The phytoantitoxin resveratrol is a plant-derived polyphenol with phytoestrogenic properties. Resveratrol protects the cardiovascular system by mechanisms that include defense against ischemic-reperfusion injury, promotion of vasorelaxation, protection and maintenance of intact endothelium, anti-atherosclerotic properties, inhibition of low-density lipoprotein oxidation, suppression of platelet aggregation, and estrogen-like actions. The purpose of this article is to review the mechanisms of these effects.

BackgroundEndoplasmic reticulum (ER) stress-mediated phenotypic switching of vascular smooth muscle cells (VSMCs) is key to vascular calci cation (VC) in patients with chronic kidney disease (CKD). Terpinen-4-ol exerts protective effect against cardiovascular disease, but its role and speci c mechanism in VC remain unclear. We explored whether terpinen-4-ol alleviates ER stress-mediated VC through sirtuin 1 (sirt1) and elucidated its mechanism to provide evidence for its application in the clinical prevention and treatment of VC. MethodsIn this study, CKD-related VC animal model and β-glycerophosphate (β-GP)-induced VSMCs calci cation model were established. We investigated the part of terpinen-4-ol in ER stress-induced VC in vitro and in vivo. However, in order to clarify whether terpinen-4-ol inhibits the molecular mechanism of ERs-induced VC through sirt1, we further veri ed the above signal transduction by knocking down sirt1 in vitro and in vivo. ResultsTerpinen-4-ol inhibited calcium deposition, phenotypic switching, and ER stress of VSMCs in vitro and in vivo. Furthermore, pre-incubation with terpinen-4-ol or a sirt1 agonist and transfection with lentivirus overexpressing sirt1 decreased β-GP-induced calcium salt deposition, increased sirt1 protein level, and inhibited PERK-eIF2α-ATF4 pathway activation in VSMCs, thus, alleviating VC. The opposite results were obtained in sirt1-knockdown models. Moreover, sirt1 physically interacted with and deacetylated PERK.Mass spectrometry analysis identi ed lysine K889 as the acetylation site of sirt1, which regulates PERK.Finally, inhibition of sirt1 reduced the effect of terpinen-4-ol on the deacetylation of PERK in vitro and in vivo and weakened the inhibitory effect of terpinen-4-ol against ER stress-mediated VC. ConclusionsTerpinen-4-ol inhibits the post-transcriptional modi cation of PERK at the lysine K889 acetylation site by upregulating sirt1 expression level, thereby ameliorating VC by regulating ER stress. This provides evidence of the molecular mechanism of terpinen-4-ol, which supports its development as a promising therapeutic agent for CKD-VC.

:Essential oil from fructus of Alpinia zerumbet (EOFAZ) protects vascular endothelial cell (VEC) injury. Stimulation and injury factors can induce phenotypic changes in VECs and the occurrence of endothelial-mesenchymal transformation (EndMT), accelerating the occurrence and development of cardiovascular diseases. We investigated the role of EOFAZ in EndMT induced by transforming growth factor-β1 (TGF-β1). All experiments were performed using human umbilical vein endothelial cells (HUVECs). HUVECs were preincubated with EOFAZ for 2 hours and then coincubated with TGF-β1 for 72 hours. Krüpple-like factor 4 (KLF4) was inhibited by small interfering RNA or overexpressed by adenovirus infection. Wound healing, transwell, and angiogenesis assays were used to evaluate the migration ability of HUVECs. Quantitative RT-PCR and Western blotting were used for mRNA and protein expression analyses, respectively. Immunofluorescence staining was used to detect expression of related markers. A coimmunoprecipitation assay verified the interaction between KLF4 and acetylated histone H3. TGF-β1 contributed to EndMT in HUVECs in a time-dependent manner, mainly manifested as an increase in cell migration ability and changes in the expression of EndMT-related mRNAs and proteins. EOFAZ could inhibit EndMT induced by TGF-β1. The results after transfection with siKLF4 were similar to those of EOFAZ treatment. After EOFAZ treatment, the expression of KLF4 and acetylated histone H3 decreased, and protein interactions between them decreased, while expression of the Notch/Snail signal axis decreased. EOFAZ can attenuate endothelial injuries and suppress EndMT in HUVECs under TGF-β1 stimulation conditions because it may downregulate KLF4, decrease histone H3 acetylation, and inhibit the transduction of the Notch/Snail signaling axis.