Geranylgeranylacetone induced delayed cardiac preconditioning requires caveolin‐3

Abstract

Geranylgeranylacetone (GGA) is a Japanese, anti-ulcer drug that has been shown to protect the myocardium against ischemia/reperfusion injury via upregulation of heat shock protein (HSP). Furthermore, caveolin-3 (Cav-3) is necessary in delayed anesthetic preconditioning. In this study we investigated the effect of Cav-3 and caveolae on GGA induced delayed cardiac preconditioning. We utilized an in vivo mouse model where mice were exposed to GGA via gavage and allowed to recover for 24 hrs. After 24 hrs of recovery, mice underwent 30-min coronary artery occlusion followed by 2 hrs of reperfusion at which time infarct size was determined. Infarct size as a percent of the area at risk was significantly reduced by GGA in control mice (22.3 ± 3.0% vs. 41.6 ± 3.0%). However, this protection was not observed in Caveolin-3 knockout mice. Furthermore, GGA administration increased caveolae formation and HSP70 expression in control mice, but was ineffective in Cav-3 knockout mice. In conclusion, GGA increases HSP 70 expression and caveolae formation which is dependent on Cav-3 expression.