Affiliation:
1. From the Departments of Medicine (W.S., M.E.H., M.-L.J., D.M.S., A.J.L.), Microbiology and Molecular Genetics (A.J.L.), and Physiological Science (M.E.H.), University of California Los Angeles.
Abstract
Background
—Oxidized LDL has been found within the subendothelial space, and it exhibits numerous atherogenic properties, including induction of inflammatory genes. We examined the possibility that variations in endothelial response to minimally modified LDL (MM-LDL) constitute one of the genetic components in atherosclerosis.
Methods and Results
—By a novel explant technique, endothelial cells (ECs) were isolated from the aorta of inbred mouse strains with different susceptibilities to diet-induced atherosclerosis. Responses to MM-LDL were evaluated by examining the expression of inflammatory genes involved in atherosclerosis, including monocyte chemotactic protein-1 (MCP-1) and macrophage-colony–stimulating factor (M-CSF), an oxidative stress gene, heme oxygenase-1 (HO-1), and other, noninflammatory, genes. ECs from the susceptible mouse strain C57BL/6J exhibited dramatic induction of MCP-1, M-CSF, and HO-1, whereas ECs from the resistant strain C3H/HeJ showed little or no induction. In contrast, ECs from the 2 strains responded similarly to lipopolysaccharide.
Conclusions
—These data provide strong evidence that genetic factors in atherosclerosis act at the level of the vessel wall.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Physiology (medical),Cardiology and Cardiovascular Medicine
Reference46 articles.
1. Motulsky AG Brunzell JD. The genetics of coronary atherosclerosis. In: King RA Rotter JI Motulsky AG eds. The Genetic Basis of Common Disease. New York NY: Oxford University Press; 1992:150–169.
2. Lusis AJ Weinreb A Drake TA. Genetics of atherosclerosis. In: Topol EJ ed. Textbook of Cardiovascular Medicine. Philadelphia Pa: Lippincott-Raven Publishers; 1998:2389–2413.
3. Isolation, purification, and characterization of a lipoprotein containing apo B from the human aorta
4. Malondialdehyde-altered protein occurs in atheroma of Watanabe heritable hyperlipidemic rabbits
5. Evidence for the presence of oxidatively modified low density lipoprotein in atherosclerotic lesions of rabbit and man.
Cited by
163 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献