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(Circulation. 2000;102:5.)
© 2000 American Heart Association, Inc.

Editorials

Genetic Differences in Endothelial Cells May Determine Atherosclerosis Susceptibility

Jan L. Breslow, MD

From the Laboratory of Biochemical Genetics and Metabolism, Rockefeller University, New York, NY.

Correspondence to Jan L. Breslow, MD, Laboratory of Biochemical Genetics and Metabolism, The Rockefeller University, 1230 York Ave, Box 179, New York, NY 10021-6399. E-mail breslow@rockvax.rockefeller.edu

Key Words: Editorials • endothelium • inflammation • genetics • atherosclerosis

Atherosclerotic cardiovascular disease is a complex genetic disorder that involves many genes and has significant gene-environment interactions. The extensive study of candidate genes in pathways relevant to atherosclerotic cardiovascular disease risk factors has had limited success in explaining the population’s susceptibility to this disease. With the advent of the Genome Program, it is now becoming possible to use positional cloning techniques to reveal new genes involved in atherosclerosis susceptibility. Studies in human populations are underway, but they may be difficult because of the heterogeneity of human populations and the very real possibility that large numbers of genes are involved, each with very small effects. The probable difficulties of human genetic studies strongly suggest that parallel approaches should be undertaken to identify genes for atherosclerosis susceptibility by positional cloning in animal models. Genes identified through the study of animal models can be used to identify human homologues. These can be used to search for mutations associated with disease in human populations and/or to identify important pathways involved in atherogenesis that might lend themselves to the development of novel therapeutic approaches.

The most ideal mammal for such studies is the laboratory mouse.¹ Mice are small (25 to 40 g) and have short generation times (9 to 10 weeks) and large litter sizes (5 to 10 pups); in addition, there are many inbred strains available. However, laboratory strains of mice fed the normal chow diet do not develop atherosclerotic lesions. To circumvent this problem, Paigen et al² proposed a model in which mice . . . [Full Text of this Article]

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