title: Genetic control of susceptibility to atherosclerosis (with special emphasis on the role of the macrophage).
abstract: The pathogenesis of atherosclerosis involves a complex interplay of arterial endothelium, multiple cellular constituents, and circulating lipo/apolipoproteins. Early work implicated a single etiology--either excess of circulating lipids, disruption of endothelial integrity, or clonal proliferation of smooth muscle cells. However, current research supports a hypothesis unifying endothelial disruption with lipid imbibation. The macrophage is recognized as having an integral role in atherogenesis due to its capacity to adhere to endothelium, internalize and metabolize lipids, and liberate proteases, apolipoproteins, and mitogens. Genetically determined susceptibility or resistance to atherosclerosis has long been described in animals and man, and differences in lipo/apolipoproteins have been proposed to explain these variations. Genetically defined variants of inbred mice have been used to pursue hereditary influences in atherogenesis. Strain variations in lipid metabolism have been advanced as one possibility to explain a polygenic mode of inheritance--those strains most replete in cholesterol-enriched lipoproteins demonstrating the greatest susceptibility. However, there is now a substantial body of evidence suggesting that the diverse functions of the macrophage may be the mechanism underlying the genetic polymorphism in atherosclerosis. Recombinant inbred strains of mice may serve as a vehicle through which this concept can be explored.
authors.affiliation: Department of Medicine, Montreal General Hospital, Quebec, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Clarke
authors.forename: J L
authors.initials: JL
authors.lastname: Stewart-Phillips
authors.forename: E
authors.initials: E
authors.lastname: Skamene
mesh_terms: D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology / Q000235:genetics*; D002784:Cholesterol / Q000235:genetics; D003324:Coronary Artery Disease / Q000235:genetics; D004198:Disease Susceptibility; D004730:Endothelium, Vascular / Q000293:injuries; D006801:Humans; D008074:Lipoproteins / Q000097:blood / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000502:physiology*; D051379:Mice
chemical_list: D008074:Lipoproteins; D002784:Cholesterol