@article{Qin_Xie_Li_Zhang_Yan_2021, title={Protective effects of astragaloside IV against hypertension-induced vascular remodeling involves the DNMT1 and TET2 signaling pathway}, volume={73}, url={https://serbiosoc.org.rs/arch/index.php/abs/article/view/6547}, DOI={10.2298/ABS210426024Q}, abstractNote={<p><strong>Paper description:</strong></p> <ul> <li>Astragaloside IV (AS-IV), a triterpene saponin from <em>Astragalus membranaceus</em>, has a beneficial effect in cardiovascular disease.</li> <li>In two-kidney one-clip (2K1C) hypertensive rats, AS-IV: reduced blood pressure; reversed hypertension-induced thoracic media thickness; inhibited DNMT1, MMP2, PCNA; increased SM22α, ACTA2, TET2 expression in the aorta; <em>in vitro</em> it inhibited the proliferation and migration in VSMCs treated with angiotensin II; induced SM22α, ACTA2, TET2; reduced COL-1a, COL-3a, DNMT1, MMP2, PCNA expression; modulated 5-methylcytosine expression<em>.</em></li> <li>AS-IV reversed hypertension-induced vascular remodeling by inhibiting DNMT1, upregulating TET2.</li> <li>Novel insight for As-IV treatment of vascular disease is provided.</li> </ul> <p><strong>Abstract: </strong>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 <em>Astragalus membranaceus</em>, 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 22α protein (SM22α), α-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 SM22α, ACTA2 and TET2, and decreased the expression of collagen Ia (COL-1a), collagen IIIa (COL-3a), DNMT1, MMP2 and PCNA<em> in vitro</em>. 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.</p>}, number={2}, journal={Archives of Biological Sciences}, author={Qin, Yingchun and Xie, Yilin and Li, Aihua and Zhang, Xiaoqin and Yan, Zhiqiang}, year={2021}, month={Jul.}, pages={303–313} }