Department of Endocrinology, Institute of Endocrine and Metabolic Diseases, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Clinical Research Hospital of Chinese Academy of Sciences (Hefei), University of Science and Technology of China, Hefei 230001, China.
Department of Medical Biotechnology, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
Nutrients. 2022 Oct 27;14(21):4518. doi: 10.3390/nu14214518.
Atherosclerosis is a chronic inflammatory vascular disease in which endothelial cells play an important role in maintaining vascular homeostasis. Endotheliitis caused by endothelial dysfunction (ED) is the key cause for the development of cardiovascular and cerebrovascular diseases as well as other vascular system diseases. Resveratrol (RES), a multi-functional polyphenol present in edible plants and fruits, prevents cardiovascular disease by regulating a variety of athero-relevant signaling pathways. By transcriptome profiling of RES-treated human umbilical vein endothelial cells (HUVECs) and in-depth bioinformatic analysis, we observed that differentially expressed genes (DEGs) were enriched in KEGG pathways of fluid shear stress and atherosclerosis, suggesting that the RES may serve as a good template for a shear stress mimetic drug that hold promise in combating atherosclerosis. A heat map and multiple datasets superimposed screening revealed that RES significantly down-regulated phosphatase and actin modulator 1 (PHACTR1), a pivotal coronary artery disease risk gene associated with endothelial inflammation and polyvascular diseases. We further demonstrate that RES down-regulated the gene and protein expression of PHACTR1 and inhibited TNF-α-induced adhesion of THP-1 monocytes to activated endothelial cells via suppressing the expression of PHACTR1. Taken together, our study reveals that PHACTR1 represents a new molecular target for RES to maintain endothelial cell homeostasis and prevent atherosclerotic cardiovascular disease.
动脉粥样硬化是一种慢性炎症性血管疾病，其中内皮细胞在维持血管稳态方面发挥着重要作用。内皮功能障碍（ED）引起的内皮炎症是心血管和脑血管疾病以及其他血管系统疾病发展的关键原因。白藜芦醇（RES）是一种存在于食用植物和水果中的多功能多酚，通过调节多种动脉粥样硬化相关信号通路来预防心血管疾病。通过对 RES 处理的人脐静脉内皮细胞（HUVEC）进行转录组谱分析和深入的生物信息学分析，我们观察到差异表达基因（DEGs）在流体切应力和动脉粥样硬化的 KEGG 途径中富集，这表明 RES 可能是一种良好的切应力模拟药物模板，有望用于对抗动脉粥样硬化。热图和多个数据集叠加筛选显示，RES 显著下调了磷酸酶和肌动蛋白调节剂 1（PHACTR1），这是一个与内皮炎症和多血管疾病相关的冠心病风险基因。我们进一步证明 RES 通过抑制 PHACTR1 的表达下调了 PHACTR1 的基因和蛋白表达，并抑制了 TNF-α诱导的 THP-1 单核细胞与激活的内皮细胞的黏附。综上所述，我们的研究表明 PHACTR1 是 RES 维持内皮细胞稳态和预防动脉粥样硬化性心血管疾病的新分子靶标。
