Published Online
on November 17, 2003

A more recent version of this article appeared on December 16, 2003

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Submitted on May 28, 2003
Revised on August 4, 2003
Accepted on August 7, 2003

Heat Shock Transcription Factor 1 Protects Cardiomyocytes From Ischemia/Reperfusion Injury

Yunzeng Zou MD, PhD, Weidong Zhu MD, PhD, Masaya Sakamoto MD, Yingjie Qin MD, Hiroshi Akazawa MD, Haruhiro Toko MD, PhD, Miho Mizukami MD, Norihiko Takeda MD, Tohru Minamino MD, PhD, Hiroyuki Takano MD, PhD, Toshio Nagai MD, PhD, Akira Nakai MD, PhD, and Issei Komuro MD, PhD^*

From the Department of Cardiovascular Science and Medicine (Y.Z., W.Z., M.S., Y.Q., H.A., H.T., M.M., T.M., H.T., T.N., I.K.), Chiba University Graduate School of Medicine, Chiba; Department of Cardiovascular Medicine (N.T.), University of Tokyo Graduate School of Medicine, Tokyo; and Department of Bio-Signal Analysis, Applied Medical Engineering Science (A.N.), Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan.

^* To whom correspondence should be addressed. E-mail: komuro-tky{at}umin.ac.jp.

Background--Because cardiomyocyte death causes heart failure, it is important to find the molecules that protect cardiomyocytes from death. The death trap is a useful method to identify cell-protective genes.

Methods and Results--In this study, we isolated the heat shock transcription factor 1 (HSF1) as a protective molecule by the death trap method. Cell death induced by hydrogen peroxide was prevented by overexpression of HSF1 in COS7 cells. Thermal preconditioning at 42°C for 60 minutes activated HSF1, which played a critical role in survival of cardiomyocytes from oxidative stress. In the heart of transgenic mice overexpressing a constitutively active form of HSF1, ischemia followed by reperfusion-induced ST-segment elevation in ECG was recovered faster, infarct size was smaller, and cardiomyocyte death was less than wild-type mice. Protein kinase B/Akt was more strongly activated, whereas Jun N-terminal kinase and caspase 3 were less activated in transgenic hearts than wild-type ones.

Conclusions--These results suggest that HSF1 protects cardiomyocytes from death at least in part through activation of Akt and inactivation of Jun N-terminal kinase and caspase 3.

Key words: ischemia • reperfusion • survival

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