SUBSTANTIAL DECREASE OF HEAT-SHOCK PROTEIN-90 IN VENTRICULAR TISSUES OF 2 SUDDEN-DEATH PIGS WITH HYPERTROPHIC CARDIOMYOPATHY

We recently developed a pig model with naturally occurring hypertrophi c cardiomyopathy (HCM). To further characterize the biochemical featur es of high frequency of sudden death affected by this disease, the pro tein profiles of ventricular tissues were analyzed on normal, HCM, and HCM with sudden-death pigs. By sodium dodecylsulfate-polyacrylamide g el electrophoresis, a protein corresponding to an apparent molecular m ass of 90 kDa (p90) was found to be markedly decreased in the HCM-affe cted tissues of sudden-death pigs, but not in HCM or normal pigs. Furt her study showed that the primary decrease of p90 in HCM pigs with sud den death was located mainly in the interventricular septum. As determ ined by the molecular mass and isoelectric point on 2-dimensional gels and Western immunoblot with a specific 90 kDa heat shock protein (HSP 90) monoclonal antibody, the unknown protein was identified as HSP90. Our findings indicate for the first time that substantially decreased heart HSP90 is associated with HCM pigs with sudden death. Although th e role that HSP90 may play in protecting pigs with HCM from sudden dea th is still unclear, the model itself may provide further insight into understanding the role of heat shock proteins in cardiac sudden death .