title: Angiotensin-converting enzyme gene and atherosclerosis.
abstract: Common variants of the angiotensin-converting enzyme (ACE) gene (ACE ie humans, Ace in mice) associated with changes in circulating ACE activities have been suggested to confer differential risks for atherosclerosis. Using a mouse model of atherosclerosis induced by heterozygosity for apolipoprotein E gene disruption and an atherogenic diet, we have studied the impact on atherogenesis of a mutation that changes the level of function of Ace. We find that this genetically determined change does not influence the size or complexity of atherosclerotic lesions. Ace genotype was not a significant determinant of lesion size in female (+/+ = 12.9 +/- 1.5 and +/- = 11.7 +/- 1.6 microns2 x 10(4)) or male (+/+ = 0.95 +/- 0.25 and +/- = 1.83 +/- 0.59 microns2 x 10(4)) mice; however, lesions were significantly larger (P < .001) in female than male mice. Ace genotype also did not affect lesion complexity; however, lesions in females showed significantly increased frequency of cholesterol clefts, acellular cores, fibrous caps, and calcifications compared with those in males. The hypothesis that genetic variation in the level of ACE gene expression affects the development of atherosclerosis is not supported by these findings.
authors.affiliation: Department of Internal Medicine, University of North Carolina at Chapel Hill 27599, USA. krege@med.unc.edu
authors.forename: J H
authors.initials: JH
authors.lastname: Krege
authors.forename: J S
authors.initials: JS
authors.lastname: Moyer
authors.forename: L L
authors.initials: LL
authors.lastname: Langenbach
authors.forename: L
authors.initials: L
authors.lastname: Peng
authors.forename: S H
authors.initials: SH
authors.lastname: Zhang
authors.forename: N
authors.initials: N
authors.lastname: Maeda
authors.forename: R L
authors.initials: RL
authors.lastname: Reddick
authors.forename: O
authors.initials: O
authors.lastname: Smithies
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D001161:Arteriosclerosis / Q000235:genetics* / Q000473:pathology; D015992:Body Mass Index; D004036:Diet, Atherogenic; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D012737:Sex Factors
chemical_list: D001057:Apolipoproteins E; D007703:Peptidyl-Dipeptidase A