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Patterns of Vascular Cell Adhesion Molecule-1 and Intercellular Adhesion Molecule-1 Expression in Rabbit and Mouse Atherosclerotic Lesions and at Sites Predisposed to Lesion Formation

The recruitment of mononuclear leukocytes and formation of intimal macrophage-rich lesions at specific sites of the arterial tree are key events in atherogenesis. Inducible endothelial cell adhesion molecules may participate in this process. In aortas of normal chow-fed wild-type mice and rabbits, v...

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Published in:Circulation research 1999-07, Vol.85 (2), p.199-207
Main Authors: Iiyama, Kaeko, Hajra, Leena, Iiyama, Motoi, Li, Hongmei, DiChiara, Maria, Medoff, Benjamin D, Cybulsky, Myron I
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description The recruitment of mononuclear leukocytes and formation of intimal macrophage-rich lesions at specific sites of the arterial tree are key events in atherogenesis. Inducible endothelial cell adhesion molecules may participate in this process. In aortas of normal chow-fed wild-type mice and rabbits, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), but not E-selectin, were expressed by endothelial cells in regions predisposed to atherosclerotic lesion formation. En face confocal microscopy of the mouse ascending aorta and proximal arch demonstrated that VCAM-1 expression was increased on the endothelial cell surface in lesion-prone areas. ICAM-1 expression extended into areas protected from lesion formation. Hypercholesterolemia induced atherosclerotic lesion formation in rabbits, LDL receptor and apolipoprotein E knockout mice, and Northern blot analysis demonstrated increased steady-state mRNA levels of VCAM-1 and ICAM-1, but not of E-selectin. Immunohistochemical staining revealed that VCAM-1 and ICAM-1 were expressed predominantly by endothelium in early lesions and by intimal cells in more advanced lesions. In early and advanced lesions, staining was most intense in endothelial cells at and adjacent to lesion borders. ICAM-1 staining extended into the uninvolved aorta. These expression patterns were highly reproducible in both species. The only difference was that VCAM-1 expression in endothelium over the central portions of lesions was found frequently in rabbits and rarely in mice. The expression of VCAM-1 by arterial endothelium in normal animals may represent a pathogenic mechanism or a phenotypic marker of predisposition to atherogenesis.
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Immunohistochemical staining revealed that VCAM-1 and ICAM-1 were expressed predominantly by endothelium in early lesions and by intimal cells in more advanced lesions. In early and advanced lesions, staining was most intense in endothelial cells at and adjacent to lesion borders. ICAM-1 staining extended into the uninvolved aorta. These expression patterns were highly reproducible in both species. The only difference was that VCAM-1 expression in endothelium over the central portions of lesions was found frequently in rabbits and rarely in mice. The expression of VCAM-1 by arterial endothelium in normal animals may represent a pathogenic mechanism or a phenotypic marker of predisposition to atherogenesis.</abstract><cop>Hagerstown, MD</cop><pub>American Heart Association, Inc</pub><pmid>10417402</pmid><doi>10.1161/01.res.85.2.199</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record>
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source Freely Accessible Science Journals - check A-Z of ejournals
subjects Animals
Aorta - metabolism
Aorta - pathology
Apolipoproteins E - genetics
Arteriosclerosis - metabolism
Arteriosclerosis - pathology
Arteriosclerosis - physiopathology
Atherosclerosis (general aspects, experimental research)
Biological and medical sciences
Blood and lymphatic vessels
Blotting, Northern
Cardiology. Vascular system
Disease Models, Animal
Endothelium, Vascular - chemistry
Endothelium, Vascular - pathology
Female
Gene Expression - physiology
Hypercholesterolemia - metabolism
Hypercholesterolemia - pathology
Hypercholesterolemia - physiopathology
Intercellular Adhesion Molecule-1 - analysis
Intercellular Adhesion Molecule-1 - genetics
Lipopolysaccharides - pharmacology
Male
Medical sciences
Mice
Mice, Inbred C57BL
Mice, Knockout
Microscopy, Confocal
Rabbits
Receptors, LDL - genetics
RNA, Messenger - analysis
Tunica Intima - metabolism
Tunica Intima - pathology
Up-Regulation - physiology
Vascular Cell Adhesion Molecule-1 - analysis
Vascular Cell Adhesion Molecule-1 - genetics
title Patterns of Vascular Cell Adhesion Molecule-1 and Intercellular Adhesion Molecule-1 Expression in Rabbit and Mouse Atherosclerotic Lesions and at Sites Predisposed to Lesion Formation
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