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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Cuff-induced vascular intima thickening is influenced by titration of the Ace gene in mice

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Author(s):
Lacchini, Silvia ; Heimann, Andrea S. ; Evangelista, Fabiana S. ; Cardoso, Leandro ; Silva, Gustavo J. J. ; Krieger, Jose E. [1]
Total Authors: 6
Affiliation:
[1] Univ Sao Paulo, Sch Med, Heart Inst InCor, Lab Genet & Mol Cardiol LIM 13, BR-05403000 Sao Paulo - Brazil
Total Affiliations: 1
Document type: Journal article
Source: Physiological Genomics; v. 37, n. 3, p. 225-230, MAY 2009.
Web of Science Citations: 7
Abstract

Lacchini S, Heimann AS, Evangelista FS, Cardoso L, Silva GJ, Krieger JE. Cuff-induced vascular intima thickening is influenced by titration of the Ace gene in mice. Physiol Genomics 37: 225-230, 2009. First published March 3, 2009; doi:10.1152/physiolgenomics.90288.2008.-We tested the hypothesis that small changes in angiotensin I-converting enzyme (ACE) expression can alter the vascular response to injury. Male mice containing one, two, three, and four copies of the Ace gene with no detectable vascular abnormality or changes in blood pressure were submitted to cuff-induced femoral artery injury. Femoral thickening was higher in 3- and 4-copy mice (42.4 +/- 4.3% and 45.7 +/- 6.5%, respectively) compared with 1- and 2-copy mice (8.3 +/- 1.3% and 8.5 +/- 0.9%, respectively). Femoral ACE levels from control and injured vessels were assessed in 1- and 3-copy Ace mice, which represent the extremes of the observed response. ACE vascular activity was higher in 3- vs. 1-copy Ace mice (2.4-fold, P < 0.05) in the control uninjured vessel. Upon injury, ACE activity significantly increased in both groups {[}2.41-fold and 2.14-fold (P < 0.05) for 1- and 3-copy groups, respectively] but reached higher levels in 3- vs. 1-copy Ace mice (P < 0.05). Pharmacological interventions were then used as a counterproof and to indirectly assess the role of angiotensin II (ANG II) on this response. Interestingly, ACE inhibition (enalapril) and ANG II AT(1) receptor blocker (losartan) reduced intima thickening in 3-copy mice to 1-copy mouse values (P < 0.05) while ANG II treatment significantly increased intima thickening in 1-copy mice to 3-copy mouse levels (P < 0.05). Together, these data indicate that small physiologically relevant changes in ACE, not associated with basal vascular abnormalities or blood pressure levels, do influence the magnitude of cuff-induced neointima thickening in mice. (AU)

FAPESP's process: 01/00009-0 - An integrated approach for the dissection of primary hypertension: molecular and functional characterization of the cardiovascular system
Grantee:Eduardo Moacyr Krieger
Support Opportunities: Research Projects - Thematic Grants