Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 883, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.ejphar.2020.173384
Keywords
Alamandine; G protein-coupled receptor; Member D; Vascular fibrosis; Vascular smooth muscle cell; p38 MAPK
Categories
Funding
- National Natural Science Foundation of China [81400315, 81627802, 81570247]
- Six Talent Peaks project in Jiangsu Province [2015WSN-29]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
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Alamandine attenuates hypertension and cardiac remodeling in spontaneously hypertensive rats (SHRs). We examined whether alamandine attenuates vascular remodeling in mice, and regulates angiotensin II (Ang II)induced fibrosis in rat vascular smooth muscle cells (VSMCs). Alamandine attenuated hypertension in mice induced by Ang II. Ang II increased the fibrosis of thoracic aorta in mice, which was attenuated by alamandine treatment. Increased levels of collagen I, transforming growth factor-beta (TGF-beta), and connective tissue growth factor (CTGF) levels in thoracic aortas after Ang II treatment in mice were inhibited by alamandine. Ang II-stimulated collagen I, TGF-beta, and CTGF level increases were inhibited by alamandine in rat VSMCs. This could be reversed by Mas-related G protein-coupled receptor, member D (MrgD) antagonist D-Pro(7) -Ang-(1-7) but not Mas receptor antagonist A779. MrgD expression was increased in the thoracic aortas of mice or VSMCs treatment with Ang II. Ang II increased p-p38 and cAMP levels in rat VSMCs, and alamandine blocked Ang II-induced these increases. Cyclic adenosine monophosphate (cAMP) reversed the inhibitory effects of alamandine on the Ang II-induced increases in collagen I, TGF-beta, and CTGF levels. These results demonstrate alamandine attenuates vascular fibrosis by stimulating MrgD expression and decreases arterial fibrosis by blocking p-p38 expression. Alamandine/MrgD axis is a potential target for the treatment of vascular remodeling.
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