Zedoarondiol inhibits atherosclerosis by regulating monocyte migration and adhesion via CXCL12/CXCR4 pathway. (August 2022)

• Record Type: Journal Article
• Authors: Chai, Hua; Qu, Hua; He, Shan; Song, Lei; Yang, Yu; Huang, Hongbo; Shi, Dazhuo
• Is Part Of: Pharmacological research. Volume 182(2022)
• Publication Date: 2022-08
• Subjects: AS atherosclerosis -- THP-1 human monocytic macrophage-like cell line -- scRNA-seq single-cell RNA sequencing analysis -- CXCL12/CXCR4 CXC chemokine ligand 12/CXC chemokine receptor 4 -- PI3K phosphoinositide 3-kinase -- AKT protein kinase B -- NF/κB nuclear factor-kappa B; Zedoarondiol -- Atherosclerosis -- Monocyte -- Migration -- Adhesion -- Single-cell RNA sequencing; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2022.106328
• Languages: English
• ISSNs: 1043-6618

Abstract

Abstract: Atherosclerosis (AS) is an essential pathological changes of ischemic cardio-cerebrovascular disease, and monocyte migration and adhesion to endothelial cells are the critical pathological process in AS. Our previous studies demonstrated a beneficial effect of zedoarondiol in AS, but whether the mechanism is associated with monocyte migration and adhesion to endothelial cells remains unclear. In this study, we investigated whether the anti-atherosclerotic effects of zedoarondiol were associated with decreasing migration and adhesion of monocytes. The oil red O staining demonstrated that zedoarondiol ameliorated AS plaques in en face aorta and aortic root of apolipoprotein E gene knocked (apoE -/- ) mice. In vitro, zedoarondiol decreased human monocytic macrophage-like cell line (THP-1) monocytes migration and adhesion to endothelial cells. Single-cell RNA sequencing analysis (scRNA-seq) in mice indicated that zedoarondiol decreased monocytes adhesion to endothelial cells by regulating CXC chemokine ligand 12/CXC chemokine receptor 4 (CXCL12/CXCR4) pathway, which was verified by Western blot of THP-1 monocytes；zedoarondiol also decreased the expressions of phosphoinositide 3-kinase (PI3K), protein kinase B (AKT) and nuclear factor-kappa B (NF/κB), the downstream proteins of CXCL12/CXCR4 pathway. In conclusion, zedoarondiol ameliorated AS plaque and inhibited monocyte migration and adhesion to endothelial cells via regulating CXCL12/CXCR4 pathway, suggesting that zedoarondiol might be a new promising drug for AS. Graphical Abstract: ga1 Highlights: Zedoarondiol decreased the AS plaques of ApoE -/- mice, and the mechanisms were predicted by scRNA-seq. Zedoarondiol inhibited monocyte migration and adhesion to the endothelial cells via regulating CXCL12/CXCR4 pathway.