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 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Atherosclerosis, and the resulting coronary heart disease and stroke, is the most common cause of death in developed countries. Atherosclerosis is an inflammatory process that results in the development of complex lesions or plaques that protrude into the arterial lumen. Plaque rupture and thrombosis result in the acute clinical complications of myocardial infarction (MI) and stroke. Although certain risk factors (dyslipidemias, diabetes, hypertension) and humoral markers of plaque vulnerability (C-reactive protein, interleukin-6, 10 and 18, CD40L) have been identified, a highly sensitive and specific biomarker or protein profile, which could provide information on the stability/vulnerability of atherosclerotic lesions, remains to be identified. In this review, we report several proteomic approaches which have been applied to circulating or resident cells, atherosclerotic plaques or plasma, in the search for new proteins that could be used as cardiovascular biomarkers. First, an example using a differential proteomic approach (2-DE and MS) comparing the secretome from control mammary arteries and atherosclerotic plaques is displayed. Among the different proteins identified, we showed that low levels of HSP-27 could be a potential marker of atherosclerosis. Second, we have revised several studies performed in cells involved in the pathogenesis of atherosclerosis (foam cells and smooth muscle cells). Another approach consists of performing proteomic analysis on circulating cells or plasma, which will provide a global view of the whole body response to atherosclerotic aggression. Circulating cells can bear information reflecting directly an inflammatory or pro-coagulant state related to the pathology. As an illustration, we report that circulating monocytes and plasma in patients with acute coronary syndromes has disclosed that mature Cathepsin D is increased both in the plasma and monocytes of these patients. Finally, the problems of applying proteomic approach directly to plasma will be discussed. The purpose of this review is to provide the reader with an overview of different proteomic approaches that can be used to identify new biomarkers in vascular diseases.
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PMID:Quest for novel cardiovascular biomarkers by proteomic analysis. 1608 68

The measurement of coronary flow velocity reserve (CFVR) by transthoracic Doppler echocardiography (TTDE) with invasive intracoronary Doppler flow wire technique (ICD) was validated and the pathological factors which influence CFVR in patients with angiographically normal coronary arteries were analyzed. CFVR was determined successfully in left anterior descending artery (LAD) in 37 of 40 patients with angiographically normal coronary arteries (men 22, women 15, age 20-75 years, mean age 54 +/- 12 years). Coronary flow velocity was measured in the distal LAD by TTDE with contrast enhancement at baseline and during intravenous adenosine infusion of 140 microg/kg per min within 48 h after ICD technique. Average peak velocity at baseline (APVb), average peak velocity during hyperemia (APVh) and CFVR determined from TTDE were correlated closely with those from ICD measurements (APVb: y = 0.64x + 5.04, r = 0.86, P < 0.001; APVh: y = 0.63x + 14.36, r = 0.82, P < 0.001; CFVR: y = 0.65x + 0.92, r = 0.88, P < 0.001). For CFVR measurements, the mean differences between TTDE and ICD methods were 0.12 +/- 0.39. CFVR in patients with history of hypertension was significantly lower than that in patients without history of hypertension (P < 0.05). Intravascular ultrasound (IVUS) was performed in 34 patients. Plaque formation was found in LAD by IVUS in 17 (50%) patients. No significant difference in CFVR was found between the patients without plaque formation (3.11 +/- 0.49) and those with plaque formation (2.76 +/- 0.53, P = 0.056). It is suggested that TTDE with contrast enhancement provides reliable measurement of APV and CFVR in the distal LAD. The early stage of atherosclerosis could be detected by IVUS, which may be normal in angiography. CFVR is impaired in patients with history of hypertension compared with that in patients without history of hypertension.
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PMID:Assessment of coronary flow velocity reserve by noninvasive transthoracic Doppler echocardiography in patients with angiographically normal coronary arteries. 1646 84

We assessed clinical predictors of the process of cardiac allograft vasculopathy (CAV) in 39 consecutive patients (mean 49 years old) using three-dimensional intravascular ultrasound (3-D IVUS) examination of the left anterior descending coronary artery at 36 +/- 38 months and 47 +/- 40 months after cardiac allotransplantation (TX). Compared with 17 patients with plaque progression, 22 patients with plaque regression were more likely to be male (P < .01), to have a higher use of angiotensin-converting enzyme inhibitors (ACEI, P < .05), and to have a lower volumetric remodeling index (P < .001). The changes in plaque volume correlated with the changes in total cholesterol (P < .005) and low-density lipoprotein cholesterol (P < .02). Plaque progression of CAV was independently associated with time after TX, hypertension, nonuse of ACEI, donor age, and changes in total cholesterol and triglycerides. In conclusion, plaque progression is associated with positive vascular remodeling and plaque regression is associated with lower serum lipids and ACEI in patients after TX.
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PMID:Association of angiotensin-converting enzyme inhibitors and serum lipids with plaque regression in cardiac allograft vasculopathy. 1706 Aug 62

Atherosclerosis is one of the most common causes of death in developed countries. Atherosclerosis is an inflammatory process that results in the development of complex lesions or plaques that protrude into the arterial lumen. Plaque rupture and thrombosis result in the acute clinical complications of myocardial infarction and stroke. Although certain risk factors (dyslipidemias, diabetes, hypertension) and humoral markers of plaque vulnerability (C-reactive protein, interleukin-6, -10 and -18, CD-40L) have been identified, a highly sensitive and specific biomarker or protein profile, which could provide information on the stability/vulnerability of atherosclerotic lesions, remains to be identified. Recently, we have described a novel strategy consisting in the proteomic analysis of proteins released by normal and atherosclerotic arterial walls in culture. This method enables harvesting of proteins that are only secreted by pathological or normal arterial walls. By focusing only on the secreted proteins found in the tissue culture media, there is an intended bias toward those molecules that would have a higher probability of later being found in plasma. Using this approach, we have shown that carotid atherosclerotic plaques cultured in vitro are able to secrete proteins, and also that a differential pattern of protein secretion of normal arteries vs pathological ones has been observed. In this chapter, the proteomic analysis of the human atheroma plaque secretome is described.
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PMID:Characterization of the human atheroma plaque secretome by proteomic analysis. 1717 85

Angiotensin II and aldosterone both promote endothelial dysfunction and atherosclerosis. We investigated the effect of a combination of eplerenone, a selective aldosterone antagonist, and enalapril, an angiotensin-converting enzyme inhibitor, on NO bioavailability and spontaneous atherosclerotic changes. Twenty-four myocardial infarction-prone Watanabe heritable hyperlipidemic rabbits were treated with vehicle (control), eplerenone (50 mg/kg per day), enalapril (3 mg/kg per day), or eplerenone plus enalapril for 8 weeks (n=6 in each group). After treatment, acetylcholine-induced NO production was measured as a surrogate for endothelium-protective function, and vascular peroxynitrite (a product of superoxide and NO) was measured to assess dysfunctional endothelial NO synthase activity. Plaque area was quantified by histology. Intra-aortic infusion of acetylcholine produced an increase in plasma NO concentration that was significantly higher with all of the drug treatments compared with the control. Eplerenone and enalapril, in combination, increased acetylcholine-induced NO by 7.9 nM, which was significantly higher than with either eplerenone or enalapril alone. Vascular peroxynitrite was significantly higher in the control group (1.3 pmol/mg of protein) and significantly lower with combination treatment (0.4 pmol/mg of protein) compared with the enalapril or eplerenone group. The highest tetrahydrobiopterin levels were observed after cotreatment with eplerenone and enalapril. Histology of the thoracic aorta showed a significantly decreased plaque area with combination therapy compared with monotherapy. Combined treatment with a selective aldosterone antagonist and an angiotensin-converting enzyme inhibitor has additive protective effects on endothelial function and on atherosclerotic changes via decreased nitrosative stress.
Hypertension 2008 Mar
PMID:Addition of eplerenone to an angiotensin-converting enzyme inhibitor effectively improves nitric oxide bioavailability. 1822 2

We investigated whether aliskiren, a direct renin inhibitor, improves NO bioavailability and protects against spontaneous atherosclerotic changes. We also examined the effects of cotreatment with aliskiren and valsartan, an angiotensin II receptor blocker, on the above-mentioned outcomes. Watanabe heritable hyperlipidemic rabbits were treated with vehicle (control), aliskiren, valsartan, or aliskiren plus valsartan for 8 weeks. Then, acetylcholine-induced NO production was measured as a surrogate index of endothelium protective function, and both superoxide and vascular peroxynitrite were measured. Tetrahydrobiopterin in aortic segments was assessed by high-performance liquid chromatography with fluorescence detection. Plaque area was quantified by histology. Increase in plasma NO concentration in response to intra-aortic acetylcholine infusion was significantly greater in all of the test groups than in controls. Aliskiren+valsartan cotreatment increased acetylcholine-induced NO by 6.2 nmol/L, which was significantly higher than that with either aliskiren or valsartan alone. Vascular superoxide and peroxynitrite levels were both significantly higher in controls and significantly lower in the aliskiren+valsartan group than in the aliskiren or valsartan group. The highest tetrahydrobiopterin levels were observed after aliskiren+valsartan cotreatment. Histology of the thoracic aorta revealed that the plaque area was significantly decreased with combination therapy compared with monotherapy. Treatment with a direct renin inhibitor has protective effects on endothelial function and atherosclerotic changes. Furthermore, cotreatment with a direct renin inhibitor and an angiotensin II receptor blocker has additive protective effects on both.
Hypertension 2008 Sep
PMID:Renin inhibitor aliskiren improves impaired nitric oxide bioavailability and protects against atherosclerotic changes. 1864 47

A 61-year-old woman with hypercholesterolemia, hypertension and diabetes mellitus was referred to hospital for the evaluation of chest pain at rest. Eccentric 50% stenosis in the proximal right coronary artery was detected by 64-slice multidetector row computed tomography (MDCT). The plaque morphology was considered as soft by Color Code Plaque (CCP) analysis. Seven days after MDCT, chest pain continued and transient ST-elevation was detected on the II-lead ECG monitor during echocardiography. Therefore, emergency coronary angiography was performed and confirmed the 50% stenosis as shown on MDCT. Her disease was diagnosed as vasospastic angina. For the purpose of plaque stabilization, lipid-lowering therapy with atorvastatin was instituted and her symptoms improved. After 11 months, serum total cholesterol and LDL-cholesterol levels were reduced. A second MDCT was performed and plaque morphology had changed from soft to intermediate. Cross-sectional multiplanar reconstruction of MDCT images indicated reduction of total vessel area, expansion of the lumen area and improvement of the remodeling index at the site of stenosis. The lipid-lowering therapy contributed to plaque stabilization, and CCP analysis by noninvasive MDCT was useful for plaque characterization. This case suggests that differences between vulnerable and stable plaques can be classified using MDCT to predict acute coronary syndrome.
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PMID:Coronary plaque stabilization followed by Color Code Plaque analysis with 64-slice multidetector row computed tomography. 1907 20

Atherosclerosis is the underlying cause of most myocardial infarction (MI) and ischemic strokes. B-mode ultrasound of carotid arteries provides measures of intima-media thickness (IMT) and plaques, both widely used as surrogate measures of cardiovascular disease. Although IMT and plaques are highly intercorrelated, IMT's role as a marker of atherosclerosis has been questioned, especially when measurements include the common carotid artery (CCA) only. Plaque and intima-media thickening may reflect different biological aspects of atherogenesis with distinctive relations to clinical vascular disease. Plaque measured in the carotid bulb or internal carotid artery is stronger related to hyperlipidemia and smoking and is a stronger predictor for MI, whereas CCA-IMT is stronger related to hypertension and ischemic stroke. Echolucent plaque morphology (ie, lipid-rich plaques) seems to increase the risk for MI and stroke. New evidence suggests that total plaque area is the most strongly predictive of cardiovascular risk of the ultrasound phenotypes.
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PMID:Carotid plaque compared with intima-media thickness as a predictor of coronary and cerebrovascular disease. 1909 Nov 71

Studies in general population, in elderly people, and in groups of patients with arterial hypertension, myocardial infarction, stable coronary heart disease, diabetes mellitus, and after coronary bypass surgery have shown that elevated heart rate (HR) is prognostically unfavorable factor of cardiovascular and total mortality independent of other risk factors. Moreover, it has been shown that tachycardia to a certain extent correlates with severity and progression of atherosclerosis and can promote damage of integrity of atherosclerotic plaque. Plaque rupture plays main role in pathogenesis of acute coronary syndrome (ACS). Lowering of HR is one of therapeutic approaches to prevention of plaque rupture, i.e. to lowering of risk of ACS development. Mechanisms of interrelationships between HR and ACS and possibilities to influence HR with drugs in ACS are presented in this review.
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PMID:[Heart rate and acute coronary syndrome: crosslink mechanisms and possibilities of drug intervention]. 1977 9

This review discusses the pathological changes in the heart and vessels underlying brain ischaemic injury, with a major focus on atherosclerotic disease of the brain induced by lesions of the extracranial cervical and major intracranial arteries and small-vessel disease of the brain. The carotid bifurcation is the primary site for atherosclerotic changes, for which extensive clinical trials and pathological analyses on carotid endarterectomy specimens have been performed. Plaque rupture and erosion give rise to thrombus formation, which leads to brain ischaemic injury. These changes have much in common with atherosclerotic lesions of the subepicardial coronary arteries. Emboli of various types of particles are characteristics of brain ischaemic injury. Thrombi rich in fibrin and red blood cells (red thrombi) that develop in the cardiac chambers are common sources of cerebral emboli. Small-vessel disease of the brain induces fibrinoid necrosis, microaneurysm, fibrohyalinosis, lipohyalinosis and microatheroma, changes commonly associated with hypertension. The acute hypertensive small-vessel changes organize to create segmental arterial disorganization and deep small infarcts when they escape from rupture. Some specific vascular diseases responsible for brain ischaemic injury are briefly reviewed also.
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PMID:Review: role of cerebral vessels in ischaemic injury of the brain. 2103 51


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