Targeted deletion of p53 prevents cardiac rupture after myocardial infarction in mice
| Autor: | Masaki Ikeuchi, Kenji Sunagawa, Toru Kubota, Shintaro Kinugawa, Hidenori Matsusaka, Hiroyuki Tsutsui, Tomomi Ide, Shouji Matsushima |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Male
Heterozygote medicine.medical_specialty Time Factors Physiology Myocardial Infarction Infarction Apoptosis Myocardial rupture Mice Ventricular Dysfunction Left Left coronary artery Physiology (medical) Internal medicine medicine.artery medicine Animals Myocardial infarction Ventricular remodeling Heart Rupture Post-Infarction Mice Knockout Ventricular Remodeling business.industry Cardiac Rupture medicine.disease Matrix Metalloproteinases Mice Inbred C57BL Oncogene Protein v-akt Blood pressure Endocrinology Echocardiography Models Animal Circulatory system Cardiology Female Tumor Suppressor Protein p53 Cardiology and Cardiovascular Medicine business Gene Deletion |
| Zdroj: | Cardiovascular Research. 70:457-465 |
| ISSN: | 0008-6363 |
| Popis: | 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.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.By day 7, p53(+/-) mice had significantly better survival rate than p53(+/+) mice (89% vs. 69%, P0.05). Notably, p53(+/-) mice had a significantly lower incidence of left ventricular (LV) rupture (7% vs. 28%, P0.05) 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, P0.01).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. |
| Databáze: | OpenAIRE |
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