NOTCH4 and heart failure: Therefore, elevated level of Klf6 may play a role in cardiac-specific fibrosis; iv) Notch4, a 230 kDa Notch signaling receptor, is significantly elevated in heart failure and may play a role in myocardial matrix remodeling [55], indicating elevated levels of Notch4 in PAI-1 knockout hearts may have a positive role in cardiac fibrogenesis; v) Egr1, a target of TGF-ß-induced ERK1/2 MAP kinase signaling, plays a significant role in fibrogenesis [28]–[31].