ATTENUATION OF HEAT-SHOCK-PROTEIN EXPRESSION BY CORONARY-OCCLUSION INHYPERTROPHIED HEARTS

Hearts hypertrophied by pressure-overload are more susceptible to isch emia than nonhypertrophied hearts, which may result from the attenuati on of self-protective responses. Because heat shock proteins (HSPs) ar e reported to protect against ischemic injuries, we hypothesized that HSP expression by coronary occlusion may be attenuated in hypertrophie d hearts. We banded the ascending aorta to develop ventricular hypertr ophy 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 an d nonischemic myocardial tissues were obtained after the snare was tig htly tied, and dye was infused from the aorta. The mRNAs and protein o f 72-kDa HSP (HSP 72) and/or 73-kDa HSP (HSP 73) were detected by Nort hern and Western blot analyses. Protein and mRNA levels of HSPs expres sed by 5-min coronary occlusion in hypertrophied hearts (left ventricu lar weight, 577 +/- 16 mg) were lower compared with those in control h earts (462 +/- 9 mg). A longer period of coronary occlusion (10 min) e levated the attenuated expression to a level similar to that in contro l hearts. Treatment with an angiotensin-converting enzyme (ACE) inhibi tor (cilazapril, 10-15 mg.kg(-1).day(-1)) for 4 wk preserved HSP mRNA expression even in hearts with ascending aortic banding. In hypertroph ied hearts, HSP 72 and 73 expression by coronary occlusion was attenua ted and was modulated by the duration of coronary occlusion and by ACE inhibitor treatment.