Oxidized low-density lipoprotein receptor LOX-1 and apoptosis in human atherosclerotic lesions.
BACKGROUND
Lectin-like oxidized LDL receptor-1 (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.


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 transcriptase-polymerase 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-1 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.


CONCLUSIONS
These observations indicate that LOX-1 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.
Li
D Y
DY
Department of Surgery, University of Florida and the VA Medical Center, Gainesville, FL, USA.
Chen
H J
HJ
Staples
E D
ED
Ozaki
K
K
Annex
B
B
Singh
B K
BK
Vermani
R
R
Mehta
J L
JL
D000368:Aged; D017209:Apoptosis / Q000502:physiology*; D001161:Arteriosclerosis / Q000378:metabolism* / Q000473:pathology; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012313:RNA / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D011973:Receptors, LDL / Q000032:analysis / Q000096:biosynthesis*; D051131:Receptors, Oxidized LDL; D051127:Scavenger Receptors, Class E
C495137:OLR1 protein, human; D012333:RNA, Messenger; D011973:Receptors, LDL; D051131:Receptors, Oxidized LDL; D051127:Scavenger Receptors, Class E; D012313:RNA