Document Detail


Inhibition of apoptosis by the intrinsic but not the extrinsic apoptotic pathway in myocardial ischemia-reperfusion.
MedLine Citation:
PMID:  23410819     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
SUMMARY: The detailed molecular mechanisms following activation of apoptosis in ischemia-reperfusion injury are unknown. This study using different transgenic mouse models provided first evidence that apoptosis in myocardial ischemia-reperfusion injury is rather linked to the mitochondrial pathway than to death receptor pathway. INTRODUCTION: There is a wealth of evidence for activation of apoptosis in ischemia-reperfusion injury. However, the understanding of detailed molecular mechanism is lacking. METHODS: The extent of myocardial infarction after ligation of the left anterior descending artery in mice carrying different transgenes for inhibition of either the intrinsic or the extrinsic or a combination of both apoptotic cascades was evaluated. The extent of myocardial damage was assessed by echocardiographic determination of left ventricular (LV) ejection fraction, LV hemodynamics, troponin T, and histology. The rate of apoptosis was analyzed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and caspase-3 staining. RESULTS: Highest perioperative rate of death was observed in the dominant-negative form of a truncated Fas-associated death domain (FADD-DN) group. Infarction size by 2,3,5-triphenyltetrazolium chloride (TTC) staining was smaller in the Bcl-2, but not in the other groups as compared to wild-type mice. This was accompanied by lower troponin T values in Bcl-2 transgenic mice as compared to the all other groups. Troponin T correlated well with macroscopic extent of myocardial infarction by TTC staining. A lower decline of LV ejection fraction was seen in the Bcl-2 as compared to wild-type or FADD-DN mice. A smaller number of TUNEL- and caspase-3-positive myocyte nuclei were observed in the Bcl-2 and FADD-DN group as compared to wild-type mice. CONCLUSIONS: We provide first evidence for protective effects on the myocardium in a transgenic mouse model of myocardial ischemia-reperfusion due to inhibition of the Bcl-2, but not the FADD pathway despite that reduced apoptotic cells were observed in both groups as compared to wild-type mice.
Authors:
Arnt V Kristen; Katrin Ackermann; Sebastian Buss; Lorenz Lehmann; Philipp A Schnabel; Armin Haunstetter; Hugo A Katus; Stefan E Hardt
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-2-11
Journal Detail:
Title:  Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology     Volume:  -     ISSN:  1879-1336     ISO Abbreviation:  Cardiovasc. Pathol.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-2-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9212060     Medline TA:  Cardiovasc Pathol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2013 Elsevier Inc. All rights reserved.
Affiliation:
Department of Cardiology, University of Heidelberg, Im Neuenheimer Feld 410, D-69120 Heidelberg, Germany.
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