Cellular and Genetic Control of Atherosclerosis Susceptibility

来源 :2005 WHTS3rd Annual Congress of International Drug Discovery | 被引量 : 0次 | 上传用户:a692039471
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  Our research is directed at identifying cellular components and genes that contribute to the development of atherosclerosis and restenosis.Mouse strains C57BL/6J (B6) and C3H/HeJ (C3H) are well characterized as models for diet-induced atherosclerosis.When fed a high fat/cholesterol diet containing cholate, B6 mice readily develop fatty streak lesions at the aortic root, whereas C3H mice are nearly completely resistant to lesion formation.However, interpretation of the results is complicated by differences between the two strains in plasma lipid levels and systemic inflammatory changes induced by cholate.To exclude influence from the cholate-containing diet, we have constructed a congenic strain of C3H mice carrying the apoE null allele.Despite comparable plasma lipid levels, C3H.apoE-deficient mice developed much smaller lesions than their B6.apoE-deficient counterpart.By reciprocal bone-marrow transplantation, we have demonstrated that the difference in atherosclerosis susceptibility is not associated with bone marrow-derived cells.In ex vivo stud ies, we have observed that endothelial cells are a source of differences between the two strains in atherosclerosis susceptibility.We are now performing reciprocal aorta transplantation to determine the role of the arterial wall in control of atherosclerosis susceptibility.We are also using an F2 cross to define the chromosomal locations of genes that modulate atherosclerotic lesions.
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