Heart failure is a major cause of morbidity and mortality. The transient receptor potential canonical (TRPC) family of channels mediate pathologic cardiac remodeling. In particular, TRPC6 participates in a self-propagating circuit that amplifies cardiac hypertrophy and fibrosis. The objective of this study was to explore biventricular expression of TRPCs in advanced heart failure.
Methods: Viable left (LV) and right (RV) ventricular free wall tissue was obtained from human subjects with end-stage heart failure (n=12) referred for transplantation or biventricular assist devices. Control LV and RV tissue was obtained from the National Disease Research Interchange (n=3/group). To explore TRPC expression in a murine model, adult male C57BL/6 mice underwent thoracic aortic constriction (TAC) for 10 weeks (n=6/group). Biventricular tissue was analyzed by real-time polymerase chain reaction.
Results: Compared to normal LV and RV, levels of TRPC 1, 3, 4 and 6 were increased in failing LV and RV samples, respectively. Levels of TRPC1 and TRPC6 were greater in failing RV than failing LV samples. TRPC 5 and 7 expression were not consistently detected in normal or failing tissue samples. Compared to sham LV, levels of TPRC 1, 4 and 6 increased in the LV after TAC. Compared to sham RV, levels of TRPC 3, 4, and 6 increased in the RV after TAC. Levels of TRPC3 were greater in the RV than LV after TAC.
Conclusions: Our results identify distinct profiles of TRPC expression in the RV versus LV in both human tissue and in a murine model of advanced biventricular failure. Levels of select TRPCs are higher in the failing RV compared to LV, suggesting a potentially important role for TRPCs in RV remodeling.