TRPC6 inhibitor BI 749327 improved cardiac function and reduced chamber dilation and fibrosis in models of cardiac and renal disease.
Does the TRPC6 antagonist BI 749327 improve cardiac function and reduce fibrosis in murine models of pressure overload and renal obstruction?
Pharmacological inhibition of TRPC6 with the novel, orally bioavailable antagonist BI 749327 ameliorates cardiac dysfunction and reduces fibrosis in murine models of pressure overload and renal injury.
Absolute Event Rate: 0% vs 0%
Significance Transient receptor potential canonical 6 (TRPC6) is an important mediator of pathological hypertrophy and fibrosis, contributing to renal and cardiac disease. However, no selective TRPC6 inhibitor with in vivo efficacy has been developed and tested to determine if nongenetic channel suppression ameliorates disease in intact animals. We developed and tested an orally bioavailable TRPC6-specific inhibitor, BI 749327, revealing its capacity to improve cardiac function and reduce chamber dilation and fibrosis in the context of abnormal hemodynamic stress. Similarly, BI 749327 suppressed myofibroblast activation and fibrosis in a renal disease model. These data support BI 749327 as a representative of a therapeutic class for treating cardiac and renal disease and provide a tool for studying the biological function of TRPC6.
Lin et al. (Fri,) reported a other. TRPC6 inhibitor BI 749327 improved cardiac function and reduced chamber dilation and fibrosis in models of cardiac and renal disease.