Rupture of the Atherosclerotic Plaque is the Primary Cause of Sudden Cardiac Death

GJs mediate metabolites, a cules between synchronizatio for the contrac for the transm the organ dev and more th described (11 hemi-channel channel. Ma assemble into has its proper addition, the e plex with mult is enhanced b (~1–5 h), indic times daily (10 sion modulati nism to regula At least fou vascular syste blood vessel w varies between Thus Cx37 an (145); Cx43 Furthermore, exposed to tu lesion formation (83). Beside selectins, activated ECs express integrins such as vascular cell-adhesion molecule 1 (VCAM-1) in response to cholesterol accumulation in the intima (23). T-cells and monocytes, expressing both the very late antigen 4 (VLA-4), bind thereafter to endothelium and transmigrate under the influence of chemokines such as macrophage colonystimulating factor that is produced by low-density lipoprotein (LDL)-stimulated ECs and smooth muscle cells (SMCs) (99). SMCs may also express VCAM-1, promoting further recruitment and retention of mononuclear cells in the intima (72). Once migrated within the plaque, two phenotypes of macrophages appear: inflammatory macrophages and foam cells. The latter cells are characterized by the accumulation of cholesterol in their cytoplasm, resulting from the uptake of oxidized lipoprotein by these cells (113). Besides macrophages, T-cells are the second most important cell population in the atherosclerotic plaque (~10%) (61). They are important determinants in the disease by governing the transition from a latent plaque to a vulnerable plaque (46). CD4+ clones of Tcells isolated from atherosclerotic plaques recognize oxidized LDL (114), suggesting a local stimulation of T-cells by monocytes/macrophages in the plaque through major histo-compatibility antigen II. These Tcells express a pro-inflammatory (TH1) phenotype, suggesting that atherosclerosis is a TH1-driven pathology (114, 148). TH1-type cytokines are predominant in plaques, but IL-4, a TH2-type cytokine, is also produced by a few cells (37). Thus the initiation of atherosclerotic lesions is induced by many cell types within the vasculature, circulating or resident.