Effects of geranylgeranylacetone upon cardiovascular diseases

Heat shock proteins (HSPs) are an important family of protective proteins. They are involved actively in an array of cellular processes, including protective effects on the cardiovascular system in response to various stimuli. Increasing evidence shows that pharmacologic interventions that induce expression of HSPs may be a novel approach for the treatment of cardiovascular diseases. However, agents that induce expression of HSPs used previously are toxic or have harmful side effects, which limit their clinical application. Geranylgeranylacetone (GGA) is not only a widely used antiulcer agent in Asia, but also a nontoxic inducer of HSPs expression. It increases the expression of HSPs rapidly in the presence of ischemia, anoxia, oxidative stress, and toxicants, thereby having significant protective effects. The cardioprotective effects of GGA have been corroborated by experiments in vivo and in vitro. Importantly, several derivatives of GGA have been synthesized that have improved pharmaco-chemical and HSPs-boosting properties. In this review, the current knowledge and potential cardioprotective mechanisms of GGA are summarized comprehensively. We discuss the protective effects of GGA in cardiovascular diseases and myocardial injury induced by physical or chemical injury. Currently available information suggests that GGA could be employed as a novel pharmacologic intervention against cardiovascular disease.