Alexios S Antonopoulos1, Marios Margaritis1, Patricia Coutinho1, Janet Digby1, Rikhil Patel1, Constantinos Psarros1, Ntobeko Ntusi1, Theodoros D Karamitsos1, Regent Lee1, Ravi De Silva1, Mario Petrou1, Rana Sayeed1, Michael Demosthenous1, Constantinos Bakogiannis1, Paul B Wordsworth1, Dimitris Tousoulis1, Stefan Neubauer1, Keith M Channon1, Charalambos Antoniades2. 1. 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.). 2. 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.
Abstract
OBJECTIVE: To explore the role of systemic inflammation in the regulation of adiponectin levels in patients with ischemic heart disease. APPROACH AND 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.
OBJECTIVE: To explore the role of systemic inflammation in the regulation of adiponectin levels in patients with ischemic heart disease. APPROACH AND 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: Sarah R Anthony; Adrienne R Guarnieri; Anamarie Gozdiff; Robert N Helsley; Albert Phillip Owens; Michael Tranter Journal: Clin Sci (Lond) Date: 2019-11-29 Impact factor: 6.124
Authors: Gai-Zhen Liu; Bin Liang; Wayne Bond Lau; Yang Wang; Jianli Zhao; Rui Li; Xi Wang; Yuexing Yuan; Bernard L Lopez; Theodore A Christopher; Chuanshi Xiao; Xin-Liang Ma; Yajing Wang Journal: Free Radic Biol Med Date: 2015-10-08 Impact factor: 7.376