Objective: Apoptosis may play an important role in cardiac remodeling after myocardial infarction (MI). p53 is a well-known proapoptotic factor. However, its pathophysiological significance in these conditions remains unclear. We thus examined the effects of target deletion of the p53 gene on post-MI hearts. Methods: Anterior MI was created in male heterozygous p53-deficient (p53+/-; n = 28) mice and sibling wild-type (p53+/+; n = 29) mice by ligating the left coronary artery. Results: By day 7, p53+/- mice had significantly better survival rate than p53+/+ mice (89% vs. 69%, P < 0.05). Notably, p53+/- mice had a significantly lower incidence of left ventricular (LV) rupture (7% vs. 28%, P < 0.05) despite comparable infarct size (60 ± 2% vs. 59 ± 2%, P = NS), heart rate (488 ± 15 vs. 489 ± 17 bpm, P = NS), or mean arterial blood pressure (80 ± 2 vs. 78 ± 3 mm Hg, P = NS). The extent of infiltrating interstitial cells including macrophages into the post-MI hearts was not altered by the deletion of p53. Further, collagen deposition as well as the zymographic MMP-2 and -9 activities were comparable between p53+/- and p53+/+ mice with MI. However, the p53+/- mice had a significantly thicker infarct wall. The number of TUNEL-positive cells in the infarct area was significantly lower in p53+/- mice than in p53+/+ mice (423 ± 86 vs. 1330 ± 275/105 cells, P < 0.01). Conclusions: p53 is involved in cardiac rupture after MI, probably via the induction of a proapoptotic pathway. The inhibition of p53 may be a potentially useful therapeutic strategy to manage post-MI patients.
All Science Journal Classification (ASJC) codes
- Cardiology and Cardiovascular Medicine
- Physiology (medical)