The hydrogen sulfide donor, GYY4137, exhibits anti‐atherosclerotic activity in high fat fed apolipoprotein E−/− mice

• DOI: 10.1111/bph.12246
• Publication Date: 2013-05-28T11:27:11Z
• Authors: Zhen Liu; Yi Han; Ling Li; Hui Lu; Guoliang Meng; Xiaozhen Li; Mohammed Shirhan; Meng Teng Peh; Liping Xie; Suming Zhou; Xiaowei Wang; Qi Chen; Weilu Dai; Choon‐Hong Tan; Shiyang Pan; Philip K Moore; Yong Ji
• Keywords: Scavenger Receptor; Monocyte

Atherosclerosis is associated with reduced vascular hydrogen sulfide (H2 S) biosynthesis. GYY4137 a novel slow-releasing H2 S compound that may effectively mimic the time course of release in vivo. However, it not known whether affects atherosclerosis.RAW 264.7 cells and human blood monocyte-derived macrophages were incubated oxidized low density lipoprotein (ox-LDL) with/without GYY4137. ApoE(-/-) mice fed high-fat diet for 4 weeks administered 30 days. Lipid atherosclerotic lesions measured by oil red O staining. Endothelium-dependent relaxation was assessed response to acetylcholine. Superoxide production detected dihydroethidium Expression mRNA protein evaluated quantitative real-time PCR Western blot.GYY4137 inhibited ox-LDL-induced foam cell formation cholesterol esterification cultured cells. decreased expression lectin-like ox-LDL receptor-1, iNOS, phosphorylated IκBα, NF-κB, ICAM-1, VCAM-1 chemokines, including CXCL2, CXCR4, CXCL10 CCL17, but increased scavenger CD36, ox-LDL-treated RAW In vivo, aortic plaque partially restored endothelium-dependent apoE(-/-) mice. TNF-α IL-6 as well superoxide (O2 (-) ) generation aorta. addition, eNOS phosphorylation PI3K, enhanced Akt Ser(473) down-regulated LOX-1.GYY4137 inhibits lipid accumulation induced inflammation oxidative stress, improved endothelial function