Anti-apoptotic Serpins as Therapeutics in Cardiovascular Diseases

Johan      Kuiper; Paul   H.A.   Quax; Ilze      Bot

Abstract

Acute cardiovascular syndromes such as myocardial infarction and stroke are a major cause of death in the Western society and are generally caused by rupture of an atherosclerotic plaque. Treatment of atherosclerosis, the main underlying cause of acute cardiovascular syndromes, is still inadequate for most of the patients. Therefore, there is a need for new therapeutic strategies in addition to the existing lipid-lowering drugs such as statins. Lipid accumulation, inflammation and matrix degradation are generally considered key processes in the pathogenesis of atherosclerosis and that of plaque rupture. Furthermore, apoptosis or programmed cell death of plaque cells, depending on the disease stage, is thought to be of importance in the development and progression of atherosclerosis and the incidence of acute cardiovascular syndromes. Serine protease inhibitors or so-called serpins have been demonstrated to be involved in both the induction and inhibition of apoptosis and may thus be of interest as therapeutics in cardiovascular diseases such as atherosclerosis. In this review, we will discuss the current knowledge on the role of serpins in cardiovascular diseases with particular emphasis on apoptotic cell death and the potential therapeutic applications.

Keywords: Serpin, atherosclerosis, apoptosis, plaque stability, proteases.