Atherosclerosis atheromatous plaque

Carotenoids and cardiovascular diseases — Numerous epidemiological studies aimed to study the relationship of carotenoids and cardiovascular diseases (CVDs) including coronary accident risk and stroke. It appeared then that observational studies, namely prospective and case-control studies, pointed to a protective effect of carotenoids on myocardial infarct and stroke, but also on some atherosclerosis markers such as intima media thickness (IMT) of the common carotid artery (CCA) and atheromatous plaque formation. 

In atherosclerosis, ox-LDL is taken up ultimately by macrophages and smooth muscle cells in the arterial intima. Once loaded with lipid, these cells have a foamy appearance when examined histologically. The accumulation of these so-called foam cells in the artery wall leads to the formation of fatty streaks , which can lead to atheromatous plaque formation and consequent coronary heart disease. 

NO also reduces endothelial adhesion of monocytes and leukocytes, key features of the early development of atheromatous plaques. This effect is due to the inhibitory effect of NO on the expression of adhesion molecules on the endothelial surface. In addition, NO may act as an antioxidant, blocking the oxidation of low-density lipoproteins and thus preventing or reducing the formation of foam cells in the vascular wall. Plaque formation is also affected by NO-dependent reduction in endothelial cell permeability to lipoproteins. The importance of eNOS in cardiovascular disease is supported by experiments showing increased atherosclerosis in animals deficient in eNOS by pharmacologic inhibition. Atherosclerosis risk factors, such as smoking, hyperlipidemia, diabetes, and hypertension, are associated with decreased endothelial NO production, and thus enhance atherogenesis. 

Abstract. The significance of free radical oxidation of phospholipids in tissues of animals with experimental atherosclerosis was investigated. By using modem physico-chemical methods an elevated content of polyunsaturated fatty acids and other lipids peroxides was discovered in the blood and the aorta of rabbits with experimental atheromatosis. The human blood demonstrated a low level of protective enzymatic systems and a high content of products secondary to peroxidal oxidation of the lipids. The mechanism accounting for the action of lipids peroxides on the vascular wall resulting in the formation of atheromatous plaques is considered. 

Atherosclerosis is a multifactorial pathology, and genetic and enviromental factors contribute to the development of the disease. Endothelial and smooth muscle cells and blood components, including monocytes/macrophages, platelets and LDL play a crucial role in the formation of the atheromatous plaque "Fig. (4)", [62]. 

Multiple angiographic trials with fibrates have demonstrated the ability of these drugs to reduce rates of atheromatous plaque progression. The Bezafibrate Coronary Atherosclerosis Intervention Trial (BEC AIT)... 

A large fraction of the cholesterol present in lymph and blood plasma is found in the chylomicrons and about two-thirds of the plasma cholesterol is esterified with fatty acids giving cholesteryl esters. Cholesterol and its esters constitute a large fraction of the lipid present in the atheromatous plaques which are deposited in the intima of arteries in the condition of atherosclerosis (page 267). Cholesterol, which is insoluble in aqueous media, is also a major constituent of most gallstones. 

The atheromatous plaque develops plate-like areas of calcium which have a characteristic roentgenographic appearance clearly distinguishable from non-atherosclerotic calcification which occurs in peripheral, carotid, and cerebral vessels. In the coronary artery visualization of calcification is pathognomonic for atherosclerosis no other forms of vascular calcification occur (6). 

While the occurrence of atheromatous plaques within expanded PTFE grafts may be rare, their presence indicates that the disease for which the patient received the vascular graft, atherosclerosis, may involve the graft material. Thus, the expected life of the graft may be decreased and the graft truly represents a temporary measure in controlling the progression of atherosclerosis and its systemic effects. 

Growing clinical data also points to the importance of IL-8 in atherogenesis. IL-8 has been found in atheromatous lesions from patients with atherosclerotic disease including carotid artery stenosis (103), CAD (118), abdominal aortic aneurysms (AAA) (103,104,114), and peripheral vascular disease (PVD) (104). Furthermore, studies using plaque explant samples have yielded more direct evidence for IL-8 involvement. Media from cultured AAA tissue induced IL-8-dependent human aortic endothelial cell (HAEC) chemotaxis (122). Homocysteine, implicated as a possible biomarker for CAD, is also capable of inducing IL-8 (123-125) by direct stimulation of endothelial cells (123,124) and monocytes (125). When patients with hyperhomocysteinemia were treated with low-dose folic acid, decreases in homocysteine levels correlated with decreases in IL-8 levels (126). Statins significantly decrease serum levels of IL-6, IL-8, and MCP-1, as well as expression of IL-6, IL-8, and MCP-1 mRNA by peripheral blood monocytes and HUVECs (127). Thus, IL-8 may be an underappreciated factor in the pathogenesis of atherosclerosis. 

Vink A, Schoneveld AH, Lamers D, Houben AJ, van der Groep P, van Diest PJ, Pasterkamp G (2007) HIF-1 alpha expression is associated with an atheromatous inflammatory plaque phenotype and upregulated in activated macrophages. Atherosclerosis 195(2) e69-75... 

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