Skip Navigation

Cardiovascular Research 2006 70(3):457-465; doi:10.1016/j.cardiores.2006.02.001
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Matsusaka, H.
Right arrow Articles by Tsutsui, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Matsusaka, H.
Right arrow Articles by Tsutsui, H.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Copyright © 2006, European Society of Cardiology

Targeted deletion of p53 prevents cardiac rupture after myocardial infarction in mice

Hidenori Matsusakaa, Tomomi Idea, Shouji Matsushimaa, Masaki Ikeuchia, Toru Kubotaa, Kenji Sunagawaa, Shintaro Kinugawab and Hiroyuki Tsutsuib,*

aDepartment of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
bDepartment of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Kita-15, Nishi-7, Kita-ku, Sapporo 060-8638, Japan

* Corresponding author. Tel.: +81 11 706 6970; fax: +81 11 706 7874. Email address: htsutsui{at}med.hokudai.ac.jp

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.

KEYWORDS Apoptosis; Extracellular matrix; Infarction; Myocytes; Remodeling

Time for primary review 43 days


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.