Attenuation of heat shock protein expression by coronary occlusion in hypertrophied hearts.
Hearts hypertrophied by pressure-overload are more susceptible to ischemia than nonhypertrophied hearts, which may result from the attenuation of self-protective responses. Because heat shock proteins (HSPs) are reported to protect against ischemic injuries, we hypothesized that HSP expression by coronary occlusion may be attenuated in hypertrophied hearts. We banded the ascending aorta to develop ventricular hypertrophy and put a snare around the left coronary artery in rats. After 4 wk, coronary occlusion was applied by tightening the snare for 5 or 10 min in rats with and without aortic banding. The hearts were excised 0, 0.5, 1, 2, 4, 8, 12, and 24 h after coronary occlusion. Ischemic and nonischemic myocardial tissues were obtained after the snare was tightly tied, and dye was infused from the aorta. The mRNAs and protein of 72-kDa HSP (HSP 72) and/or 73-kDa HSP (HSP 73) were detected by Northern and Western blot analyses. Protein and mRNA levels of HSPs expressed by 5-min coronary occlusion in hypertrophied hearts (left ventricular weight, 577 +/- 16 mg) were lower compared with those in control hearts (462 +/- 9 mg). A longer period of coronary occlusion (10 min) elevated the attenuated expression to a level similar to that in control hearts. Treatment with an angiotensin-converting enzyme (ACE) inhibitor (cilazapril, 10-15 mg.kg(-1).day(-1)) for 4 wk preserved HSP mRNA expression even in hearts with ascending aortic banding. In hypertrophied hearts, HSP 72 and 73 expression by coronary occlusion was attenuated and was modulated by the duration of coronary occlusion and by ACE inhibitor treatment.
Tajima
M
M
First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Isoyama
S
S
Nitta
Y
Y
Abe
K
K
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001835:Body Weight; D006332:Cardiomegaly / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D017315:Cilazapril / Q000494:pharmacology; D003327:Coronary Disease / Q000378:metabolism* / Q000473:pathology; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009929:Organ Size; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D002352:Carrier Proteins; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C494373:Hspa8 protein, rat; D012333:RNA, Messenger; D017315:Cilazapril