Differential expression of heat shock proteins in normal and failing human hearts.
BACKGROUND
Heat shock proteins (hsp) constitute an endogenous stress response that protects cells from injury. Most work on these important proteins has focused on the immediate response to acute stress in cell culture systems and mammalian models of heart disease. Little is known about the expression of the hsps in human hearts. We were interested in whether there was increased expression of the hsps in heart failure, a setting of chronic, sustained stress. Five different hsps were examined: hsp27, hsp60, hsp72, hsc70 and hsp90.


RESULTS
Three groups of explanted hearts were studied: dilated cardiomyopathy (DCM), ischemic cardiomyopathy (IHD), and normal controls. Western-blotting with a standard curve of purified protein on each blot was used to quantify the expression of the hsps. Hsp27 was increased almost two-fold in DCM compared to normal hearts, and was significantly greater than in IHD hearts. Levels of hsp60 were doubled in both DCM and IHD hearts (P < 0.05). Hsp72, hsc70 and hsp90 were not significantly changed.


CONCLUSIONS
This study shows for the first time that differential changes in hsp levels occur in end-stage heart failure. Since hsps can render cells resistant to apoptosis, and are associated with the mitochondria and the cytoskeleton, which are known to be abnormal in heart failure, these studies may lead to new insights into the pathogenesis of cardiac decompensation.
Knowlton
A A
AA
Cardiology Section, V.A. Medical Center and Baylor College of Medicine, Houston, TX 77030, USA.
Kapadia
S
S
Torre-Amione
G
G
Durand
J B
JB
Bies
R
R
Young
J
J
Mann
D L
DL
D000328:Adult; D002311:Cardiomyopathy, Dilated / Q000378:metabolism*; D002352:Carrier Proteins / Q000096:biosynthesis; D018834:Chaperonin 60 / Q000096:biosynthesis; D005260:Female; D015870:Gene Expression; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D050884:HSP72 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins / Q000096:biosynthesis; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis; D000099190:MAP-Kinase-Activated Kinase 2
D002352:Carrier Proteins; D018834:Chaperonin 60; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D050884:HSP72 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D000099190:MAP-Kinase-Activated Kinase 2; C494371:HSPA8 protein, human