Alterations in angiotensin converting enzyme during rodent aortic aneurysm formation.
BACKGROUND
The renin-angiotensin system (RAS) has been implicated in vessel wall remodeling. This investigation tested the hypothesis that the RAS is altered during experimental rodent aneurysm formation.


METHODS
Rat aortas were perfused with saline (controls, N = 45) or elastase (6 U/ml, N = 45). At 4, 7, and 14 days after aortic perfusion, aortic diameters were measured (n = 15/time point/group) and aortic wall mRNA and protein were extracted. Real time polymerase chain reation (PCR) measured RNA levels of angiotensin, angiotensin converting enzyme (ACE), angiotensin II receptor 1 (AT(1)), and angiotensin II receptor 2 (AT(2)). Western blot analysis measured ACE protein levels. Immunohistochemical studies localized ACE within the aortic wall. Statistical analyses were performed with the unpaired t-test and ANOVA.


RESULTS
Elastase perfusion significantly increased aortic diameter (P < 0.01), with no significant changes in saline control aortic diameters. ACE mRNA did not become elevated in elastase-perfused aortas, yet ACE protein levels were elevated on days 4 and 7 of perfusion (P < 0.01) compared to controls, and ACE staining was noted in these aortas. This difference resolved by 14 days. In neither group were there significant alterations in AT(1), AT(2), or An mRNA levels, although ACE mRNA was elevated in controls after 7 days of perfusion compared to elastase perfused aortas (P < 0.005).


CONCLUSIONS
Experimental aortic aneurysm formation may be associated with increased aortic wall ACE protein levels. The mechanisms by which these proteins contribute to, or serve as markers of, aneurysm formation in vivo requires further intervention.
Eagleton
Matthew J
MJ
Department of Surgery, Jobst Vascular Surgery Research Laboratories, University of Michigan, Section of Vascular Surgery, Ann Arbor, USA. eagletm@ccf.org
Cho
Brenda
B
Lynch
Erin
E
Roelofs
Karen
K
Woodrum
Derek
D
Stanley
James C
JC
Upchurch
Gilbert R
GR
D000818:Animals; D001011:Aorta / Q000201:enzymology / Q000473:pathology; D001014:Aortic Aneurysm / Q000201:enzymology* / Q000517:prevention & control; D004195:Disease Models, Animal; D007700:Kinetics; D008297:Male; D010196:Pancreatic Elastase / Q000008:administration & dosage / Q000627:therapeutic use*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism*; D010477:Perfusion; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012084:Renin-Angiotensin System / Q000502:physiology*
D012333:RNA, Messenger; D007703:Peptidyl-Dipeptidase A; D010196:Pancreatic Elastase