You are here:
TARGETED DELETION OF INDUCIBLE HEAT SHOCK PROTEIN 70 ABROGATES THE LATE INFARCT-SPARING EFFECT OF MYOCARDIAL ISCHEMIC PRECONDITIONING
Citation:
Hampton, C. R., J. GriscavageEnnis, C. L. Rothnie, A. Shimamoto, D J. Dix, T. H. Pohlman, AND E. D. Verrier. TARGETED DELETION OF INDUCIBLE HEAT SHOCK PROTEIN 70 ABROGATES THE LATE INFARCT-SPARING EFFECT OF MYOCARDIAL ISCHEMIC PRECONDITIONING. Presented at 82nd Annual Meeting of the American Association for Thoracic Surgery, Washington, DC, May 4-8, 2002.
Description:
Abstract submitted for 82nd annual meeting of the American Association for Thoracic Surgery, May 4-8, 2002 in Washington D.C.
Targeted Deletion of Inducible Heat Shock Protein 70 Abrogates the Late Infarct-Sparing Effect of Myocardial Ischemic Preconditioning
Craig R Hampton, MD, Jeaneatte Griscavage-Ennis, PhD, Christine L Rothnie, Akira Shimamoto, MD, PhD, David J Dix, PhD*, Timothy H Pohlman, MD, Edward D Verrier, MD
Division of Cardiothoracic Surgery, The University of Washington, Seattle, WA 98195
*National Health and Environmental Effects Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina.
Objective:The goal of this study was to assess the role of the inducible heat shock protein 70sin the late phase of myocardial ischemic preconditioning (IP) in-vivo.
Methods: Wild type mice (C57Bl/6) served as controls. Mice homozygous for null Hsp70i -/- alleles (Hsp70-1 and Hsp70-3) were used for experimental groups. Mice underwent 30 minutes regional myocardial ischemia followed by three hours reperfusion (I/R). Preconditioned mice underwent three five-minute cycles of alternating ischemia and reperfusion (IP), followed in 24 hours by I/R. Hearts were examined for infarct size, cytoplasmic Hsp70 expression by Western immunoblotting, nuclear heat shock factor (HSF) activation, and Hsp70i mRNA by RT-PCR.
Results: Wild type mice exhibited a dramatic increase in Hsp70 expression 24 hours after IP (figure 1.). When wild type mice underwent IP 24 hours prior to I/R, infarct size was reduced by 43% compared to controls (17.4% ? 2.3 vs 30.6% ? 3.1) [p<0.006] and was not affected by sham operation. In contrast, IP of Hsp70i -/- mice had no infarct sparing effect compared to controls (30.6% ?2.0 vs 30.6% ? 3.1)[ p=NS]. Hsp70 mRNA was correlated as outlined.
Conclusions: These results suggest that the late phase of protection following IP coincides with dramatic upregulation of inducible Hsp70s. Further, targeted deletion of inducible Hsp70 abrogates the late infarct-sparing effects of IP. Taken together, these data provide direct evidence that inducible Hsp70 plays an obligatory role in mediating the late phase of cardioprotection following IP.
Figure 1. Western Blot for Hsp70
This is an abstract of a proposed presentation and does not necessarily reflect EPA policy.