Increased ICAM-1 and PECAM-1 transcription levels in the heart of Apo-E deficient mice in comparison to wild type (C57BL6).
Adhesion molecules and chemoattractants are thought to play a critical role in the homing of leukocytes to sites of vascular lesions. Apo-E deficiency in mice creates an atherosclerotic model that mimics vascular lesions in man. Little is known on the effect of Apo-E deficiency on expression of adhesion molecules in the hearts of these animals. In this study, male C57BL6 and Apo-E deficient mice were fed a chow diet over periods of time (0 to 20 weeks). The transcription levels of major adhesion molecules (ICAM-1, PECAM-1), present in the heart, were followed by northern blots. Immunohistochemistry was used to localize these adhesion molecules in the heart. Results show a significant increase in gene transcription levels of ICAM-1 and PECAM-1 in Apo-E animals, but not wild type, at 16 and 20 weeks of chow diet. Such increase in levels of transcription was not observed in younger Apo-E and C57BL6 animals (0, 6 weeks of diet). ICAM-1 and PECAM-1 were strongly expressed in the endocardium and heart microvessels. In contrast, VCAM-1 was poorly stained, with only an occasional expression on the endocardium and arterioles. Enhanced gene expression levels of heart ICAM-1 and PECAM-1 observed in Apo-E deficient mice, but not in control animals, appears to induce the initial stages of an inflammatory reaction. Such observations, not previously reported, may induce heart vascular remodeling.
Zibara
K
K
Thrombosis Research Institute, Post Genomics Atherothrombosis Laboratory, London, UK. zibara@tri-london.ac.uk
Chettab
K
K
McGregor
B
B
Poston
R
R
McGregor
J
J
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics / Q000494:pharmacology; D001161:Arteriosclerosis / Q000209:etiology; D002784:Cholesterol / Q000097:blood; D003331:Coronary Vessels / Q000737:chemistry / Q000166:cytology; D018752:Diet, Fat-Restricted; D004730:Endothelium, Vascular / Q000737:chemistry; D005786:Gene Expression Regulation / Q000187:drug effects; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis* / Q000187:drug effects
D001057:Apolipoproteins E; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D002784:Cholesterol