HSP27保护心肌作用研究的新发现

由中科院健康所杨黄恬研究员带领的分子心脏学课题组发现，HSP27能明显改善缺血后的心肌收缩功能，此作用至少部分与其和肌钙蛋白I与T的相互作用，从而防止肌钙蛋白I与T被降解，改善肌丝钙敏感性有关。

心肌梗塞等缺血性心肌损伤及由此导致的心力衰竭是现代社会常见疾病和主要致死病因。缺血/复灌后心肌收缩抑顿与肌丝蛋白降解导致的肌丝钙敏感性下降密切相关。热休克蛋白27（heat shock protein 27，HSP27）在保护心肌抵抗应激损伤过程中起着十分重要的作用，但在缺血损伤时对肌丝的确切作用尚不清。

新研究发现不仅揭示了HSP27的新作用，并提示hsp27在治疗心肌缺血性损伤改善心功能中的重要价值。这一研究结果发表在《心血管研究》（Cardiovasc Res. 2008 Apr 25）

Cardiovascular Research，doi:10.1093/cvr/cvn091，Xi-Yuan Lu, Le Chen, Xiao-Long Cai and Huang-Tian Yang

Overexpression of heat shock protein 27 protects against ischaemia/reperfusion-induced cardiac dysfunction via stabilization of troponin I and T

Xi-Yuan Lu, Le Chen, Xiao-Long Cai and Huang-Tian Yang*

Laboratory of Molecular Cardiology, Institute of Health Sciences (IHS), Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) and Shanghai Jiao Tong University School of Medicine (SJTUSM), 225 Chong Qing Nan Rd, Build. No. 1 of Institute of Health Sciences, Rm. 613, Shanghai 200025, China

^* Corresponding author. Tel: +86 21 63852593; fax: +86 21 63852593. E-mail address: htyang@sibs.ac.cn

Aims: Heat shock protein 27 (Hsp27) renders cardioprotection from ischaemia/reperfusion (I/R) injury, but little is known about its role in myofilaments. We proposed that increased expression of Hsp27 may improve post-ischaemic contractile dysfunction by preventing I/R-induced cardiac troponin I (cTnI) and troponin T (cTnT) degradation.

Methods and results: Adenovirus-mediated Hsp27 overexpression improved contractile function in perfused rat hearts subjected to global no-flow I/R (30-min/30-min). Such improvement was further confirmed in Hsp27-overexpressing cardiomyocytes subjected to simulated I/R (20-min/30-min). Moreover, these cells showed restored myofilament response to Ca²⁺ but not intracellular Ca²⁺ transients. The protection correlated with attenuation of I/R-induced cTnI and cTnT degradation. Confocal microscopy revealed co-localization of Hsp27 with these proteins. Co-immunoprecipitation and pull-down assays further confirmed that Hsp27 interacted with the COOH-terminus of cTnI and the NH₂-terminus of cTnT and that Hsp27 overexpression decreased the interaction between µ-calpain (a protease mediating proteolysis of cTnI and cTnT) and cTnI or cTnT under I/R.

Conclusion: The findings reveal a novel role of Hsp27 in the protection of cTnI and cTnT from I/R-induced degradation by preventing their proteolytic cleavage via interacting with these proteins. Such protection may result in restored post-ischaemic myofilament response to Ca²⁺ and improved post-ischaemic contractile function.