Decreased expression of insulin-like growth factor-1 and apoptosis of vascular smooth muscle cells in human atherosclerotic plaque

Insulin-like growth factor-1 (IGF-1) plays an important role in migration, cell cycle progression and survival of Vascular smooth muscle cells (VSMC). We investigated the specific localization of IGF-1 and its receptor (IGF-1 R) and their association with apoptosis and the expression of apoptosis-rel ated proteins in early and advanced atherosclerotic lesions. Human atherosc lerotic plaques n=23) from patients undergoing aortic, carotid or femoral a rterial surgery were studied. Immunohistochemistry and in situ hybridizatio n revealed significantly higher expression of IGF-1 and IGF-1R in the media than in the intima of early atherosclerotic lesions (P<0.01). Medial VSMC positive for BAX. a proapoptotic protein of the B-cell CLL/lymphoma 2 (BCL2 ) family, showed colocalization of IGF-1. Apoptosis. as detected by DNA in situ terminal deoxynucleotidyl transferase end labeling (TUNEL), was not pr esent in these early lesions. In advanced atherosclerotic plaques. the expr ession of IGF-1 and IGF-1R was significantly lower in the intimal regions w ith macrophage infiltration than in those without macrophage infiltration o r than in the media (P<0.01). Furthermore, IGF-1 and IGF-IR immunoreactivit y was markedly lower in intimal TUNEL-positive VSMC compared with intimal B AX-positive and medial VSMC (P<0.01). We conclude that IGF-1 and IGF-1R exp ression are reduced in the deep intima of early atherosclerotic lesions and in areas of advanced plaques with macrophage infiltration, Since IGF-1 is a potent survival factor for VSMC, poor expression of IGF-1 and IGF-1R in i ntimal regions with macrophage infiltration would likely contribute to trig gering VSMC apoptosis potentially leading to plaque weakening, plaque ruptu re and acute coronary events. (C) 2001 Academic Press.