Keypoints in Cells and Atherogenesis

Abstract

Endothelial dysfunction is the initial event in the atherogenic process, resulting from several events, such as expression of leukocyte binding sites, production of growth factors, chemotactic and vasoreactive molecules, ability to oxidize low-density lipoprotein (LDL) and respond to oxidized lipoproteins, ability to express procoagulant activity, and modulation of vascular permeability. Thus, the endothelium, when subjected to different conditions and factors, plays an active role in the development of atherosclerotic plaque. The expression of several adhesion molecules, such as intracellular adhesion molecule-1 (ICAM-1), E-selectin, vascular cell adhesion molecule-1 (VCAM-1), P-selectin in atherosclerotic plaques, mediating the interaction between endothelial cells and leukocytes, has been described. The modification of LDLs, in conjunction with other chemotactic factors produced by injured endothelial cells, recruit circulating monocytes into the subendothelial space, where they become macrophages. The proliferation of smooth muscle cells is an important event in the progression of arterial injury, occurring in 3 stages: smooth muscle cell replication still within the media layer; migration from the middle layer to the intima and proliferation within the intima. Apoptotic cells were evidenced in the atherosclerotic lesion, suggesting that apoptosis is part of the normal vascular healing process. The final stage of atherosclerotic lesion development is conversion of the fibrotic lesion to an advanced lesion, a lesion in which a thrombus forms as a result of plaque ulceration or intraplaque hemorrhage.