Cardiac hypertrophy is considered a necessary compensatory response to increased afterload.
The complex network of signaling pathways governing this response is only now being elucidated. Calcineurin, a calcium and calmodulin-dependent phosphatase, is a central mediator of transcriptional control in the hypertrophic response. In CsA-treated mice, we have observed dramatic inhibition of hypertrophy with no signs of cardiovascular compromise. The CaV1.2a calcium current is significantly upregulated in hypertrophied myocytes, and these changes can be antagonized by calcineurin inhibition with cyclosporine.