Pharmacological inhibition of EZH2 by GSK126 decreases atherosclerosis by modulating foam cell formation and monocyte adhesion in apolipoprotein E-deficient mice

xlomafota13 shared this article with you from Inoreader Pharmacological inhibition of EZH2 by GSK126 decreases atherosclerosis by modulating foam cell formation and monocyte adhesion in apolipoprotein E-deficient mice Via Experimental and therapeutic medicine Exp Ther Med. 2021 Aug;22(2):841. doi: 10.3892/etm.2021.10273. Epub 2021 Jun 6. ABSTRACT Histone modifications play an important role in the occurrence and development of atherosclerosis in human and atherosclerosis-prone mice. Histone methylation in macrophages, monocytes and endothelial cells markedly influence the progression of atherosclerosis. However, it remains unclear whether treatment with a histone methyltransferase enhancer of zeste homolog 2 (EZH2) inhibitor may suppress atherosclerosis. The present study aimed to determine the effects of the EZH2 inhibitor, GSK126, on the suppression and regression of atherosclerosis in apolipoprotein E-deficient mouse models. In vitro, it was found that pharmacological inhibition of EZH2 by GSK126 markedly reduced lipid transportation and monocyte adhesion during atherogenesis, predominantly through increasing the expression levels of ATP-binding cassette transporter A1 and suppres sing vascular cell adhesion molecule 1 in human THP-1 cells. In vivo, it was found that atherosclerotic plaques in GSK126-treated mice were significantly decreased when comparing with the vehicle-treated animals. These results indicated that the GSK126 has the ability to attenuate the progression of atherosclerosis by reducing macrophage foam cell formation and monocyte adhesion in cell and mouse models. In conclusion, the present study provided new insights into the molecular mechanism behind the action of GSK126 and suggested its therapeutic potential for the treatment of atherosclerosis. PMID:34149887 | PMC:PMC8210282 | DOI:10.3892/etm.2021.10273 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.