SGLT2 Inhibitor Ameliorates Smooth-Muscle Cell Proliferation via Endothelial Microparticles Stimulated by Indoxyl Sulfate

Background: Endothelial microparticles (EMPs) are closely associated with vascular dysfunction. Recent research has revealed a link between SGLT2 inhibition and improved endothelial functions. We investigated the effects of SGLT2 inhibitors (SGLT2i) on EMP generation from indoxyl sulfate-stimulated endothelial cells and their impact on smooth muscle cell (SMC) proliferation. Methods: We measured CD31+CD42-EMP counts by flow cytometry in supernatants of human umbilical vein endothelial cells (HUVECs) incubated with indoxyl sulfate. We examined the EMP responses to SGLT2i by incubating EMPs from indoxyl sulfate-stimulated HUVECs with or without SGLT2i. Results: 1. Indoxyl sulfate induced EMP release in HUVECs. 2. SGLT2i inhibited EMP generation induced by indoxyl sulfate. 3. The EMPs induced by indoxyl sulfate stimulated smooth muscle cell proliferation, and this effect was reversed by treatment with SGLT2i. Conclusion: SGLT2 inhibitor ameliorates smooth muscle cell proliferation via endothelial microparticles stimulated by indoxyl sulfate. SGLT2i could be a treatment option for neointimal hyperplasia in vascular access stenosis.