Abstract 13437: Sirt7 Deficiency Increases the Risk of Cardiac Rupture after Murine Model of Myocardial Infarction
Introduction: Sirt7, one of the seven members of the mammalian sirtuin family, is involved in age-dependent cardiac malfunction. However, the role of Sirt7 in acute cardiac insult has not been investigated.
Hypothesis: Sirt7 attenuates cardiac damages after experimental myocardial infarction through inactivation of p53 by deacetylation.
Methods: Myocardial infarction (MI) was created in 10-week-old male homozygous Sirt7 deficient (Sirt7−/−) and wild-type (WT) mice by the permanent ligation of the left anterior descending coronary artery. A sham operation without coronary artery ligation was also performed in both Sirt7−/− and WT mice. Cardiac function and structure were assessed by echocardiography. Hemodynamics were assessed by using 1.4-Fr Millar catheter. Acetylation of p53 was analyzed in cardiac tissue homogenates by western blot analysis.
Results: There were no significant differences in body weight, heart rate and systolic blood pressure between Sirt7−/− and WT mice at 3 and 14 days after MI. Sirt7 transcript expression was increased by 2.5-fold in the border zone (BZ) of myocardial tissues at 3 days after MI in WT mice (P<0.01. n=5). There were no significant differences in echocardiographic and hemodynamic parameters at day 3 post-MI. However, the number of mice that died of cardiac rupture within 1 weeks after MI was significantly higher in Sirt7−/− mice (68%, 11 of 16 mice) than in WT mice (23%, 5 of 22 mice) (P<0.01). In the BZ of myocardium, mRNA expression of fibrosis-related genes, such as Collagen I, III and TGF-β were significantly lower in Sirt7−/− mice than in WT mice. Western blot analysis showed that the expression of acetyled-p53 within the BZ of myocardial tissues in Sirt7−/− mice was 1.5-fold greater than that of WT mice (P<0.05. n=4). mRNA expression of HIf-1α, which is negatively regulated by p53, was increased in BZ of myocardial tissues 3 days after MI in WT mice, however, upregulation of HIf-1alfa was not detected in Sirt7−/− mice (P<0.05. n=5).
Conclusions: Inactivation of p53 by Sirt7-mediated deacetylation in BZ of myocardium is important protective mechanism to prevent cardiac rupture after MI.
- © 2010 by American Heart Association, Inc.