Upregulation of LOX-1 expression in aorta of hypercholesterolemic rabbits: modulation by losartan.
Angiotensin-II (Ang-II) enhances the modification of LDL and the expression of its lectin-like receptor (LOX-1) by activating type 1 (AT(1)) receptors. This study was designed to determine the effect of hypercholesterolemia on LOX-1 expression in aorta and its modulation by the AT(1) receptor blocker losartan. Male New Zealand White rabbits were fed regular chow (Control group), chow with 1% cholesterol and 4% peanut oil (HC-diet group), or 1% cholesterol and 4% peanut oil diet plus losartan (25 mg/kg/day) (Losartan + HC-diet group) for 10 weeks. Animal body weight, serum cholesterol levels, and arterial blood pressure were measured. Aortic intimal thickening was quantitated in H&E-stained segments. LOX-1 expression in aortas was examined by immunohistochemistry and semi-quantitative RT-PCR. High-cholesterol diet did not affect body weight, but induced hypercholesterolemia and extensive intimal thickening. Aortas of rabbits in the control group showed a modest LOX-1 expression in the endothelium. Aortic intimal proliferation in HC-diet group was associated with a marked increase in LOX-1 expression (protein and mRNA) in the endothelium and neointima. Treatment with losartan attenuated aortic intimal proliferation and markedly decreased the enhanced LOX-1 expression. Thus high-cholesterol diet induces the upregulation of LOX-1 expression in neointima of aortas of rabbits. Treatment with losartan, an AT(1) blocker, markedly decreases this enhanced LOX-1 expression.
Chen
H
H
Department of Medicine, VA Medical Center, Gainesville, Florida, USA.
Li
D
D
Sawamura
T
T
Inoue
K
K
Mehta
J L
JL
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001161:Arteriosclerosis / Q000188:drug therapy / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006937:Hypercholesterolemia / Q000188:drug therapy / Q000378:metabolism*; D007150:Immunohistochemistry; D019808:Losartan / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D011817:Rabbits; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000378:metabolism; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism*; D051131:Receptors, Oxidized LDL; D017539:Tunica Intima / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects*
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D002791:Cholesterol, Dietary; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D011973:Receptors, LDL; D051131:Receptors, Oxidized LDL; D002784:Cholesterol; D019808:Losartan