Cross‐talk between angiotensin II and IGF‐1‐induced connexin 43 expression in human saphenous vein smooth muscle cells

• Published in: Journal of cellular and molecular medicine 2011-08, Vol.15 (8), p.1695-1702
• Main Authors: Jia, Guanghong, Aggarwal, Anshu, Yohannes, Amanuel, Gangahar, Deepak M., Agrawal, Devendra K.
• Format: Article
• Language: English
• Subjects: Activator protein 1; Aged; Angioplasty; Angiotensin; Angiotensin II; Angiotensin II - pharmacology; Antibodies; Atherosclerosis; Blotting, Western; Cell cycle; Cell proliferation; Cells, Cultured; Connexin 43; Connexin 43 - metabolism; connexins; Coronary artery; Dose-Response Relationship, Drug; Flow Cytometry; Humans; Hyperplasia; Insulin-like growth factor I; Insulin-Like Growth Factor I - pharmacology; Insulin-like growth factor I receptors; Insulin-like growth factors; intimal hyperplasia; Kinases; Middle Aged; Mitogen-Activated Protein Kinase 1 - genetics; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - genetics; Mitogen-Activated Protein Kinase 3 - metabolism; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; Myocytes, Smooth Muscle - drug effects; Myocytes, Smooth Muscle - metabolism; Pathogenesis; Phosphorylation; Phosphorylation - drug effects; Protein expression; Proteins; Receptor Cross-Talk - drug effects; Receptor, Angiotensin, Type 1 - genetics; Receptor, Angiotensin, Type 1 - metabolism; Receptor, IGF Type 1 - genetics; Receptor, IGF Type 1 - metabolism; Restenosis; RNA Interference; Saphenous Vein - cytology; Saphenous Vein - drug effects; Saphenous Vein - metabolism; Signal transduction; siRNA; Smooth muscle; Statistical analysis; Time Factors; Transcription activation; Transcription Factor AP-2 - genetics; Transcription Factor AP-2 - metabolism; Transcription factors; Up-Regulation - drug effects; vascular smooth muscle cells; vein graft disease; Veins & arteries
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/j.1582-4934.2010.01161.x

Vascular restenosis following coronary artery bypass graft can cause major clinical complications due to intimal hyperplasia in venous conduits. However, the precise underlying mechanisms of intimal hyperplasia are still unclear. We have recently reported that increased expression of connexin43 (Cx43) is involved in the proliferation of vascular smooth muscle cells (SMCs) in human saphenous vein (SV). In this study, we investigated the signalling transduction pathway involved in Cx43 expression and SV SMC proliferation. Angiotensin‐II (AT‐II, 100 ng/ml) increased AT‐II receptor 1 (AT‐1R) protein expression and insulin‐like growth factor‐1 (IGF‐1) (100 ng/ml) up‐regulated IGF‐1 receptor (IGF‐1R) protein expression in SV SMCs. Interestingly, AT‐1R expression was also increased by IGF‐1 treatment, and IGF‐1R expression was increased by AT‐II treatment, which was blocked by siRNA‐IGF‐1R and siRNA‐AT‐1R, respectively. Furthermore, the effect of AT‐II and IGF‐1 signal cross‐talk i nducing up‐regulation of their reciprocal receptors was blocked by siRNA against extracellular signal‐regulated kinases 1/2 (Erk 1/2) in SMCs of SV. Moreover, AT‐II and IGF‐1‐induced Cx43 expression via phosphorylation of Erk 1/2 and activation of transcription factor activator protein 1 (AP‐1) through their reciprocal receptors in SV SMCs. These data demonstrate a cross‐talk between IGF‐1R and AT‐1R in AT‐II and IGF‐1‐induced Cx43 expression in SV SMCs involving Erk 1/2 and downstream activation of the AP‐1 transcription factor.