Project Description

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

Lu XY, Chen L, Cai XL, Yang HT


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 overexpressiondecreased the interaction between µ-calpain (a proteasemediating proteolysis of cTnI and cTnT) and cTnI or cTnT underI/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.