title: Reciprocal effects of systemic inflammation and brain natriuretic peptide on adiponectin biosynthesis in adipose tissue of patients with ischemic heart disease.
abstract: OBJECTIVE
  To explore the role of systemic inflammation in the regulation of adiponectin levels in patients with ischemic heart disease.
  
  
  RESULTS
  In a cross-sectional study of 575 subjects, serum adiponectin was compared between healthy subjects, patients with coronary artery disease with no/mild/severe heart failure (HF), and patients with nonischemic HF. Adiponectin expression and release from femoral, subcutaneous and thoracic adipose tissue was determined in 258 additional patients with coronary artery bypass grafting. Responsiveness of the various human adipose tissue depots to interleukin-6, tumor necrosis factor-α, and brain natriuretic peptide (BNP) was examined by using ex vivo models of human fat. The effects of inducible low-grade inflammation were tested by using the model of Salmonella typhi vaccine-induced inflammation in healthy individuals. In the cross-sectional study, HF strikingly increased adiponectin levels. Plasma BNP was the strongest predictor of circulating adiponectin and its release from all adipose tissue depots in patients with coronary artery bypass grafting, even in the absence of HF. Femoral AT was the depot with the least macrophages infiltration and the largest adipocyte cell size and the only responsive to systemic and ex vivo proinflammatory stimulation (effect reversible by BNP). Low-grade inflammation reduced circulating adiponectin levels, while circulating BNP remained unchanged.
  
  
  CONCLUSIONS
  This study demonstrates the regional variability in the responsiveness of human adipose tissue to systemic inflammation and suggests that BNP (not systemic inflammation) is the main driver of circulating adiponectin in patients with advanced atherosclerosis even in the absence of HF. Any interpretation of circulating adiponectin as a biomarker should take into account the underlying disease state, background inflammation, and BNP levels.
authors: From the Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom (A.S.A., M.M., P.C., J.D., R.P., N.N., T.D.K., R.L., S.N., K.M.C., C.A.); 1st Cardiology Department, Athens University Medical School, Athens, Greece (C.P., M.D., C.B., D.T.); Department of Cardiac Surgery, John Radcliffe Hospital, Oxford, United Kingdom (R.D.S., M.P., R.S.); and NIHR Oxford Musculoskeletal Biomedical Research Unit & Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom (P.B.W.).
authors: Alexios S
authors: AS
authors: Antonopoulos
authors: From the Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom (A.S.A., M.M., P.C., J.D., R.P., N.N., T.D.K., R.L., S.N., K.M.C., C.A.); 1st Cardiology Department, Athens University Medical School, Athens, Greece (C.P., M.D., C.B., D.T.); Department of Cardiac Surgery, John Radcliffe Hospital, Oxford, United Kingdom (R.D.S., M.P., R.S.); and NIHR Oxford Musculoskeletal Biomedical Research Unit & Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom (P.B.W.).
authors: Marios
authors: M
authors: Margaritis
authors: From the Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom (A.S.A., M.M., P.C., J.D., R.P., N.N., T.D.K., R.L., S.N., K.M.C., C.A.); 1st Cardiology Department, Athens University Medical School, Athens, Greece (C.P., M.D., C.B., D.T.); Department of Cardiac Surgery, John Radcliffe Hospital, Oxford, United Kingdom (R.D.S., M.P., R.S.); and NIHR Oxford Musculoskeletal Biomedical Research Unit & Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom (P.B.W.).
authors: Patricia
authors: P
authors: Coutinho
authors: From the Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom (A.S.A., M.M., P.C., J.D., R.P., N.N., T.D.K., R.L., S.N., K.M.C., C.A.); 1st Cardiology Department, Athens University Medical School, Athens, Greece (C.P., M.D., C.B., D.T.); Department of Cardiac Surgery, John Radcliffe Hospital, Oxford, United Kingdom (R.D.S., M.P., R.S.); and NIHR Oxford Musculoskeletal Biomedical Research Unit & Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom (P.B.W.).
authors: Janet
authors: J
authors: Digby
authors: From the Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom (A.S.A., M.M., P.C., J.D., R.P., N.N., T.D.K., R.L., S.N., K.M.C., C.A.); 1st Cardiology Department, Athens University Medical School, Athens, Greece (C.P., M.D., C.B., D.T.); Department of Cardiac Surgery, John Radcliffe Hospital, Oxford, United Kingdom (R.D.S., M.P., R.S.); and NIHR Oxford Musculoskeletal Biomedical Research Unit & Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom (P.B.W.).
authors: Rikhil
authors: R
authors: Patel
authors: From the Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom (A.S.A., M.M., P.C., J.D., R.P., N.N., T.D.K., R.L., S.N., K.M.C., C.A.); 1st Cardiology Department, Athens University Medical School, Athens, Greece (C.P., M.D., C.B., D.T.); Department of Cardiac Surgery, John Radcliffe Hospital, Oxford, United Kingdom (R.D.S., M.P., R.S.); and NIHR Oxford Musculoskeletal Biomedical Research Unit & Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom (P.B.W.).
authors: Constantinos
authors: C
authors: Psarros
authors: From the Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom (A.S.A., M.M., P.C., J.D., R.P., N.N., T.D.K., R.L., S.N., K.M.C., C.A.); 1st Cardiology Department, Athens University Medical School, Athens, Greece (C.P., M.D., C.B., D.T.); Department of Cardiac Surgery, John Radcliffe Hospital, Oxford, United Kingdom (R.D.S., M.P., R.S.); and NIHR Oxford Musculoskeletal Biomedical Research Unit & Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom (P.B.W.).
authors: Ntobeko
authors: N
authors: Ntusi
authors: From the Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom (A.S.A., M.M., P.C., J.D., R.P., N.N., T.D.K., R.L., S.N., K.M.C., C.A.); 1st Cardiology Department, Athens University Medical School, Athens, Greece (C.P., M.D., C.B., D.T.); Department of Cardiac Surgery, John Radcliffe Hospital, Oxford, United Kingdom (R.D.S., M.P., R.S.); and NIHR Oxford Musculoskeletal Biomedical Research Unit & Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom (P.B.W.).
authors: Theodoros D
authors: TD
authors: Karamitsos
authors: From the Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom (A.S.A., M.M., P.C., J.D., R.P., N.N., T.D.K., R.L., S.N., K.M.C., C.A.); 1st Cardiology Department, Athens University Medical School, Athens, Greece (C.P., M.D., C.B., D.T.); Department of Cardiac Surgery, John Radcliffe Hospital, Oxford, United Kingdom (R.D.S., M.P., R.S.); and NIHR Oxford Musculoskeletal Biomedical Research Unit & Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom (P.B.W.).
authors: Regent
authors: R
authors: Lee
authors: From the Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom (A.S.A., M.M., P.C., J.D., R.P., N.N., T.D.K., R.L., S.N., K.M.C., C.A.); 1st Cardiology Department, Athens University Medical School, Athens, Greece (C.P., M.D., C.B., D.T.); Department of Cardiac Surgery, John Radcliffe Hospital, Oxford, United Kingdom (R.D.S., M.P., R.S.); and NIHR Oxford Musculoskeletal Biomedical Research Unit & Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom (P.B.W.).
authors: Ravi
authors: R
authors: De Silva
authors: From the Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom (A.S.A., M.M., P.C., J.D., R.P., N.N., T.D.K., R.L., S.N., K.M.C., C.A.); 1st Cardiology Department, Athens University Medical School, Athens, Greece (C.P., M.D., C.B., D.T.); Department of Cardiac Surgery, John Radcliffe Hospital, Oxford, United Kingdom (R.D.S., M.P., R.S.); and NIHR Oxford Musculoskeletal Biomedical Research Unit & Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom (P.B.W.).
authors: Mario
authors: M
authors: Petrou
authors: From the Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom (A.S.A., M.M., P.C., J.D., R.P., N.N., T.D.K., R.L., S.N., K.M.C., C.A.); 1st Cardiology Department, Athens University Medical School, Athens, Greece (C.P., M.D., C.B., D.T.); Department of Cardiac Surgery, John Radcliffe Hospital, Oxford, United Kingdom (R.D.S., M.P., R.S.); and NIHR Oxford Musculoskeletal Biomedical Research Unit & Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom (P.B.W.).
authors: Rana
authors: R
authors: Sayeed
authors: From the Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom (A.S.A., M.M., P.C., J.D., R.P., N.N., T.D.K., R.L., S.N., K.M.C., C.A.); 1st Cardiology Department, Athens University Medical School, Athens, Greece (C.P., M.D., C.B., D.T.); Department of Cardiac Surgery, John Radcliffe Hospital, Oxford, United Kingdom (R.D.S., M.P., R.S.); and NIHR Oxford Musculoskeletal Biomedical Research Unit & Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom (P.B.W.).
authors: Michael
authors: M
authors: Demosthenous
authors: From the Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom (A.S.A., M.M., P.C., J.D., R.P., N.N., T.D.K., R.L., S.N., K.M.C., C.A.); 1st Cardiology Department, Athens University Medical School, Athens, Greece (C.P., M.D., C.B., D.T.); Department of Cardiac Surgery, John Radcliffe Hospital, Oxford, United Kingdom (R.D.S., M.P., R.S.); and NIHR Oxford Musculoskeletal Biomedical Research Unit & Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom (P.B.W.).
authors: Constantinos
authors: C
authors: Bakogiannis
authors: From the Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom (A.S.A., M.M., P.C., J.D., R.P., N.N., T.D.K., R.L., S.N., K.M.C., C.A.); 1st Cardiology Department, Athens University Medical School, Athens, Greece (C.P., M.D., C.B., D.T.); Department of Cardiac Surgery, John Radcliffe Hospital, Oxford, United Kingdom (R.D.S., M.P., R.S.); and NIHR Oxford Musculoskeletal Biomedical Research Unit & Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom (P.B.W.).
authors: Paul B
authors: PB
authors: Wordsworth
authors: From the Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom (A.S.A., M.M., P.C., J.D., R.P., N.N., T.D.K., R.L., S.N., K.M.C., C.A.); 1st Cardiology Department, Athens University Medical School, Athens, Greece (C.P., M.D., C.B., D.T.); Department of Cardiac Surgery, John Radcliffe Hospital, Oxford, United Kingdom (R.D.S., M.P., R.S.); and NIHR Oxford Musculoskeletal Biomedical Research Unit & Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom (P.B.W.).
authors: Dimitris
authors: D
authors: Tousoulis
authors: From the Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom (A.S.A., M.M., P.C., J.D., R.P., N.N., T.D.K., R.L., S.N., K.M.C., C.A.); 1st Cardiology Department, Athens University Medical School, Athens, Greece (C.P., M.D., C.B., D.T.); Department of Cardiac Surgery, John Radcliffe Hospital, Oxford, United Kingdom (R.D.S., M.P., R.S.); and NIHR Oxford Musculoskeletal Biomedical Research Unit & Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom (P.B.W.).
authors: Stefan
authors: S
authors: Neubauer
authors: From the Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom (A.S.A., M.M., P.C., J.D., R.P., N.N., T.D.K., R.L., S.N., K.M.C., C.A.); 1st Cardiology Department, Athens University Medical School, Athens, Greece (C.P., M.D., C.B., D.T.); Department of Cardiac Surgery, John Radcliffe Hospital, Oxford, United Kingdom (R.D.S., M.P., R.S.); and NIHR Oxford Musculoskeletal Biomedical Research Unit & Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom (P.B.W.).
authors: Keith M
authors: KM
authors: Channon
authors: From the Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom (A.S.A., M.M., P.C., J.D., R.P., N.N., T.D.K., R.L., S.N., K.M.C., C.A.); 1st Cardiology Department, Athens University Medical School, Athens, Greece (C.P., M.D., C.B., D.T.); Department of Cardiac Surgery, John Radcliffe Hospital, Oxford, United Kingdom (R.D.S., M.P., R.S.); and NIHR Oxford Musculoskeletal Biomedical Research Unit & Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom (P.B.W.). antoniad@well.ox.ac.uk.
authors: Charalambos
authors: C
authors: Antoniades
mesh_terms: D052242:Adiponectin / Q000096:biosynthesis* / Q000235:genetics; D000273:Adipose Tissue / Q000378:metabolism*; D000368:Aged; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000503:physiopathology; D001026:Coronary Artery Bypass; D003324:Coronary Artery Disease / Q000150:complications / Q000378:metabolism; D003430:Cross-Sectional Studies; D005260:Female; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D015850:Interleukin-6 / Q000097:blood / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000150:complications / Q000378:metabolism*; D020097:Natriuretic Peptide, Brain / Q000097:blood / Q000502:physiology*; D009924:Organ Culture Techniques; D009928:Organ Specificity; D012307:Risk Factors; D050151:Subcutaneous Fat; D013848:Thigh; D013909:Thorax; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014463:Ultrasonography; D014664:Vasodilation; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000503:physiopathology
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; C508600:IL6 protein, human; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D020097:Natriuretic Peptide, Brain
keywords: adiponectin; adipose tissue; heart failure; inflammation; natriuretic peptide, brain