1. Artemisinin inhibits glycosaminoglycan chain synthesizing gene expression but not proliferation of human vascular smooth muscle cells
- Author
-
Ying Zhou, Salifya Sichone, Suowen Xu, Peter J. Little, Hirushi Kumarapperuma, Zheng Jie Chia, and Danielle Kamato
- Subjects
0301 basic medicine ,Vascular smooth muscle ,medicine.medical_treatment ,Biophysics ,Smad2 Protein ,SMAD ,Biochemistry ,Muscle, Smooth, Vascular ,Cell Line ,Glycosaminoglycan ,03 medical and health sciences ,0302 clinical medicine ,Transforming Growth Factor beta ,Gene expression ,medicine ,Humans ,Glucuronosyltransferase ,Phosphorylation ,Molecular Biology ,Cell Proliferation ,Glycosaminoglycans ,Chemistry ,Biglycan ,Growth factor ,Cell Biology ,Multifunctional Enzymes ,Artemisinins ,Cell biology ,030104 developmental biology ,Gene Expression Regulation ,030220 oncology & carcinogenesis ,N-Acetylgalactosaminyltransferases ,Sulfotransferases ,Transforming growth factor - Abstract
Pleotropic growth factor, transforming growth factor (TGF)-β drives the modification and elongation of glycosaminoglycan (GAG) chains on proteoglycans. Hyperelongated GAG chains bind and trap lipoproteins in the intima leading to the formation of atherosclerotic plaques. We have identified that phosphorylation of Smad2 linker region drives GAG chain modification. The identification of an inhibitor of Smad2 linker region phosphorylation and GAG chain modification signifies a potential therapeutic for cardiovascular diseases. Artemisinin renowned for its potent anti-malarial effects possesses a broad range of biological effects. Our aim was to characterise the anti-atherogenic role of artemisinin in vascular smooth muscle cells (VSMCs). We demonstrate that TGF-β mediated Smad2 linker region phosphorylation and GAG chain elongation was attenuated by artemisinin; however, we observed no effect on VSMC proliferation. Our data demonstrates the potential for artemisinin to be developed as a therapy to inhibit the development of atherosclerosis by prevention of lipid deposition in the vessel wall without affecting the proliferation of VSMCs.
- Published
- 2020