Journal article
CRYAB and HSPB2 deficiency alters cardiac metabolism and paradoxically confers protection against myocardial ischemia in aging mice
American journal of physiology. Heart and circulatory physiology, Vol.293(5), pp.H3201-H3209
11/2007
DOI: 10.1152/ajpheart.01363.2006
PMCID: PMC3683980
PMID: 17873008
Abstract
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 (~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 × 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.
Details
- Title: Subtitle
- CRYAB and HSPB2 deficiency alters cardiac metabolism and paradoxically confers protection against myocardial ischemia in aging mice
- Creators
- Ivor J Benjamin - Center for Cardiovascular Translational Biomedicine, University of Utah, School of Medicine, Salt Lake City, UtahYiru Guo - Institute of Molecular Cardiology, University of Louisville, Louisville, KentuckySathyanarayanan Srinivasan - Center for Cardiovascular Translational Biomedicine, University of Utah, School of Medicine, Salt Lake City, UtahSihem Boudina - Program in Human Molecular Biology and Genetics, Division of Endocrinology and Metabolism, University of Utah, Salt Lake City, UtahRyan P Taylor - Center for Cardiovascular Translational Biomedicine, University of Utah, School of Medicine, Salt Lake City, UtahNamakkal S Rajasekaran - Center for Cardiovascular Translational Biomedicine, University of Utah, School of Medicine, Salt Lake City, UtahRoberta Gottlieb - Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CaliforniaEric F Wawrousek - National Eye Institute, National Institutes of Health, Bethesda, MarylandE. Dale Abel - Program in Human Molecular Biology and Genetics, Division of Endocrinology and Metabolism, University of Utah, Salt Lake City, UtahRoberto Bolli - Institute of Molecular Cardiology, University of Louisville, Louisville, Kentucky
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Heart and circulatory physiology, Vol.293(5), pp.H3201-H3209
- DOI
- 10.1152/ajpheart.01363.2006
- PMID
- 17873008
- PMCID
- PMC3683980
- NLM abbreviation
- Am J Physiol Heart Circ Physiol
- ISSN
- 0363-6135
- eISSN
- 1522-1539
- Grant note
- R01 HL063834 || HL / National Heart, Lung, and Blood Institute : NHLBI R01 HL055757 || HL / National Heart, Lung, and Blood Institute : NHLBI R01 HL043151 || HL / National Heart, Lung, and Blood Institute : NHLBI
- Language
- English
- Date published
- 11/2007
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984025291602771
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