Figure 3.

p38 in heart failure and cardiac arrhythmia. p38 activation participates in the development of heart failure and cardiac arrhythmia through three main mechanisms: (A) Increased cardiac fibrosis by induction of TNF-α and IL-6 in cardiomyocytes, differentiation of fibroblasts, and induction of TGF-β in cardiac myofibroblasts; (B) Reduced cardiac contractility due to dephosphorylation of a-tropomyosin and troponin I via PP2C-α/PP2C-β; (C) Promotion of cardiac arrhythmias due to reduced expression and activity of SERCA2 (Atp2a2), increased expression of NCX1 (Ncx1) and Cx43 (Cnx43), and altered Cx43 phosphorylation, inducing cardiac contractile dysfunction and altered action potential propagation. ↑ increase, ↓ decrease.