Effects of arginine vasopressin on differentiation of cardiac fibroblasts into myofibroblasts.
2010
BACKGROUND: Differentiation of cardiac fibroblasts (CFs) into myofibroblasts is a critical event in the initiation of myocardial fibrosis (MF). Previous studies have shown that arginine vasopressin (AVP) facilitates MF. However, the effects of AVP on CFs-myofibroblasts transformation, and its possible mechanisms are still unknown. METHODS: CFs obtained from neonatal Sprague-Dawley rats were stimulated with AVP in the absence or presence of AVP V1a receptor specific antagonist [d(CH2)5Tyr(Me)]AVP. CFs-myofibroblast transformation was detected by expression of alpha-smooth muscle actin (alpha-SMA) and collagen synthesis. Western bolt and immunofluorescent staining were used to detect expression of alpha-SMA, [H]Proline incorporation was used to detect collagen synthesis. AVP-induced transforming growth factor-beta1 (TGF-beta1) secretion was detected by enzyme-linked immunosorbent assay. CFs was also stimulated with exogenous TGF-beta1 to find out the required dose to induce CFs-myofibroblast transformation. RESULTS: 10 mol/L AVP increased alpha-SMA expression and collagen synthesis significantly, and this effect was blocked by [d(CH2)5Tyr(Me)]AVP at the concentration of 10 mol/L. Meanwhile, AVP significantly increased TGF-beta1 secretion of CFs in a dose-dependent manner, and this effect was also blocked by 10 mol/L [d(CH2)5Tyr(Me)]AVP. However, the maximum production of biologic active TGF-beta1 induced by AVP is far less than the dose of exogenous TGF-beta1 needed to induce CFs-myofibroblast transformation. CONCLUSIONS: AVP can induce CFs-myofibroblast transformation via its V1a receptor, AVP-induced increase of TGF-beta1 synthesis, which also is mediated by V1a receptor, may play a minor role in the transformation. Inducing differentiation of CFs into myofibroblasts may be a mechanism of AVP contributing to MF.
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