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

Autor(es)

Lacchini, Silvia ; Heimann, Andrea S. ; Evangelista, Fabiana S. ; Cardoso, Leandro ; Silva, Gustavo J. J. ; Krieger, Jose E. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Med, Heart Inst InCor, Lab Genet & Mol Cardiol LIM 13, BR-05403000 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Physiological Genomics; v. 37, n. 3, p. 225-230, MAY 2009.
• Citações Web of Science: 7

Resumo

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)

• Processo FAPESP: 99/11908-4 - Influencia da enzima conversora da angiotensina (eca) nas respostas a injuria vascular.
• Beneficiário: Silvia Lacchini
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 01/11478-1 - O papel da enzima conversora de angiotensina I no controle do peso durante a mudança de hábito alimentar
• Beneficiário: Andrea Sterman Heimann
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 01/00009-0 - Estudo integrado da hipertensão arterial: caracterização molecular e funcional do sistema cardiovascular
• Beneficiário: Eduardo Moacyr Krieger
• Modalidade de apoio: Auxílio à Pesquisa - Temático