| First Author | Matsusaka H | Year | 2006 |
| Journal | Cardiovasc Res | Volume | 70 |
| Issue | 3 | Pages | 457-65 |
| PubMed ID | 16533502 | Mgi Jnum | J:111145 |
| Mgi Id | MGI:3653128 | Doi | 10.1016/j.cardiores.2006.02.001 |
| Citation | Matsusaka H, et al. (2006) Targeted deletion of p53 prevents cardiac rupture after myocardial infarction in mice. Cardiovasc Res 70(3):457-65 |
| abstractText | 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 +/- 275/10(5) 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. |
