Angiotensin II promotes an osteoblast-like phenotype in porcine aortic valve myofibroblasts

• Published in: Aging clinical and experimental research Vol. 28; no. 2; pp. 181 - 187
• Main Authors: Xie, Cuihong, Shen, Yingnian, Hu, Weilin, Chen, Zhengping, Li, Yongsheng
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01-04-2016; Springer Nature B.V
• Subjects: Actins - metabolism; Alkaline Phosphatase - metabolism; Angiotensin II - metabolism; Angiotensin II - pharmacology; Angiotensin II Type 1 Receptor Blockers - pharmacology; Animals; Aortic Valve - pathology; Bone Morphogenetic Protein 2 - metabolism; Calcification; Calcinosis - metabolism; Cell Transdifferentiation - drug effects; Cells, Cultured; Gene expression; Genotype & phenotype; Geriatrics/Gerontology; Medicine; Medicine & Public Health; Myofibroblasts - drug effects; Myofibroblasts - metabolism; Original Article; Osteoblasts - physiology; Phenotype; Swine; Valsartan - pharmacology; Wnt Signaling Pathway - drug effects; Wnt Signaling Pathway - physiology; Valvular calcification; Angiotensin II; Myofibroblast; Wnt/β-Catenin
• ISSN: 1720-8319; 1594-0667; 1720-8319
• DOI: 10.1007/s40520-015-0408-2

Objectives
The mechanisms for pathogenesis of cardiac valve calcification were explored by studying the regulation of the Wnt signaling pathway during the transformation from cardiac valvular myofibroblasts to osteoblast-like phenotype.
Methods
Studies were carried on primary cultured porcine aortic valvular myofibroblasts. The cells were randomly divided into four groups and treated with angiotensin II (Ang II) according to the following: Ang II (10
−6
mol/l), Valsartan (Val) (10
−5
mol/l), Ang II plus Val (Ang II 10
−6
mol/l + Val 10
−5
mol/l) or mock treated as the control. Protein expression of Bone morphogenetic protein 2 (BMP2), Alkaline phosphatase (ALP), and Wnt pathway components, Wnt3a and β-catenin, was investigated to assess the activation of the Wnt signaling pathway and determine whether cells undergo the transformation to osteoblast-like phenotype.
Result
Ang II treatment of myofibroblasts led to significant up-regulation of α-SMA expression and activation of the cells. Neither the BMP2 or ALP proteins, nor the mRNA was detectable in the control group or the Val-treated group; however, there was a significant increase in Ang II-treated group (
P
 < 0.01). The Wnt/β-catenin signaling ligand, Wnt3a, was not expressed in the control or Val-treated groups, whereas in Ang II-treated cells, both Wnt3a and β-catenin gene expression were enhanced (
P
 < 0.01).The effect of Ang II can be inhibited by the addition of Val (
P
 < 0.05).
Conclusion
Ang II might act on the Ang II receptor on valvular interstitial cells (VICs) and lead to activation of the Wnt/β-catenin pathway and hence cause the activation, differentiation and proliferation of myofibroblasts, and finally, osteoblast-like phenotype transformation, leading to calcification of heart valves.