Oxidized low-density lipoprotein is associated with apoptosis of vascular smooth muscle cells in human atherosclerotic plaques

Background-Cytotoxic oxidized LDL (oxLDL) has been shown to promote apoptos is in cultured vascular smooth muscle cells (VSMCs). We investigated the lo calization of oxLDL and its association with apoptosis and the expression o f apoptosis-related proteins in early and advanced atherosclerotic lesions. Methods and Results-Atherosclerotic plaques (n=23) from patients undergoing aortic, carotid, or femoral arterial surgery were studied. In early lesion s, oxLDL was located predominantly in the superficial intima and in the med ia just beneath the internal elastic lamina. Medial VSMCs staining positive for oxLDL showed expression of BAX, a proapoptotic protein of the BCL-2 fa mily. Apoptosis, as detected by DNA in situ terminal deoxynucleotidyl trans ferase end-labeling (TUNEL), was not present in these early lesions. In adv anced plaques, areas of the intima positive for oxLDL showed lower alpha -s mooth muscle actin immunoreactivity (P<0.01) and higher BAX immunoreactivit y (P<0.05). Furthermore, these areas showed an increased number of apoptoti c VSMCs (P<0.01). Western blot analysis revealed that oxLDL increases BAX e xpression in cultured human coronary VSMCs. Conclusions-We conclude that in early atherosclerotic lesions, oxLDL-positi ve VSMCs express BAX, which increases the susceptibility of these cells to undergo apoptosis. This could be important in our understanding of the tran sition of early lesions into advanced atherosclerotic plaques, which are ch aracterized by regions of cell death. In advanced plaques, oxLDL-positive a reas of the intima show higher BAX immunoreactivity and TUNEL-positive VSMC s, and this may contribute to plaque instability and rupture.