EDN1 and hyperhomocysteinemia: For the underlying mechanism of transition process, previous studies have revealed the roles of TGFβ, hypoxia, angiotension II, endothelin-1, IL-6, hyperhomocysteinemia (HHcy), cylindromatosis (CYLD), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (Nox4), and Fizzl (50, 52–55).