Overexpression of calpastatin ameliorates functional recovery from ischemic injury in the rat heart

Abstract

Calpain, a Ca(2+)-dependent cytosolic cystein protease, is as an important key protease involved in the ischemic reperfusion injury such as cardiac stunning. Myocardial stunning is a postischemic reversible contractile dysfunction of the heart. It was hypothesized that overexpression of calpastatin, an endogenous calpain inhibitor, would attenuate the ischemia/reperfusion injury in the heart. Rat hearts were transfected with human calpastatin gene incorporated into adenovirus vectors. The hearts infected with adenovirus containing lacZ gene were used as controls. The hearts after transfection were heterotopically transplanted into the abdomens of recipient rats and excised on the fourth day after the surgery. The functional recovery from 30-min global ischemia was studied in the isolated hearts perfused in-vitro. The recovery of left ventricular developed pressure, max dP/dt, and min dP/dt during 60-min reperfusion was significantly greater in the calpastatin transfected group than control group heart by gene transfer. Adenovirus-mediated overexpression of calpastatin could be a novel biological storage to improve heart transplantation by minimizing ischemia/reperfusion injury.