Document Detail


CRYAB and HSPB2 deficiency alters cardiac metabolism and paradoxically confers protection against myocardial ischemia in aging mice.
MedLine Citation:
PMID:  17873008     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The abundantly expressed small molecular weight proteins, CRYAB and HSPB2, have been implicated in cardioprotection ex vivo. However, the biological roles of CRYAB/HSPB2 coexpression for either ischemic preconditioning and/or protection in situ remain poorly defined. Wild-type (WT) and age-matched ( approximately 5-9 mo) CRYAB/HSPB2 double knockout (DKO) mice were subjected either to 30 min of coronary occlusion and 24 h of reperfusion in situ or preconditioned with a 4-min coronary occlusion/4-min reperfusion x 6, before similar ischemic challenge (ischemic preconditioning). Additionally, WT and DKO mice were subjected to 30 min of global ischemia in isolated hearts ex vivo. All experimental groups were assessed for area at risk and infarct size. Mitochondrial respiration was analyzed in isolated permeabilized cardiac skinned fibers. As a result, DKO mice modestly altered heat shock protein expression. Surprisingly, infarct size in situ was reduced by 35% in hearts of DKO compared with WT mice (38.8 +/- 17.9 vs. 59.8 +/- 10.6% area at risk, P < 0.05). In DKO mice, ischemic preconditioning was additive to its infarct-sparing phenotype. Similarly, infarct size after ischemia and reperfusion ex vivo was decreased and the production of superoxide and creatine kinase release was decreased in DKO compared with WT mice (P < 0.05). In permeabilized fibers, ADP-stimulated respiration rates were modestly reduced and calcium-dependent ATP synthesis was abrogated in DKO compared with WT mice. In conclusion, contrary to expectation, our findings demonstrate that CRYAB and HSPB2 deficiency induces profound adaptations that are related to 1) a reduction in calcium-dependent metabolism/respiration, including ATP production, and 2) decreased superoxide production during reperfusion. We discuss the implications of these disparate results in the context of phenotypic responses reported for CRYAB/HSPB2-deficient mice to different ischemic challenges.
Authors:
Ivor J Benjamin; Yiru Guo; Sathyanarayanan Srinivasan; Sihem Boudina; Ryan P Taylor; Namakkal S Rajasekaran; Roberta Gottlieb; Eric F Wawrousek; E Dale Abel; Roberto Bolli
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2007-09-14
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  293     ISSN:  0363-6135     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2007 Nov 
Date Detail:
Created Date:  2007-11-08     Completed Date:  2008-01-07     Revised Date:  2013-09-03    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H3201-9     Citation Subset:  IM    
Affiliation:
Center for Cardiovascular Translational Biomedicine, University of Utah, School of Medicine, Salt Lake City, UT, USA. ivor.benjamin@hsc.utah.edu
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MeSH Terms
Descriptor/Qualifier:
Aging / metabolism*,  pathology*
Animals
Female
HSP27 Heat-Shock Proteins
Heat-Shock Proteins / genetics,  metabolism*
Male
Mice
Mice, Knockout
Myocardial Ischemia / pathology*,  physiopathology*,  prevention & control
Myocardium / metabolism*,  pathology*
alpha-Crystallin B Chain / genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
R01 HL043151/HL/NHLBI NIH HHS; R01 HL055757/HL/NHLBI NIH HHS; R01 HL063834/HL/NHLBI NIH HHS; R01-HL-63834/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Cryab protein, mouse; 0/HSP27 Heat-Shock Proteins; 0/Heat-Shock Proteins; 0/Hspb2 protein, mouse; 0/alpha-Crystallin B Chain
Comments/Corrections

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