Genome-Wide Transcriptional Profiling Reveals PHACTR1 as a Novel Molecular Target of Resveratrol in Endothelial Homeostasis.
Meiming SuWenqi ZhaoYujie LiHong LiJianping WengJian-Ping WengPublished in: Nutrients (2022)
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.
Keyphrases
- endothelial cells
- cardiovascular disease
- genome wide
- high glucose
- dna methylation
- coronary artery disease
- single cell
- transcription factor
- vascular endothelial growth factor
- copy number
- signaling pathway
- type diabetes
- gene expression
- emergency department
- cardiovascular events
- rna seq
- genome wide identification
- cardiovascular risk factors
- poor prognosis
- rheumatoid arthritis
- drug induced
- heart failure
- optical coherence tomography
- cell migration
- long non coding rna
- left ventricular
- cell proliferation
- escherichia coli
- coronary artery bypass grafting
- deep learning
- biofilm formation
- pi k akt
- staphylococcus aureus
- artificial intelligence
- electronic health record
- stress induced
- transcatheter aortic valve replacement
- protein kinase
- heat shock