Open AccessInhibition of p38 Mitogen-Activated Protein Kinase Improves Nitric Oxide–Mediated Vasodilatation and Reduces Inflammation in Hypercholesterolemia
Author(s) -
Joseph Cheriyan,
David J. Webb,
Lea SarovBlat,
Maysoon Elkhawad,
Sheila J. Wallace,
Kaisa Mäki-Petäjä,
David Collier,
John M. Morgan,
Zixing Fang,
Robert N. Willette,
John J. Lepore,
John R. Cockcroft,
Dennis L. Sprecher,
Ian B. Wilkinson
Publication year - 2011
Publication title -
circulation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.795
H-Index - 607
eISSN - 1524-4539
pISSN - 0009-7322
DOI - 10.1161/circulationaha.110.971986
Subject(s) - medicine , nitric oxide , inflammation , protein kinase a , p38 mitogen activated protein kinases , vasodilation , mitogen activated protein kinase , pharmacology , kinase , endocrinology , microbiology and biotechnology , biology
Oxidized low-density lipoprotein reduces endothelial nitric oxide production (an important mediator of vasoregulation) and activates p38 mitogen-activated protein kinase (MAPK), a mediator of vascular inflammation. Animal models of vascular stress have previously predicted improvements in vascular function after p38 MAPK inhibition. We hypothesized that a selective p38α/β MAPK inhibitor (losmapimod; GW856553) would improve compromised nitric oxide-mediated vasoregulation in patients with hypercholesterolemia.