Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Atherosclerosis is a chronic disease that affects medium and large arteries. This process originates from the interaction between cells of the arterial wall, lipoproteins and inflammatory cells, leading to the development of complex lesions or plaques that protrude into the arterial lumen. Plaque rupture and thrombosis result in acute clinical complications such as myocardial infarction and stroke. Owing to the heterogeneous cellular composition of the plaques, a proteomic analysis of the whole lesion is not appropriate. Therefore, we have studied the proteins secreted by human carotid atherosclerotic plaques, obtained by endarterectomy. Normal artery segments and different regions of the surgical pieces (noncomplicated plaque, complicated plaque with thrombus) were cultured in protein-free medium and the secreted proteins (supernatants) analyzed by two-dimensional gel electrophoresis. Normal artery segments secreted a moderate number of proteins (42 spots). However in the two-dimensional (2-D) gels (pH 3-10) of segments bearing a plaque, the number of spots increased markedly (154). The number of spots also increased (202) in the 2-D gels of artery segments with a ruptured plaque and thrombus. Thus, the more complicated the lesion, the higher the number of secreted proteins, suggesting the production of specific proteins relating to the complexity of the atherosclerotic lesion.
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PMID:Proteomic analysis of human vessels: application to atherosclerotic plaques. 1283 22

It is generally established that the unstable plaque is the major cause of acute clinical sequelae of atherosclerosis. Unfortunately, terms indicating lesions prone to plaque instability, such as "vulnerable plaque," and the different phenotypes of unstable plaques, such as plaque rupture, plaque fissuring, intraplaque hemorrhage, and erosion, are often used interchangeably. Moreover, the different phenotypes of the unstable plaque are mostly referred to as plaque rupture. In the first part of this review, we will focus on the definition of true plaque rupture and the definitions of other phenotypes of plaque instability, especially on intraplaque hemorrhage, and discuss the phenotypes of available animal models of plaque instability. The second part of this review will address the pathogenesis of plaque rupture from a local and a systemic perspective. Plaque rupture is thought to occur because of changes in the plaque itself or systemic changes in the patient. Interestingly, contributing factors seem to overlap to a great extent and might even be interrelated. Finally, we will propose an integrative view on the pathogenesis of plaque rupture.
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PMID:Atherosclerotic plaque rupture: local or systemic process? 1451 72

As it is well-known, a thrombus evolving into a disrupted/eroded atherosclerotic plaque causes most acute coronary syndromes. Plaque stabilization via reduction of the lipid core and/or thickening of the fibrous cap is one of the possible mechanisms accounted for the clinical benefits displayed by different anti-atherosclerotic strategies. The concept of plaque stabilization was developed to explain how lipid-lowering agents could decrease adverse coronary events without substantial modifications of the atherosclerotic lesion. A number of imaging modalities (vascular ultrasound, MRI, and coronary computed tomography) are used for non-invasive assessment of atherosclerosis; most of them can identify luminal stenosis, wall thickness and plaque volume and composition, and can even characterize the rupture-prone vulnerable plaques. Several classes of drugs, including statins, ACE inhibitors, -blockers, and antithrombotics, are able to reduce the plaque burden and the incidence of cardiovascular events; this may be attibutable, at least in part, to plaque-stabilizing effects and the improvement of endothelial dysfunction.
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PMID:[Atheroma plaque stabilization: a new concept based on the dynamic biology of atherosclerosis]. 1462 26

Studies on carotid artery atherosclerosis have been performed in order to understand the high risk for cardiovascular disease in chronic renal failure (CRF). The purpose of this study was to evaluate the extent and nature of carotid artery atherosclerosis in patients with CRF. Of the 135 patients with CRF (52 +/- 11 years), 58 had moderate to severe predialysis CRF (PR), 36 were on dialysis treatment (DI), and 41 were renal transplant recipients (TR). In addition, 58 control subjects (CO) were examined. Common carotid artery intima-media thickness (IMT), plaque prevalence, plaque score, and stiffness index beta were determined. Furthermore, plaque calcification and internal carotid artery stenoses were classified. Plaque prevalence (PR 64%, DI 61%, TR 51%, CO 28%; P < 0.001) and plaque score (PR 3.3 +/- 4.3, DI 3.0 +/- 3.4, TR 2.5 +/- 3.2, CO 0.8 +/- 1.7 mm; P < 0.001) were significantly greater in the CRF patient groups compared to the controls, whereas no difference in IMT was noted between the study groups. The prevalences of plaque calcification and internal carotid artery stenoses were higher among the CRF patient groups. In addition, the stiffness index beta was higher in the CRF patient groups. The present study shows that the characteristic alterations of the carotid arteries in CRF include increased plaque burden, calcification and increased arterial stiffness.
Atherosclerosis 2003 Dec
PMID:Carotid atherosclerosis in chronic renal failure-the central role of increased plaque burden. 1464

Atherosclerosis is the leading cause of death in North America and within the next two decades will be the leading cause worldwide. Atherosclerosis is characterized by vascular obstruction from the deposits of plaque, resulting in reduced blood flow. Plaque rupture and the consequent thrombosis may lead to sudden blockage of the arteries and cause heart attack. High serum lipid levels, especially the elevated level of low-density lipoprotein (LDL), have been shown to be strongly related to the development of atherosclerosis. It is generally accepted that atherosclerotic lesions are initiated via an enhancement of LDL uptake by monocytes and macrophages. In the liver, uptake of plasma LDL is mediated via specific LDL receptors, but a scavenger receptor system is employed by macrophages. Plasma LDL must be modified prior to uptake by macrophages. Analysis of the lipid content in the oxidatively modified LDL from hyper lipidemic patients revealed that the level of lysophosphatidylcholine was greatly elevated, and the high level of the lysolipid was shown to impair the endothelium-dependent relaxation of the blood vessels. In a separate study, we showed that a high level of homocysteine caused the increase in cholesterol production and apolipoprotein B-100 secretion in hepatic cells. Statins have been used effectively to control the production of cholesterol in the liver, and recently, ezetimibe has been shown to supplement the efficacy of statins by inhibiting cholesterol absorption. The factor of elevated levels of triglyceride-rich lipoproteins in association with depressed high-density lipoproteins, usually in the context of insulin resistance, is an important contributor to atherosclerosis and can be effectively treated with fibric acid derivatives. In hyperhomocysteinemia, folic acid supplements may have a role in the control of cholesterol by reducing the plasma homocysteine level.
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PMID:Lipids and atherosclerosis. 1505 39

Atherosclerotic plaques develop as a consequence of the accumulation of circulating lipid and the subsequent migration of inflammatory cells (macrophages and T-lymphocytes) and VSMCs (vascular smooth muscle cells). Advanced plaques consist of a lipid-rich core, separated from the lumen by a fibrous cap composed of VSMCs, collagen and extracellular matrix. Plaque enlargement ultimately narrows the lumen (stenosis) causing angina. However, recent studies have emphasized that acute coronary syndromes (unstable angina/myocardial infarction) are caused by lesion erosion/rupture with superimposed thrombus formation on often small non-stenotic plaques. Thus current therapies work predominantly on stabilization of plaques rather than plaque regression. Apoptosis (programmed cell death) is increasingly observed as plaques develop, although the exact mechanisms and consequences of apoptosis in the development and progression of atherosclerosis are still controversial. Increased endothelial cell apoptosis may initiate atherosclerosis, whereas apoptosis of VSMCs and macrophages localizes in 'vulnerable' lesions, i.e. those most likely to rupture, and at sites of rupture. This review will focus on the regulation of apoptosis of cells within the vasculature, concentrating on the relevance of apoptosis to plaque progression and clinical consequences of vascular cell apoptosis.
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PMID:Role of apoptosis in atherosclerosis and its therapeutic implications. 1523 Jun 90

Intima-media thickness (IMT) is increasingly used in clinical trials as a surrogate end point for determining the success of interventions that lower risk factors for atherosclerosis. The necessity for unified criteria to distinguish early atherosclerotic plaque formation from thickening of IMT and to standardize IMT measurements is addressed in this consensus statement. Plaque is defined as a focal structure that encroaches into the arterial lumen of at least 0.5 mm or 50% of the surrounding IMT value or demonstrates a thickness of > or =1.5 mm as measured from the media-adventitia interface to the intima-lumen interface. Standard use of IMT measurements is recommended in all epidemiological and interventional trials dealing with vascular diseases to improve characterization of the population investigated. The consensus concludes that there is no need to 'treat IMT values' nor to monitor IMT values in individual patients apart from few exceptions. Although IMT has been suggested to represent an important risk marker, it does not fulfill the characteristics of an accepted risk factor. Standardized methods recommended in this consensus statement will foster homogenous data collection and analysis. This will help to improve the power of studies incorporating IMT measurements and to facilitate the merging of large databases for meta-analyses.
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PMID:Mannheim intima-media thickness consensus. 1654 9

Recent publications have reanimated the point of view that there exist links between atherosclerosis--inflammation and hypercholesterolemia. The aim of our study was to investigate the possible influence of statins on some inflammatory parameters in persons with severe primary hypercholesterolemia (PHC). The effects of the HMG CoA reductase inhibitor--Atorvastatin--on serum lipids, apoproteins, C reactive protein (CRP), soluble Intercellular Adhesion Molecule (sICAM), lipid peroxides, antibodies to oxidized LDL (Ab oxLDL) and homocystein were evaluated in 21 persons (52.9 +/- 8.38 years old) with severe PHC, 12 of these having significant coronary-artery stenosis (diameter stenosis > or = 70%), in at least one major coronary artery branch. Ab oxLDL, sICAM, TBARS, CRP and homocystein were significantly increased (p < 0.05) in patients with coronary-artery stenosis. Following a 4 weeks hypolipemiant free baseline period, all persons were treated with Atorvastatin 40 mg once daily for 8 weeks. Atorvastatin 40 mg resulted in a reduction of LDL-C with 57.8% (baseline 259.6 +/- 71.39 mg%) p < 0.001, total Cholesterol with 44.08% (baseline 343.1 +/- 71.72 mg%) p < 0.001, Apo B with 50.6% (baseline 194.7 +/- 48.71 mg%) p < 0.001, TG with 12.02% (baseline 177.4 +/- 83.63 mg%) and HDL-C was increased with 6.84% (baseline 48.0 +/- 7.86 mg%). In coronary heart disease patients, Atorvastatin reduced homocystein concentrations with 19.41% (baseline 17.7 +/- 11.16 microM/l) (p < 0.01), and CRP with 21.9% (baseline 4.8 +/- 4.19 mg/l) p < 0.01 and TBARS with 52% (baseline 0.87 +/- 0.89 nM/ml) p < 0.001, but did not influence sICAM and Ab oxLDL. Thus atherogenic concentrations of LDL-C have to be closely modulated by minimal changes in LDL oxidative state. The effects of Atorvastatin on inflammatory parameters may crucially contribute to the clinical benefit of statins, independent of cholesterol lowering. Plaque stabilization may be a paradigm for antiinflammatory mechanism of action by this class of drugs.
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PMID:Effects of Atorvastatin on some inflammatory parameters in severe primary hypercholesterolemia. 1552 41

Intimal thickening, the accumulation of cells and extracellular matrix within the inner vessel wall, is a physiological response to mechanical injury, increased wall stress, or chemical insult (e.g., atherosclerosis). If excessive, it can lead to the obstruction of blood flow and tissue ischemia. Together with expansive or constrictive remodeling, the extent of intimal expansion determines final lumen size and vessel wall thickness. Plaque rupture represents a failure of intimal remodeling, where the fibrous cap overlying an atheromatous core of lipid undergoes catastrophic mechanical breakdown. Plaque rupture promotes coronary thrombosis and myocardial infarction, the most prevalent cause of premature death in advanced societies. The matrix metalloproteinases (MMPs) can act together to degrade the major components of the vascular extracellular matrix. All cells present in the normal and diseased blood vessel wall upregulate and activate MMPs in a multistep fashion driven in part by soluble cytokines and cell-cell interactions. Activation of MMP proforms requires other MMPs or other classes of protease. MMP activation contributes to intimal growth and vessel wall remodeling in response to injury, most notably by promoting migration of vascular smooth muscle cells. A broader spectrum and/or higher level of MMP activation, especially associated with inflammation, could contribute to pathological matrix destruction and plaque rupture. Inhibiting the activity of specific MMPs or preventing their upregulation could ameliorate intimal thickening and prevent myocardial infarction.
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PMID:Dual role of matrix metalloproteinases (matrixins) in intimal thickening and atherosclerotic plaque rupture. 1561 76

Artery calcification occurring in atherosclerosis is connected with a high risk of cardiovascular events. Quantitative calcification evaluation using electron beam tomography indicated a correlation between artery calcification and well-known cardiovascular risk factors, i.e. smoking, obesity, and hyperlipidemia. Elevated calcium scores are especially observed in diabetic patients, which may even explain the higher mortality in this group. Calcification leads to increased blood vessel rigidity and, consequently, elevated arterial vascular resistance and left ventricular hypertrophy. An increased risk of plaque rupture in relation to calcium-rich atherosclerotic lesions was not proved. Plaque rupture and thromboembolitic complications are probably higher in the case of lipid-rich lesions. Atherosclerotic calcification is an active process in which many cells (monocytes/macrophages, vascular smooth muscle cells, and endothelial cells) participate. Many substances and transcription factors normally participating in the bone remodeling process are found in calcified atherosclerotic lesions (e.g. Cbfa-1, osteocalcin, alkaline phosphatase, BMP-2, osteopontin, osteoprotegrin, and RANKL). On monocytes, cells playing an important role in atherosclerosis progression, the presence of a calcium-sensing receptor (CaR) has been demonstrated. Increase in monocyte chemotaxis and increased interleukin 6 secretion in response to extracellular calcium were observed. Monocytes also directly and indirectly enhance vascular calcification. Immune cells and cytokines participating in vascular calcification are connected in one pathogenetic mechanism, i.e. atherosclerosis as an inflammatory disease and calcification.
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PMID:[The role of calcium ions in the pathomechanism of the artery calcification accompanying atherosclerosis]. 1576 85


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