Mutual Regulation of Epicardial Adipose Tissue and Myocardial Redox State by PPAR-γ/Adiponectin Signalling

被引：158

作者：

Antonopoulos, Alexios S. ^{[1
]}

Margaritis, Marios ^{[1
]}

Verheule, Sander ^{[2
]}

Recalde, Alice ^{[1
]}

Sanna, Fabio ^{[1
]}

Herdman, Laura ^{[1
]}

Psarros, Costas ^{[1
]}

Nasrallah, Hussein ^{[2
]}

Coutinho, Patricia ^{[1
]}

Akoumianakis, Ioannis ^{[1
]}

Brewer, Alison C. ^{[4
]}

Sayeed, Rana ^{[5
]}

Krasopoulos, George ^{[5
]}

Petrou, Mario ^{[5
]}

Tarun, Akansha ^{[1
]}

Tousoulis, Dimitris ^{[3
]}

Shah, Ajay M. ^{[4
]}

Casadei, Barbara ^{[1
]}

Channon, Keith M. ^{[1
]}

Antoniades, Charalambos ^{[1
]}

机构：

[1] Univ Oxford, Div Cardiovasc Med, Radcliffe Dept Med, Oxford OX3 9DU, England

[2] Maastricht Univ, Dept Physiol, Cardiac Electrophysiol Grp, NL-6200 MD Maastricht, Netherlands

[3] Univ Athens, Sch Med, Dept Cardiol, GR-11527 Athens, Greece

[4] Kings Coll London, BHF Ctr, Cardiovasc Div, London WC2R 2LS, England

[5] John Radcliffe Hosp, Dept Cardiac Surg, Oxford OX3 9DU, England

来源：

CIRCULATION RESEARCH | 2016年 / 118卷 / 05期

基金：

欧盟第七框架计划;

关键词：

obesity; adipose tissue; adiponectin; oxidative stress; myocardium; TYPE-2; DIABETES-MELLITUS; OXIDATIVE STRESS; NAD(P)H OXIDASE; NADPH OXIDASES; ADIPONECTIN; ASSOCIATION; DISEASE; PATHOPHYSIOLOGY; INHIBITION; INJURY;

D O I：

10.1161/CIRCRESAHA.115.307856

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

Rationale: Adiponectin has anti-inflammatory effects in experimental models, but its role in the regulation of myocardial redox state in humans is unknown. Although adiponectin is released from epicardial adipose tissue (EpAT), it is unclear whether it exerts any paracrine effects on the human myocardium. Objective: To explore the cross talk between EpAT-derived adiponectin and myocardial redox state in the human heart. Methods and Results: EpAT and atrial myocardium were obtained from 306 patients undergoing coronary artery bypass grafting. Functional genetic polymorphisms that increase ADIPOQ expression (encoding adiponectin) led to reduced myocardial nicotinamide adenine dinucleotide phosphate oxidase-derived O-2(-), whereas circulating adiponectin and ADIPOQ expression in EpAT were associated with elevated myocardial O-2(-). In human atrial tissue, we demonstrated that adiponectin suppresses myocardial nicotinamide adenine dinucleotide phosphate oxidase activity, by preventing AMP kinase-mediated translocation of Rac1 and p47(phox) from the cytosol to the membranes. Induction of O-2(-) production in H9C2 cardiac myocytes led to the release of a transferable factor able to induce peroxisome proliferator-activated receptor-gamma-mediated upregulation of ADIPOQ expression in cocultured EpAT. Using a NOX2 transgenic mouse and a pig model of rapid atrial pacing, we found that oxidation products (such as 4-hydroxynonenal) released from the heart trigger peroxisome proliferator-activated receptor-gamma-mediated upregulation of ADIPOQ in EpAT. Conclusions: We demonstrate for the first time in humans that adiponectin directly decreases myocardial nicotinamide adenine dinucleotide phosphate oxidase activity via endocrine or paracrine effects. Adiponectin expression in EpAT is controlled by paracrine effects of oxidation products released from the heart. These effects constitute a novel defense mechanism of the heart against myocardial oxidative stress.

引用

页码：842 / 855

页数：14

共 42 条

[1]

Adiponectin: from obesity to cardiovascular disease [J].

Antoniades, C. ;

Antonopoulos, A. S. ;

Tousoulis, D. ;

Stefanadis, C. .

OBESITY REVIEWS, 2009, 10 (03) :269-279

[2]

Myocardial Redox State Predicts In-Hospital Clinical Outcome After Cardiac Surgery Effects of Short-Term Pre-Operative Statin Treatment [J].

Antoniades, Charalambos ;

Demosthenous, Michael ;

Reilly, Svetlana ;

Margaritis, Marios ;

Zhang, Mei-Hua ;

Antonopoulos, Alexios ;

Marinou, Kyriakoula ;

Nahar, Keshav ;

Jayaram, Raja ;

Tousoulis, Dimitris ;

Bakogiannis, Constantinos ;

Sayeed, Rana ;

Triantafyllou, Costas ;

Koumallos, Nikolaos ;

Psarros, Costas ;

Miliou, Antigoni ;

Stefanadis, Christodoulos ;

Channon, Keith M. ;

Casadei, Barbara .

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2012, 59 (01) :60-70

[3]

Preoperative Atorvastatin Treatment in CABG Patients Rapidly Improves Vein Graft Redox State by Inhibition of Rae1 and NADPH-Oxidase Activity [J].

Antoniades, Charalambos ;

Bakogiannis, Constantinos ;

Tousoulis, Dimitris ;

Reilly, Svetlana ;

Zhang, Mei-Hua ;

Paschalis, Andreas ;

Antonopoulos, Alexios S. ;

Demosthenous, Michael ;

Miliou, Antigoni ;

Psarros, Costas ;

Marinou, Kyriakoula ;

Sfyras, Nikolaos ;

Economopoulos, George ;

Casadei, Barbara ;

Channon, Keith M. ;

Stefanadis, Christodoulos .

CIRCULATION, 2010, 122 (11) :S66-S73

[4]

Reciprocal Effects of Systemic Inflammation and Brain Natriuretic Peptide on Adiponectin Biosynthesis in Adipose Tissue of Patients With Ischemic Heart Disease [J].

Antonopoulos, Alexios S. ;

Margaritis, Marios ;

Coutinho, Patricia ;

Digby, Janet ;

Patel, Rikhil ;

Psarros, Constantinos ;

Ntusi, Ntobeko ;

Karamitsos, Theodoros D. ;

Lee, Regent ;

De Silva, Ravi ;

Petrou, Mario ;

Sayeed, Rana ;

Demosthenous, Michael ;

Bakogiannis, Constantinos ;

Wordsworth, Paul B. ;

Tousoulis, Dimitris ;

Neubauer, Stefan ;

Channon, Keith M. ;

Antoniades, Charalambos .

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2014, 34 (09) :2151-2159

[5]

Lipid Peroxidation: Production, Metabolism, and Signaling Mechanisms of Malondialdehyde and 4-Hydroxy-2-Nonenal [J].

Ayala, Antonio ;

Munoz, Mario F. ;

Argueelles, Sandro .

OXIDATIVE MEDICINE AND CELLULAR LONGEVITY, 2014, 2014

[6]

Nox4 regulates Nrf2 and glutathione redox in cardiomyocytes in vivo [J].

Brewer, Alison C. ;

Murray, Thomas V. A. ;

Arno, Matthew ;

Zhang, Min ;

Anilkumar, Narayana P. ;

Mann, Giovanni E. ;

Shah, Ajay M. .

FREE RADICAL BIOLOGY AND MEDICINE, 2011, 51 (01) :205-215

[7]

Nox proteins in signal transduction [J].

Brown, David I. ;

Griendling, Kathy K. .

FREE RADICAL BIOLOGY AND MEDICINE, 2009, 47 (09) :1239-1253

[8]

High glucose causes upregulation of cyclooxygenase-2 and alters prostanoid profile in human endothelial cells -: Role of protein kinase C and reactive oxygen species [J].

Cosentino, F ;

Eto, M ;

De Paolis, P ;

van der Loo, B ;

Bachschmid, M ;

Ullrich, V ;

Kouroedov, A ;

Gatti, CD ;

Joch, H ;

Volpe, M ;

Lüscher, TF .

CIRCULATION, 2003, 107 (07) :1017-1023

[9]

Effects of NADH and NADPH on superoxide levels and cerebral vascular tone [J].

Didion, SP ;

Faraci, FM .

AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2002, 282 (02) :H688-H695

[10]

Circulating adiponectin concentrations in patients with congestive heart failure [J].

George, J. ;

Patal, S. ;

Wexler, D. ;

Sharabi, Y. ;

Peleg, E. ;

Kamari, Y. ;

Grossman, E. ;

Sheps, D. ;

Keren, G. ;

Roth, A. .

HEART, 2006, 92 (10) :1420-1424

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