Atherosclerosis, Autoimmunity, and Systemic Lupus Erythematosus

Abstract

Atherosclerosis can be considered a chronic inflammatory condition of the vessel wall. Fatty streaks, the earliest morphological lesions of atherosclerosis, are caused by lipids (primarily of cholesteryl esters) accumulated within the macrophages (foam cells) and smooth muscle cells in the intimal layer. These lesions progress into atherosclerotic plaques containing extracellular matrix components, smooth muscle cells, macrophages, connective tissues, lymphocytes, and a fibrous cap over a pool of extracellular lipid. The primary pathogenic event in atherosclerosis is not clear. The “response to injury hypothesis” postulates that long-term endothelial cell injury, from a variety of mechanisms, alters endothelial permeability and induces leukocyte and platelet adhesion.1 The release of mitogenic factors from platelets and leukocytes was proposed to induce the migration and proliferation of smooth muscle cells from the media. The “lipid hypothesis” proposes that the retention and oxidation of LDL in the subendothelium play a central role in the atherosclerotic process.2,3 The uptake of oxidatively modified LDL by the macrophage via the scavenger receptor induces foam cell formation, but unmodified native LDL has no effect. Products of LDL oxidation, such as oxidized cholesterol, phospholipids, and isoprostanes have been detected in atherosclerotic plaques.4 Oxidized LDL has a number of pro-atherogenic effects, such as being chemotactic to monocytes and T cells, promoting inflammatory gene expression in vascular cells, and inducing the expression of the macrophage scavenger receptor. …