Effects of arginine vasopressin on differentiation of cardiac fibroblasts into myofibroblasts.
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.
Yan-Hong
Fan
F
Department of Cardiology, Xijing Hospital, The Fourth Military Medical University, Xi'an, PR China.
Hui
Dong
D
Qing
Pan
P
Lei
Shang
S
Hai-Chang
Wang
W
Wei
Zhang
Z
Yan-Jie
Cao
C
D000199:Actins / Q000096:biosynthesis; D000818:Animals; D000831:Animals, Newborn; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects* / Q000473:pathology; D009206:Myocardium / Q000166:cytology* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017483:Receptors, Vasopressin / Q000502:physiology*; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis* / Q000378:metabolism
D000199:Actins; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin; D003094:Collagen; D017483:Receptors, Vasopressin; D053773:Transforming Growth Factor beta1; C498862:Acta2 protein, rat; C025043:vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-