SMAD2 and Myocardial fibrosis: TMZ has been shown to alleviate myocardial fibrosis in several preclinical studies by modulating the mitogen-activated protein kinase (MAPK) pathway16, downregulating the protein expression of Collagen Ι, Collagen III, Connective tissue growth factor (CTGF)17, reducing gene expression of CTGF, TGF-β1, smad2 and smad332.