HSPA12B Attenuated Acute Myocardial Ischemia/reperfusion Injury via Maintaining Endothelial Integrity in a PI3K/Akt/mTOR-dependent Mechanism.

Endothelial damage is a critical mediator of myocardial ischemia/reperfusion (I/R) injury. is an endothelial-cell-specifically expressed heat shock protein. However, the roles of Hduanyu184212B in acute myocardial I/R injury is unknown. Here we reported that myocardial I/R upregulated Hduanyu184212B expression in ventricular tissues, and endothelial overexpression of Hduanyu184212B in transgenic mice (Tg) limited infarct size, attenuated cardiac dysfunction and improved cardiomyocyte survival compared with their wild type littermates. These improvements were accompanied with the diminished myocardial no-reflow phenomenon, decreased microvascular leakage, and better maintained endothelial tight junctions. The I/R-evoked neutrophil infiltration was also suppressed in Tg hearts compared with its wild type (WT) littermates. Moreover, Tg hearts exhibited the enhanced activation of PI3K/Akt//mTOR signaling following I/R challenge. However, pharmacological inhibition of PI3K abolished the cardioprotection against myocardial I/R injury. The data demonstrate for the first time that the endothelial Hduanyu184212B protected hearts against myocardial I/R injury. This cardioprotective action of Hduanyu184212B was mediated, at least in part, by improving endothelial integrity in a PI3K/Akt/mTOR-dependent mechanism. Our study suggests that targeting endothelial Hduanyu184212B could be an alternative approach for the management of patients with myocardial I/R injury.

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