Coronary and aortic endothelial function affected by feedback between adiponectin and tumor necrosis factor α 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 diabetic mice.


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.
Zhang
Hanrui
H
Department of Internal Medicine, University of Missouri, Columbia, MO 65211, USA.
Park
Yoonjung
Y
Zhang
Cuihua
C
D052242:Adiponectin / Q000494:pharmacology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D001158:Arteries / Q000187:drug effects* / Q000502:physiology; D002317:Cardiovascular Agents / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D025461:Feedback, Physiological; D008297:Male; D051379:Mice; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D052242:Adiponectin; D000911:Antibodies, Monoclonal; D002317:Cardiovascular Agents; D014409:Tumor Necrosis Factor-alpha
Diabetologia. 2003 Nov;46(11):1543-9
14551684
Basic Res Cardiol. 2008 Sep;103(5):407-16
18600366
Biochem Biophys Res Commun. 2005 Feb 11;327(2):460-7
15629137
Cardiovasc Res. 2007 Sep 1;75(4):719-27
17617391
J Biol Chem. 2003 Jan 24;278(4):2461-8
12431986
J Clin Invest. 1995 May;95(5):2409-15
7738205
J Lipid Res. 2008 Feb;49(2):308-23
17986714
Nat Med. 2001 Aug;7(8):947-53
11479628
J Biol Chem. 1996 May 3;271(18):10697-703
8631877
Diabetes. 2007 Mar;56(3):804-8
17327451
Am J Physiol Heart Circ Physiol. 2010 Sep;299(3):H605-12
20581092
Biochem Biophys Res Commun. 1999 Apr 2;257(1):79-83
10092513
Biochem Biophys Res Commun. 2004 Mar 5;315(2):264-71
14766203
Nat Med. 2005 Oct;11(10):1096-103
16155579
Am J Physiol Heart Circ Physiol. 2008 Dec;295(6):H2242-9
18849334
Arterioscler Thromb Vasc Biol. 2009 Jan;29(1):67-74
18988888
Nature. 2001 Dec 13;414(6865):782-7
11742409
Cell Immunol. 2005 Nov;238(1):19-30
16438946
Nature. 2003 Jun 12;423(6941):762-9
12802337
J Mol Cell Cardiol. 2009 Mar;46(3):413-9
19027750
Biochem Biophys Res Commun. 2004 Oct 8;323(1):242-8
15351728
Am J Physiol Lung Cell Mol Physiol. 2008 Jun;294(6):L1035-42
18326826
Br J Nurs. 2007 Sep 13-27;16(16):1002-7
18026039
Circulation. 2007 Jan 16;115(2):245-54
17200442
Arterioscler Thromb Vasc Biol. 2000 Jun;20(6):1595-9
10845877
Clin Sci (Lond). 2009 Feb;116(3):219-30
19118493
Arterioscler Thromb Vasc Biol. 2009 Aug;29(8):1164-71
19478208
Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):2005-10
11172066
FASEB J. 2004 Jan;18(1):215-7
14630696
Nat Med. 2002 Nov;8(11):1288-95
12368907
Proc Natl Acad Sci U S A. 2002 Dec 10;99(25):16309-13
12456889
Diabetes. 2007 May;56(5):1387-94
17287464
Horm Metab Res. 2007 Apr;39(4):250-5
17447161
Vitam Horm. 2006;74:443-77
17027526
Nat Med. 2002 Jul;8(7):731-7
12068289
J Biol Chem. 2008 Oct 3;283(40):26850-8
18678874
Circulation. 2000 Sep 12;102(11):1296-301
10982546
Int J Obes (Lond). 2010 Jan;34(1):165-71
19823181
J Clin Endocrinol Metab. 2004 Jun;89(6):2548-56
15181022