Atherosclerotic lesions pathogenesis

The oxidation hypothesis of atherosclerosis states that the oxidative modification of LDL (or other lipoproteins) is important and possibly obligatory in the pathogenesis of the atherosclerotic lesion thus, it has been suggested that inhibiting the oxidation of LDL will decrease or prevent atherosclerosis and clinical sequelae. LDL oxidation also has important implications for vascular health function. High concentrations of LDL may inhibit arterial function in terms of the release of nitric oxide from the endothelium and many of these effects are mediated by lipid oxidation products. Furthermore, oxidized LDL inhibits endothelium-dependent nitric oxide-mediated relaxations in isolated rabbit coronary arter-... 

Small, D.M. 1988. Progression and regression of atherosclerotic lesions. Arteriosclerosis 8 103-129. Aikawa, M., Libby, P. 2004. The vulnerable atherosclerotic plaque pathogenesis and therapeutic approach. 

It is quite clear that macrophages play a key role in the pathogenesis of atheroma, that is, in atherosclerotic lesions (Ley et al. 2011). Attracted by chanotactic factors, and favored by the expression of adhesion molecules on ECs, monocytic cells move from the blood stream into the snb-intimal space, where they are induced by various stimuli to differentiate into macrophages and, subsequently into foam cells. SMCs also contribute to the formation of foam cells. The crucial event that differentiates monocytic cells and SMCs into cells that can take up and accumnlate oxLDL is the expression of scavenger receptor of class B CD36 on the cell surface (Figure 15.5). 

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. 

Fields of atherosclerotic research which remain only partially tilled are the understanding of atheromata pathogenesis and the chemotherapy of lesion regression. 

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