Knockdown of Long Non-coding RNA-MALAT1 Ameliorates Diabetic Lower Limb Atherosclerotic Disease Through...

We observed the expression of long non-coding RNA (lncRNA) MALAT1 and microRNA (miR)-17-5p in patients with diabetic lower extremity atherosclerosis (LEAD) and EA. hy926 human endothelial cells (EA. Hy926 cells). We further investigated whether knockdown of MALAT1 (sh-MALAT1) could protect endothelial cells and improve the occurrence of atherosclerosis through miR-17-5p, aiming to dissect the underlying mechanism. Patients with type 2 diabetes were stratified into two groups: those with lower extremity atherosclerotic lesions (LEAD group) and those without (T2DM group). For in vitro studies, EA. hy926 cell cultures were treated with high glucose concentrations and transfected. The mRNA expression levels of MALAT1 and miR-17-5p were accessed. The relationship between molecules was verified by double luciferase assay. Biological function was evaluated using lactate dehydrogenase (LDH) assay, Hoechst 33342/propidium iodide (PI) fluorescence staining, and Western blotting. MALAT1 was highly expressed and miR-17-5p was lowly expressed in both peripheral blood samples from LEAD patients and high glucose-cultured endothelial cells. Knockdown of MALAT1 (sh-MALAT1) or miR-17-5p mimic attenuated the release of LDH, the levels of pyroptosis-associated protein, and the number of PI-positive cells in high glucose-treated endothelial cells, while the miR-17-5p inhibitors had the opposite effect. The dual-luciferase assay determined that miR-17-5p is a downstream target of MALAT1. Finally, co-transfection with sh-MALAT1 and miR-17-5p inhibitors attenuated the protective effect of silenced MALAT1 on high glucose-mediated endothelial cell pyroptosis. MALAT1 may play an essential role in high glucose-induced endothelial cell pyroptosis by regulating miR-17-5p.