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Attenuation of heat shock protein expression by coronary occlusion in hypertrophied hearts
1First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Insights
Pressure-overloaded hearts show reduced heat shock protein (HSP) expression during coronary occlusion. This attenuated response, particularly in hypertrophied hearts, can be improved by longer occlusion or ACE inhibitor treatment, suggesting a protective mechanism.
Area of Science:
- Cardiovascular Physiology
- Molecular Biology
- Proteomics
Background:
- Pressure-overloaded hearts exhibit increased susceptibility to ischemia.
- Heat shock proteins (HSPs) are known to confer protection against ischemic injury.
- The expression of HSPs in hypertrophied hearts during ischemic events remains unclear.
Purpose of the Study:
- To investigate the hypothesis that heat shock protein (HSP) expression is attenuated in pressure-overloaded, hypertrophied hearts during coronary occlusion.
- To determine the effect of occlusion duration and angiotensin-converting enzyme (ACE) inhibitor treatment on HSP expression in these hearts.
Main Methods:
- Ventricular hypertrophy was induced in rats via ascending aortic banding.
- Coronary artery occlusion was performed for 5 or 10 minutes.
- Messenger RNA (mRNA) and protein levels of HSP 72 and HSP 73 were quantified using Northern and Western blot analyses.
- Hearts were analyzed at various time points post-occlusion.
Main Results:
- Hypertrophied hearts showed significantly lower HSP 72 and HSP 73 mRNA and protein levels after 5 minutes of coronary occlusion compared to control hearts.
- A 10-minute occlusion period increased HSP expression in hypertrophied hearts to levels comparable to controls.
- Treatment with an ACE inhibitor (cilazapril) for 4 weeks maintained normal HSP mRNA expression in banded, hypertrophied hearts.
Conclusions:
- Coronary occlusion-induced HSP expression is attenuated in pressure-overloaded, hypertrophied hearts.
- The duration of coronary occlusion and ACE inhibitor treatment can modulate this attenuated HSP response.
- These findings suggest that impaired HSP expression may contribute to the increased ischemic susceptibility of hypertrophied hearts.
Abstract:
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.