Figure 8.

Flow chart showing oxidative stress signaling pathways for H₂O₂ (panel A) and ATII (panel B) in isolated ventricular myocytes and whole normal and fibrotic hearts. While EADs are readily induced by the proposed oxidative signaling pathways in the isolated ventricular myocytes, the initiation of EADs and VT/VF in the whole heart is restricted only to structurally remodeled heart with increased fibrosis. Induction of fibrosis by either H₂O₂ or ATII promotes EADs in isolated cardiac myocytes however, at the whole heart level only the presence of enhanced cardiac fibrosis could lead to propagated EADs by the mechanism of triggered activity leading to VT/VF. ASK1 is apoptosis signaling kinase 1, is a member of mitogen-activated protein kinase kinase kinase family that activates JNK (c-Jun N-terminal kinase) and p38 kinase (p38 mitogen-activated kinase) eventually initiating transcription causing hypertrophy and fibrosis.