Cardioprotective effects of 70-kDa heat shock protein in transgenic mice.
Heat shock proteins are proposed to limit injury resulting from diverse environmental stresses, but direct metabolic evidence for such a cytoprotective function in vertebrates has been largely limited to studies of cultured cells. We generated lines of transgenic mice to express human 70-kDa heat shock protein constitutively in the myocardium. Hearts isolated from these animals demonstrated enhanced recovery of high energy phosphate stores and correction of metabolic acidosis following brief periods of global ischemia sufficient to induce sustained abnormalities of these variables in hearts from nontransgenic littermates. These data demonstrate a direct cardioprotective effect of 70-kDa heat shock protein to enhance postischemic recovery of the intact heart.
Radford
N B
NB
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235, USA.
Fina
M
M
Benjamin
I J
IJ
Moreadith
R W
RW
Graves
K H
KH
Zhao
P
P
Gavva
S
S
Wiethoff
A
A
Sherry
A D
AD
Malloy
C R
CR
Williams
R S
RS
D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D004734:Energy Metabolism; D018840:HSP70 Heat-Shock Proteins / Q000502:physiology*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008822:Mice, Transgenic; D009206:Myocardium / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism*
D000227:Adenine Nucleotides; D018840:HSP70 Heat-Shock Proteins