Caspase-3 as a therapeutic target for heart failure.

INTRODUCTION

Heart failure is a condition with significant morbidity and high mortality. It is likely to become unmanageable in the rapidly increasing aging population, due mainly to lack of effective treatment. Apoptosis is one of the major mechanisms causing cardiomyocyte loss in the failing hearts of both human patients and animal models. Thus, anti-apoptosis has been proposed as a provocative new concept for preventive and therapeutic strategies for heart failure.

AREAS COVERED

This review summarizes evidence that apoptotic cells in heart are not completely committed to death. They are likely to be targeted for reversing the cardiac dysfunction. Drugs that inhibit the progression of apoptosis help restore systolic function, reverse remodeling or even prevent heart failure. Inhibitors of caspase-3, the major executors of apoptosis, have been shown to hold great promises for apoptosis interruption in heart tissues.

EXPERT OPINION

Although the underlying cause and the pathophysiological role of apoptosis remain elusive, antiapoptotic therapy has emerged as an enigma for heart failure. Caspases promote the progressive loss of contractile function in heart failure by facilitating the degradation of myofibrillar proteins. Selective inhibition of the proteolytic functions of caspase-3 may represent an attractive approach to attenuate or reverse heart failure.