Oxidized Low-Density Lipoprotein Receptor LOX-1 and Apoptosis in Human Atherosclerotic Lesions

• Published in: Journal of cardiovascular pharmacology and therapeutics 2002-07, Vol.7 (3), p.147-153
• Main Authors: Li, D. Y., Chen, H. J., Staples, E. D., Ozaki, K., Annex, B., Singh, B. K., Vermani, R., Mehtat, J. L.
• Format: Article
• Language: English
• Subjects: Aged; Apoptosis - physiology; Arteriosclerosis - metabolism; Arteriosclerosis - pathology; Atherosclerosis; Endothelium, Vascular - metabolism; Endothelium, Vascular - pathology; Female; Gene Expression Regulation - physiology; Humans; Low density lipoproteins; Male; Middle Aged; Physiological aspects; Receptors, LDL - analysis; Receptors, LDL - biosynthesis; Receptors, Oxidized LDL; RNA - biosynthesis; RNA, Messenger - biosynthesis; Scavenger Receptors, Class E
• ISSN: 1074-2484; 1940-4034
• DOI: 10.1177/107424840200700304

Background: Lectin-like oxidized LDL receptor-I (LOX-1), a novel receptor for oxidized low-density lipoprotein, mediates oxidized low-density lipoprotein-induced apoptosis of endothelial cells, monocyte adhesion to endothelium, and phagocytosis of aged cells. The present study examined the role of LOX-1 and apoptosis in human atherosclerotic lesions. Methods and Results: Grafted vein (n = 8), human carotid artery endarterectomy (n = 11), and normal human internal mammary artery (n = 8) specimens were used to study the expression of LOX-1 and apoptosis. LOX-1 expression was determined by reverse transcriptasepolymerase chain reaction, Western analysis, and immunostaining. Presence of apoptosis was determined by fluorescent in situ nick end-labeling staining and by the presence of poly (ADP-ribose) polymerase protein (an apoptotic marker). Expression of LOX-1 was significantly increased in atherosclerotic grafted vein and carotid artery specimens compared with that in normal arteries. LOX-1 was expressed in endothelial cells, macrophages, and smooth muscle cells. LOX-I was extensively expressed in the new blood vessels in the core of advanced atherosclerotic lesions. Double immunostaining showed LOX-1 expression to be colocalized with apoptotic cells. Fluorescent in situ nick end-labeling staining showed that the apoptotic cells were present mostly in the rupture-prone regions of the atherosclerotic plaque. Conclusion: These observations indicate that LOX-I is extensively expressed in the proliferated intima of grafted veins and in advanced atherosclerotic carotid arteries. Further, LOX-1 is colocalized with apoptotic cells. These observations may relate to the phenomenon of plaque rupture, and provide targets for developing new therapies.