Vascular wall ACE is not required for atherogenesis in ApoE(-/-) mice.
BACKGROUND
It has been proposed that elements of the renin angiotensin system expressed in the arterial wall are critical for the development of atherosclerosis. Angiotensin converting enzyme (ACE) is highly expressed by the endothelium and is responsible for a critical enzymatic step in the generation of angiotensin II. However, the functional contribution of ACE expression in the vascular wall in atherogenesis is unknown. Therefore, we made use of unique genetic models in which mice without the expression of ACE in the vascular wall were crossed with ApoE(-/-) mice in order to determine the contribution of tissue ACE expression to atherosclerotic lesion formation.


RESULTS
Mice expressing either a soluble form of ACE (ACE 2/2) or mice with somatic ACE expression restricted to the liver and kidney (ACE 3/3) on an ApoE(-/-) background were placed on a standard chow or Western diet for 6 months. Atherosclerotic lesion area in the ACE 2/2 mice was significantly lower than that seen in the ACE 3/3 mice. However, these animals also had significantly lower blood pressure and reduced plasma ACE activity which precluded establishing a specific causal relationship between absent tissue ACE activity and decreased atherosclerotic lesion extent. Therefore, we studied the ACE 3/3 mice which are normotensive and lack vascular ACE expression. In the ACE 3/3 animals, atherosclerotic lesion area was not different from wild type controls despite reduced plasma ACE activity.


CONCLUSIONS
We concluded that under these experimental conditions, expression of ACE in the arterial wall is not required for atherosclerotic lesion formation.
Weiss
Daiana
D
Department of Medicine, Emory University School of Medicine, Atlanta, GA, United States.
Bernstein
Kenneth E
KE
Fuchs
Sebastian
S
Adams
Jonathan
J
Synetos
Andreas
A
Taylor
W Robert
WR
D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology; D001808:Blood Vessels / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*
D001057:Apolipoproteins E; C522402:Ace3 protein, mouse; D007703:Peptidyl-Dipeptidase A; C000705328:Ace2 protein, mouse; D000085962:Angiotensin-Converting Enzyme 2