Cardiac fibrosis is integral in chronic heart disease, and one of the cellular processes contributing to cardiac fibrosis is endothelial-to-mesenchymal transition (EndMT). We recently found that hypoxia efficiently induces human coronary artery endothelial cells (HCAEC) to undergo EndMT through a hypoxia inducible factor-1α (HIF1α)-dependent pathway. Promoter hypermethylation of Ras-Gap-like protein 1 (RASAL1) has also been recently associated with EndMT progression and cardiac fibrosis. Our findings suggest that HIF1α and transforming growth factor (TGF)/SMAD signalling pathways synergistically regulate hypoxia-induced EndMT through both DNMT3a-mediated hypermethylation of RASAL1 promoter and direct SNAIL induction. The findings indicate that multiple cascades may be activated simultaneously to mediate hypoxia-induced EndMT.
Keywords: DNMT3a; EndMT; RASAL1; hypoxia; methylation.
© 2016 Federation of European Biochemical Societies.