstrated that CXCL5 modulated macrophage activation, increased expression of the cholesterol efflux regulatory protein ABCA1, and enhanced cholesterol efflux activity in macrophages. These findings reveal a protective role for CXCL5, in the context of atherosclerosis, centered on the regulation of macrophage foam cell formation. PMID:23376791

Rousselle, Anthony; Qadri, Fatimunnisa; Leukel, Lisa; Yilmaz, Rüstem; Fontaine, Jean-Fred; Sihn, Gabin; Bader, Michael; Ahluwalia, Amrita; Duchene, Johan

2013-03-01

236

CXCL5 limits macrophage foam cell formation in atherosclerosis  

PubMed Central

The ELR+-CXCL chemokines have been described typically as potent chemoattractants and activators of neutrophils during the acute phase of inflammation. Their role in atherosclerosis, a chronic inflammatory vascular disease, has been largely unexplored. Using a mouse model of atherosclerosis, we found that CXCL5 expression was upregulated during disease progression, both locally and systemically, but was not associated with neutrophil infiltration. Unexpectedly, inhibition of CXCL5 was not beneficial but rather induced a significant macrophage foam cell accumulation in murine atherosclerotic plaques. Additionally, we demonstrated that CXCL5 modulated macrophage activation, increased expression of the cholesterol efflux regulatory protein ABCA1, and enhanced cholesterol efflux activity in macrophages. These findings reveal a protective role for CXCL5, in the context of atherosclerosis, centered on the regulation of macrophage foam cell formation.

Rousselle, Anthony; Qadri, Fatimunnisa; Leukel, Lisa; Yilmaz, Rustem; Fontaine, Jean-Fred; Sihn, Gabin; Bader, Michael; Ahluwalia, Amrita; Duchene, Johan

2013-01-01

237

Quantitative nonlinear optical assessment of atherosclerosis progression in rabbits.  

PubMed

Quantification of atherosclerosis has been a challenging task owing to its complex pathology. In this study, we validated a quantitative approach for assessing atherosclerosis progression in a rabbit model using a numerical matrix, optical index for plaque burden, derived directly from the nonlinear optical microscopic images captured on the atherosclerosis-affected blood vessel. A positive correlation between this optical index and the severity of atherosclerotic lesions, represented by the age of the rabbits, was established based on data collected from 21 myocardial infarction-prone Watanabe heritable hyperlipidemic rabbits with age ranging between new-born and 27 months old. The same optical index also accurately identified high-risk locations for atherosclerotic plaque formation along the entire aorta, which was validated by immunohistochemical fluorescence imaging. PMID:24892226

Mostaço-Guidolin, Leila B; Kohlenberg, Elicia K; Smith, Michael; Hewko, Mark; Major, Arkady; Sowa, Michael G; Ko, Alex C-T

2014-07-01

238

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.

Yoo, Hye Jin; Choi, Kyung Mook

2014-01-01

239

Adipokines as a novel link between obesity and atherosclerosis.  

PubMed

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

2014-06-15

240

A novel dilute and shoot HPLC assay method for quantification of irbesartan and hydrochlorothiazide in combination tablets and urine using second generation C18-bonded monolithic silica column with double gradient elution.  

PubMed

Irbesartan (IRB) and hydrochlorothiazide (HCT) are angiotensin-II receptor antagonist and thiazide-class diuretic compounds, respectively, which are in use in the treatment of hypertension. A novel dilute-and-shoot HPLC assay method for simultaneous quantification of IRB and HCT in fixed-dose combination tablets and urine samples was described. The separation of IRB, HCT and agomelatine (internal standard) was carried out using a second generation C18-bonded monolithic silica column (Chromolith(®) High Resolution RP-18e, 100×4.6mm, Merck KGaA), utilizing both mobile phase and flow rate gradient elution programs. The analytes were detected at 230 nm wavelength using photodiode array detector within 24 minutes with high resolution, observing about 50 percent more peak capacity when using second generation C18-bonded monolithic silica column. Urine samples were introduced into the system effortlessly, with only filtration and subsequent dilution. Validation studies were performed according to the official recommendations of USP and ICH, and the developed method was successfully applied to pharmaceutical tablets and urine samples. PMID:24876066

Koyuturk, Sema; Can, Nafiz Oncu; Atkosar, Zeki; Arli, Goksel

2014-08-01

241

MAOA Genotype, Childhood Trauma and Subclinical Atherosclerosis: A Twin Study  

PubMed Central

Objective A functional promoter polymorphism in the MAOA gene has been implicated in neuropsychiatric disorders and also moderates the association between early life stress and mental disorders, which often co-occur with cardiovascular disease. No study has examined the relationship between MAOA genotype, childhood trauma and subclinical atherosclerosis. The objective of this investigation was to examine whether childhood trauma moderates the association between MAOA genotype and subclinical atherosclerosis. Methods A sample including 289 middle-aged male twin pairs was studied. Subclinical atherosclerosis was assessed by brachial flow-mediated dilation (FMD) using ultrasound. Childhood trauma, before age 18, was measured with the Early Trauma Inventory and included physical, emotional, and sexual abuse as well as general trauma. Generalized estimating equation models were used to test the main and interactive effects of the MAOA genotype and each domain of childhood trauma on FMD, adjusting for known risk factors. Results General trauma was the most prevalent childhood trauma (28.4%), followed by physical abuse (25.0%), emotional abuse (19.4%) and sexual abuse (11.6%). MAOA genotype was not associated with any domain of childhood trauma (? ? 0.36). There was no significant evidence for a main effect for the MAOA genotype (? = 0.02, p = 0.82) or childhood trauma (0.005 < ? < 0.10, p > 0.54) on early atherosclerosis. However, a significant interaction was observed between MAOA genotype and physical (?interaction = 0.37, p = 0.026) or emotional abuse (?interaction = 0.43, p = 0.025) on subclinical atherosclerosis. Conclusion This study provides initial evidence that childhood trauma modulates the impact of MAOA variant on subclinical atherosclerosis, independent of traditional cardiovascular risk factors.

Zhao, Jinying; Bremner, James D.; Goldberg, Jack; Quyyumi, Arshed A.; Vaccarino, Viola

2013-01-01

242

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

243

Molecular imaging in atherosclerosis, thrombosis and vascular inflammation  

PubMed Central

Appreciation of the molecular and cellular processes of atherosclerosis, thrombosis and vascular inflammation has identified new targets for imaging. The common goals of molecular imaging approaches are to accelerate and refine diagnosis, provide insights that reveal disease diversity, guide specific therapies and monitor the effects of those therapies. Here we undertake a comparative analysis of imaging modalities that have been used in this disease area. We consider the elements of contrast agents, emphasizing how an understanding of the biology of atherosclerosis and its complications can inform optimal design. We address the potential and limitations of current contrast approaches in respect of translation to clinically usable agents and speculate on future applications.

Choudhury, Robin P.; Fisher, Edward A.

2009-01-01

244

In-111 platelet scintigraphy: carotid atherosclerosis and stroke  

SciTech Connect

An association between atherosclerosis of the internal carotid artery and ischemia or infarction of the ipsilateral cerebral hemisphere has been demonstrated by numerous radiographic and pathologic studies. The precise mechanism by which carotid atherosclerosis causes these problems, however, remains unclear. Several observations suggest that fibrin-platelet thrombi form on atherosclerotic plaques in the neck arteries and then embolize distally into the intracranial circulation. Unfortunately, platelet embolization does not adequately explain a variety of clinical and pathological findings in patients with cerebrovascular disease. This editorial will discuss these findings. It is obvious that the understanding of the role of platelets in the pathogenesis of ischemic cerebrvascular disease is far from complete.

Powers, W.J.

1984-05-01

245

Preterm birth, vascular function, and risk factors for atherosclerosis.  

PubMed

Low birthweight may predispose to the development of atherosclerosis later in life. We have tested the hypothesis that low birthweight as a result of preterm birth is associated with reduced flow-mediated endothelial-dependent vasodilation (FMD), which is an early stage in the development of atherosclerosis. Mean FMD in adolescents born preterm who had a low birthweight did not differ from that for controls born at term (0.225 mm vs 0.220 mm, SD 0.1 for both means, p=0.78). Our findings indicate that low birthweight attributable to prematurity does not increase the risk of vascular disease later in life. PMID:11597675

Singhal, A; Kattenhorn, M; Cole, T J; Deanfield, J; Lucas, A

2001-10-01

246

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.

Swirski, Filip K.; Nahrendorf, Matthias

2013-01-01

247

Leukocyte behavior in atherosclerosis, myocardial infarction, and heart failure.  

PubMed

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, MI, and heart failure. PMID:23307733

Swirski, Filip K; Nahrendorf, Matthias

2013-01-11

248

Optical and Multimodality Molecular Imaging Insights Into Atherosclerosis  

PubMed Central

Imaging approaches that visualize molecular targets rather than anatomic structures aim to illuminate vital molecular and cellular aspects of atherosclerosis biology in vivo. Several such molecular imaging strategies are poised for rapid clinical application. This review describes the growing role of in vivo optical molecular imaging in atherosclerosis and highlights its ability to visualize atheroma inflammation, calcification, and angiogenesis. In addition we discuss advances in multimodality probes, both in the context of multimodal imaging as well as multifunctional, or “theranostic,” nanoparticles. This review highlights particular molecular imaging strategies that possess strong potential for clinical translation.

Jaffer, Farouc A.; Libby, Peter; Weissleder, Ralph

2009-01-01

249

Suppression and dissociation  

Microsoft Academic Search

The present study examined the connection between susppression and dissociation. Fifty-four normal subjects completed the White Bear Suppression Inventory and the Dissociative Experiences Scale. Results showed that suppression and dissociation were significantly correlated. Furthermore, both suppression and dissociation correlated positively with less adaptive defense categories as indexed by the Defense Style Questionnaire: suppression was found to be related to immature

Peter Muris; Harald Merckelbach

1997-01-01

250

Promotion of Vascular Smooth Muscle Cell Growth by Homocysteine: A Link to Atherosclerosis  

Microsoft Academic Search

Plasma homocysteine levels are elevated in 20-30% of all patients with premature atherosclerosis. Although elevated homocysteine levels have been recognized as an independent risk factor for myocardial infarction and stroke, the mechanism by which these elevated levels cause atherosclerosis is unknown. To understand the role of homocysteine in the pathogenesis of atherosclerosis, we examined the effect of homocysteine on the

Jer-Chia Tsai; Mark A. Perrella; Masao Yashizumi; Chung-Ming Hsieh; Edgar Haber; Robert Schlegel; Mu-En Lee

1994-01-01

251

Relationship of Cigarette Smoking to the Severity of Coronary and Thoracic Aortic Atherosclerosis  

Microsoft Academic Search

We studied the relationship of cigarette smoking to the severity of coronary and thoracic aortic atherosclerosis in 116 men who received coronary angiography and transesophageal echocardiography. Severity of coronary atherosclerosis was assessed in terms of Gensini’s score (GS), and that of thoracic aortic atherosclerosis was assessed by the average sclerotic length (ASL) and average sclerotic area (ASA). The plasma fibrinogen

Toji Inoue; Keiko Oku; Kazuyuki Kimoto; Makiko Takao; Junko Nomoto; Koichi Handa; Suminori Kono; Kikuo Arakawa

1995-01-01

252

Association of Mitochondrial Genetic Variation with Carotid Atherosclerosis  

PubMed Central

In human pathology, several diseases are associated with somatic mutations in the mitochondrial genome (mtDNA). Even though mitochondrial dysfunction leads to increased oxidative stress, the role of mitochondrial mutations in atherosclerosis has not received much attention so far. In this study we analyzed the association of mitochondrial genetic variation with the severity of carotid atherosclerosis, as assessed by carotid intima-media thickness (cIMT) and the presence of coronary heart disease (CHD) in 190 subjects from Moscow, Russia, a population with high CHD occurrence. cIMT was measured by high-resolution B-mode ultrasonography and mtDNA heteroplasmies by a pyrosequencing-based method. We found that heteroplasmies for several mutations in the mtDNA in leukocytes, including C3256T, T3336C, G12315A, G13513A, G14459A, G14846A, and G15059A mutations, were significantly (p<0.001) associated with both the severity of carotid atherosclerosis and the presence of CHD. These findings indicate that somatic mitochondrial mutations have a role in the development of atherosclerosis.

Sobenin, Igor A.; Sazonova, Margarita A.; Postnov, Anton Y.; Salonen, Jukka T.; Bobryshev, Yuri V.; Orekhov, Alexander N.

2013-01-01

253

Inflammation: A pivotal link between autoimmune diseases and atherosclerosis  

Microsoft Academic Search

Premature coronary heart disease has emerged as a major cause of morbidity and mortality in systemic autoimmune diseases. Recent epidemiologic and pathogenesis studies have suggested a great deal in common between the pathogenesis of prototypic autoimmune disease such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) and that of atherosclerosis. Some of the most remarkable data in support of

Anna Abou-Raya; Suzan Abou-Raya

2006-01-01

254

Association Between Local Atherosclerosis and Renal Cell Carcinomas  

Microsoft Academic Search

Objective: Atherosclerosis induce changes in reactive oxygen species and oxidative stress by hypoxia leading to oxidative DNA damage and therefore it could be expected that the cancer risk in patients with atherosclerotic diseases is increased. Materials and Methods: The present study therefore aimed to morphometrically compare atherosclerotic changes (e.g., intima-to-media ratio [IMR]) in renal cell cancer (n = 514) and

Martina Hager; Gregor Mikuz; Christian Kolbitsch; Patrizia Lucia Moser

2008-01-01

255

Vascular proliferation and atherosclerosis: New perspectives and therapeutic strategies  

Microsoft Academic Search

In atherosclerosis, the vascular smooth muscle cell (VSMC) contributes to vessel wall inflammation and lipoprotein retention, as well as to the formation of the fibrous cap that provides stability to the plaque. The VSMC can undergo a proliferative response that underlies the development of in-stent restenosis, bypass graft occlusion and transplant vasculopathy. Although the benefit\\/risk of therapeutic inhibition of VSMC

Victor J. Dzau; Ruediger C. Braun-Dullaeus; Daniel G. Sedding

2002-01-01

256

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.

2012-01-01

257

Cerebrovascular atherosclerosis correlates with Alzheimer pathology in neurodegenerative dementias.  

PubMed

A growing body of evidence demonstrates an association between vascular risk factors and Alzheimer's disease. This study investigated the frequency and severity of atherosclerotic plaques in the circle of Willis in Alzheimer's disease and multiple other neurodegenerative diseases. Semi-quantitative data from gross and microscopic neuropathological examinations in 1000 cases were analysed, including 410 with a primary diagnosis of Alzheimer's disease, 230 with synucleinopathies, 157 with TDP-43 proteinopathies, 144 with tauopathies and 59 with normal ageing. More than 77% of subjects with Alzheimer's disease had grossly apparent circle of Willis atherosclerosis, a percentage that was significantly higher than normal (47%), or other neurodegenerative diseases (43-67%). Age- and sex-adjusted atherosclerosis ratings were highly correlated with neuritic plaque, paired helical filaments tau neurofibrillary tangle and cerebral amyloid angiopathy ratings in the whole sample and within individual groups. We found no associations between atherosclerosis ratings and ?-synuclein or TDP-43 lesion ratings. The association between age-adjusted circle of Willis atherosclerosis and Alzheimer's disease-type pathology was more robust for female subjects than male subjects. These results provide further confirmation and specificity that vascular disease and Alzheimer's disease are interrelated and suggest that common aetiologic or reciprocally synergistic pathophysiological mechanisms promote both vascular pathology and plaque and tangle pathology. PMID:23204143

Yarchoan, Mark; Xie, Sharon X; Kling, Mitchel A; Toledo, Jon B; Wolk, David A; Lee, Edward B; Van Deerlin, Vivianna; Lee, Virginia M-Y; Trojanowski, John Q; Arnold, Steven E

2012-12-01

258

Hematologic Parameters and Angiographic Progression of Coronary Atherosclerosis  

Microsoft Academic Search

Hematologic parameters have prognostic importance in cardiovascular disease. However, the relation between atherosclerosis progression and hematologic parameters is not well defined. A total of 394 patients requiring repeat coronary angiography were included in the study. According to angiography, patients were divided into 2 groups, progressive (n = 196) and nonprogressive (n = 198) diseases. Hematologic parameters including mean platelet volume

Nihat Kalay; Orhan Dogdu; Fatih Koc; Mikail Yarl?oglues; Idris Ardic; Mahmut Akpek; Davran Cicek; Abdurrahman Oguzhan; Ali Ergin; Mehmet G. Kaya

2012-01-01

259

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

260

Atherosclerosis - The Future Challenge for Europe's Health Economies  

Microsoft Academic Search

Atherosclerotic disease has been a feature of more affluent societies since ancient times. Currently, cardiovascular disease accounts for almost half of all mortality across Europe, causing over two million deaths within the EU and costing EU health economies €192 billion per year. The pathogenesis of atherosclerosis is complex, and our understanding of it has come a long way over the

Andrew Carson

2010-01-01

261

Atherosclerosis Assessment by Angiographic Image Processing and Ultrasound.  

National Technical Information Service (NTIS)

The research has two major goals: (1) To extend the use of image averaging of angiograms to provide non-invasive measures for atherosclerosis assessment; and (2) determination of the physical properties of human arterial tissue relative to the velocity, a...

D. H. Blankenhorn R. Barndt S. H. Brooks H. P. Chin D. W. Crawford

1979-01-01

262

Atherosclerosis Assessment by Angiographic Image Processing and Ultrasound.  

National Technical Information Service (NTIS)

The research has two major goals: (1) To extend the use of image averaging of angiograms to provide non-invasive measures for atherosclerosis assessment; and (2) determination of the physical properties of human arterial tissue relative to the velocity, a...

D. H. Blankenhorn R. Barndt S. H. Brooks H. P. Chin D. W. Crawford

1978-01-01

263

A role of the bile salt receptor FXR in atherosclerosis.  

PubMed

This study reviews current insights into the role of bile salts and bile salt receptors on the progression and regression of atherosclerosis. Bile salts have emerged as important modifiers of lipid and energy metabolism. At the molecular level, bile salts regulate lipid and energy homeostasis mainly via the bile salt receptors FXR and TGR5. Activation of FXR has been shown to improve plasma lipid profiles, whereas Fxr(-/-) mice have increased plasma triglyceride and very-low-density lipoprotein levels. Nevertheless, high-density lipoprotein cholesterol levels are increased in these mice, suggesting that FXR has both anti- and proatherosclerotic properties. Interestingly, there is increasing evidence for a role of FXR in "nonclassical" bile salt target tissues, eg, vasculature and macrophages. In these tissues, FXR has been shown to influence vascular tension and regulate the unloading of cholesterol from foam cells, respectively. Recent publications have provided insight into the antiinflammatory properties of FXR in atherosclerosis. Bile salt signaling via TGR5 might regulate energy homeostasis, which could serve as an attractive target to increase energy expenditure and weight loss. Interventions aiming to increase cholesterol turnover (eg, by bile salt sequestration) significantly improve plasma lipid profiles and diminish atherosclerosis in animal models. Bile salt metabolism and bile salt signaling pathways represent attractive therapeutic targets for the treatment of atherosclerosis. PMID:20631352

Hageman, Jurre; Herrema, Hilde; Groen, Albert K; Kuipers, Folkert

2010-08-01

264

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.

Park, Young Mi

2014-01-01

265

Generalized atherosclerosis, cognitive decline, and depressive symptoms in old age  

Microsoft Academic Search

Background: Atherosclerosis may be linked to cognitive decline and depression in old age. Methods: The Leiden 85-Plus Study is a prospective population-based study of 599 subjects from age 85 onward. The generalized atherosclerotic burden was rated by the number of cardiovascular pathologies at baseline, as assessed by history taking from treating physicians and EKG. Cardiovascular pathologies included myocardial infarction, angina

D. J. Vinkers; M. L. Stek; Mast van der R. C; Craen de M. R. J; J. Jolles

2005-01-01

266

Association of carotid atherosclerosis and left ventricular hypertrophy  

Microsoft Academic Search

Objectives. This study was undertaken to determine the prevalence of carotid atherosclerosis in a large group of asymptomatic hypertensive and normotensive adults and to examine its relation to the presence of left ventricular hypertrophy.Background. Both electrocardiographic and echocardiographic left ventricular hypertrophy predict an increased risk of cardiovascular events and mortality, including cerebrovascular disease, but the mechanism of association is unknown.Methods.

Mary J Roman; Thomas G Pickering; Joseph E Schwartz; Riccardo Pini; Richard B Devereux

1995-01-01

267

High-Resolution Association Mapping of Atherosclerosis Loci in Mice  

PubMed Central

Objective To fine map previously identified quantitative trait loci (QTL) affecting atherosclerosis in mice using association analysis. Methods and Results We recently showed that high-resolution association analysis using common inbred strains of mice is feasible if corrected for population structure. To utilize this approach for atherosclerosis, which requires a sensitizing mutation, we bred human apoB100 transgenic mice with 22 different inbred strains to produce F1 heterozygotes. Mice carrying the dominant transgene were tested for association with high-density SNP maps. Here we focus on high-resolution mapping of the previously described Ath30 locus on Chr 1. As compared to the previous linkage analysis, association improved the resolution of the Ath30 locus by more than an order of magnitude. Using expression quantitative trait locus analysis, we identified one of the genes in the region, Des, as a strong candidate. Conclusions Our high-resolution mapping approach accurately identifies and fine maps known atherosclerosis QTL. These results suggest that high-resolution genome-wide association analysis for atherosclerosis is feasible in mice.

Bennett, Brian J.; Orozco, Luz; Kostem, Emrah; Erbilgin, Ayca; Dallinga, Marchien; Neuhaus, Isaac; Guan, Bo; Wang, Xuping; Eskin, Eleazar; Lusis, Aldons J.

2012-01-01

268

Retarding Effect of Lowered Heart Rate on Coronary Atherosclerosis  

Microsoft Academic Search

The role of heart rate in the development of coronary atherosclerosis was assessed in adult male cynomolgus monkeys (Macaca fascicularis). Heart rate was lowered in six animals by surgical ablation of the sinoatrial node. A sham procedure, which included all of the surgical steps except for sinoatrial node ablation, was carried out in eight animals. All of the monkeys were

Polly A. Beere; Seymour Glagov; Christopher K. Zarins

1984-01-01

269

Translating molecular discoveries into new therapies for atherosclerosis  

Microsoft Academic Search

Atherosclerosis is characterized by the thickening of the arterial wall and is the primary cause of coronary artery disease and cerebrovascular disease, two of the most common causes of illness and death worldwide. Clinical trials have confirmed that certain lipoproteins and the renin-angiotensin-aldosterone system are important in the pathogenesis of atherosclerotic cardiovascular disease, and that interventions targeted towards these are

Daniel J. Rader; Alan Daugherty

2008-01-01

270

Progress and challenges in translating the biology of atherosclerosis  

Microsoft Academic Search

Atherosclerosis is a chronic disease of the arterial wall, and a leading cause of death and loss of productive life years worldwide. Research into the disease has led to many compelling hypotheses about the pathophysiology of atherosclerotic lesion formation and of complications such as myocardial infarction and stroke. Yet, despite these advances, we still lack definitive evidence to show that

Paul M Ridker; Göran K. Hansson; Peter Libby

2011-01-01

271

Premature Coronary-Artery Atherosclerosis in Systemic Lupus Erythematosus  

Microsoft Academic Search

background Premature coronary artery disease is a major cause of illness and death in patients with systemic lupus erythematosus, but little is known about the prevalence, extent, and caus- es of coronary-artery atherosclerosis. methods We used electron-beam computed tomography to screen for the presence of coronary- artery calcification in 65 patients with systemic lupus erythematosus (mean ( ± SD) age,

Yu Asanuma; Annette Oeser; Ayumi K. Shintani; Elizabeth Turner; Nancy Olsen; Sergio Fazio; MacRae F. Linton; Paolo Raggi; C. Michael Stein

2003-01-01

272

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

273

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

274

Atherosclerosis-susceptible and atherosclerosis-resistant pigeon aortic cells express different genes in vivo.  

PubMed

Spontaneous atherosclerosis in the White Carneau (WC-As) pigeon is inherited as a single gene disorder, and its progression closely mirrors the human disease. Representational difference analysis and microarray were used to identify genes that were differentially expressed between the susceptible WC-As and resistant Show Racer (SR-Ar) aortic tissue. The RNA extracted from 1-d-old squab aortas was used to make cDNA for each experiment. Fifty-six unique genes were found using representational difference analysis, with 25 exclusively expressed in the WC-As, 15 exclusive to the SR-Ar, and 16 nonexclusive genes having copy number variation between breeds. Caveolin and ?-actin were expressed in the WC-As, whereas the proteasome maturation protein and the transcription complex CCR4-NOT were exclusive to the SR-Ar. Microarray analysis revealed 48 genes with differential expression. Vascular endothelial growth factor and p53 binding protein were among the 17 genes upregulated in the WC-As. Thirty-one genes were upregulated in the SR-Ar including the transforming growth factor-? signaling factor SMAD2 and heat shock protein 90. Genes representing several biochemical pathways were distinctly different between breeds. The most striking divergences were in cytoskeletal remodeling, proteasome activity, cellular respiration, and immune response. Actin cytoskeletal remodeling appears to be one of the first differences between susceptible and resistant breeds, lending support to the smooth muscle cell phenotypic reversion hypothesis of human atherogenesis. PMID:24046414

Anderson, J L; Ashwell, C M; Smith, S C; Shine, R; Smith, E C; Taylor, R L

2013-10-01

275

Associations between surface markers on blood monocytes and carotid atherosclerosis in HIV-positive individuals.  

PubMed

Chronic HIV infection is associated with increased risk of cardiovascular disease (CVD), including in patients with virological suppression. Persistent innate immune activation may contribute to the development of CVD via activation of monocytes in these patients. We investigated whether changes in monocyte phenotype predict subclinical atherosclerosis in virologically suppressed HIV-positive individuals with low cardiovascular risk. We enroled 51 virologically suppressed HIV-positive individuals not receiving protease inhibitors or statins and 49 age-matched uninfected controls in this study. Carotid artery intima-media thickness (cIMT) was used as a surrogate marker for CVD, and traditional risk factors, including Framingham risk scores, were recorded. Markers of monocyte activation (CD14, CD16, CCR2, CX3CR1, CD38, HLA-DR and CD11b) were measured in whole-blood samples by flow cytometry. Associations were assessed using univariate and multivariate median regressions. Median cIMT was similar between HIV-positive and HIV-negative participants (P=0.3), although HIV-positive patients had significantly higher Framingham risk score (P=0.009) and systemic inflammation. Expression of two monocyte markers, CD11b and CX3CR1, independently predicted carotid artery thickness in HIV-positive individuals after controlling for Framingham risk score (P=0.025 and 0.015, respectively). These markers were not predictive of carotid artery thickening in controls. Our study indicates that monocyte surface markers may serve as novel predictors of CVD in HIV-positive individuals and is consistent with an important role for monocyte activation in the progression of HIV-related cardiovascular pathology. PMID:24296810

Westhorpe, Clare L V; Maisa, Anna; Spelman, Tim; Hoy, Jennifer F; Dewar, Elizabeth M; Karapanagiotidis, Sofie; Hearps, Anna C; Cheng, Wan-Jung; Trevillyan, Janine; Lewin, Sharon R; Sviridov, Dmitri; Elliott, Julian H; Jaworowski, Anthony; Dart, Anthony M; Crowe, Suzanne M

2014-02-01

276

Dexamethasone suppression test  

MedlinePLUS

DST; ACTH suppression test; Cortisol suppression test ... During this test, you will receive dexamethasone. This is a strong man-made (synthetic) glucocorticoid medication. Afterward, your blood is drawn ...

277

Interferon-beta attenuates angiotensin II-accelerated atherosclerosis and vascular remodeling in apolipoprotein E deficient mice.  

PubMed

Atherosclerotic vascular disease is an inflammatory disease. Interferon-beta (IFN-beta) is an important immune modulator. However, the role of IFN-beta in atherosclerotic vascular disease is still not clear. The present study is designed to determine the effects of IFN-beta on atherosclerosis, abdominal aortic aneurysm (AAA) formation and proliferative vascular remodeling in apolipoprotein E (apoE) deficient mice. Six-month-old male apoE deficient mice fed a normal chow underwent ligation of the common left carotid artery, and were randomly assigned to receive either vehicle or angiotensin II (Ang II, 1.4 mg/kg daily) via a subcutaneously implanted osmotic infusion pump. The animals were further assigned to groups that were subjected to subcutaneous injection of vehicle or murine IFN-beta (10 MIU/kg, daily). Ang II increased atherosclerotic area in the non-ligated carotid artery and aortic arch, induced AAA, and exacerbated ligation-induced adventitial proliferation and neointimal hyperplasia characterized by smooth muscle cell (SMC) proliferation and macrophage infiltration in the ligated carotid artery. Co-treatment with IFN-beta, had no effects by itself, significantly attenuated Ang II-accelerated increase in the areas of neointima, adventitia, SMC and macrophage in the ligated carotid artery and suppressed Ang II-exacerbated atherosclerosis, but did not affect Ang II-induced AAA formation. These data indicate that IFN-beta can play a prominent anti-atherosclerosis, anti-inflammation, and anti-proliferation role of vasculoprotection. PMID:17466308

Zhang, Le-Ning; Velichko, Sharlene; Vincelette, Jon; Fitch, Richard M; Vergona, Ronald; Sullivan, Mark E; Croze, Ed; Wang, Yi-Xin

2008-03-01

278

Abdominal Aortic Diameter and Vascular Atherosclerosis: The Multi-Ethnic Study of Atherosclerosis  

PubMed Central

Objectives To gain insight into early mechanisms of aortic widening, we examined associations between the diameter of the abdominal aorta (AD) and cardiovascular disease (CVD) risk factors and biomarkers, as well as measures of subclinical atherosclerosis, in a multi-ethnic population. Design Cross-sectional cohort Methods A total of 1926 participants (mean age 62, 50% women) underwent chest and abdomen scanning by computed tomography, ultrasound of the carotid arteries, and CVD risk factor assessment. AD was measured 5 cm above and at the bifurcation. Results In a model containing traditional CVD risk factors, biomarkers and ethnicity, only age (standardized ?=0.97), male sex (?=1.88), body surface area (standardized ?=0.92), current smoking (?=0.42), D-dimer levels (?=0.19) and hypertension (?=0.53) were independently and significantly associated with increasing AD (in mm) at the bifurcation; use of cholesterol-lowering medications predicted smaller AD (?=-0.70) (P<.01 for all). These findings were similar for AD 5 cm above the bifurcation with one exception: compared to Caucasian-Americans, Americans of Chinese, African and Hispanic descent had significantly smaller AD 5 cm above the bifurcation (?'s= -0.59, -0.49, and -0.52, respectively, all P<.01), whereas AD at the bifurcation did not differ by ethnicity. Physical activity, alcohol consumption, diabetes and levels of IL-6, CRP and homocysteine were not independently associated with AD. Higher aortic and coronary artery calcium burden, but not common carotid artery intima-media thickness, were independently, but modestly (?=0.11 to 0.19), associated with larger AD. Conclusions Incremental widening of the aortic diameter shared some, but not all, risk factors for occlusive vascular disease.

Laughlin, Gail A.; Allison, Matthew A.; Jensky, Nicole; Aboyans, Victor; Wong, Nathan D.; Detrano, Robert; Criqui, Michael H.

2011-01-01

279

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.

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

2013-01-01

280

Hyperglycemia promotes myelopoiesis and impairs the resolution of atherosclerosis  

PubMed Central

SUMMARY Diabetes is a major risk factor for atherosclerosis. Although atherosclerosis is initiated by deposition of cholesterol-rich lipoproteins in the artery wall, the entry of inflammatory leukocytes into lesions fuels disease progression and impairs resolution. We show that diabetic mice have increased numbers of circulating neutrophils and Ly6-Chi monocytes, reflecting hyperglycemia-induced proliferation and expansion of bone marrow myeloid progenitors and release of monocytes into the circulation. Increased neutrophil production of S100A8/A9, via an interaction with the receptor for advanced glycation end products on common myeloid progenitor cells, leads to enhanced myelopoiesis. Treatment of hyperglycemia reduces monocytosis, entry of monocytes into atherosclerotic lesions and promotes regression. In patients with type I diabetes plasma S100A8/A9 levels correlate with leukocyte counts and coronary artery disease. Thus, hyperglycemia drives myelopoiesis and thus promotes atherogenesis in diabetes.

Nagareddy, Prabhakara R.; Murphy, Andrew J.; Stirzaker, Roslynn A.; Hu, Yunying; Yu, Shiquing; Miller, Rachel G.; Ramkhelawon, Bhama; Distel, Emilie; Westerterp, Marit; Huang, Li-Shin; Schmidt, Ann Marie; Orchard, Trevor J.; Fisher, Edward A.; Tall, Alan R.; Goldberg, Ira J.

2014-01-01

281

Hyperglycemia promotes myelopoiesis and impairs the resolution of atherosclerosis.  

PubMed

Diabetes is a major risk factor for atherosclerosis. Although atherosclerosis is initiated by deposition of cholesterol-rich lipoproteins in the artery wall, the entry of inflammatory leukocytes into lesions fuels disease progression and impairs resolution. We show that diabetic mice have increased numbers of circulating neutrophils and Ly6-C(hi) monocytes, reflecting hyperglycemia-induced proliferation and expansion of bone marrow myeloid progenitors and release of monocytes into the circulation. Increased neutrophil production of S100A8/S100A9, and its subsequent interaction with the receptor for advanced glycation end products on common myeloid progenitor cells, leads to enhanced myelopoiesis. Treatment of hyperglycemia reduces monocytosis, entry of monocytes into atherosclerotic lesions, and promotes regression. In patients with type 1 diabetes, plasma S100A8/S100A9 levels correlate with leukocyte counts and coronary artery disease. Thus, hyperglycemia drives myelopoiesis and promotes atherogenesis in diabetes. PMID:23663738

Nagareddy, Prabhakara R; Murphy, Andrew J; Stirzaker, Roslynn A; Hu, Yunying; Yu, Shiquing; Miller, Rachel G; Ramkhelawon, Bhama; Distel, Emilie; Westerterp, Marit; Huang, Li-Shin; Schmidt, Ann Marie; Orchard, Trevor J; Fisher, Edward A; Tall, Alan R; Goldberg, Ira J

2013-05-01

282

Defects in regulation of local immune responses resulting in atherosclerosis.  

PubMed

Atherosclerosis is nowadays generally accepted as an inflammatory disease but the mechanism of its origin and development have not yet been fully clarified. The present review focuses on the role of the local immune system as one of the key players in the pathogenesis of the complex process. Its part represented by vascular-associated lymphoid tissue (VALT) within the arterial wall participates directly in the vascular wall's homeostatis. Its inordinate activation during ontogenic development of an individual, this formerly defensive and physiologic mechanism transform into a pathological process resulting in an impairing inflammation. Hsp60, CRP and oxidized or otherwise modified LDL are serious candidates for triggering these pathological changes. The principal role is played by anti-Hsp60 antibodies and by shear stress originating on the surface of endothelium due to blood flow. The experimental and clinical data supporting this immunological hypothesis of atherosclerosis are discussed. PMID:16295529

Ferencík, Miroslav; Stvrtinová, Viera; Hulín, Ivan

2005-09-01

283

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.

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

2012-01-01

284

Innate immunity and monocyte-macrophage activation in atherosclerosis  

PubMed Central

Innate inflammation is a hallmark of both experimental and human atherosclerosis. The predominant innate immune cell in the atherosclerotic plaque is the monocyte-macrophage. The behaviour of this cell type within the plaque is heterogeneous and depends on the recruitment of diverse monocyte subsets. Furthermore, the plaque microenvironment offers polarisation and activation signals which impact on phenotype. Microenvironmental signals are sensed through pattern recognition receptors, including toll-like and NOD-like receptors - the latter of which are components of the inflammasome - thus dictating macrophage behaviour and outcome in atherosclerosis. Recently cholesterol crystals and modified lipoproteins have been recognised as able to directly engage these pattern recognition receptors. The convergent role of such pathways in terms of macrophage activation is discussed in this review.

2011-01-01

285

Impact of Ezetimibe on Atherosclerosis: Is the Jury Still Out?  

PubMed Central

Ezetimibe is a new lipid-lowering agent that inhibits intestinal absorption of dietary cholesterol. It substantially lowers low-density lipoprotein cholesterol levels when used alone or in combination with statins. However, its effect on cardiovascular mortality remains unknown. We reviewed peer-reviewed published literature on the effect of ezetimibe on different phases of atherosclerosis. MEDLINE, EMBASE, BIOSIS, and other Web of Knowledge databases were searched for relevant abstracts and articles published in the English language that compared ezetimibe and statins as modulators of atherosclerosis. On the basis of the available evidence, ezetimibe appears to reduce inflammation when used in combination with statins, but its effect on endothelial function is mixed and less clear. The effect of ezetimibe on coronary disease progression or prevention of cardiovascular events is currently unknown. Use of ezetimibe as a second- or third-line agent to achieve low-density lipoprotein cholesterol treatment goals seems appropriate on the basis of the available evidence.

Al Badarin, Firas J.; Kullo, Iftikhar J.; Kopecky, Stephen L.; Thomas, Randal J.

2009-01-01

286

Imaging of coronary atherosclerosis and identification of the vulnerable plaque  

PubMed Central

Identification of the vulnerable plaque responsible for the occurrence of acute coronary syndromes and acute coronary death is a prerequisite for the stabilisation of this vulnerable plaque. Comprehensive coronary atherosclerosis imaging in clinical practice should involve visualisation of the entire coronary artery tree and characterisation of the plaque, including the three-dimensional morphology of the plaque, encroachment of the plaque on the vessel lumen, the major tissue components of the plaque, remodelling of the vessel and presence of inflammation. Obviously, no single diagnostic modality is available that provides such comprehensive imaging and unfortunately no diagnostic tool is available that unequivocally identifies the vulnerable plaque. The objective of this article is to discuss experience with currently available diagnostic modalities for coronary atherosclerosis imaging. In addition, a number of evolving techniques will be briefly discussed. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5Figure 6Figure 7

de Feyter, P.J.; Serruys, P. W.; Nieman, K.; Mollet, N.; Cademartiri, F.; van Geuns, R. J.; Slager, C.; van der Steen, A.F.W.; Krams, R.; Schaar, J.A.; Wielopolski, P.; Pattynama, P.M.T.; Arampatzis, A.; van der Lugt, A.; Regar, E.; Ligthart, J.; Smits, P.

2003-01-01

287

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.

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

288

Hybrid FMT-MRI applied to in vivo atherosclerosis imaging  

PubMed Central

Combining Fluorescent Molecular Tomography (FMT) with anatomical imaging, e.g. MRI facilitates interpreting functional information. Furthermore, using a heterogeneous model for light propagation has been shown in simulations to be superior to homogeneous modeling to quantify fluorescence. Here, we present a combined FMT-MRI system and apply it to heart and aorta molecular imaging, a challenging area due to strong tissue heterogeneity and the presence of air-voids due to lungs. First investigating performance in a phantom and mouse corpse, the MRI-enabled heterogeneous models resulted in an improved quantification of fluorescence reconstructions. The system was then used in mice for in vivo atherosclerosis molecular imaging. Results show that, when using the heterogeneous model, reconstructions were in agreement with the ex vivo measurements. Therefore, the proposed system might serve as a powerful imaging tool for atherosclerosis in mice.

Li, Baoqiang; Maafi, Foued; Berti, Romain; Pouliot, Philippe; Rheaume, Eric; Tardif, Jean-Claude; Lesage, Frederic

2014-01-01

289

Hybrid FMT-MRI applied to in vivo atherosclerosis imaging.  

PubMed

Combining Fluorescent Molecular Tomography (FMT) with anatomical imaging, e.g. MRI facilitates interpreting functional information. Furthermore, using a heterogeneous model for light propagation has been shown in simulations to be superior to homogeneous modeling to quantify fluorescence. Here, we present a combined FMT-MRI system and apply it to heart and aorta molecular imaging, a challenging area due to strong tissue heterogeneity and the presence of air-voids due to lungs. First investigating performance in a phantom and mouse corpse, the MRI-enabled heterogeneous models resulted in an improved quantification of fluorescence reconstructions. The system was then used in mice for in vivo atherosclerosis molecular imaging. Results show that, when using the heterogeneous model, reconstructions were in agreement with the ex vivo measurements. Therefore, the proposed system might serve as a powerful imaging tool for atherosclerosis in mice. PMID:24877023

Li, Baoqiang; Maafi, Foued; Berti, Romain; Pouliot, Philippe; Rhéaume, Eric; Tardif, Jean-Claude; Lesage, Frederic

2014-05-01

290

Local proliferation dominates lesional macrophage accumulation in atherosclerosis.  

PubMed

During the inflammatory response that drives atherogenesis, macrophages accumulate progressively in the expanding arterial wall. The observation that circulating monocytes give rise to lesional macrophages has reinforced the concept that monocyte infiltration dictates macrophage buildup. Recent work has indicated, however, that macrophage accumulation does not depend on monocyte recruitment in some inflammatory contexts. We therefore revisited the mechanism underlying macrophage accumulation in atherosclerosis. In murine atherosclerotic lesions, we found that macrophages turn over rapidly, after 4 weeks. Replenishment of macrophages in these experimental atheromata depends predominantly on local macrophage proliferation rather than monocyte influx. The microenvironment orchestrates macrophage proliferation through the involvement of scavenger receptor A (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

2013-09-01

291

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.

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

292

Inflammation and Diabetes-Accelerated Atherosclerosis: Myeloid Cell Mediators  

PubMed Central

Monocytes and macrophages respond to and govern inflammation by producing a plethora of inflammatory modulators, including cytokines, chemokines and arachidonic acid (C20:4)-derived lipid mediators. One of the most prevalent inflammatory diseases is cardiovascular disease, caused by atherosclerosis, and accelerated by diabetes. Recent research has demonstrated that monocytes/macrophages from diabetic mice and humans with type 1 diabetes show upregulation of the enzyme, acyl-CoA synthetase 1 (ACSL1), which promotes C20:4 metabolism, and that ACSL1 inhibition selectively protects these cells from the inflammatory and pro-atherosclerotic effects of diabetes, in mice. Increased understanding of the role of ACSL1 and other culprits in monocytes/macrophages in inflammation and diabetes-accelerated atherosclerosis offers hope for new treatment strategies to combat diabetic vascular disease.

Kanter, Jenny E.; Bornfeldt, Karin E.

2012-01-01

293

Association between genetic polymorphisms and sites of cervicocerebral artery atherosclerosis.  

PubMed

Ischemic stroke is a multifactorial disease with strong genetic elements. The purpose of this case-control study was to find relationships between apolipoprotein E (APOE), angiotensin-converting enzyme (ACE), and methylenetetrahydrofolate reductase (MTHFR) genotypes and atherosclerosis of the extracranial internal carotid and intracranial arteries in the Thai population. Patients aged >45 years with significant intracranial stenosis (IC group) or extracranial carotid artery stenosis (EC group) diagnosed by duplex ultrasound and/or computed tomography angiography (CTA) or magnetic resonance angiography (MRA) were studied. The control group comprised volunteers with no history of stroke and no evidence of significant cervicocerebral artery stenosis by ultrasound. Genomic DNA was extracted and genotyped for APOE isoforms, ACE insertion/deletion (I/D) polymorphism, and MTHFR C677T polymorphisms. There were 141 cases (83 in the IC group and 58 in the EC group) and 167 controls. The APOE ?3/?4 genotype and APOE ?4 allele were significantly associated with extracranial carotid artery stenosis (odds ratio, 2.55; 95% confidence interval, 1.07-6.05 and odds ratio, 2.85; 95% confidence interval, 1.35-5.99, respectively). These associations were not observed in patients with intracranial atherosclerosis. There was no significant association between ACE and MTHFR polymorphisms and stenosis at any site. In a multivariate model, sex, diabetes mellitus, hypertension, ischemic heart disease, and APOE ?4 allele remained predictive of extracranial atherosclerosis. In our Thai population, the ?4 allele in the APOE gene contributes to the genetic susceptibility of extracranial internal carotid atherosclerosis. The low prevalence of extracranial carotid stenosis in this population might result from low frequencies of the APOE ?4 allele. PMID:21296594

Chutinet, Aurauma; Suwanwela, Nijasri C; Snabboon, Thiti; Chaisinanunkul, Napasri; Furie, Karen L; Phanthumchinda, Kammant

2012-07-01

294

Attenuation of the development of hypercholesterolemic atherosclerosis by thymoquinone  

PubMed Central

Thymoquinone (TQ), derived from Nigella sativa seed, is an antioxidant. The present study investigated whether TQ attenuates the development of atherosclerosis, and/or reduces the serum lipid levels and oxidative stress in rabbits. New Zealand white female rabbits were assigned to four groups of six animals each: group I, control; group II, 1% cholesterol diet; group III, 1% cholesterol plus TQ (10 mg/kg/day; through a nasogastric tube) diet; and group IV, 1% cholesterol plus TQ (20 mg/kg/day; through a nasogastric tube) diet. Blood samples were collected at baseline and after four and eight weeks on the experimental diets for measurement of serum lipids, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), TC/HDL-C ratio and oxidative stress biomarkers (malondialdehyde [MDA] and protein carbonyls). At the end of the eight weeks, the aorta was removed for the assessment of atherosclerotic changes, MDA and protein carbonyls. Group II animals developed atherosclerosis (45%±11% of the intimal surface of aorta was covered with atherosclerotic plaques), which was associated with an increase in the serum TC, TG, LDL-C, HDL-C, TC/HDL-C, MDA and protein carbonyls. In group III, TQ decreased serum TC, LDL-C, MDA and protein carbonyls by 26%, 29%, 85% and 62%, respectively, and aortic MDA by 73%, which was associated with a 40% reduction of the development of aortic atherosclerosis. The higher dose of TQ in group IV had effects similar to the lower dose (group III), except that this dose further decreased serum TG. It is concluded that TQ attenuates hypercholesterolemic atherosclerosis and this effect is associated with a decrease in serum lipids and oxidative stress.

Ragheb, Ahmed; Elbarbry, Fawzy; Prasad, Kailash; Mohamed, Adel; Ahmed, Mohamed S; Shoker, Ahmed

2008-01-01

295

Necrosis of the penis with multiple vessel atherosclerosis.  

PubMed

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; Kim, Young-Joo

2014-04-01

296

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.

Kim, Sung Dae; Huh, Jung Sik

2014-01-01

297

Chemokine-like functions of MIF in atherosclerosis  

Microsoft Academic Search

The cytokine macrophage migration inhibitory factor (MIF) is a unique pro-inflammatory regulator of many acute and chronic\\u000a inflammatory diseases. In the pathogenesis of atherosclerosis, chronic inflammation of the arterial wall characterized by\\u000a chemokine-mediated influx of leukocytes plays a central role. The contribution of MIF to atherosclerotic vascular disease\\u000a has come into focus of many studies in recent years. MIF is

Andreas Schober; Jürgen Bernhagen; Christian Weber

2008-01-01

298

Endogenous Nitric Oxide Synthase Inhibitor A Novel Marker of Atherosclerosis  

Microsoft Academic Search

Background—Exposure to risk factors such as hypertension or hypercholesterolemia decreases the bioavailability of endothelium-derived nitric oxide (NO) and impairs endothelium-dependent vasodilation. Recently, a circulating endogenous NO synthase inhibitor, asymmetric dimethylarginine (ADMA), has been detected in human plasma. The purpose of this study was to examine the relationship between plasma ADMA and atherosclerosis in humans. Methods and Results—Subjects (n 5116; age,

Hiroshi Miyazaki; Hidehiro Matsuoka; John P. Cooke; Michiaki Usui; Seiji Ueda; Seiya Okuda; Tsutomu Imaizumi

2010-01-01

299

Patterns and Risk Factors for Systemic Calcified Atherosclerosis  

Microsoft Academic Search

Objective—Complex atherosclerotic lesions contain radio-opaque calcium hydroxyapatite deposits with the degree of calcification correlating with the extent of atherosclerosis. In this study, we aim to determine the patterns of systemic atherosclerotic calcification. Methods and Results—Whole-body electron beam computed tomography scans were performed on 650 asymptomatic subjects to assess the carotid, coronary, proximal, and distal aorta and iliac vessels for atherosclerotic

Matthew A. Allison; Michael H. Criqui; C. Michael Wright

2010-01-01

300

Evaluation of subclinical atherosclerosis in Egyptian psoriatic patients  

PubMed Central

Background Psoriasis (Ps) is a common, relapsing, immune-mediated, inflammatory skin disorder of unknown etiology. Ps is not single organ disease confined to the skin but it is systematic inflammatory condition analogous to other inflammatory immune disorders which are known to have increased risk of heart disease. On other hand, inflammation plays also an important role in the pathogenesis of atherosclerosis. So, there is striking similarity between molecular and inflammatory pathway in Ps and atherosclerosis. Aim of the work Was to assess the presence of subclinical atherosclerosis in patients with Ps by using carotid ultrasonography. Patients and Methods 60 patients with Ps were enrolled in this study after exclusion of traditional cardiovascular risk factors and cardiovascular diseases (CVD). In addition, 20 age and gender matched healthy persons served as controls. Patients were classified according to Ps area and severity index (PASI) score into group I (20 mild patients), group II (20 moderate) and group III (20 severe). The average common carotid artery (CCA) intima media thickness (IMT), internal diameter (ID) and arterial wall mass index (AWMI) were measured using high resolution B- mode ultrasound. Results Psoriatic patients showed statistically significant increase in CCA-IMT (P value 0.001), AWMI (P value 0.010) and significant decrease in ID (P value 0.001), as compared to controls. Conclusion Psoriasis patients could be suggested as a group with an increased atherosclerotic risk especially in older ages with longer duration of Ps. The carotid IMT, ID and AWMI can identify patients with subclinical atherosclerosis who need special follow up to reduce cardiovascular morbidity and mortality.

Elsheikh, Raghda Ghonimy; Amin, Tarek El-Sayed; El-Ashmawy, Amal Ahmad; Abdalla, Samah Ibrahim Abd El-fttah

2013-01-01

301

Adducin Polymorphism, Atherosclerosis, and Cardiovascular and Cerebrovascular Risk  

Microsoft Academic Search

Background and Purpose—Carriers of the 460Trp allele of the -adducin gene (ADD1) show higher rates of sodium reabsorption compared with homozygous carriers of the Gly460 allele and were found to have an increased risk of hypertension and cardiovascular disease. We studied the association between the Gly460Trp polymorphism and atherosclerosis, cardiovascular disease, and cerebrovascular disease. Methods—Intima-media thickness of the common carotid

Marie Josee; E. van Rijn; Michiel J. Bos; Mojgan Yazdanpanah; Aaron Isaacs; Alejandro Arias-Vasquez; Peter J. Koudstaal; Albert Hofman; Jacqueline C. Witteman; Cornelia M. van Duijn; Monique M. B. Breteler

302

Numerical and analytical study of an atherosclerosis inflammatory disease model.  

PubMed

We study a reaction-diffusion mathematical model for the evolution of atherosclerosis as an inflammation process by combining analytical tools with computer-intensive numerical calculations. The computational work involved the calculation of more than sixty thousand solutions of the full reaction-diffusion system and lead to the complete characterisation of the ?-limit for every initial condition. Qualitative properties of the solution are rigorously proved, some of them hinted at by the numerical study. PMID:23719743

Hidalgo, A; Tello, L; Toro, E F

2014-06-01

303

Uric acid and serum antioxidant capacity: a reaction to atherosclerosis?  

Microsoft Academic Search

Background: the evidence of a potential beneficial role of antioxidants in preventing atherosclerotic disease is not entirely consistent. Objective: to assess the longitudinal association of serum total antioxidant capacity and serum antioxidants with the presence of subclinical carotid atherosclerosis. Methods: Prospective case-control study nested within an historical cohort. Cases were 150 individuals with elevated carotid intimal-medial thickness measured by B-mode

F. Javier Nieto; Carlos Iribarren; Myron D. Gross; George W. Comstock; Richard G. Cutler

2000-01-01

304

MicroRNAs in endothelial senescence and atherosclerosis.  

PubMed

Aging is an important risk factor for the development of many cardiovascular diseases as atherosclerosis and is accompanied by the decline of endothelial function. Senescence of endothelial cells has been proposed to be involved in endothelial dysfunction and atherogenesis. Therefore, the study of new target therapies to prevent or reverse this process represents a field of great interest. MicroRNAs (miRNAs), a class of short RNAs, play key roles in various biological processes and in the development of human disease through specific posttranscriptional downregulation of gene expression. In particular, miRNAs that are highly expressed by endothelial cells can be detected in high concentration in human atherosclerotic plaques and in the circulation, suggesting their potential translation to bedside to determine the dysfunction of specific signaling pathways which play a role in coronary artery disease in the individual patient, a path towards a stratified medicine approach for early preventive treatment of disease. Here, we review the most recent advances in the field of atherosclerosis that implicate a role for miRNAs with a special emphasis on endothelial senescence and its involvement in the atherosclerotic process. Finally, we briefly discuss the potential use of miRNAs signatures to map atherosclerosis progression and in particular underlying the relevance of circulating plasma miRNAs that can be used clinically as biomarkers of vascular pathology. PMID:23812745

Menghini, Rossella; Casagrande, Viviana; Federici, Massimo

2013-12-01

305

Sublingual vaccine with GroEL attenuates atherosclerosis.  

PubMed

Autoimmune responses to heat-shock protein 60 (HSP60) contribute to the progression of atherosclerosis, whereas immunization with HSP60 may induce atheroprotective responses. We assessed the capacity of an atheroprotective vaccine that targeted a recombinant HSP60 from Porphyromonas gingivalis (rGroEL) to induce a protective mucosal immune response. Female apolipoprotein E-deficient spontaneously hyperlipidemic (Apoe(shl)) mice received sublingual delivery of rGroEL prior to P. gingivalis 381 injection. The animals were euthanized 16 weeks later. Sublingual immunization with rGroEL induced significant rGroEL-specific serum IgG responses. Antigen-specific cells isolated from spleen produced significantly high levels of IL-10 and IFN-? after antigen re-stimulation in vitro. Flow cytometric analysis indicated that the frequencies of both IL-10(+) and IFN-?(+) CD4(+) Foxp3(+) cells increased significantly in submandibular glands (SMG). Furthermore, sublingual immunization with rGroEL significantly reduced atherosclerosis lesion formation in the aortic sinus and decreased serum CRP, MCP-1, and ox-LDL levels. These findings suggest that sublingual immunization with rGroEL is associated with the increase of IFN?(+) or IL-10(+) Foxp3(+) cells in SMG and a systemic humoral response, which could be an effective strategy for the prevention of naturally occurring or P. gingivalis-accelerated atherosclerosis. PMID:24554540

Hagiwara, M; Kurita-Ochiai, T; Kobayashi, R; Hashizume-Takizawa, T; Yamazaki, K; Yamamoto, M

2014-04-01

306

DNA modifications in atherosclerosis: from the past to the future.  

PubMed

The role of DNA damage in the pathogenesis of atherosclerosis has been extensively investigated in recent decades. There is now clear that oxidative stress is an important inducer of both DNA damage and telomere attrition which, in turn, can gives rise to genome instability and vascular senescence. This review discusses the role of the DNA damage response, including the key DNA repair pathways (base excision repair, nucleotide excision repair, homologous recombination and non-homologous end joining), deregulated cell cycle and apoptosis in atherosclerosis. We also highlight emerging evidence suggesting that epigenetic changes (DNA methylation and microRNA-mediated mechanisms), not associated with alterations in DNA sequences, may play a critical role in the regulation of the DNA damage response. Nevertheless, further investigation is still required to better understand the complexity of DNA repair and DNA damage response in atherosclerosis, making this topic an exciting and promising field for future investigation. Unraveling these molecular mechanisms provide the rationale for the development of novel efficient therapies to combat the vascular aging process. PMID:24075745

Borghini, Andrea; Cervelli, Tiziana; Galli, Alvaro; Andreassi, Maria Grazia

2013-10-01

307

Pathogens and atherosclerosis: update on the potential contribution of multiple infectious organisms to the pathogenesis of atherosclerosis.  

PubMed

It is currently unclear what causes the chronic inflammation within atherosclerotic plaques. One emerging paradigm suggests that infection with bacteria and/or viruses can contribute to the pathogenesis of atherosclerosis either via direct infection of vascular cells or via the indirect effects of cytokines or acute phase proteins induced by infection at non-vascular sites. This paradigm has been supported by multiple epidemiological studies that have established positive associations between the risk of cardiovascular disease morbidity and mortality and markers of infection. It has also been supported by experimental studies showing an acceleration of the development of atherosclerosis following infection of hyperlipidaemic animal models. There are now a large number of different infectious agents that have been linked with an increased risk of cardiovascular disease. These include: Chlamydia pneumoniae, Porphyromonas gingivalis, Helicobacter pylori , influenza A virus, hepatitis C virus, cytomegalovirus, and human immunodeficiency virus. However, there are significant differences in the strength of the data supporting their association with cardiovascular disease pathogenesis. In some cases, the infectious agents are found within the plaques and viable organisms can be isolated suggesting a direct effect. In other cases, the association is entirely based on biomarkers. In the following review, we evaluate the strength of the data for individual or groups of pathogens with regard to atherosclerosis pathogenesis and their potential contribution by direct or indirect mechanisms and discuss whether the established associations are supportive of the infectious disease paradigm. We also discuss the failure of antibiotic trials and the question of persistent infection. PMID:22012133

Rosenfeld, M E; Campbell, L A

2011-11-01

308

High-resolution B-mode ultrasonography in evaluation of atherosclerosis in uremia  

Microsoft Academic Search

High-resolution B-mode ultrasonography in evaluation of atherosclerosis in uremia. We sought to determine whether atherosclerosis may be accelerated in uremic patients on maintenance hemodialysis and investigated the risk factors for carotid and femoral atherosclerosis in such patients. High-resolution B-mode ultrasonography was used to determine the intima-media thickness (IMT) of the carotid and femoral arteries in 199 hemodialysis patients and 81

Takahiko Kawagishi; Yoshiki Nishizawa; Toshiaki Konishi; Koichi Kawasaki; Masanori Emoto; Tetsuo Shoji; Tsutomu Tabata; Takashi Inoue; Hirotoshi Morii

1995-01-01

309

Atherosclerotic Risks from Chemicals: Part I. Toxicological Observations and Mechanisms of Atherosclerosis  

Microsoft Academic Search

.   Atherosclerosis is a common disease, primarily of the large arteries, that begins in childhood and progresses with advancing\\u000a age. Atherosclerosis leads to coronary heart disease, the major cause of death in the United States. Several risk factors\\u000a affect atherosclerosis, but high LDL cholesterol is the most important risk factor. In addition, high levels of lipoprotein\\u000a (a) appear to be

S. R. Basavaraju; T. D. Jones

1998-01-01

310

Mixed allogeneic chimerism with wild-type strains ameliorates atherosclerosis in apolipoprotein E-deficient mice  

Microsoft Academic Search

Atherosclerosis involves inflammatory processes between vascular tissues and hemato- cytes with a hyperlipidemic background. To exam- ine whether variations of hematocytes constitute one of the genetic components in atherosclerosis, irradiated apolipoprotein E (apoE)-deficient (apoE2\\/2) mice with hypercholesterolemia and preexisting athero- sclerotic lesions were reconstituted with mixed bone marrow cells (BMC) from syngeneic and wild-type (apoE1\\/1; atherosclerosis-resistant SJL or -suscep- tible

Naoki Ishimori; Kazuya Iwabuchi; Satoshi Fujii; Keiko Watano; Chikako Iwabuchi; Manabu Ato; Hitoshi Chiba; Shinya Tanaka; Akira Kitabatake; Kazunori Onoe ´

2001-01-01

311

Effective suppressibility of chaos.  

PubMed

Suppression of chaos is a relevant phenomenon that can take place in nonlinear dynamical systems when a parameter is varied. Here, we investigate the possibilities of effectively suppressing the chaotic motion of a dynamical system by a specific time independent variation of a parameter of our system. In realistic situations, we need to be very careful with the experimental conditions and the accuracy of the parameter measurements. We define the suppressibility, a new measure taking values in the parameter space, that allows us to detect which chaotic motions can be suppressed, what possible new choices of the parameter guarantee their suppression, and how small the parameter variations from the initial chaotic state to the final periodic one are. We apply this measure to a Duffing oscillator and a system consisting on ten globally coupled He?non maps. We offer as our main result tool sets that can be used as guides to suppress chaotic dynamics. PMID:23822472

López, Álvaro G; Seoane, Jesús M; Sanjuán, Miguel A F

2013-06-01

312

Effective suppressibility of chaos  

NASA Astrophysics Data System (ADS)

Suppression of chaos is a relevant phenomenon that can take place in nonlinear dynamical systems when a parameter is varied. Here, we investigate the possibilities of effectively suppressing the chaotic motion of a dynamical system by a specific time independent variation of a parameter of our system. In realistic situations, we need to be very careful with the experimental conditions and the accuracy of the parameter measurements. We define the suppressibility, a new measure taking values in the parameter space, that allows us to detect which chaotic motions can be suppressed, what possible new choices of the parameter guarantee their suppression, and how small the parameter variations from the initial chaotic state to the final periodic one are. We apply this measure to a Duffing oscillator and a system consisting on ten globally coupled Hénon maps. We offer as our main result tool sets that can be used as guides to suppress chaotic dynamics.

López, Álvaro G.; Seoane, Jesús M.; Sanjuán, Miguel A. F.

2013-06-01

313

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

314

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.

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

315

MafB promotes atherosclerosis by inhibiting foam-cell apoptosis.  

PubMed

MafB is a transcription factor that induces myelomonocytic differentiation. However, the precise role of MafB in the pathogenic function of macrophages has never been clarified. Here we demonstrate that MafB promotes hyperlipidemic atherosclerosis by suppressing foam-cell apoptosis. Our data show that MafB is predominantly expressed in foam cells found within atherosclerotic lesions, where MafB mediates the oxidized LDL-activated LXR/RXR-induced expression of apoptosis inhibitor of macrophages (AIM). In the absence of MafB, activated LXR/RXR fails to induce the expression of AIM, a protein that is normally responsible for protecting macrophages from apoptosis; thus, Mafb-deficient macrophages are prone to apoptosis. Haematopoietic reconstitution with Mafb-deficient fetal liver cells in recipient LDL receptor-deficient hyperlipidemic mice revealed accelerated foam-cell apoptosis, which subsequently led to the attenuation of the early atherogenic lesion. These findings represent the first evidence that the macrophage-affiliated MafB transcription factor participates in the acceleration of atherogenesis. PMID:24445679

Hamada, Michito; Nakamura, Megumi; Tran, Mai Thi Nhu; Moriguchi, Takashi; Hong, Cynthia; Ohsumi, Takayuki; Dinh, Tra Thi Huong; Kusakabe, Manabu; Hattori, Motochika; Katsumata, Tokio; Arai, Satoko; Nakashima, Katsuhiko; Kudo, Takashi; Kuroda, Etsushi; Wu, Chien-Hui; Kao, Pei-Han; Sakai, Masaharu; Shimano, Hitoshi; Miyazaki, Toru; Tontonoz, Peter; Takahashi, Satoru

2014-01-01

316

Deconstructing continuous flash suppression.  

PubMed

In this paper, we asked to what extent the depth of interocular suppression engendered by continuous flash suppression (CFS) varies depending on spatiotemporal properties of the suppressed stimulus and CFS suppressor. An answer to this question could have implications for interpreting the results in which CFS influences the processing of different categories of stimuli to different extents. In a series of experiments, we measured the selectivity and depth of suppression (i.e., elevation in contrast detection thresholds) as a function of the visual features of the stimulus being suppressed and the stimulus evoking suppression, namely, the popular "Mondrian" CFS stimulus (N. Tsuchiya & C. Koch, 2005). First, we found that CFS differentially suppresses the spatial components of the suppressed stimulus: Observers' sensitivity for stimuli of relatively low spatial frequency or cardinally oriented features was more strongly impaired in comparison to high spatial frequency or obliquely oriented stimuli. Second, we discovered that this feature-selective bias primarily arises from the spatiotemporal structure of the CFS stimulus, particularly within information residing in the low spatial frequency range and within the smooth rather than abrupt luminance changes over time. These results imply that this CFS stimulus operates by selectively attenuating certain classes of low-level signals while leaving others to be potentially encoded during suppression. These findings underscore the importance of considering the contribution of low-level features in stimulus-driven effects that are reported under CFS. PMID:22408039

Yang, Eunice; Blake, Randolph

2012-01-01

317

Deconstructing continuous flash suppression  

PubMed Central

In this paper, we asked to what extent the depth of interocular suppression engendered by continuous flash suppression (CFS) varies depending on spatiotemporal properties of the suppressed stimulus and CFS suppressor. An answer to this question could have implications for interpreting the results in which CFS influences the processing of different categories of stimuli to different extents. In a series of experiments, we measured the selectivity and depth of suppression (i.e., elevation in contrast detection thresholds) as a function of the visual features of the stimulus being suppressed and the stimulus evoking suppression, namely, the popular “Mondrian” CFS stimulus (N. Tsuchiya & C. Koch, 2005). First, we found that CFS differentially suppresses the spatial components of the suppressed stimulus: Observers' sensitivity for stimuli of relatively low spatial frequency or cardinally oriented features was more strongly impaired in comparison to high spatial frequency or obliquely oriented stimuli. Second, we discovered that this feature-selective bias primarily arises from the spatiotemporal structure of the CFS stimulus, particularly within information residing in the low spatial frequency range and within the smooth rather than abrupt luminance changes over time. These results imply that this CFS stimulus operates by selectively attenuating certain classes of low-level signals while leaving others to be potentially encoded during suppression. These findings underscore the importance of considering the contribution of low-level features in stimulus-driven effects that are reported under CFS.

Yang, Eunice; Blake, Randolph

2012-01-01

318

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.

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

1995-01-01

319

The occurrence of dental caries is associated with atherosclerosis  

PubMed Central

OBJECTIVE: Previous studies have suggested that marginal periodontitis is a risk factor for developing atherosclerosis. The objective of this study was to determine whether caries may also be associated with atherosclerosis. METHODS: The computed tomography data sets of 292 consecutive patients, 137 women and 155 men with a mean age of 54.1±17.3 years, were analyzed. Caries were quantified based on the number of decayed surfaces of all the teeth, and periodontitis was quantified on the basis of the horizontal bone loss in the jaw. The presence of chronic apical periodontitis (CAP) was assessed, and the aortic atherosclerotic burden was quantified using a calcium scoring method. RESULTS: The patients with <1 caries surfaces/tooth had a lower atherosclerotic burden (0.13±0.61 mL) than patients with ?1 caries surfaces/tooth. The atherosclerotic burden was greater in patients with a higher number of lesions with pulpal involvement and more teeth with chronic apical periodontitis. In the logistical regression models, age (Wald 49.3), number of caries per tooth (Wald 26.4), periodontitis (Wald 8.6), and male gender (Wald 11) were found to be independent risk factors for atherosclerosis. In the linear regression analyses, age and the number of decayed surfaces per tooth were identified as influencing factors associated with a higher atherosclerotic burden, and the number of restorations per tooth was associated with a lower atherosclerotic burden. CONCLUSION: Dental caries, pulpal caries, and chronic apical periodontitis are associated positively, while restorations are associated inversely, with aortic atherosclerotic burden. Prospective studies are required to confirm these observations and answer the question of possible causality.

Glodny, Bernhard; Nasseri, Parinaz; Crismani, Adriano; Schoenherr, Elisabeth; Luger, Anna K.; Bertl, Kristina; Petersen, Johannes

2013-01-01

320

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

321

In vitro experimental photodynamic diagnosis of artery atherosclerosis  

NASA Astrophysics Data System (ADS)

Background: Although there are several methods for atherosclerosis detection available, none of them seems to be accurate enough to identify the vulnerable atheroscleroitc plaque. Photodynamic diagnosis (PDD) and therapy (PDT) -- a new method evaluated for neoplasms treatment is a modern approach to detecting and treating atherosclerosis. Aim: The purpose of this study was to assess in vitro the capability of PDD with use of chlorin e6 to recognize atherosclerotic plaque and its usefulness as a feedback system for photoangioplasty treatment. Methods: 30 specimens of human aorta. The samples were soaked with chlorin e6 and then washed out. The luminescence spectra were then collected. All samples were examined with light microscopy. Results: Tissue fluorescence is seen as green light. We noted a very strong red fluorescence of chlorin e6 originating from lipid reach plaque. We established a quantitative factor which would be the ratio R of chlorin e6 red intensity in its 660 nm maximum compared to the area of green luminescence centered at 515 nm. The highest value of the ratio was reached at atheromatous samples, then calcified and normal ones R2 = 3.51 +/- 0.62, R3 = 1.63 +/- 0.31, R1 = 1.51 +/- 0.15 respectively. Statistically significant difference was noted between group two and one and between group two and three R2 = 3.51 +/- 0.62 vs R3 = 1.63 +/- 0.31 (p < 0,05); R2 = 3.51 +/- 0.62 vs. R1 = 1.51 +/- 0.15 (p<0.05) respectively. Conclusions: the following in vitro study confirms that photosensitizer chlorin e6 accumulates within atheromatous plaque. It may be a specific tool for atheromatous and normal or calcified segments discrimination. The advantage of the above method is a possibility of a real time imaging followed by targeted therapy of various forms and stages of atherosclerosis.

Bialy, Dariusz; Derkacz, Arkadiusz; Wawrzynska, M.; Kwasny, Miroslaw; Strek, Wieslaw; Protasiewicz, Marcin

2004-07-01

322

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.

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

323

The Role of Phospholipid Oxidation Products in Atherosclerosis  

PubMed Central

There is increasing clinical evidence that phospholipid oxidation products (Ox-PL) play a role in atherosclerosis. This review focuses on the mechanisms by which Ox-PL interact with endothelial cells, monocyte/macrophages, platelets, smooth muscle cells and HDL to promote atherogenesis. In the last few years major progress has been made in identifying these mechanisms. It has been recognized that Ox-PL promote phenotypic changes in these cell types that have long term consequences for the vessel wall. Individual Ox-PL responsible for specific cellular effects has been identified. A model of the configuration of bioactive truncated Ox-PL within membranes has been developed that demonstrates that the oxidized fatty acid moiety protrudes into the aqueous phase, rendering it accessible for receptor recognition. Receptors and signaling pathways for individual Ox-PL species are now determined and receptor independent signaling pathways identified. The effects of Ox-PL are mediated both by gene regulation and transcription independent processes. It has now become apparent that Ox-PL affects multiple genes and pathways some of which are pro-atherogenic and some are protective. However, at concentrations that are likely present in the vessel wall in atherosclerotic lesions, the effects promote atherogenesis. There have also been new insights on enzymes that metabolize Ox-PL and the significance of these enzymes for atherosclerosis. With the knowledge we now have on the regulation and effects of Ox-PL in different vascular cell types, it should be possible to design experiments to test the role of specific Ox-PL on the development of atherosclerosis.

Lee, Sangderk; Birukov, Konstantin G.; Romanoski, Casey E.; Springstead, James R.; Lusis, Aldons J.; Berliner, Judith A.

2012-01-01

324

Rotating stall suppression  

NASA Technical Reports Server (NTRS)

Rotating stall in an axial-flow compressor is suppressed by the positioning of a fixed inlet flow divider in the annular inlet flow passage upstream of the compressor. The inlet flow divider is aligned with the flow of fluid through the duct and acts to block or interfere with any rotating wave in the inlet and thereby suppresses rotating stall in the compressor.

Moore, Franklin K. (Inventor)

1994-01-01

325

Decoder based noise suppression  

Microsoft Academic Search

Abstract Acoustic background noise in mobile speech communication systems, while largely inevitable, can have a severely detrimental efiect on speech intelligibility. Noise suppression is highly desirable in these systems. However, the process of reducing noise in a speech signal is associated with distortion of the processed signal, the severity of which is generally proportional to the amount of noise suppression

Erik Hennix

2006-01-01

326

Inflammatory and oxidative markers in atherosclerosis: relationship to outcome.  

PubMed

Inflammation and oxidative processes are key components of atherosclerosis, from fatty streak formation to plaque rupture and thrombosis. Recent basic and clinical studies have identified a number of inflammatory and oxidative processes that appear to play a direct role in atherothrombosis and identify potentially clinically useful markers of inflammation and oxidative stress. In this review, we highlight recent results on several of the more promising markers of inflammation for cardiovascular disease risk assessments, such as C-reactive protein, myeloperoxidase, and soluble CD40 ligand and nitrotyrosine, as well as other potential markers. PMID:15068750

Shishehbor, Mehdi H; Hazen, Stanley L

2004-05-01

327

Potential roles of vessel wall heparan sulfate proteoglycans in atherosclerosis.  

PubMed

Heparan sulfate proteoglycans (HSPGs) are present in several compartments and cell types in blood vessels. Their expression, as well as the activity of their degrading enzyme heparanase, are strongly regulated, with changes in gene expression, protein levels, and activity in response to environmental and metabolic stresses, including diabetes. HSPGs likely play an important role in the development and progression of atherosclerosis. Many functions of HSPGs, such as the promotion of monocyte adhesion, smooth muscle cell proliferation, and low density lipoproteins (LDL) binding, are determined by interactions between cells and specific regions of the HSPG core proteins. Here we review the role of HSPGs expressed in vascular wall in atherosclerotic vascular disease. PMID:24333941

Madonna, Rosalinda; De Caterina, Raffaele

2014-02-01

328

Studies of atherosclerosis determinants and precursors during childhood and adolescence*  

PubMed Central

At a Meeting of Investigators on Epidemiological Studies of Atherosclerosis Determinants and Precursors, which was held in Geneva on 7-9 November 1983, representatives from 26 countries reviewed the current status of epidemiological studies in this area. Particular interest was shown in the following determinants of cardiovascular disease: blood pressure, blood lipid levels, body weight, pathological studies, and tobacco use. Working papers on each determinant were prepared, and recommendations were made on areas for research, and on the need for prevention programmes and pathological studies. This article summarizes the work of the meeting.

Tell, G. S.; Tuomilehto, J.; Epstein, F. H.; Strasser, T.

1986-01-01

329

Preventive Effect of Dipeptidyl Peptidase-4 Inhibitor on Atherosclerosis Is Mainly Attributable to Incretin's Actions in Nondiabetic and Diabetic Apolipoprotein E-Null Mice  

PubMed Central

Aim Several recent reports have revealed that dipeptidyl peptidase (DPP)-4 inhibitors have suppressive effects on atherosclerosis in apolipoprotein E-null (Apoe?/?) mice. It remains to be seen, however, whether this effect stems from increased levels of the two active incretins, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Methods Nontreated Apoe?/? mice, streptozotocin-induced diabetic Apoe?/? mice, and db/db diabetic mice were administered the DPP-4 inhibitor vildagliptin in drinking water and co-infused with either saline, the GLP-1 receptor blocker, exendin(9–39), the GIP receptor blocker, (Pro3)GIP, or both via osmotic minipumps for 4 weeks. Aortic atherosclerosis and oxidized low-density lipoprotein-induced foam cell formation in exudate peritoneal macrophages were determined. Results Vildagliptin increased plasma GLP-1 and GIP levels without affecting food intake, body weight, blood pressure, or plasma lipid profile in any of the animals tested, though it reduced HbA1c in the diabetic mice. Diabetic Apoe?/? mice exhibited further-progressed atherosclerotic lesions and foam cell formation compared with nondiabetic counterparts. Nondiabetic and diabetic Apoe?/? mice showed a comparable response to vildagliptin, namely, remarkable suppression of atherosclerotic lesions with macrophage accumulation and foam cell formation in peritoneal macrophages. Exendin(9–39) or (Pro3)GIP partially attenuated the vildagliptin-induced suppression of atherosclerosis. The two blockers in combination abolished the anti-atherosclerotic effect of vildagliptin in nondiabetic mice but only partly attenuated it in diabetic mice. Vildagliptin suppressed macrophage foam cell formation in nondiabetic and diabetic mice, and this suppressive effect was abolished by infusions with exendin(9–39)+(Pro3)GIP. Incubation of DPP-4 or vildagliptin in vitro had no effect on macrophage foam cell formation. Conclusions Vildagliptin confers a substantial anti-atherosclerotic effect in both nondiabetic and diabetic mice, mainly via the action of the two incretins. However, the partial attenuation of atherosclerotic lesions by the dual incretin receptor antagonists in diabetic mice implies that vildagliptin confers a partial anti-atherogenic effect beyond that from the incretins.

Terasaki, Michishige; Nagashima, Masaharu; Nohtomi, Kyoko; Kohashi, Kyoko; Tomoyasu, Masako; Sinmura, Kyoko; Nogi, Yukinori; Katayama, Yuki; Sato, Kengo; Itoh, Fumiko; Watanabe, Takuya; Hirano, Tsutomu

2013-01-01

330

Conjugated Equine Estrogens Inhibit Progression of Atherosclerosis but Have No Effect on Intimal Hyperplasia or Arterial Remodeling Induced by Balloon Catheter Injury in Monkeys 1 1 This work was supported in part by Grant PO1HL45666 from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland. Wyeth-Ayerst, Princeton, New Jersey provided the Premarin used in this study  

Microsoft Academic Search

Objectives. This study sought to determine the effects of estrogen treatment on atherosclerosis progression and the proliferative and structural responses of the atherosclerotic arteries to injury.Background. Estrogen treatment suppresses the intimal response to arterial injury in nonatherosclerotic rodents and rabbits and inhibits the in vitro proliferation of smooth muscle cells. However, the effect of estrogen on the response of atherosclerotic

Randolph L Geary; Michael R Adams; Marshall E Benjamin; J. Koudy Williams

1998-01-01

331

Superoxide Production in Vascular Smooth Muscle Contributes to Oxidative Stress and Impaired Relaxation in Atherosclerosis  

Microsoft Academic Search

The endothelium is a source of reactive oxygen species in short-term models of hypercholesterolemia and atherosclerosis. We examined a chronic model of atherosclerosis for increased vascular production of superoxide (O 22z) and determined whether endothelial overexpression of superoxide dismutase (SOD) would improve endothelium- dependent relaxation. Superoxide generation was 3 times higher in isolated aortas from Watanabe heritable hyperlipidemic (WHHL) rabbits

Francis J. Miller; David D. Gutterman; C. David Rios; Donald D. Heistad; Beverly L. Davidson

332

Renal insufficiency accelerates atherosclerosis in patients with type 2 diabetes mellitus  

Microsoft Academic Search

Diabetes mellitus is a strong risk factor for the progression of atherosclerosis. In patients with chronic renal failure on hemodialysis, advanced atherosclerosis is reported to be present. We examined how renal insufficiency affects intima-medial thickness (IMT) of the carotid and femoral arteries in patients with type 2 diabetes mellitus. IMT was measured by B-mode ultrasonography in 115 patients with type

Eiji Ishimura; Tetsuo Shoji; Masanori Emoto; Kouka Motoyama; Kayo Shinohara; Naoki Matsumoto; Hiromichi Taniwaki; Masaaki Inaba; Yoshiki Nishizawa

2001-01-01

333

Elevated expression of phospholipid transfer protein in bone marrow derived cells causes atherosclerosis  

Microsoft Academic Search

Background: Phospholipid transfer protein (PLTP) is expressed by various cell types. In plasma, it is associated with high density lipoproteins (HDL). Elevated levels of PLTP in transgenic mice result in decreased HDL and increased atherosclerosis. PLTP is present in human atherosclerosis lesions, where it seems to be macrophage derived. The aim of the present study is to evaluate the atherogenic

Rien van Haperen; Hannelore Samyn; Matthijs Moerland; Teus van Gent; Marian Peeters; Frank Grosveld; Arie van Tol; Crom de M. P. G

2008-01-01

334

Metabolic syndrome, insulin resistance, and atherosclerosis in Japanese type 2 diabetic patients  

Microsoft Academic Search

The aim of the present study was to investigate the relationships between metabolic syndrome and atherosclerosis in 57 Japanese type 2 diabetic patients. Metabolic syndrome was diagnosed based on the criteria raised by the Japan Internal Medicine Society. Insulin resistance was estimated by the insulin resistance index of homeostasis model assessment. Ultrasonographically measured carotid atherosclerosis, brachial-ankle pulse wave velocity (ba-PWV),

Ataru Taniguchi; Mitsuo Fukushima; Akira Kuroe; Kenji Sakaguchi; Hiroko Hashimoto; Ikuko Yoshioka; Naomi Kitatani; Tomoko Tsuji; Michihiro Ohya; Minako Ohgushi; Shoichiro Nagasaka; Okihisa Isogai; Yoshikatsu Nakai; Nobuya Inagaki; Yutaka Seino

2007-01-01

335

Relationship between Pulse Wave Velocity and Carotid Atherosclerosis in Geriatric People  

Microsoft Academic Search

Objective: To investigate the relationship between the pulse wave velocity (PWV) and angiographic carotid atherosclerosis in elderly patients. Method: 103 consecutive elderly patients were divided into two groups according to the results of cerebral angiography: carotid atherosclerosis group and normal carotid angiogram group. Basic clinical information was required by a standardized questionnaire. Carotid-femoral PWV (cfPWV) as a marker of Stiffness

L. Shen; W. Wu; B. You; H. Gao; C. Wang; Y. Liu

2011-01-01

336

Mechanisms of Disease: macrophage migration inhibitory factor in SLE, RA and atherosclerosis  

Microsoft Academic Search

The past decade has seen the emergence of two new paradigms in inflammatory disease: first, cardiovascular complications of atherosclerosis are markedly increased in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE); and second, inflammatory mechanisms are important in the pathogenesis of atherosclerosis. These concurrent developments have lead to the concept that inflammatory mediators operative in RA and SLE

Sally Ayoub; Michael J Hickey; Eric F Morand

2008-01-01

337

Influence of Crocetin on experimental atherosclerosis in hyperlipidamic-diet quails  

Microsoft Academic Search

Antioxidants have been expected to have potential as antiatherogenic agents. Crocetin is a natural carotenoid antioxidant isolated from Gardenia jasminoids Ellis. Therefore, in the present study, we investigated the inhibitory effect of Crocetin on experimental atherosclerosis in quails. The atherosclerosis model was established by feeding hyperlipidamic diet to quail and Crocetin (25, 50, 100 mg\\/kg\\/day) was administered by oral gavage. At

Shu-Ying He; Zhi-Yu Qian; Na Wen; Fu-Tian Tang; Guang-Lin Xu; Cheng-Hua Zhou

2007-01-01

338

Sleep and Biomarkers of Atherosclerosis in Elderly Alzheimer Caregivers and Controls  

Microsoft Academic Search

Background: Perturbed sleep might contribute to cardiovascular disease by accelerating atherosclerosis. Sleep is poor in Alzheimer caregivers who are also a group at increased cardiovascular risk. Objective: To test the hypothesis that impaired sleep relates to elevated levels of biomarkers of atherosclerosis in community-dwelling elderly and that this association would possibly be stronger in caregivers than in non-caregiving controls. Methods:

Roland von Känel; Sonia Ancoli-Israel; Joel E. Dimsdale; Paul J. Mills; Brent T. Mausbach; Michael G. Ziegler; Thomas L. Patterson; Igor Grant

2010-01-01

339

The possible role of the ubiquitin proteasome system in the development of atherosclerosis in diabetes  

Microsoft Academic Search

We have reviewed the impact of the ubiquitin proteasome system (UPS) on atherosclerosis progression of diabetic patients. A puzzle of many pieces of evidence suggests that UPS, in addition to its role in the removal of damaged proteins, is involved in a number of biological processes including inflammation, proliferation and apoptosis, all of which constitute important characteristics of atherosclerosis. From

Raffaele Marfella; Michele D' Amico; Clara Di Filippo; Mario Siniscalchi; Ferdinando Carlo sasso; Franca Ferraraccio; Francesco Rossi; Giuseppe Paolisso

2007-01-01

340

Obesity, atherosclerosis and the vascular endothelium: mechanisms of reduced nitric oxide bioavailability in obese humans  

Microsoft Academic Search

It is now well established that obesity is an independent risk factor for the development of coronary artery atherosclerosis. The maintenance of vascular homeostasis is critically dependent on the continued integrity of vascular endothelial cell function. A key early event in the development of atherosclerosis is thought to be endothelial cell dysfunction. A primary feature of endothelial cell dysfunction is

IL Williams; SB Wheatcroft; AM Shah; MT Kearney

2002-01-01

341

Monitoring SERS-based contrast agents in atherosclerosis experimental models  

NASA Astrophysics Data System (ADS)

There have been enormous progresses in developing a class of multimodal contrast agents, which combine MRI with optical imaging. Contrast agent targeting can provide enhanced diagnostic information, allowing differentiation between variable and stable atherosclerotic plaques. Recently an intensive efforts have been working on the development of contrast agents that can improve the ability to detect and characterize atherosclerosis in clinical and preclinical applications. Earlier studies on hyperlipidemic rabbits using in vivo MRI have shown accumulation of USPIOs in plaques with a high macrophage content that induces magnetic resonance (MR) signal changes correlated to the absolute iron content in the aortic arch. A potent new class of nanoparticles contrast agents have recently drawn much attention for its wide diverse diagnostic and potential therapeutic applications particularly in monitoring the inflammatory responses. In our previous studies we have investigated SPIO contrast agents uptakes in hepatic and spleen tissues taken from NZW rabbits. The scope of this work encompasses application of an emerging hybrid imaging modality, SERSbased nonlinear optical microscopy, in investigating atherosclerosis experimental models. In this work experiments are performed on contrast treated tissue sections taken from aortic arch of atherosclerotic animal model. Marked contrast enhancement has been observed in the treated aortic sections compared with the untreated control. The obtained images are compared with immunohistochemistry .The work presented can be promising for future studies on in vivo detection of macrophages in human plaques and early detection of atherosclerotic diseases.

Machtoub, Lina H.

2011-02-01

342

Spectroscopic intravascular photoacoustic imaging of lipids in atherosclerosis.  

PubMed

The natural history of atherosclerosis is marked by changes in the lipid biochemistry in the diseased arterial wall. As lesions become more vulnerable, different cholesterol species accumulate in the plaque. Understanding unstable atherosclerosis as a pharmacological and interventional therapeutic target requires chemically specific imaging of disease foci. In this study, we aim to image atherosclerotic plaque lipids and other vessel wall constituents with spectroscopic intravascular photoacoustics (sIVPA). sIVPA imaging can identify lipids in human coronary atherosclerotic plaque by relying on contrast in the near-infrared absorption spectra of the arterial wall components. Using reference spectra acquired on pure compounds, we analyzed sIVPA data from human coronary plaques ex vivo, to image plaque composition in terms of cholesterol and cholesterol ester content. In addition, we visualized the deeper lying connective tissue layers of the adventitia, as well as the fatty acid containing adipose cells in the peri-adventitial tissue. We performed simultaneous coregistered IVUS imaging to obtain complementary morphological information. Results were corroborated by histopathology. sIVPA imaging can distinguish the most prevalent lipid components of human atherosclerotic plaques and also visualize the connective tissue layers of the adventitia and the fatty acid containing adipose cells in the peri-adventitial tissue. PMID:24522806

Jansen, Krista; van der Steen, Antonius F W; Wu, Min; van Beusekom, Heleen M M; Springeling, Geert; Li, Xiang; Zhou, Qifa; Shung, K Kirk; de Kleijn, Dominique P V; van Soest, Gijs

2014-02-01

343

The Association Between Physical Activity and Subclinical Atherosclerosis  

PubMed Central

Prior reports regarding the association between physical activity and subclinical cardiovascular disease have not been consistent. The authors assessed physical activity and walking pace via questionnaire among 6,482 US adults aged 45–84 years without prior clinical cardiovascular disease participating in the Multi-Ethnic Study of Atherosclerosis from 2000 to 2002. Ankle-brachial index (ABI), coronary artery calcification, and internal and common carotid intima-media thickness (IMT) were measured. Metabolic equivalent-hours/week of physical activity were calculated. These data were analyzed by using multivariable linear or relative prevalence regression in gender-specific strata. After adjustment for age, race/ethnicity, clinic site, education, income, and smoking (model 1), increasing total, moderate + vigorous, and intentional-exercise physical activity were not associated with IMT or coronary artery calcification in either gender. These factors were associated with increased ABI (P?atherosclerosis; these associations may be mediated by cardiovascular disease risk factors.

Whitt-Glover, Melicia C.; Chung, Hyoju; Le, Katherine Y.; Barr, R. Graham; Mahesh, Mahadevappa; Jenny, Nancy S.; Burke, Gregory L.; Jacobs, David R.

2009-01-01

344

Socioeconomic Status and Subclinical Atherosclerosis in Older Adults  

PubMed Central

Objective This study investigated the long-term effects of socioeconomic status (SES) on atherosclerosis. Methods Data from the Epidemiology of Hearing Loss Study and the Beaver Dam Eye Study (Beaver Dam, WI, 1998-2000), were used to examine adult SES (education, household income, longest-held job) and childhood SES (household density and parental home ownership at age 13) associations with carotid intima-media thickness (IMT) and carotid plaque in a cohort of 2,042 men and women aged 53 to 94 years. Results For education, income, and occupation (women), those in the lowest SES group had statistically larger age-sex-adjusted IMT than those in the highest SES group (<12 vs. >12 years education: 0.92 vs. 0.86 mm respectively, P<0.0001), (<$10,000 vs. >$45,000: 0.97 vs. 0.87 mm, P<0.0001), (operator/fabricator/labor vs. manager/professional: 0.89 vs. 0.82 mm, P<0.001). Associations were similar using carotid plaque as the outcome. Participants with low levels of both adult and childhood SES measures had age-sex-adjusted IMT greater than those with persistently high levels of SES (0.93 vs. 0.84 mm, P<0.0001). Conclusions Measures of SES at two points in the life-span were associated with subclinical atherosclerosis.

Nash, Scott D.; Cruickshanks, Karen J.; Klein, Ronald; Klein, Barbara E. K.; Nieto, F. Javier; Ryff, Carol D.; Krantz, Elizabeth M.; Shubert, Carla R.; Nondahl, David M.; Acher, Charles W.

2011-01-01

345

Non-invasive MRI of mouse models of atherosclerosis.  

PubMed

Early detection and characterization of atherosclerotic lesions susceptible to sudden rupture and thrombosis may decrease morbidity and mortality. Plaque development has been extensively studied using MRI in animal models of rapidly progressing atherosclerosis. These transgenic mice develop atherosclerotic plaques in the aortic root by 10 weeks of age and throughout the vasculature thereafter. Transplantation of lesion-containing segments of the thoracic aorta into wild-type mice results in nearly total reversal of atherosclerosis, making it possible to study both progression and regression of plaques in this model. MRI permits the non-invasive accurate assessment of atherosclerotic plaque burden and the differentiation between the lipid and fibrous content of individual plaques, thus providing a non-invasive approach to serially monitor the evolution of individual plaques in the mouse models. Emergence of novel contrast agents that target a diverse set of molecules within the plaque are now helping to elucidate the changes at the cellular and molecular levels during plaque progression and regression. PMID:17451174

Weinreb, David B; Aguinaldo, Juan Gilberto S; Feig, Jonathan E; Fisher, Edward A; Fayad, Zahi A

2007-05-01

346

Interleukin-17A in lipid metabolism and atherosclerosis.  

PubMed

Interleukin-17 (IL-17) A, the most important cytokine of the IL-17 family predominantly secreted by T helper 17 (Th17) cells, plays a critical role in the development of inflammatory diseases. Its receptor is an obligate heterodimer composed of IL-17 receptor (IL-17R) A and C, the main members of the IL-17R family. Binding of IL-17A to the IL-17RA/C complex can activate a variety of downstream signaling pathways such as nuclear factor kappa-B (NF-?B), activator protein 1 (AP1) and CCAAT/enhancer-binding protein (C/EBP) to induce the expression of proinflammatory cytokines and chemokines. IL-17A also promotes mRNA stability. Growing evidence shows that IL-17A is involved in lipid metabolism and the pathogenesis of atherosclerosis, a chronic inflammatory arterial disease driven by both innate and adaptive immune responses to modified lipoproteins. In the current review, we describe recent progress on regulation and signaling of IL-17A, and highlight its impacts on lipid metabolism and atherosclerosis. PMID:24508995

Yu, Xiao-Hua; Jiang, Na; Zheng, Xi-Long; Cayabyab, Francisco S; Tang, Zhi-Bin; Tang, Chao-Ke

2014-04-20

347

Studies on regression of atherosclerosis--role of lipid containers.  

PubMed

The appearance of the aortic wall of rabbits fed a lanolin containing diet was examined by scanning (SEM) and transmission electron microscopy (TEM) in order to clarify the mechanism of removal of lipids deposited in the aorta. SEM study showed that circulating leukocytes penetrated into the arterial wall in the early phase of the experimental atherosclerosis. In some specimens, spherical bodies with a diameter of 10-30 mu were observed along the cleavage of the marginal folds between the endothelial cells. TEM demonstrated that these bodies contained many lipid particles, and numerous active microvilli were seen on the body surface. In the deeper subendothelial space, villi of each body interdigitated. From these results, it is postulated that the circulating leukocytes penetrate under the endothelium and take up the deposited lipids. Then, they return to the blood stream, containing lipid rich particles. The deposited lipids in the atherosclerotic lesion would be removed by this process. We named this phenomenon as "exo-tissuesis with lipid containers". While lipids are believed to be removed from the atherosclerotic lesion by HDL, lecithin cholesterol acyltransferase and others at the molecular level, we suggest that lipid containers play important roles in the regression and prevention of atherosclerosis on a major scale-cellular and tissue level. PMID:6275137

Sekimoto, H; Nakanishi, M; Shimada, O; Uemura, E; Nakada, I

1982-01-01

348

Update on medical management of dyslipidemia and atherosclerosis.  

PubMed

Scientific achievements revealing the pathogenesis of atherosclerosis resulted in the second half of the 20th century in major improvement in prevention and therapy of cardiovascular disorders (CVD). Essential became the understanding of a critical pathogenetic role of the low-density lipoproteins (LDL), mainly their oxidized form (oxLDL) and also the protective potential of the high-density lipoproteins (HDL). CVD is now regarded to be an inflammatory disease in which a systemic inflammatory reaction is combined with an accumulation of immune cells in atherosclerotic plaques. Higher intake of antioxidants in fruit and vegetable, life style modifications, cessation of smoking, physical exercise and introduction of medications that lower LDL and promote HDL (statins, niacin and fibrates) resulted in a substantial decline of the killer effect of unmanaged CVD. In the United Kingdom the male CVD mortality declined between 1970 and 2009 from 700 to 200 deaths per 100,000. In France, CVD mortality in the middle age population (25-64 years) is now responsible for death in only 15 % men and in 11 % women. Unfortunately, in many parts of the world CVD mortality remains a prominent population scourge. Recent discoveries, especially on the role of peroxisome proliferator-activated receptors (PPAR) and antisense compounds used in addition to established anti-atherogenic medications, promise further gains in the fight against atherosclerosis (Fig. 4, Ref. 54). PMID:23611048

Ginter, E; Simko, V

2013-01-01

349

Effects of physical exercise on inflammatory markers of atherosclerosis.  

PubMed

It is well established that physically fit individuals have a reduced risk of developing CVD (cardiovascular disease) and other age-related chronic disorders. Regular exercise is an established therapeutic intervention with an enormous range of benefits. Chronic low-grade systemic inflammation may be involved in atherosclerosis, diabetes and in pathogenesis of several chronic pathological conditions; recent findings confirm that physical activity induces an increase in the systemic levels of a number of cytokines and chemokines with anti-inflammatory properties. The possibility that regular physical exercise exerts anti-inflammation activity, being the interaction between contracting muscle and the other tissues and the circulating cells mediated through signals transmitted by "myokines" produced with muscle contractions. To date the list of myokines includes IL-6, IL-8, and IL-15. During muscle contractions are also released IL-1 receptor antagonis and sTNF-R, molecules that contribute to provide anti-inflammatory actions. Nevertheless discrepancies, analysis of available researches seem to confirm the efficacy of regular physical training as a nonpharmacological therapy having target chronic low-grade inflammation. Given this, physical exercise could be considerate a useful weapon against local vascular and systemic inflammation in atherosclerosis. Several mechanisms explain the positive effect of chronic exercise, nevertheless, these mechanisms do not fully enlighten all pathways by which exercise can decrease inflammation and endothelial dysfunction, and hence modulate the progression of the underlying disease progress. PMID:22390642

Pinto, A; Di Raimondo, D; Tuttolomondo, A; Buttà, C; Milio, G; Licata, G

2012-01-01

350

From genotype to phenotype in human atherosclerosis - recent findings  

PubMed Central

Purpose of review Since 2007, genome-wide association studies (GWAS) have led to the identification of numerous loci of atherosclerotic cardiovascular disease. The majority of these loci harbor genes previously not known to be involved in atherogenesis. In this review, we summarize the recent progress in understanding the pathophysiology of genetic variants in atherosclerosis. Recent findings Fifty-eight loci with P?atherosclerosis is limited and implicate a role of hitherto unknown mechanisms, such as epigenetic gene regulation in atherogenesis.

Holdt, Lesca M.; Teupser, Daniel

2013-01-01

351

Role of Suppressor of Cytokine Signaling-1 In Murine Atherosclerosis  

PubMed Central

Background While the impact of inflammation as the substantial driving force of atherosclerosis has been investigated in detail throughout the years, the influence of negative regulators of pro-atherogenic pathways on plaque development has remained largely unknown. Suppressor of cytokine signaling (SOCS)-1 potently restricts transduction of various inflammatory signals and, thereby modulates T-cell development, macrophage activation and dendritic cell maturation. Its role in atherogenesis, however has not been elucidated so far. Methods and Results Loss of SOCS-1 in the low-density lipoprotein receptor deficient murine model of atherosclerosis resulted in a complex, systemic and ultimately lethal inflammation with increased generation of Ly-6Chi monocytes and activated macrophages. Even short-term exposure of these mice to high-cholesterol dieting caused enhanced atherosclerotic plaque development with accumulation of M1 macrophages, Ly-6C positive cells and neutrophils. Conclusion Our data not only imply that SOCS-1 is athero-protective but also emphasize the fundamental, regulatory importance of SOCS-1 in inflammation-prone organisms.

Hillmer, Anja; Lumpe, Stefan; Grote, Karsten; Ballmaier, Matthias; Bleich, Andre; Glage, Silke; Tietge, Uwe J. F.; Luchtefeld, Maren; Schieffer, Bernhard

2012-01-01

352

Lipid glycation and protein glycation in diabetes and atherosclerosis.  

PubMed

Recent instrumental analyses using a hybrid quadrupole/linear ion trap spectrometer in LC-MS/MS have demonstrated that the Maillard reaction progresses not only on proteins but also on amino residues of membrane lipids such as phosphatidylethanolamine (PE), thus forming Amadori-PE (deoxy-D: -fructosyl PE) as the principal products. The plasma Amadori-PE level is 0.08 mol% of the total PE in healthy subjects and 0.15-0.29 mol% in diabetic patients. Pyridoxal 5'-phosphate and pyridoxal are the most effective lipid glycation inhibitors, and the PE-pyridoxal 5'-phosphate adduct is detectable in human red blood cells. These findings are beneficial for developing a potential clinical marker for glycemic control as well as potential compounds to prevent the pathogenesis of diabetic complications and atherosclerosis. Glucose and other aldehydes, such as glyoxal, methylglyoxal, and glycolaldehyde, react with the amino residues of proteins to form Amadori products and Heynes rearrangement products. Because several advanced glycation end-product (AGE) inhibitors such as pyridoxamine and benfotiamine inhibit the development of retinopathy and neuropathy in streptozotocin (STZ)-induced diabetic rats, AGEs may play a role in the development of diabetic complications. In the present review, we describe the recent progress and future applications of the Maillard reaction research regarding lipid and protein modifications in diabetes and atherosclerosis. PMID:20957396

Miyazawa, Teruo; Nakagawa, Kiyotaka; Shimasaki, Satoko; Nagai, Ryoji

2012-04-01

353

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

354

Blood level of osteonectin in stenosing atherosclerosis and calcinosis of coronary arteries.  

PubMed

Blood levels of stem cell marker proteins CD34 and osteonectin were studied in male patients with coronary atherosclerosis by direct biomagnetic separation of proteins with magnetic microspheres using the PureProteome Protein A and Protein G Magnetic Beads proteomic technology. High concentration of osteonectin in the blood was detected, particularly in men with stenosing atherosclerosis and coronary artery calcinosis. Blood osteonectin concentration correlated significantly with some key biomarkers of atherosclerosis and with stenosing atherosclerosis and calcinosis of coronary arteries. The results indicate that osteonectin as a marker of stromal stem cells with osteogenic potential presumably plays an important role in atherogenesis and can serve as a new biomarker of stenosing atherosclerosis and calcinosis of coronary arteries. PMID:22451890

Ragino, Yu I; Kashtanova, E V; Chernjavski, A M; Volkov, A M; Polonskaya, Ya V; Tsimbal, S Yu; Eremenko, N V; Ivanova, M V

2011-07-01

355

Immunization using an Apo B100 related epitope reduces atherosclerosis and plaque inflammation in hypercholesterolemic apo E (?\\/?) mice  

Microsoft Academic Search

Immune system modulates atherosclerosis and immunization using homologous LDL reduces atherosclerosis in hyperlipidemic animals. The nature of athero-protective antigenic epitopes in LDL remains unclear. We have recently identified nearly a 100 antigenic epitopes in human apo B-100 and in this study we evaluated the effects of immunization with two such epitopes on atherosclerosis in hypercholesterolemic apo E (?\\/?) mice. Male

Kuang-Yuh Chyu; Xiaoning Zhao; Odette S. Reyes; Stephanie M. Babbidge; Paul C. Dimayuga; Juliana Yano; Bojan Cercek; Gunilla Nordin Fredrikson; Jan Nilsson; Prediman K. Shah

2005-01-01

356

Cough suppression disorders spectrum.  

PubMed

Volitional cough suppression, identified exclusively in females, is an unusual causal mechanism for instances of lobar atalectasis and bronchiectasis. It is a postulated mechanism for the genesis of Lady Windermere Syndrome. PMID:24462261

Reich, Jerome M

2014-02-01

357

Cable Strumming Suppression.  

National Technical Information Service (NTIS)

This report presents a consolidation of existing data on various devices used to suppress vortex-induced motions of cables and circular cylinders in the ocean. The types of devices discussed herein include 'fringe,' 'hair,' and ribbon flexible fairings an...

B. E. Hafen D. J. Meggitt

1977-01-01

358

Cochannel Talker Interference Suppression.  

National Technical Information Service (NTIS)

Cochannel talker interference suppression is defined as the processing of a waveform containing two simultaneous speech signals, referred to as the target and the jammer, to produce a signal containing an estimate of the target speech signal alone. The fi...

M. A. Zissman

1991-01-01

359

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

360

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

361

A histological investigation into the correlation of central retinal artery atherosclerosis with the systemic circulation.  

PubMed

Current research suggests that retinal arterial changes such as arteriovenous nicking and arterial narrowing are pathologically distinct from atherosclerosis. Other studies have found a positive correlation between retinal changes and systemic atherosclerosis. However, limited recent histopathologic evidence assessing atherosclerosis in the central retinal artery exists. We investigated atherosclerosis in the central retinal artery and how it correlates to atherosclerosis in the carotid and coronary arteries. Twenty-two cadavers (12 males, 10 females) were dissected, obtaining one orbit, one carotid artery, and one coronary artery from each. The specimens were sectioned and stained for histologic analysis by light microscopy using hematoxylin and eosin, Verhoeff's elastic, and Gomori's trichrome stains. The degree of atherosclerosis was graded from absent, or I (least severe) to VIII (most severe) based on the current American Heart Association guidelines. Atherosclerotic changes were present in the central retinal, coronary, and carotid arteries. A positive correlation was found between the central retinal artery and the carotid artery (r?=?0.23, P?=?0.15), the central retinal artery and the coronary artery (r?=?0.31, P?=?0.08), and the carotid artery and the coronary artery (r?=?0.45, P?=?0.02). The presence of low-grade atherosclerosis in the central retinal artery is prevalent in a population of advanced vascular disease. However, central retinal artery atherosclerotic lesion severity is poorly correlated with disease severity in the carotid and coronary arteries. Anat Rec, 297:1430-1434, 2014. © 2014 Wiley Periodicals, Inc. PMID:24841620

Schear, Matthew J; Beatty, Brian Lee

2014-08-01

362

Epigenetic regulation of vascular smooth muscle cell function in atherosclerosis.  

PubMed

Epigenetics involve heritable and acquired changes in gene transcription that occur independently of the DNA sequence. Epigenetic mechanisms constitute a hierarchic upper-level of transcriptional control through complex modifications of chromosomal components and nuclear structures. These modifications include, for example, DNA methylation or post-translational modifications of core histones; they are mediated by various chromatin-modifying enzymes; and ultimately they define the accessibility of a transcriptional complex to its target DNA. Integrating epigenetic mechanisms into the pathophysiologic concept of complex and multifactorial diseases such as atherosclerosis may significantly enhance our understanding of related mechanisms and provide promising therapeutic approaches. Although still in its infancy, intriguing scientific progress has begun to elucidate the role of epigenetic mechanisms in vascular biology, particularly in the control of smooth muscle cell phenotypes. In this review, we will summarize epigenetic pathways in smooth muscle cells, focusing on mechanisms involved in the regulation of vascular remodeling. PMID:23630979

Findeisen, Hannes M; Kahles, Florian K; Bruemmer, Dennis

2013-05-01

363

Epigenetic regulation of vascular smooth muscle cell function in atherosclerosis.  

PubMed

Epigenetics involve heritable and acquired changes in gene transcription that occur independently of the DNA sequence. Epigenetic mechanisms constitute a hierarchic upper-level of transcriptional control through complex modifications of chromosomal components and nuclear structures. These modifications include, for example, DNA methylation or post-translational modifications of core histones; they are mediated by various chromatin-modifying enzymes; and ultimately they define the accessibility of a transcriptional complex to its target DNA. Integrating epigenetic mechanisms into the pathophysiologic concept of complex and multifactorial diseases such as atherosclerosis may significantly enhance our understanding of related mechanisms and provide promising therapeutic approaches. Although still in its infancy, intriguing scientific progress has begun to elucidate the role of epigenetic mechanisms in vascular biology, particularly in the control of smooth muscle cell phenotypes. In this review, we will summarize epigenetic pathways in smooth muscle cells, focusing on mechanisms involved in the regulation of vascular remodeling. PMID:23423526

Findeisen, Hannes M; Kahles, Florian K; Bruemmer, Dennis

2013-04-01

364

G protein polymorphisms in hypertension, atherosclerosis, and diabetes.  

PubMed

A common C825T polymorphism in the gene GNB3, which encodes the beta 3 subunit of heterotrimeric G proteins, was identified in cell lines from patients with hypertension. The 825T allele is associated with increased intracellular signal transduction. Many population-based and case-control studies in different ethnicities have investigated an association between this polymorphism and hypertension, obesity, and atherosclerosis. A critical assessment of published studies suggests that 825T allele carriers have an increased risk for hypertension combined with features of the metabolic syndrome, such as dyslipidemia, hypercholesterolemia, insulin resistance, and obesity. It is anticipated that this polymorphism will be used in clinical practice to better characterize hypertension and for individualized treatment regimens. PMID:15660499

Siffert, Winfried

2005-01-01

365

Imaging of cell populations in atherosclerosis using quantum dot nanocrystals.  

PubMed

Atherosclerosis, a leading cause of morbidity and mortality worldwide, is characterized by the accumulation of lipid deposits inside arterial walls, leading to narrowing of the arterial lumen. A significant challenge in the development of diagnostic and therapeutic strategies is to elucidate the contribution of the various cellular participants, including macrophages, endothelial cells, and smooth muscle cells, in the initiation and progression of the atheroma. This protocol details a strategy using quantum dot nanocrystals to monitor homing and distribution of cell populations within atherosclerotic lesions with high signal to noise ratios over prolonged periods of analysis. This fluorescence-based approach enables the loading of quantum dots into cells such as macrophages without perturbing native cell functions in vivo, and has been used for the multiplexed imaging of quantum dot-labeled cells with biomarkers of atherosclerotic disease using conventional immunofluorescence techniques. PMID:23749567

Trantum, Joshua R; Jayagopal, Ashwath

2013-01-01

366

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.

Ponticos, Markella; Smith, Barbara D.

2014-01-01

367

[Biochemical risk factor for atherosclerosis in young men. Preliminary report].  

PubMed

Atherosclerotic damage of cardiovascular system, including kidneys, is an increasing problem not only in the modern cardiology but also in nephrology and dialysotherapy. The purpose of our study was to evaluate the frequency of particular biochemical risk factors for atherosclerosis (RFfA) in young men being over-pressed with psychological stress because of decisive character of their professional job. There were 68 men in mean age 33.3 +/- 7.4 years, being employed in the state administration for mean 10.9 +/- 7.5 years. On the basis of the results of environmental questionnaire the studied group was divided into two subgroups: subgroup A "passive" (30 persons) which was physically passive (employed in the administration) and subgroup B "active" (38 persons) whose professional job was connected with physical activity. The following biochemical RFfA in the blood were examined: cholesterol and its fractions, triglycerides, urea acid, glucose, fibrinogen, C-reactive protein, homocysteine and antibodies against Chlamydia pneumoniae. The results were as follows: total cholesterol above 200 mg/dl in 63%, LDL cholesterol above 130 mg/dl in 60% and HDL cholesterol below 50 mg/dl in 31% of men. Among "new" RFfA we found "cardiological" (above 0.2 mg/dl) levels of CRP almost in 25% of the whole group. There were no statistically significant differences with respect to the studied RFfA between "active" and "passive" group. On the basis of these preliminary results we presume, that potentially healthy men over-pressed with psychological stress because of decisive character of their professional job, are characterized--independently on the proclaimed physical activity--by high frequency of risk factors for premature atherosclerosis. PMID:12026514

Wierzbicki, P; Prokopiuk, M; Kade, G; Wa?kowicz, Z

2001-11-01

368

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.

2013-01-01

369

Biodegradable synthetic high-density lipoprotein nanoparticles for atherosclerosis.  

PubMed

Atherosclerosis remains one of the most common causes of death in the United States and throughout the world because of the lack of early detection. Macrophage apoptosis is a major contributor to the instability of atherosclerotic lesions. Development of an apoptosis targeted high-density lipoprotein (HDL)-mimicking nanoparticle (NP) to carry contrast agents for early detection of vulnerable plaques and the initiation of preventative therapies that exploit the vascular protective effects of HDL can be attractive for atherosclerosis. Here, we report the construction of a synthetic, biodegradable HDL-NP platform for detection of vulnerable plaques by targeting the collapse of mitochondrial membrane potential that occurs during apoptosis. This HDL mimic contains a core of biodegradable poly(lactic-co-glycolic acid), cholesteryl oleate, and a phospholipid bilayer coat that is decorated with triphenylphosphonium (TPP) cations for detection of mitochondrial membrane potential collapse. The lipid layer provides the surface for adsorption of apolipoprotein (apo) A-I mimetic 4F peptide, and the core contains diagnostically active quantum dots (QDs) for optical imaging. In vitro uptake, detection of apoptosis, and cholesterol binding studies indicated promising detection ability and therapeutic potential of TPP-HDL-apoA-I-QD NPs. In vitro studies indicated the potential of these NPs in reverse cholesterol transport. In vivo biodistribution and pharmacokinetics indicated favorable tissue distribution, controlled pharmacokinetic parameters, and significant triglyceride reduction for i.v.-injected TPP-HDL-apoA-I-QD NPs in rats. These HDL NPs demonstrate excellent biocompatibility, stability, nontoxic, and nonimmunogenic properties, which prove to be promising for future translation in early plaque diagnosis and might find applications to prevent vulnerable plaque progression. PMID:23671083

Marrache, Sean; Dhar, Shanta

2013-06-01

370

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.

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

2009-01-01

371

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.

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

2014-01-01

372

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

373

Leukotrienes as a molecular link between obstructive sleep apnoea and atherosclerosis.  

PubMed

Leukotrienes are biologically active lipid mediators of inflammation involved in atherogenesis. Obstructive sleep apnoea (OSA) patients exhibit early atherosclerosis and activation of the leukotriene pathway. In OSA patients, the production of leukotrienes is increased in relation to OSA severity and in vitro exposure of immune cells to intermittent hypoxia increases leukotriene pathway transcription. Moreover, the leukotriene transcriptional pathway is associated with early vascular remodelling. Lastly, obesity is a major confounding factor for leukotriene activation in OSA. The aim of this review was to focus on the intricate network of leukotrienes, chronic intermittent hypoxia, and atherosclerosis, with an emphasis on the role of leukotrienes in the early atherosclerosis observed in OSA patients. PMID:24204032

Stanke-Labesque, Françoise; Pépin, Jean-Louis; Gautier-Veyret, Elodie; Lévy, Patrick; Bäck, Magnus

2014-02-01

374

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

375

Effect on coronary atherosclerosis of decrease in plasma cholesterol concentrations in normocholesterolaemic patients. Harvard Atherosclerosis Reversibility Project (HARP) Group.  

PubMed

Lipid-lowering therapy ameliorates coronary atherosclerosis in patients with raised concentrations of low-density-lipoprotein (LDL) cholesterol. We have investigated whether a similar benefit can be obtained in normocholesterolaemic patients. We studied 79 normocholesterolaemic patients with coronary heart disease (70 male, 9 female), mean age 58 years, all non-smokers, with mean total cholesterol concentration 5.5 mmol/L. All patients received diet therapy and were randomly assigned placebo (39) or active treatment (40) with pravastatin, nicotinic acid, cholestyramine, and gemfibrozil stepwise as needed to reach the specified goal (total cholesterol < or = 4.1 mmol/L, ratio of LDL/high-density-lipoprotein [HDL] cholesterol < or = 2.0). Coronary angiograms at baseline and after 2.5 years of treatment were analysed by computer-assisted quantitative techniques. There was no significant difference in coronary atherosclerosis during follow-up between the active treatment and placebo groups; the mean minimum diameter narrowed significantly but to the same extent in both groups (change baseline to 2.5 years 0.14 [SD 0.42] and 0.15 [0.42] mm, respectively, both p < 0.001). Similarly, the change in percentage stenosis did not differ between the groups (2.1 [10.6] vs 2.4 [10.3]%). By multiple regression analysis, the adjusted difference between the groups was a 0.04 mm (95% CI -0.04 to 0.12 mm) increase in minimum diameter and a 0% (-1.7 to 1.7) change in percentage stenosis. The groups differed significantly in plasma lipids (% change in active minus % change in placebo group: -28% total cholesterol, -41% LDL-cholesterol, 13% HDL-cholesterol, -26% triglycerides, -31% apolipoprotein B, all p < 0.001). Thus, intensive pharmacological treatment of normocholesterolaemic patients has significant effects on plasma lipid concentrations but no angiographically measurable benefit on the coronary arteries. PMID:7934538

Sacks, F M; Pasternak, R C; Gibson, C M; Rosner, B; Stone, P H

1994-10-29

376

Piezoelectric Pushers Suppress Vibrations  

NASA Technical Reports Server (NTRS)

Vibration-suppressing control systems including piezoelectric actuators undergoing development. Small, lightweight, and rugged. Requires simpler electronic control subsystems and does not require large electromagnet coils. Continues to provide support and some passive damping even when electronic control subsystems or power supplies fail. Intended primarily to enhance safety and prevent damage in rotating machinery by sensing and counteracting vibrations. Useful in suppressing unpredictable vibrations caused by changes in loads, losses of rotating components and consequent imbalances in rotors, and ingestion of foreign objects into turbines.

Kascak, Albert F.

1990-01-01

377

The Involvement of NFAT Transcriptional Activity Suppression in SIRT1-Mediated Inhibition of COX-2 Expression Induced by PMA/Ionomycin  

PubMed Central

SIRT1, a class III histone deacetylase, acts as a negative regulator for many transcription factors, and plays protective roles in inflammation and atherosclerosis. Transcription factor nuclear factor of activated T cells (NFAT) has been previously shown to play pro-inflammatory roles in endothelial cells. Inhibition of NFAT signaling may be an attractive target to regulate inflammation in atherosclerosis. However, whether NFAT transcriptional activity is suppressed by SIRT1 remains unknown. In this study, we found that SIRT1 suppressed NFAT-mediated transcriptional activity. SIRT1 interacted with NFAT, and the NHR and RHR domains of NFAT mediated the interaction with SIRT1. Moreover, we found that SIRT1 primarily deacetylated NFATc3. Adenoviral over-expression of SIRT1 suppressed PMA and calcium ionophore Ionomycin (PMA/Io)-induced COX-2 expression in human umbilical vein endothelial cells (HUVECs), while SIRT1 RNAi reversed the effects in HUVECs. Moreover, inhibition of COX-2 expression by SIRT1 in PMA/Io-treated HUVECs was largely abrogated by inhibiting NFAT activation. Furthermore, SIRT1 inhibited NFAT-induced COX-2 promoter activity, and reduced NFAT binding to the COX-2 promoter in PMA/Io-treated HUVECs. These results suggest that suppression of NFAT transcriptional activity is involved in SIRT1-mediated inhibition of COX-2 expression induced by PMA/Io, and that the negative regulatory mechanisms of NFAT by SIRT1 may contribute to its anti-inflammatory effects in atherosclerosis.

Huang, Yue; Liu, Guang; Gao, Peng; Wan, Yan-Zhen; Zhang, Ran; Zhang, Zhu-Qin; Yang, Rui-Feng; Tang, Xiaoqiang; Xu, Jing; Wang, Xu; Chen, Hou-Zao; Liu, De-Pei

2014-01-01

378

Chapter 14. Atherosclerosis of the aorta and coronary arteries in coronary heart disease  

PubMed Central

Aortic and coronary atherosclerosis and the prevalence of coronary stenosis and thrombosis were studied in subjects who had died of fresh or recurrent myocardial infarction or had suffered from myocardial infarction in the past. In general, severe atherosclerosis of the coronary arteries with stenosis and calcification was almost a prerequisite for the development of coronary heart disease. The frequency of coronary heart disease varied widely both in different countries and in different towns in the same country. Considerable variations were found among the various towns in the frequency of stenosis and thrombosis in those who had died of coronary heart disease. This finding indicates that although atherosclerosis is indeed a prerequisite for the development of myocardial infarction, other factors may play a significant role in its occurrence. The weight of the heart in persons (excluding hypertensives) with coronary stenosis or a first fresh myocardial infarction was considerably greater than that in the low atherosclerosis group.

Vihert, A. M.

1976-01-01

379

Toward understanding the molecular basis of atherosclerosis with genetics and genomics  

PubMed Central

Summary Atherosclerosis is a very complex disease involving both genetic and environmental risk factors, and their interactions. In the general population, genetic polymorphisms of many genes in the pathways of lipid metabolism, inflammation, and thrombogenesis are likely responsible for the wide range of susceptibilities to myocardial infarction, the most deadly consequence of atherosclerosis. To identify these polymorphisms, genetic linkage studies have been carried out in both humans and mouse models. Approximately 40 quantitative trait loci for atherosclerotic disease have been found in humans, and approximately 30 in mice. Recently, genome-wide association studies have been used to identify atherosclerosis-susceptibility polymorphisms. Although finding new atherosclerosis genes through these approaches remains challenging, the pace of finding these polymorphisms is accelerating due to the rapidly improving bioinformatics resources and biotechnologies. The results from these efforts will not only reveal the molecular basis of, but will facilitate finding drug targets and individualized medicine for, atherosclerotic disease.

Chen, Yaoyu; Rollins, Jarod; Paigen, Beverly; Wang, Xiaosong

2007-01-01

380

Testing the role of myeloid cell glucose flux in inflammation and atherosclerosis.  

PubMed

Inflammatory activation of myeloid cells is accompanied by increased glycolysis, which is required for the surge in cytokine production. Although in vitro studies suggest that increased macrophage glucose metabolism is sufficient for cytokine induction, the proinflammatory effects of increased myeloid cell glucose flux in vivo and the impact on atherosclerosis, a major complication of diabetes, are unknown. We therefore tested the hypothesis that increased glucose uptake in myeloid cells stimulates cytokine production and atherosclerosis. Overexpression of the glucose transporter GLUT1 in myeloid cells caused increased glycolysis and flux through the pentose phosphate pathway but did not induce cytokines. Moreover, myeloid-cell-specific overexpression of GLUT1 in LDL receptor-deficient mice was ineffective in promoting atherosclerosis. Thus, increased glucose flux is insufficient for inflammatory myeloid cell activation and atherogenesis. If glucose promotes atherosclerosis by increasing cellular glucose flux, myeloid cells do not appear to be the key targets. PMID:24726364

Nishizawa, Tomohiro; Kanter, Jenny E; Kramer, Farah; Barnhart, Shelley; Shen, Xia; Vivekanandan-Giri, Anuradha; Wall, Valerie Z; Kowitz, Jason; Devaraj, Sridevi; O'Brien, Kevin D; Pennathur, Subramaniam; Tang, Jingjing; Miyaoka, Robert S; Raines, Elaine W; Bornfeldt, Karin E

2014-04-24

381

Adaptive (T and B cells) immunity and control by dendritic cells in atherosclerosis.  

PubMed

Chronic inflammation in response to lipoprotein accumulation in the arterial wall is central in the development of atherosclerosis. Both innate and adaptive immunity are involved in this process. Adaptive immune responses develop against an array of potential antigens presented to effector T lymphocytes by antigen-presenting cells, especially dendritic cells. Functional analysis of the role of different T-cell subsets identified the Th1 responses as proatherogenic, whereas regulatory T-cell responses exert antiatherogenic activities. The effect of Th2 and Th17 responses is still debated. Atherosclerosis is also associated with B-cell activation. Recent evidence established that conventional B-2 cells promote atherosclerosis. In contrast, innate B-1 B cells offer protection through secretion of natural IgM antibodies. This review discusses the recent development in our understanding of the role of T- and B-cell subsets in atherosclerosis and addresses the role of dendritic cell subpopulations in the control of adaptive immunity. PMID:24812352

Ait-Oufella, Hafid; Sage, Andrew P; Mallat, Ziad; Tedgui, Alain

2014-05-01

382

Ultrasonic Detection, Quantification and Characterization of Atherosclerosis - Equipment Development and Evaluation.  

National Technical Information Service (NTIS)

Advanced non-invasive pulse-echo ultrasound techniques have been studied for detecting the presence, the extent, and the nature of atherosclerosis in living patients. A high resolution, large dynamic range, real-time ultrasound imaging equipment was built...

C. P. Olinger A. K. Nigam

1977-01-01

383

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

PubMed Central

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.

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

384

Porcine Models of Accelerated Coronary Atherosclerosis: Role of Diabetes Mellitus and Hypercholesterolemia  

PubMed Central

Animal models of atherosclerosis have proven to be an invaluable asset in understanding the pathogenesis of the disease. However, large animal models may be needed in order to assess novel therapeutic approaches to the treatment of atherosclerosis. Porcine models of coronary and peripheral atherosclerosis offer several advantages over rodent models, including similar anatomical size to humans, as well as genetic expression and development of high-risk atherosclerotic lesions which are similar to humans. Here we review the four models of porcine atherosclerosis, including the diabetic/hypercholesterolemic model, Rapacz-familial hypercholesterolemia pig, the (PCSK9) gain-of-function mutant pig model, and the Ossabaw miniature pig model of metabolic syndrome. All four models reliably represent features of human vascular disease.

Wilensky, Robert L.

2013-01-01

385

Conference on Radionuclide Labelled Cellular Blood Elements. Application in Atherosclerosis and Thrombosis: Abstracts.  

National Technical Information Service (NTIS)

The individual papers were presented at the conference on radionuclide labelled cellular blood elements. Applications in atherosclerosis and thrombosis are also indexed separately. These papers deal with the pathogenesis, or diagnostic techniques for thes...

1986-01-01

386

A Review of the Significance of Bovine Milk Xanthine Oxidase in the Etiology of Atherosclerosis.  

National Technical Information Service (NTIS)

The hypothesis that xanthine oxidase in homogenized bovine milk is a significant factor in the etiology of atherosclerosis holds that the enzyme is absorbed in the intestinal tract with homogenized milk fat, circulates, is deposited in arterial and myocar...

C. J. Carr J. M. Talbot K. D. Fisher

1975-01-01

387

Femoral and coronary atherosclerosis in patients with hyperlipidaemia. Arteriographic findings correlated to clinical and biochemical parameters.  

PubMed

Quantitative assessment of atherosclerosis from arteriograms was applied in clinical follow-up trials for the evaluation of lipid-modulating treatment or risk factors. Computer-estimated lumen volume and arterial edge roughness in the femoral artery and in the aorta, visual scoring of aorto-femoral arteriograms and manual measuring of coronary artery stenosis were used. In each of 276 hypercholesterolaemic patients two femoral arteriograms were made, with a 10-minute interval. The reproducibility of the computer analysis method was found to be constant over the years, with slightly better reproducibility for lumen volume than for edge roughness. A small but significant drift in the radiological equipment was confirmed by the use of phantoms. In 290 patients, atherosclerosis assessments from the femoral artery (lumen volume and roughness) and visual scoring of the aorto-femoral arteriogram were correlated with clinical symptoms of coronary artery disease or previous myocardial infarction to test whether femoral atherosclerosis estimates can replace coronary studies in clinical trials. Both men and women with coronary artery disease had lower values for femoral lumen volume and more edge roughness than patients without these symptoms. Men with previous myocardial infarction had higher mean visual scores than those without. Thus, femoral atherosclerosis is an expression of a more generalized disease associated with clinical symptoms of coronary heart disease. The 290 patients were tested for correlation between degree of peripheral atherosclerosis and various metabolic risk factors. In women, high serum triglyceride values were associated with more extensive atherosclerosis. High fasting glucose values were associated with more extensive atherosclerosis in men. In men and women, high uric acid values were associated with greater roughness in the femoral artery. The effects of smoking, hypertension, poor physical fitness and body mass index on the development of peripheral atherosclerosis in hypercholesterolaemia were also investigated. The results indicated that the hypercholesterolaemic patients most likely to develop peripheral atherosclerosis are male and female smokers who do not take any physical exercise, and who have increased values of systolic blood pressure, uric acid and fasting glucose concentrations. Aortograms from 293 subjects were digitized and circular lumen volume and edge roughness were computer-estimated in a 7.35-cm segment of the distal aorta. A correlation between atherosclerosis in the aorta and in the femoral arteries indicated that aortic atherosclerosis is a manifestation of a more general disease.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:8184697

Bergstrand, L

1994-01-01

388

Ignition Suppression Device.  

National Technical Information Service (NTIS)

An ignition detection and suppression system was developed under the scope of this contract. The objective of this machine mounted system was to detect flames caused by frictional sparking from the cutting bits of a continuous-mining machine and to suppre...

W. B. Jamison H. Hadi

1976-01-01

389

Suppressing the Zs.  

ERIC Educational Resources Information Center

In the frameword of generalized phrase-structure grammar, possessive clitics (POSS), bound words (BWs), and phrasal affixes (PAs) are analyzed. It is argued that English POSS should be treated as an edge-located inflectional affix, since POSS is suppressed in the presence of other Z affixes (plural, other possessives). (Author/LMO)

Zwicky, A. M.

1987-01-01

390

CD59 but not DAF deficiency accelerates atherosclerosis in female ApoE knockout mice  

Microsoft Academic Search

Although the complement system has been implicated in atherosclerosis, the influence of membrane-bound complement regulators in this process has not been well understood. We studied the role of two membrane complement regulators, decay-accelerating factor (DAF) and CD59, in a murine model of atherosclerosis. DAF?\\/? and CD59?\\/? mice were crossed with apolipoprotein E (ApoE)-deficient mice to generate DAF?\\/?ApoE?\\/? and CD59?\\/?ApoE?\\/? mice.

Guipeng An; Takashi Miwa; Wen-Liang Song; John A. Lawson; Daniel J. Rader; Yun Zhang; Wen-Chao Song

2009-01-01

391

Microarray gene expression profiling reveals antioxidant-like effects of angiotensin II inhibition in atherosclerosis  

PubMed Central

Reactive oxygen species (ROS) is a significant feature of atherosclerosis but the impact of ROS on atherogenesis is not clear since antioxidants such as vitamin E have little effect on atherosclerosis development in vivo. To investigate the role of ROS in atherosclerosis, we used ApoE-deficient mice, and compared the treatment effect of the antioxidant vitamin E with that of the angiotensin-converting enzyme (ACE) inhibitor, captopril, because angiotensin II is a major source of ROS in the vasculature. Dihydroethidium (DHE) staining demonstrated that vitamin E and captopril both prevented the atherosclerosis-induced increase in aortic superoxide content. In contrast, seven months of vitamin E treatment retarded the development of atherosclerotic lesions by only 45.8 ± 11.5% whereas captopril reduced the aortic plaque area by 88.1 ± 7.5%. To discriminate between vitamin E-sensitive and -insensitive effects of ACE inhibition, we performed whole genome microarray gene expression profiling. Gene ontology (GO) and immunohistology analyses showed that vitamin E and captopril prevented atherosclerosis-related changes of aortic intima and media genes. However, vitamin E did not reduce the expression of probe sets detecting the aortic recruitment of pro-inflammatory immune cells while immune cell-specific genes were normalized by captopril treatment. Moreover, vitamin E did not prevent the atherosclerosis-dependent down-regulation of perivascular nerve-specific genes, which were preserved in captopril-treated aortas. Taken together, our study detected antioxidant vitamin E-like effects of angiotensin II inhibition in atherosclerosis treatment regarding preservation of aortic intima and media genes. Additional vitamin E-insensitive effects targeting atherosclerosis-enhancing aortic immune cell recruitment and perivascular nerve degeneration could account for the stronger anti-atherogenic activity of ACE inhibition compared to vitamin E.

Abd Alla, Joshua; el Faramawy, Yasser; Quitterer, Ursula

2013-01-01

392

S100/calgranulins EN-RAGEing the blood vessels: implications for inflammatory responses and atherosclerosis  

PubMed Central

Atherosclerosis remains the leading cause of death in the western countries and represents a complex chronic inflammatory process whose regulation is dependent on a network of cytokine and chemokine signaling between key cells such as endothelial cells, monocytes, dendritic cells, lymphocytes and smooth muscle cells. This review focuses on the biology and function of S100 proteins and their receptor RAGE with respect to the multifactorial process leading to atherosclerosis, plaque rupture, and aortic wall remodeling.

Bowman, Marion A Hofmann; Schmidt, Ann Marie

2011-01-01

393

A novel mouse model that develops spontaneous arthritis and is predisposed towards atherosclerosis  

PubMed Central

Objectives Patients with rheumatoid arthritis (RA) have a reduced life expectancy due to increased cardiovascular disease. The lack of a suitable animal model resembling both RA and atherosclerosis has hindered studies demonstrating a direct link between systemic inflammation in RA and the development of atherosclerosis. Our objective was to overcome this barrier by generating an animal model (K/BxAg7) that spontaneously develops both RA-like disease and atherosclerosis. Methods Arthritis severity was evaluated using clinical indices and immunohistochemical staining of ankle joint specimens. Aortic atherosclerosis was delineated via Sudan IV staining and immunohistochemical analysis. Serum cholesterol and lipoprotein levels were measured using enzymatic assays. Serum levels of cytokines, chemokines and adipokines were determined by Luminex assays. Results K/BxAg7 mice developed a destructive arthropathy followed by prominent aortic atherosclerosis. These animals also displayed dyslipidaemia, characterised by reduced serum levels of total cholesterol and high-density lipoprotein, and increased low-density lipoprotein (LDL)/vLDL compared with control mice. Further, there were higher levels of circulating inflammatory mediators, such as interleukin-6, sRANKL and CCL5 in atherosclerotic K/BxAg7 mice compared with controls. Treatment with etanercept reduced arthritis and atherosclerosis development in K/BxAg7 mice. Conclusions K/BxAg7 mice recapitulate the same sequence of events occurring in patients with RA, namely an erosive, inflammatory arthritis followed by atherosclerosis. These data suggest that the K/BxAg7 mouse is a novel system for investigating the interplay between systemic inflammation occurring in RA and the development of atherosclerosis.

Rose, Shawn; Eren, Mesut; Murphy, Sheila; Zhang, Heng; Thaxton, Colby Shad; Chowaniec, Jaime; Waters, Emily A; Meade, Thomas J; Vaughan, Douglas E; Perlman, Harris

2013-01-01

394

C57BL\\/6 mice fed high fat diets as models for diabetes-accelerated atherosclerosis  

Microsoft Academic Search

Non-insulin-dependent diabetes mellitus (NIDDM) is a major risk factor for the development of atherosclerosis in humans. The development of an animal model that displays accelerated atherosclerosis associated with NIDDM will aid in elucidating the mechanisms that associate these disorders. C57BL\\/6 mice may provide such a model system. This strain becomes obese, hyperglycemic and insulin resistant when fed a high fat

Sandra A. Schreyer; Deborah L. Wilson; Renée C. LeBoeuf

1998-01-01

395

Brachial-ankle pulse wave velocity is independently associated with carotid atherosclerosis in hypertensive patients  

Microsoft Academic Search

Atherosclerosis is an emerging major risk factor for cardiovascular events in hypertensive patients. Carotid plaque score (PS) and carotid-femoral pulse wave velocity (cfPWV) have been shown to be good surrogate markers of systemic atherosclerosis. There are reports indicating that cfPWV is independently associated with carotid plaques. However, the relation between PS and brachial-ankle PWV (baPWV), which includes the information form

Seiichi Shibasaki; Kazuomi Kario; Yoshio Matsui; Joji Ishikawa; Kazuyuki Shimada

2005-01-01

396

Impact of glycoprotein VI and platelet adhesion on atherosclerosis—A possible role of fibronectin  

Microsoft Academic Search

Glycoprotein VI (GPVI) mediates binding of platelets to subendothelial collagen during acute arterial thrombosis. GPVI interactions with the activated atherosclerotic vascular endothelium during early atherosclerosis, however, are not well understood. In ApoE?\\/? mice, platelet adhesion to atherosclerotic arteries was increased, as measured by intravital microscopy. This platelet adhesion was significantly inhibited by IV injection of GPVI-Fc (1mg\\/kg body weight). Atherosclerosis

Andreas Bültmann; Zhongmin Li; Silvia Wagner; Mario Peluso; Tanja Schönberger; Carla Weis; Ildiko Konrad; Konstantinos Stellos; Steffen Massberg; Bernhard Nieswandt; Meinrad Gawaz; Martin Ungerer; Götz Münch

2010-01-01

397

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

398

Lethal atherosclerosis associated with abnormal plasma and tissue sterol composition in sitosterolemia with xanthomatosis  

Microsoft Academic Search

Tissue sterol composition was determined in an 18-year-old male with sitosterolemia with xanthomatosis 'who died suddenly and whose coronary and aortic vessels showed extensive atherosclerosis and, for comparison, in an 18-year-old male with minimal atherosclerosis who died accidently. Sterols in the control tissues (plasma, erythrocytes, cardiac muscle, lung, liver, aorta, and brain) contained cholesterol with only trace amounts of cholestanol.

Gerald Salen; Ivan Horak; Michael Rothkopf; Jerald L. Cohen; J. Speck; G. S. Tint; V. Shore; B. Dayal; Thomas Chen; S. Shefer

399

Role of oxidized low-density lipoprotein in the atherosclerosis of uremia  

Microsoft Academic Search

Role of oxidized low-density lipoprotein in the atherosclerosis of uremia. Lipoprotein oxidation is involved in the genesis of atherosclerosis. In chronic renal failure (CRF), oxidative stress is enhanced because of an imbalance between pro-oxidant and antioxidant systems. Oxidative modifications of low-density lipoproteins (LDLs) occur not only at the level of lipid moiety, but also of protein moiety. We have shown

Tilman B. Drueke; THAO NGUYEN KHOA; Ziad A. Massy; VÉRONIQUE WITKO-SARSAT; BERNARD LACOUR; BÉATRICE DESCAMPS-LATSCHA

2001-01-01

400

Effect of Aging on Fatty Streak Formation in a Diet-Induced Mouse Model of Atherosclerosis  

Microsoft Academic Search

Age is considered to be a major risk factor for atherosclerosis, but it is unclear whether age has a direct effect on susceptibility to atherosclerosis. Wild-type mice develop fatty streak lesions in the aortic root only when fed a cholate-containing high fat\\/cholesterol diet. To investigate the influence of age on fatty streak formation, young (10 weeks) and old (53 weeks)

Yuhua Li; Timothy R. Gilbert; Alan H. Matsumoto; Weibin Shi

2008-01-01

401

Atherosclerosis and Matrix Metalloproteinases: Experimental Molecular MR Imaging in Vivo  

PubMed Central

Purpose: To evaluate the capability of P947, a magnetic resonance (MR) imaging contrast agent that molecularly targets matrix metalloproteinases (MMPs), to aid detection and imaging of MMPs in atherosclerotic lesions in vivo; its specificity compared with that of P1135; expression and distribution of MMPs in atherosclerotic vessels; and in vivo distribution and molecular localization of fluorescent europium (Eu) P947. Materials and Methods: The Animal Care and Use Committee approved all experiments. P947 was synthesized by attaching a gadolinium chelate (1,4,7,10-tetraazacyclododecane-N,N?,N?,N?-tetraacetic acid) to a peptide that specifically binds MMPs. Scrambled form of P947 (P1135) was synthesized by replacing the targeting moiety of P947 with a scrambled peptide lacking the ability to bind MMPs. P947, P1135, and gadoterate meglumine were injected into atherosclerotic apolipoprotein E–deficient and wild-type mice. The aortic MR imaging enhancement produced by the contrast agents was measured at different times and was compared by using one-way analysis of variance. MMP expression was investigated in the aortas by using MMP immunostaining and in situ MMP zymography. A fluorescent form of P947 (Eu-P947) was synthesized to compare the in vivo distribution of the contrast agent (Eu-P947) with specific MMP immunofluorescent staining. Results: MMP-targeted P947 facilitated a 93% increase (P < .001) in MR image signal intensity (contrast-to-noise ratio [CNR], 17.7 compared with 7.7; P < .001) of atherosclerotic lesions in vivo. Nontargeted P1135 (scrambled P947) provided 33% MR image enhancement (CNR, 10.8), whereas gadoterate meglumine provided 5% (CNR, 6.9). Confocal laser scanning microscopy demonstrated colocalization between fluorescent Eu-P947 and MMPs in atherosclerotic plaques. Eu-P947 was particularly present in the fibrous cap region of plaques. Conclusion: P947 improved MR imaging for atherosclerosis through MMP-specific targeting. The results were validated and provide support for further assessment of P947 as a potential tool for the identification of unstable atherosclerosis. © RSNA, 2009

Amirbekian, Vardan; Aguinaldo, Juan Gilberto S.; Amirbekian, Smbat; Hyafil, Fabien; Vucic, Esad; Sirol, Marc; Weinreb, David B.; Le Greneur, Soizic; Lancelot, Eric; Corot, Claire; Fisher, Edward A.; Galis, Zorina S.; Fayad, Zahi A.

2009-01-01

402

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

403

ADMA/SDMA in Elderly Subjects with Asymptomatic Carotid Atherosclerosis: Values and Site-Specific Association  

PubMed Central

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.

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

2014-01-01

404

Mutation in KERA Identified by Linkage Analysis and Targeted Resequencing in a Pedigree with Premature Atherosclerosis  

PubMed Central

Aims Genetic factors explain a proportion of the inter-individual variation in the risk for atherosclerotic events, but the genetic basis of atherosclerosis and atherothrombosis in families with Mendelian forms of premature atherosclerosis is incompletely understood. We set out to unravel the molecular pathology in a large kindred with an autosomal dominant inherited form of premature atherosclerosis. Methods and Results Parametric linkage analysis was performed in a pedigree comprising 4 generations, of which a total of 11 members suffered from premature vascular events. A parametric LOD-score of 3.31 was observed for a 4.4 Mb interval on chromosome 12. Upon sequencing, a non-synonymous variant in KERA (c.920C>G; p.Ser307Cys) was identified. The variant was absent from nearly 28,000 individuals, including 2,571 patients with premature atherosclerosis. KERA, a proteoglycan protein, was expressed in lipid-rich areas of human atherosclerotic lesions, but not in healthy arterial specimens. Moreover, KERA expression in plaques was significantly associated with plaque size in a carotid-collar Apoe?/? mice (r2?=?0.69; p<0.0001). Conclusion A rare variant in KERA was identified in a large kindred with premature atherosclerosis. The identification of KERA in atherosclerotic plaque specimen in humans and mice lends support to its potential role in atherosclerosis.

van Capelleveen, Julian C.; Bot, Ilze; de Jager, Saskia C.; van Eck, Miranda; Jolley, Jennifer; Kuiper, Johan; Stephens, Jonathon; Albers, Cornelius A.; Vosmeer, C. Ruben; Kruize, Heleen; Geerke, Daan P.; van der Wal, Allard C.; van der Loos, Chris M.; Kastelein, John J. P.; Trip, Mieke D.

2014-01-01

405

Myeloid lineage cell-restricted insulin resistance protects apolipoproteinE-deficient mice against atherosclerosis  

PubMed Central

Summary Inflammatory processes play an important role in the pathogenesis of vascular diseases, and insulin-resistant diabetes mellitus type 2 represents an important risk factor for the development of atherosclerosis. To directly address the role of insulin resistance in myeloid lineage cells in the development of atherosclerosis, we have created mice with myeloid lineagespecific inactivation of the insulin receptor gene. On an ApoE-deficient background, MphIRKO mice developed smaller atherosclerotic lesions. There was a dramatic decrease in LPS-stimulated IL-6 and IL-1? expression in the presence of macrophage autonomous insulin resistance. Consistently, while insulin-resistant IRS-2-deficient mice on an ApoE-deficient background display aggravated atherosclerosis, fetal liver cell transplantation of IRS-2–/–ApoE–/– cells ameliorated atherosclerosis in Apo-E-deficient mice. Thus, systemic versus myeloid cell-restricted insulin resistance has opposing effects on the development of atherosclerosis, providing direct evidence that myeloid lineage autonomous insulin signaling provides proinflammatory signals predisposing to the development of atherosclerosis.

Baumgartl, Julia; Baudler, Stephanie; Scherner, Maximilian; Babaev, Vladimir; Makowski, Liza; Suttles, Jill; McDuffie, Marcia; Fazio, Sergio; Kahn, C. Ronald; Hotamisligil, Gokhan S.; Krone, Wilhelm; Linton, MacRae; Bruning, Jens C.

2014-01-01

406