Mutual Regulation of Epicardial Adipose Tissue and Myocardial Redox State by PPAR-γ/Adiponectin Signalling
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 myocar...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
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Lippincott, Williams and Wilkins
2016
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| _version_ | 1797063019483627520 |
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| author | Antonopoulos, A Margaritis, M Verheule, S Recalde, A Sanna, F Herdman, L Psarros, C Nasrallah, H Coutinho, P Akoumianakis, I Brewer, A Sayeed, R Krasopoulos, G Petrou, M Tarun, A Tousoulis, D Shah, A Casadei, B Channon, K Antoniades, C |
| author_facet | Antonopoulos, A Margaritis, M Verheule, S Recalde, A Sanna, F Herdman, L Psarros, C Nasrallah, H Coutinho, P Akoumianakis, I Brewer, A Sayeed, R Krasopoulos, G Petrou, M Tarun, A Tousoulis, D Shah, A Casadei, B Channon, K Antoniades, C |
| author_sort | Antonopoulos, A |
| collection | OXFORD |
| description | 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.<br/><br/> Objective: To explore the cross-talk between EpAT-derived adiponectin and myocardial redox state in the human heart.<br/><br/> Methods and Results: EpAT and atrial myocardium were obtained from 306 patients undergoing CABG. Functional genetic polymorphisms that increaseADIPOQ expression (encoding adiponectin) led to reduced myocardial NADPH oxidase-derived O2.-, whereas circulating adiponectin and ADIPOQ expression in EpAT were associated with elevated myocardial O2.-. In human atrial tissue, we demonstrated that adiponectin suppresses myocardial NADPH oxidase activity, by preventing AMP kinase-mediated translocation of Rac1 and p47phox from the cytosol to the membranes. Induction of O2.- production in H9C2 cardiac myocytes led to the release of a transferable factor able to induce PPAR-γ mediated up-regulation of ADIPOQ expression in co-cultured 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 PPAR-γ mediated up-regulation of ADIPOQ in EpAT.<br/><br/> Conclusions: We demonstrate for the first time in humans, that adiponectin directly decreases myocardial NADPH 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 defence mechanism of the heart against myocardial oxidative stress. |
| first_indexed | 2024-03-06T20:53:52Z |
| format | Journal article |
| id | oxford-uuid:388503bc-3500-4d09-9dbb-45ad58d0b5dd |
| institution | University of Oxford |
| last_indexed | 2024-03-06T20:53:52Z |
| publishDate | 2016 |
| publisher | Lippincott, Williams and Wilkins |
| record_format | dspace |
| spelling | oxford-uuid:388503bc-3500-4d09-9dbb-45ad58d0b5dd2022-03-26T13:50:38ZMutual Regulation of Epicardial Adipose Tissue and Myocardial Redox State by PPAR-γ/Adiponectin SignallingJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:388503bc-3500-4d09-9dbb-45ad58d0b5ddSymplectic Elements at OxfordLippincott, Williams and Wilkins2016Antonopoulos, AMargaritis, MVerheule, SRecalde, ASanna, FHerdman, LPsarros, CNasrallah, HCoutinho, PAkoumianakis, IBrewer, ASayeed, RKrasopoulos, GPetrou, MTarun, ATousoulis, DShah, ACasadei, BChannon, KAntoniades, CRationale: 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.<br/><br/> Objective: To explore the cross-talk between EpAT-derived adiponectin and myocardial redox state in the human heart.<br/><br/> Methods and Results: EpAT and atrial myocardium were obtained from 306 patients undergoing CABG. Functional genetic polymorphisms that increaseADIPOQ expression (encoding adiponectin) led to reduced myocardial NADPH oxidase-derived O2.-, whereas circulating adiponectin and ADIPOQ expression in EpAT were associated with elevated myocardial O2.-. In human atrial tissue, we demonstrated that adiponectin suppresses myocardial NADPH oxidase activity, by preventing AMP kinase-mediated translocation of Rac1 and p47phox from the cytosol to the membranes. Induction of O2.- production in H9C2 cardiac myocytes led to the release of a transferable factor able to induce PPAR-γ mediated up-regulation of ADIPOQ expression in co-cultured 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 PPAR-γ mediated up-regulation of ADIPOQ in EpAT.<br/><br/> Conclusions: We demonstrate for the first time in humans, that adiponectin directly decreases myocardial NADPH 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 defence mechanism of the heart against myocardial oxidative stress. |
| spellingShingle | Antonopoulos, A Margaritis, M Verheule, S Recalde, A Sanna, F Herdman, L Psarros, C Nasrallah, H Coutinho, P Akoumianakis, I Brewer, A Sayeed, R Krasopoulos, G Petrou, M Tarun, A Tousoulis, D Shah, A Casadei, B Channon, K Antoniades, C Mutual Regulation of Epicardial Adipose Tissue and Myocardial Redox State by PPAR-γ/Adiponectin Signalling |
| title | Mutual Regulation of Epicardial Adipose Tissue and Myocardial Redox State by PPAR-γ/Adiponectin Signalling |
| title_full | Mutual Regulation of Epicardial Adipose Tissue and Myocardial Redox State by PPAR-γ/Adiponectin Signalling |
| title_fullStr | Mutual Regulation of Epicardial Adipose Tissue and Myocardial Redox State by PPAR-γ/Adiponectin Signalling |
| title_full_unstemmed | Mutual Regulation of Epicardial Adipose Tissue and Myocardial Redox State by PPAR-γ/Adiponectin Signalling |
| title_short | Mutual Regulation of Epicardial Adipose Tissue and Myocardial Redox State by PPAR-γ/Adiponectin Signalling |
| title_sort | mutual regulation of epicardial adipose tissue and myocardial redox state by ppar γ adiponectin signalling |
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