Our previous study demonstrated that
periostin, an
extracellular matrix protein, plays an important role in
left ventricular remodeling through the inhibition of cell-cell interactions. Because the gene regulation of
periostin has not yet been examined, we focused on the effects of
angiotensin (Ang) II and mechanical stretch, because Ang II and mechanical stretch are related to cardiac remodeling after
myocardial infarction. First, we examined the effects of Ang II on
periostin in myocytes and fibroblasts in vitro. Ang II significantly increased
periostin through
phosphatidylinositol 3-kinase,
c-Jun N-terminal kinase, p38, and
extracellular signal-regulated kinase 1/2 pathways in myocytes and fibroblasts (P<0.05). On the other hand, mechanical stretch also significantly increased
periostin expression (P<0.05). This increase was inhibited partially, but significantly, by an Ang II receptor blocker,
valsartan, and inhibited almost completely by
valsartan with the neutralization
antibodies for
transforming growth factor-beta and
platelet-derived growth factor-BB (P<0.05). Therefore, we further examined
periostin expression in vivo.
Periostin expression was significantly increased in infarcted myocardium (P<0.05), and treatment with
valsartan significantly attenuated it at 4 weeks after
myocardial infarction (P<0.05), accompanied by a significant improvement in cardiac dysfunction (P<0.05). Overall, the present study demonstrated that Ang II, as well as mechanical stretch, stimulated
periostin expression in both cardiac myocytes and fibroblasts, whereas
valsartan significantly attenuated the increase in
periostin expression. The inhibition of
periostin by
valsartan might especially contribute to its beneficial effects on cardiac remodeling after
myocardial infarction.