Dafeng Yang, Stefan Haemmig, Haoyang Zhou, Daniel Pérez-Cremades, Xinghui Sun, Lei Chen, Jie Li, Jorge Haneo-Mejia, Tianlun Yang, Ivana Hollan, Mark W Feinberg
Endothelial cell (EC) activation is an early hallmark in the pathogenesis of chronic vascular diseases. MicroRNA-181b ( Mir181b ) is an important anti-inflammatory mediator in the vascular endothelium affecting endotoxemia, atherosclerosis, and insulin resistance. Herein, we identify that the drug methotrexate (MTX) and its downstream metabolite adenosine exert anti-inflammatory effects in the vascular endothelium by targeting and activating Mir181b expression. Both systemic and endothelial-specific Mir181a2b2 -deficient mice develop vascular inflammation, white adipose tissue (WAT) inflammation, and insulin resistance in a diet-induced obesity model...
January 8, 2021: ELife