HSP70.1 and -70.3 are required for late-phase protection induced by ischemic preconditioning of mouse hearts.
We investigated the role of inducible heat shock proteins 70.1 and 70.3 (HSP70.1 and HSP70.3, respectively) in myocardial ischemic preconditioning (IP) in mice. Wild-type (WT) mice and HSP70.1- and HSP70.3-null [HSP70.1/3(-/-)] mice were subjected to IP and examined 24 h later during the late phase of protection. IP significantly increased steady-state levels of HSP70.1 and HSP70.3 mRNA and expression of inducible HSP70 protein in WT myocardium. To assess protection against tissue injury, mice were subjected to 30 min of regional ischemia and 3 h of reperfusion. In WT mice, IP reduced infarct size by 43% compared with sham IP-treated mice. In contrast, IP did not reduce infarct size in HSP70.1/3(-/-) mice. Absence of inducible HSP70.1 and HSP70.3 had no effect, however, on classical or early-phase protection produced by IP, which significantly reduced infarct size in HSP70.1/3(-/-) mice. We conclude that inducible HSP70.1 and HSP70.3 are required for late-phase protection against infarction following IP in mice.
Hampton
Craig R
CR
Department of Surgery, University of Washington, 1959 N.E. Pacific Street, Box 356410, Seattle, WA 98195, USA. champton@u.washington.edu
Shimamoto
Akira
A
Rothnie
Christine L
CL
Griscavage-Ennis
Jeaneatte
J
Chong
Albert
A
Dix
David J
DJ
Verrier
Edward D
ED
Pohlman
Timothy H
TH
D000818:Animals; D003593:Cytoplasm / Q000502:physiology; D015870:Gene Expression; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism*; D019157:Ischemic Preconditioning, Myocardial; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000378:metabolism / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology; D015800:Protozoan Proteins / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis
D018840:HSP70 Heat-Shock Proteins; D015800:Protozoan Proteins; D012333:RNA, Messenger; C081884:heat-shock protein 70.1