Aortic Remodelling Is Improved by 2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-glucoside Involving the Smad3 Pathway in Spontaneously Hypertensive Rats

Abstract

Hypertension is a common health problem that substantially increases the risk of cardiovascular disease. The condition increases blood pressure, which causes alterations in vascular structure and leads to the development of vascular pathologies. 2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-glucoside (THSG), a resveratrol analogue extracted from a Chinese medicinal plant, has been proven to have numerous vascular protection functions. This study investigated whether THSG can improve vascular remodeling, which has thus far remained unclear. Orally administering THSG to spontaneously hypertensive rats (SHRs) aged 12 weeks for 14 weeks significantly inhibited intima-media thickness in the lower parts of the aortic arch, increased the vascular diastolic rate in response to acetylcholine, and reduced remodelling-related mRNA expression, such as that of ACTA2, CCL3, COL1A2, COL3A1, TIMP1 WISP2, IGFBP1, ECE1, KLF5, MYL1 BMP4, FN1, and PAI-1. Immunofluorescence staining also showed an inhibitory effect similar to that of THSG on PAI-1 protein expression in rat aortas. Results from immunoprecipitation and a Western blot assay showed that THSG inhibited the acetylation of Smad3. A chromatin immunoprecipitation assay showed that THSG prevented Smad3 binding to the PAI-1 proximal promoter in SHR aortas. In conclusion, our results demonstrated that the inhibitory effect of THSG on aortic remodelling involved the deacetylating role of Smad3 with increasing blood flow and with constant blood pressure.

The natural compound 2,3,5,4′‐tetrahydroxystilbene‐2‐O‐β‐d glucoside protects against adriamycin‐induced nephropathy through activating the Nrf2‐Keap1 antioxidant pathway

“…THSG can inhibit TGF‐β protein expression in rat cardiac stem cells . THSG also inhibited the acetylation of SMAD3 and suppressed FN and COL1A2, COL3A1 expression in spontaneously hypertensive rats . Our current data had also supported the potential anti‐fibrotic activities of THSG.…”

Vascular smooth muscle cells direct extracellular dysregulation in aortic stiffening of hypertensive rats

“…Compared to WKY, SHR TA VSMCs showed a higher level of mRNA level of collagen types I and III, the two predominant isoforms of collagen in the aorta, which indicates an increase in collagen synthesis in VSMCs from stiffer aortas. The TIMP1/MMP ratio was also significantly increased in SHR TA VSMCs vs. WKY TA VSMCs, which were consistent with the previous observation of aortic tissues in SHRs (Duan et al., 2015). Since TIMP1 is a well‐recognized inhibitor of MMPs, which participate in collagen degradation (Duan et al., 2015), this increase in TIMP‐1 induced by SHR aortic VSMCs might contribute to the unfavorable collagen accumulation in the aortic wall (Zhou, Lee, Stoll, Ma, Wiener, et al 2017).…”

“…The TIMP1/MMP ratio was also significantly increased in SHR TA VSMCs vs. WKY TA VSMCs, which were consistent with the previous observation of aortic tissues in SHRs (Duan et al., 2015). Since TIMP1 is a well‐recognized inhibitor of MMPs, which participate in collagen degradation (Duan et al., 2015), this increase in TIMP‐1 induced by SHR aortic VSMCs might contribute to the unfavorable collagen accumulation in the aortic wall (Zhou, Lee, Stoll, Ma, Wiener, et al 2017). In addition, using the 3D reconstituted model, we revealed that SHR TA VSMCs induced collagen disarray in both orientation and fragmentation.…”

Tetrahydroxystilbene Glycoside Improves Microvascular Endothelial Dysfunction and Ameliorates Obesity-Associated Hypertension in Obese ZDF Rats Via Inhibition of Endothelial Autophagy

“…2, 3,5, 4’-tetrahydroxystilbene-2-O- β -D-glycoside (TSG) is the main bioactive ingredient extracted from the traditional Chinese medicinal herb Polygonum multiflorum Thunb which has been used safely in China for approximately two millennia, and has been reported to have a wide spectrum of pharmacologic functions. TSG has been reported to help people live longer [18], protect impaired neural networks [19], improve blood flow [20], attenuate inflammatory responses [21], prevent the production of oxygen radicals and protect against oxidized LDL-induced endothelial dysfunction [22]. Previously, we demonstrated that TSG inhibits lysophosphatidylcholine (LPC)-induced apoptosis of human umbilical vein endothelial cells (HUVECs) by activating glutathione peroxidase and superoxide dismutase, clearing intracellular reactive oxygen species (ROS), and reducing lipid peroxidation [21, 23].…”