Summary of studies implicating BRAF in cardiac hypertrophy and fibrosis
Heart targeted knockout studies have implicated BRAF in pathological hypertrophy and interstitial fibrosis. These studies were performed on male mice only and a sex difference was not studied. Divergent results were reported for the loss of BRAF on physiological hypertrophy in male versus female mice, but these results are complicated by a reduction in RAF1 in male mice only. Expression of a targeted knockin activated BRAF mutant was found to induce hypertrophy associated with an increase in markers of pathological hypertrophy, although contractility/cardiac function improved. Pharmacological activation of BRAF (the RAF paradox via Type 1 RAF inhibitors) had similar effects with the exception of pathological gene expression. Inexplicably, pharmacological activation of BRAF attenuated Ang II-induced pathological hypertrophy (as assessed by gene expression) and improved cardiac contractility/function. None of the gain-in-function studies for BRAF enhanced cardiac fibrosis, although loss of BRAF attenuated fibrosis under pathological conditions. Red text indicates pathological hypertrophy. The symbol ‘*’ indicates that only gene expression was reported. Contractility denotes contractility and/or cardiac function.