Schematic representation of the conclusions from this study
AngII-induced hypertension activates Raf kinases (BRAF and RAF1) in the heart whether directly (particularly in cardiac non-myocytes such as fibroblasts) or indirectly (cardiomyocytes potentially respond to factors released by non-myocytes). Raf kinases signal through the ERK1/2 cascade to promote changes in gene expression and induce phenotypic responses. In cardiomyocytes, this promotes cardiomyocyte hypertrophy to combat increased workload. AngII also increases cardiac inflammation and activates Raf signalling in cardiac non-myocytes promoting cell proliferation and fibrosis. Increased cardiac fibrosis increases the workload on the heart causing further cardiomyocyte hypertrophy. Over time, this leads to pathological remodelling of the hearts that can lead to hypertensive heart disease and failure. Raf inhibitors such as dabrafenib inhibit Raf signalling in both cardiomyocytes and cardiac non-myocytes, reducing cardiac inflammation and fibrosis, reducing cardiomyocyte hypertrophy, and protecting the heart from hypertensive heart disease; ERK, extracellular signal-regulated kinase; MKK, mitogen-activated protein kinase kinase.