Key result
TRPC6 inhibitor BI 749327 improves cardiac function and reduces fibrosis in cardiorenal disease models.
Why the study?
No selective TRPC6 inhibitor with in vivo efficacy had been developed and tested to evaluate whether nongenetic channel suppression ameliorates disease in intact animals.
Does the TRPC6 antagonist BI 749327 improve cardiac function and reduce fibrosis in murine models of pressure overload and renal obstruction?
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.
Supports advancing TRPC6 inhibitors toward trials; leaves open translation beyond murine cardiac and renal models.
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.
No takes yet. Share an insight, caveat, or question.
Lin et al. (2019) studied this question. TRPC6 inhibitor BI 749327 improved cardiac function and reduced chamber dilation and fibrosis in models of cardiac and renal disease.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: