Diminished heat shock response in the aged myocardium.
Induction of heat shock proteins (Hsps), Hsp72 in particular, has been associated with myocardial protection. Since a decreased Hsp response has been reported to occur with aging, it was of interest to determine if hearts from aged animals also demonstrate an altered heat shock response and subsequent myocardial protection. Adult (6 months old) and aged (22 months old) Fischer 344 rats were heat stressed by raising their rectal temperatures to 41 degrees C for 10 min. At selected times following heat stress (0-24 h) hearts were examined for heat shock transcription factor trimerization and DNA-binding activity (Hsf1 activation), Hsp72 mRNA accumulation, Hsp72 and Hsf1 protein content, as well as, protection from ischemia using the Langendorff isolated heart model. Following heat stress, hearts from aged animals demonstrated a 47% reduction in Hsf1 activation, a reduction in Hsp72 mRNA and a 35% reduction in Hsp72 protein content, compared to hearts from adults. Interestingly, myocardial Hsf1 protein content was similar between aged and adult animals. Hearts from heat stressed adult animals (24-h prior) demonstrated an enhanced postischemic recovery as indicated by a greater recovery of left ventricular pressure and rate of contraction (P < 0.05), while hearts from heat stressed aged animals failed to demonstrate an enhanced postischemic recovery. These results suggest that hearts from aged animals exhibit an impaired ability to produce the protective Hsps and thus, may explain, at least in part, the increased susceptibility of aged hearts to stress.
Locke
M
M
School of Physical and Health Education, University of Toronto, Ontario, Canada. Locke@PHE.utoronto.ca
Tanguay
R M
RM
D000375:Aging / Q000378:metabolism*; D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism; D050884:HSP72 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D018869:Heat-Shock Response; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D012333:RNA, Messenger; D051381:Rats; D011916:Rats, Inbred F344; D014157:Transcription Factors / Q000378:metabolism
D004268:DNA-Binding Proteins; D050884:HSP72 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; C000619709:Hsf1 protein, rat; D012333:RNA, Messenger; D014157:Transcription Factors