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Targeted deletion of p53 prevents cardiac rapture after myocardial infarction in mice
Title: | Targeted deletion of p53 prevents cardiac rapture after myocardial infarction in mice |
Authors: | Matsusaka, Hidenori Browse this author | Ide, Tomomi Browse this author | Matsushima, Shouji Browse this author | Ikeuchi, Masaki Browse this author | Kubota, Toru Browse this author | Sunagawa, Kenji Browse this author | Kinugawa, Shintaro Browse this author | Tsutsui, Hiroyuki Browse this author →KAKEN DB |
Keywords: | adoptosis | extracellular matrix | infraction | myocytes | remodeling |
Issue Date: | 1-Jun-2006 |
Publisher: | Elsevier |
Journal Title: | Cardiovascular research |
Volume: | 70 |
Issue: | 3 |
Start Page: | 457 |
End Page: | 465 |
Publisher DOI: | 10.1016/j.cardiores.2006.02.001 |
Abstract: | 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. |
Rights: | Copyright © 2006 European Society of Cardiology Published by Elsevier B.V. |
Relation: | http://cardiovascres.oxfordjournals.org/ |
Type: | article (author version) |
URI: | http://hdl.handle.net/2115/14453 |
Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 筒井 裕之
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