title: Tissue angiotensin-converting-enzyme (ACE) deficiency leads to a reduction in oxidative stress and in atherosclerosis: studies in ACE-knockout mice type 2.
abstract: Background- Angiotensin II, produced by angiotensin-converting-enzyme (ACE), enhances oxidative stress and atherogenesis. In this study, we analyzed whether tissue ACE deficiency in ACE-knockout mice type-2 would affect their oxidative status. Moreover, by crossbreeding the ACE-knockout mice with atherosclerotic apolipoprotein E (apo E)-deficient (E0) mice, we questioned whether tissue ACE deficiency affects atherogenesis.
  
  
  RESULTS
  ACE-deficient mice type-2 (ACE+/-) exhibited reduced serum lipid peroxidation compared with ACE+/+ mice. Peritoneal macrophages from ACE+/- mice demonstrated lower oxidative status, as exhibited by decreases of 47%, 33% 56%, and 51%, in their lipid peroxides, superoxide release, dichlorofluorescein fluorescence, and LDL oxidation, respectively, compared with ACE+/+ mice. ACE+/- mice crossbred with E0 mice, resulting in atherosclerotic mice heterozygous for ACE (ACE+/-/E0 mice), exhibited reduced lipid peroxidation, increased paraoxonase activity, and lower macrophage LDL oxidation compared with E0 and ACE+/+/E0 mice. ACE+/-/E0 mice also exhibited reduced NADPH-induced aortic superoxide ion production by 52% and a reduction of 43% in their atherosclerotic lesion size compared with E0 mice. Finally, 2 animals genotyped as homozygous-knockout for both ACE and APOE genes (ACE-/-/E0), exhibited a striking reduction of 86% in their atherosclerotic lesion area compared with E0 mice.
  
  
  CONCLUSIONS
  Reduction of tissue ACE with the ACE-knockout mouse type-2 model inhibited oxidative stress and atherogenesis.
authors.affiliation: Lipid Research Laboratory, Bruce Rappaport Faculty of Medicine, Technion, Rappaport Institute for Research in the Medical Sciences, Rambam Medical Center, Haifa, Israel. t_hayek@rambam.health.gov.il
authors.forename: Tony
authors.initials: T
authors.lastname: Hayek
authors.forename: Elsa
authors.initials: E
authors.lastname: Pavlotzky
authors.forename: Shadi
authors.initials: S
authors.lastname: Hamoud
authors.forename: Raymond
authors.initials: R
authors.lastname: Coleman
authors.forename: Shlomo
authors.initials: S
authors.lastname: Keidar
authors.forename: Michael
authors.initials: M
authors.lastname: Aviram
authors.forename: Marielle
authors.initials: M
authors.lastname: Kaplan
mesh_terms: D000818:Animals; D001161:Arteriosclerosis / Q000201:enzymology* / Q000503:physiopathology; D043303:Aryldialkylphosphatase / Q000378:metabolism; D008078:Cholesterol, LDL / Q000378:metabolism; D050356:Lipid Metabolism; D015227:Lipid Peroxidation / Q000502:physiology; D017737:Macrophages, Peritoneal / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D007703:Peptidyl-Dipeptidase A / Q000172:deficiency*; D013481:Superoxides / Q000378:metabolism
chemical_list: D008078:Cholesterol, LDL; D013481:Superoxides; D043303:Aryldialkylphosphatase; D007703:Peptidyl-Dipeptidase A