This upregulation is driven by the activation of the AP-1 pathway and an independent NF-κB pathway, which subsequently enhances the expression of iNOS through activation of the ERK1/2 and JNK pathways.381 The medium derived from periostin-induced RVFs inhibits L-type Ca2+ channel activity in CMs through NO production.381 This implies that NO generation involving the MAPK pathway may contribute to contractile dysfunction in RV failure associated with PAH. The gene discussed is FOS; the disease is pulmonary arterial hypertension.