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

H. J. Chen

Departments of Internal Medicine, Physiology and Biophysics, University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System, Little Rock, AR

E. D. Staples

K. Ozaki

Department of Surgery, University of Florida and the VA Medical Center, Gainesville, FL

B. Annex

Department of Medicine, Duke University School of Medicine, Durham, NC

B. K. Singh

Departments of Internal Medicine, Physiology and Biophysics, University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System, Little Rock, AR

R. Vermani

Department of Cardiovascular Pathology, Arned Forces Institute of Pathology, Washington, DC

J. L. Mehtat

Departments of Internal Medicine, Physiology and Biophysics, University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System, Little Rock, AR

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.

Key Words: apoptosis • atherosclerosis • LOX-1 • ox-low-density lipoprotein.

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