| 20164786 |
Yan-Hong F, Hui D, Qing P, Lei S, Hai-Chang W, Wei Z, Yan-Jie C: Effects of Arginine Vasopressin on Differentiation of Cardiac Fibroblasts into Myofibroblasts. J Cardiovasc Pharmacol. 2010 Feb 13.
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. In the present study, the effects of AVP on differentiation of CFs into myofibroblasts were examined by the expression of myofibroblastic marker, alpha-smooth muscle actin (alpha-SMA), and collagen synthesis. The roles of AVP V1a receptor and transforming growth factor-beta1 (TGF-beta1) in the differentiation were also analyzed. The results showed that 10 mol/L AVP increased alpha-SMA expression and collagen synthesis significantly, and this effect was blocked by [d (CH2) 5Tyr (Me)] AVP, a AVP V1a receptor specific antagonist, 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) 5Tyr2 (Me)] AVP. However, the maximum production of biological active TGF-beta1 induced by AVP is far less than the dose of exogenous TGF-beta1 needed to induce CFs-myofibroblasts transformation. These results suggested that AVP can induce CFs-myofibroblasts 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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