Open AccessProtective effects of astragaloside IV against hypertension-induced vascular remodeling involves the DNMT1 and TET2 signaling pathway
Author(s) -
Yuan Qin,
Yilin Xie,
Aihua Li,
Xiaoqin Zhang,
Zhiqiang Yan
Publication year - 2021
Publication title -
archives of biological sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.217
H-Index - 25
eISSN - 1821-4339
pISSN - 0354-4664
DOI - 10.2298/abs210426024q
Subject(s) - vascular smooth muscle , proliferating cell nuclear antigen , gene knockdown , downregulation and upregulation , dnmt1 , angiotensin ii , matrix metalloproteinase , chemistry , vascular remodelling in the embryo , mmp2 , endocrinology , cell growth , medicine , microbiology and biotechnology , biology , blood pressure , apoptosis , gene expression , biochemistry , dna methylation , smooth muscle , gene
Proliferation, migration, and the phenotypic switch of vascular smooth muscle cells (VSMCs) play an important role in vascular remodeling induced by hypertension. Astragaloside IV (AS-IV), the active ingredient of Astragalus membranaceus, has been shown to exert a beneficial role in cardiovascular disease. The present study aimed to investigate the mechanism responsible for the protective effects of AS-IV on hypertension-induced vascular remodeling. AS-IV significantly reduced blood pressure and aortic media thickness in two-kidney, one-clip (2K1C) hypertensive rats. AS-IV administration downregulated the expression levels of DNA methyltransferase1 (DNMT1), matrix metalloproteinase (MMP2) and proliferating cell nuclear antigen (PCNA) and upregulated the expression of smooth muscle 22? protein (SM22?), ?-smooth muscle actin (ACTA2) and ten-eleven translocation 2 (TET2) in the aorta of hypertensive rats. AS-IV inhibited the proliferation and migration in VSMCs treated with angiotensin II (Ang II). AS-IV increased the expression of SM22?, ACTA2 and TET2, and decreased the expression of collagen Ia (COL-1a), collagen IIIa (COL-3a), DNMT1, MMP2 and PCNA in vitro. Reduction in 5-methylcytosine (5-mC) was observed in VSMCs treated with AS-IV. Knockdown of DNMT1 induced the expression of TET2, while the level of DNMT1 did not change after knockdown of TET2. These results suggest that AS-IV reversed hypertension-induced vascular remodeling by inhibiting DNMT1 and upregulating TET2.