Abstract
The pathophysiological role of periostin (POSTN), expression of which is increased in right ventricles of monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) model rats, has not been clarified. We investigated the effect of POSTN on inducible nitric oxide synthase (iNOS) expression, which causes cardiac dysfunction, in right ventricular fibroblasts (RVFbs). PAH model rats were produced by an intraperitoneal injection with MCT (60 mg/kg). In RVFbs isolated from PAH model rats, the iNOS expression and phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, c-Jun N-terminal kinase (JNK) and nuclear factor (NF)-kB were higher than RVFbs isolated from control rats. Recombinant POSTN increased iNOS expression and NO production in RVFbs isolated from normal rats, which were prevented by a pharmacological inhibition of ERK1/2, JNK or NF-kB. The culture medium of recombinant POSTN-stimulated RVFbs suppressed L-type Ca2+ channel (LTCC) activity in H9c2 cardiomyoblasts. We demonstrated that POSTN increased iNOS expression and subsequent NO production in RVFbs. The enhanced NO production in RVFbs might be associated with the right ventricular dysfunction via the suppression of LTCC activity of cardiomyocytes in PAH.
