Mitogen and Stress-Activated Kinases 1 and 2 Mediate Endothelial Dysfunction

Inflammation promotes endothelial dysfunction, but the underlying mechanisms remain poorly defined in vivo. Using translational vascular function testing myocardial infarction patients, a situation where inflammation is prevalent, and knock-out (KO) mouse models we demonstrate role for mitogen-activated-protein-kinases (MAPKs) dysfunction. Myocardial significantly lowers mitogen stress kinase 1/2 (MSK1/2) expression peripheral blood mononuclear cells diminished function. To further understand of MSK1/2 developed vivo animal to assess responses vasoactive drugs using laser Doppler imaging. Genetic deficiency mice increased plasma levels pro-inflammatory cytokines promoted through attenuated production nitric oxide (NO), which were exacerbated by cholesterol feeding. are activated toll-like receptors MyD88. MyD88 KO showed preserved reduced cytokine expression, despite significant hypercholesterolemia. kinases interact with MAPK-activated proteins 2/3 (MAPKAP2/3), limit synthesis. Cholesterol-fed MAPKAP2/3 preservation plays development dysfunction may provide novel target intervention reduce inflammation. Activation could preserve vasodilator before disease.