Artemisinin attenuates the development of atherosclerotic lesions by the regulation of vascular smooth muscle cell phenotype switching

Protein deglycase DJ‐1 deficiency induces phenotypic switching in vascular smooth muscle cells and exacerbates atherosclerotic plaque instability

“…Atherosclerosis, the primary cause of cardiovascular disease and the top cause of death globally, is a complex disease initiated by the accumulation of lipids in the subendothelial layer of the arterial wall 1‐4 . The most important clinical consequence of atherosclerosis is acute rupture or erosion of unstable plaques in which vascular smooth muscle cells (VSMCs) constitute the primary cell type; this finding has been verified by lineage‐tracing experiments and single‐cell sequencing 5‐11 . During this pathological process, VSMCs change from a contractile phenotype to a de‐differentiated phenotype (also called a synthetic phenotype), marked by reductions in various unique contractile proteins (eg α‐smooth muscle actin [SMA], calponin1, smooth muscle 22α and smooth muscle myosin heavy chain) and higher rates of migration and proliferation 8,12‐17 .…”

“…[1][2][3][4] The most important clinical consequence of atherosclerosis is acute rupture or erosion of unstable plaques in which vascular smooth muscle cells (VSMCs) constitute the primary cell type; this finding has been verified by lineage-tracing experiments and single-cell sequencing. [5][6][7][8][9][10][11] During this pathological process, VSMCs change from a contractile phenotype to a de-differentiated phenotype (also called a synthetic phenotype), marked by reductions in various unique contractile proteins (eg α-smooth muscle actin…”

The Potential Roles of Artemisinin and Its Derivatives in the Treatment of Type 2 Diabetes Mellitus

“…Abundant evidence shows that after artemisinin therapy, the area of aortic root lesions shrunk, vascular smooth muscle cell hyperplasia and fibrosis were attenuated, and the progression of atherosclerosis lesion formation was diminished, indicating the potential therapeutic effects on atherosclerosis, which is one of the most common manifestations of diabetic cardiovascular disease. Thus, we deduced that artemisinins may alleviate diabetic cardiovascular disease by inhibiting the occurrence and development of atherosclerosis (Wang et al, 2013;Jiang et al, 2016;Du et al, 2019;Cao et al, 2020;Jiang et al, 2020).…”

“…Artemisinin decreases the expression of proliferating cell nuclear antigen (PCNA) and the proliferation and migration of rat vascular smooth muscle cells (VSMCs) (Cao et al, 2015). Du et al provided in vivo and in vitro evidence demonstrating that artemisinin can decrease PDGF-activated MOVAS migration and proliferation and elevate the expression of contractile phenotypic markers (αSMA, SM22 α, calponin 1, and SMMHC), partly by inhibiting the phenotype switching that leads to a dedifferentiated phenotype (Du et al, 2019). Wang's team first found that artesunate can significantly increase the expression of KLF2 protein, which regulates the expression of multiple endothelial vascular protection genes (Wang et al, 2013).…”

“…Since then, semisynthetic derivatives of artemisinin have been gradually developed, including artesunate, artemether, dihydroartemisinin, artelinic acid, and arteether, all of which show great promise in the treatment of malaria (Klayman, 1985;Teja-Isavadharm et al, 2010;Morris et al, 2011;Morris et al, 2013) (Figure 1). As research has progressed, the effects of artemisinin and its derivatives have been greatly extended, and these compounds are widely used in antitumor (Verma et al, 2017;Wang et al, 2017;Wei and Liu, 2017), antifibrosis (Cao et al, 2016;Wang et al, 2019a), immunosuppressive (Li et al, 2013;Hou and Huang, 2016), antivirus (Sharma et al, 2014), antiatherosclerosis (Du et al, 2019;Jiang et al, 2020), antiobesity (Lu et al, 2016), and antidiabetes (Ho et al, 2014) treatments. Recently, increasing evidence has shown that artemisinins have significant therapeutic effects on metabolic diseases, especially diabetes, obesity, and hypercholesterolemia.…”