Molecular mechanisms of methylglyoxal-induced aortic endothelial dysfunction in human vascular endothelial cells

• DOI: 10.1038/s41419-020-2602-1
• Publication Date: 2020-05-28T11:04:29Z
• Authors: Jae Hyuk Lee; Amna Parveen; Moon Ho Do; Min Cheol Kang; Silvia Yumnam; Sun Yeou Kim
• Keywords: Endothelial Dysfunction

Abstract Methylglyoxal (MGO)-induced cellular apoptosis, oxidative stress, inflammation, and AGE formation are specific events that induce vascular endothelial cell (EC) toxicity in dysfunction (ED). MGO accumulates quickly various tissues plays a prominent role the pathogeneses of several diabetic complications. Unbalanced angiogenesis is gateway to development EC apoptosis autophagy work together regulate by interacting with different angiogenic factors. In addition understanding deep mechanism regarding MGO-dependent autophagy/apoptosis may provide new therapeutic applications treat diabetes Therefore, present study aimed investigate regulatory effects MGO-induced on HAoEC elucidate molecular mechanisms discover target base therapy for MGO-stimulated HAoEC, protein expression was identified using western blot, autophagosomes were observed bio-transmission electron microscopy (TEM), autophagic vacuoles flux measured confocal microscope. We found significantly induced autophagy, declined pro-angiogenic effect, decreased proliferation, migration, tube-like structures, increased vacuoles, dose-dependent manner. death inhibited ROS-mediated Akt/mTOR signaling pathway. also triggered elevating cleaved caspase-3 Bax/Bcl-2 ratio through activation MAPKs (p-JNK, p-p38, p-ERK) Collectively, these findings suggest inhibit via pathways, respectively, when treated MGO.