| First Author | Zhang H | Year | 2010 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 30 |
| Issue | 11 | Pages | 2156-63 |
| PubMed ID | 20814014 | Mgi Jnum | J:182099 |
| Mgi Id | MGI:5314711 | Doi | 10.1161/ATVBAHA.110.214700 |
| Citation | Zhang H, et al. (2010) Coronary and aortic endothelial function affected by feedback between adiponectin and tumor necrosis factor alpha in type 2 diabetic mice. Arterioscler Thromb Vasc Biol 30(11):2156-63 |
| abstractText | OBJECTIVE: To verify that adiponectin and tumor necrosis factor (TNF)-alpha reciprocally regulate their expression, thereby synergistically affecting both coronary and aortic endothelial dysfunction in type 2 diabetic mice. METHODS AND RESULTS: We examined endothelium-dependent and endothelium-independent vasodilation/vasorelaxation of coronary arterioles and aortas in control mice, diabetic mice (Lepr(db)), and Lepr(db) treated with adiponectin or neutralizing antibody to TNF-alpha (anti-TNF-alpha). Endothelium-dependent vasodilation to acetylcholine in both coronary arterioles and aortas was blunted in Lepr(db) compared with control mice. Endothelium-independent vasodilation to sodium nitroprusside was comparable. Adiponectin and anti-TNF-alpha improved acetylcholine-induced vasodilation of coronary arterioles and aortas in Lepr(db) without affecting dilator response to sodium nitroprusside. Adiponectin protein expression was significantly reduced, and TNF-alpha protein expression was significantly greater, in coronary arterioles and aortas of Lepr(db) compared with control mice. Immunofluorescence staining results indicate that adiponectin was colocalized with endothelial cells. Anti-TNF-alpha treatment upregulated adiponectin protein expression in Lepr(db) coronary arterioles and aortas. Adiponectin administration reduced TNF-alpha protein expression in Lepr(db). Although adiponectin receptor 1 protein expression in coronary arterioles and aortas was similar between control and diabetic mice, adiponectin receptor 2 protein expression was significantly reduced in Lepr(db). Both adiponectin and anti-TNF-alpha inhibited IkappaBalpha phosphorylation and nuclear factor kappaB protein expression in Lepr(db), suggesting that adiponectin and TNF-alpha signaling may converge on nuclear factor kappaB to reciprocally regulate their expression. CONCLUSIONS: A reciprocal suppression occurs between adiponectin and TNF-alpha that fundamentally affects the regulation of coronary and aortic endothelial function in type 2 diabetic mice. |
