Mouse Cardiac-specific Hsp25Gene Deletion Induced Cardiac Rupture After Myocardial Infarction

Background:Small heat shock proteins (sHsp) are widely expressed in most organisms from bacteria to humans. Heat shock protein27, with the molecular weight of27kD in humans and25kD in rodents, is one of the members of sHsp family. Transgenic mice overexpressing Hsp27have been demonstrated to protect against myocardial infarction and improve cardiac dysfunction. To determine whether a truly causative relationship existed between Hsp25and myocardial infarction, we built the myocardial infarction model in Hsp25knockout (KO) mice and found that cardiac rupture rate of KO increased significantly compared with WT mice. Furthermore, we attempted to elucidate the protective mechanism of Hsp25.Methods:Hsp25knockout (KO) mice and wild-type (WT) littermates were subjected to permanent ligation of left anterior descending coronary artery. Cardiac function was examined by echocardiography. Histological change was checked by fluorescent staining and ultrastructural analysis. Moreover, we examined the expression level of cofilin by Western blot.Results:After MI, the survival rate of KO mice are significantly reduced compared with WT mice, and90%of the KO mice died of cardiac rupture. KO mice has much worse heart function than WT mice and the activity of cofilin is increased compared with WT after myocardial infarction which suggest the actin cytoskeleton of KO is damaged seriously.Conclusions:These results indicate an important role of Hsp25in protecting against cardiac rupture after myocardial infarction.