Evidence That ADAM17 Mediates the Protective Action of CGRP against Angiotensin II-Induced Inflammation in Vascular Smooth Muscle Cells.

Abstract

Calcitonin gene-related peptide (CGRP) has a potent protective action on the cardiovascular system; however, little is known about the role of CGRP in angiotensin II- (Ang II-) induced inflammation of vascular smooth muscle cells (VSMCs). This study is aimed at determining the anti-inflammatory effect of CGRP in Ang II-treated VSMCs and whether a disintegrin and metalloproteinase 17 (ADAM17) modulates this protective action. Small interference RNA (siRNA) and inhibitors of CGRP, epidermal growth factor receptor (EGFR), and extracellular signal-regulated kinase 1/2 (ERK1/2) were adopted to investigate their effect on Ang II-induced inflammation in VSMCs. Here, we found that CGRP could inhibit inflammation and decrease ADAM17 expression and activation of EGFR and ERK1/2 in VSMCs stimulated with Ang II. Results of siRNA demonstrated that ADAM17 siRNA attenuated Ang II-induced inflammation and up-regulation of activities of EGFR and ERK1/2 in VSMCs. Furthermore, the EGFR-ERK1/2 pathway promoted Ang II-induced VSMC inflammation. In summary, these findings identify the anti-inflammatory effect of CGRP in VSMCs stimulated by Ang II and suggest that ADAM17 is involved in the protective effect of CGRP against Ang II-induced inflammation via the EGFR-ERK1/2 pathway in VSMCs.

• Authors: Si-Yu Zeng, Li Yang, Chen-Liang Hong, Hui-Qin Lu, Qiu-Jiang Yan, Yan Chen, Xu-Ping Qin
• Journal: Mediators of inflammation (Mediators Inflamm) Vol. 2018 Pg. 2109352 ( 2018) ISSN: 1466-1861 [Electronic] United States
• PMID: 30046277 (Publication Type: Journal Article)

Chemical References

• RNA, Small Interfering
• Angiotensin II
• ErbB Receptors
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3
• ADAM17 Protein
• Adam17 protein, rat
• Calcitonin Gene-Related Peptide

Topics

• ADAM17 Protein (metabolism)
• Angiotensin II (adverse effects)
• Animals
• Calcitonin Gene-Related Peptide (metabolism)
• Cell Line
• ErbB Receptors (metabolism)
• Inflammation (chemically induced, metabolism)
• Mitogen-Activated Protein Kinase 1 (metabolism)
• Mitogen-Activated Protein Kinase 3 (metabolism)
• Muscle, Smooth, Vascular (cytology)
• Myocytes, Smooth Muscle (metabolism)
• RNA, Small Interfering (metabolism)
• Rats
• Renin-Angiotensin System