OBJECTIVE: To verify that adiponectin and tumor necrosis factor (TNF)-α 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-α (anti-TNF-α). 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-α 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-α 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-α treatment upregulated adiponectin protein expression in Lepr(db) coronary arterioles and aortas. Adiponectin administration reduced TNF-α 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-α inhibited IκBα phosphorylation and nuclear factor κB protein expression in Lepr(db), suggesting that adiponectin and TNF-α signaling may converge on nuclear factor κB to reciprocally regulate their expression. CONCLUSIONS: A reciprocal suppression occurs between adiponectin and TNF-α that fundamentally affects the regulation of coronary and aortic endothelial function in type 2 diabetic mice.
OBJECTIVE: To verify that adiponectin and tumor necrosis factor (TNF)-α reciprocally regulate their expression, thereby synergistically affecting both coronary and aortic endothelial dysfunction in type 2 diabeticmice. METHODS AND RESULTS: We examined endothelium-dependent and endothelium-independent vasodilation/vasorelaxation of coronary arterioles and aortas in control mice, diabeticmice (Lepr(db)), and Lepr(db) treated with adiponectin or neutralizing antibody to TNF-α (anti-TNF-α). 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-α 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-α 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-α treatment upregulated adiponectin protein expression in Lepr(db) coronary arterioles and aortas. Adiponectin administration reduced TNF-α protein expression in Lepr(db). Although adiponectin receptor 1 protein expression in coronary arterioles and aortas was similar between control and diabeticmice, adiponectin receptor 2 protein expression was significantly reduced in Lepr(db). Both adiponectin and anti-TNF-α inhibited IκBα phosphorylation and nuclear factor κB protein expression in Lepr(db), suggesting that adiponectin and TNF-α signaling may converge on nuclear factor κB to reciprocally regulate their expression. CONCLUSIONS: A reciprocal suppression occurs between adiponectin and TNF-α that fundamentally affects the regulation of coronary and aortic endothelial function in type 2 diabeticmice.
Authors: N Ouchi; S Kihara; Y Arita; Y Okamoto; K Maeda; H Kuriyama; K Hotta; M Nishida; M Takahashi; M Muraguchi; Y Ohmoto; T Nakamura; S Yamashita; T Funahashi; Y Matsuzawa Journal: Circulation Date: 2000-09-12 Impact factor: 29.690
Authors: K Hotta; T Funahashi; Y Arita; M Takahashi; M Matsuda; Y Okamoto; H Iwahashi; H Kuriyama; N Ouchi; K Maeda; M Nishida; S Kihara; N Sakai; T Nakajima; K Hasegawa; M Muraguchi; Y Ohmoto; T Nakamura; S Yamashita; T Hanafusa; Y Matsuzawa Journal: Arterioscler Thromb Vasc Biol Date: 2000-06 Impact factor: 8.311
Authors: Yu Cao; Ling Tao; Yuexing Yuan; Xiangying Jiao; Wayne Bond Lau; Yajing Wang; Theodore Christopher; Bernard Lopez; Lawrence Chan; Barry Goldstein; Xin L Ma Journal: J Mol Cell Cardiol Date: 2008-11-05 Impact factor: 5.000
Authors: J Fruebis; T S Tsao; S Javorschi; D Ebbets-Reed; M R Erickson; F T Yen; B E Bihain; H F Lodish Journal: Proc Natl Acad Sci U S A Date: 2001-02-06 Impact factor: 11.205
Authors: T Yamauchi; J Kamon; Y Minokoshi; Y Ito; H Waki; S Uchida; S Yamashita; M Noda; S Kita; K Ueki; K Eto; Y Akanuma; P Froguel; F Foufelle; P Ferre; D Carling; S Kimura; R Nagai; B B Kahn; T Kadowaki Journal: Nat Med Date: 2002-10-07 Impact factor: 53.440