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Epicardial Adipocyte-Derived TNF-α Modulates Local Inflammation in Patients with Advanced Coronary Artery Disease

Author(s):

Nikoleta Karampetsou , Aspasia Tzani*, Ilias P. Doulamis, Evanthia Bletsa, Aggeliki Minia, Vaia Pliaka , Nikos Tsolakos, Evangelos Oikonomou , Dimitris Tousoulis , Konstantinos Kontzoglou , Leonidas G. Alexopoulos, Despoina N. Perrea , Paulos Patapis and Ioannis A. Chloroyiannis   Pages 1 - 7 ( 7 )

Abstract:


Background: Epicardial adipose tissue (EAT) surrounds the epicardium and can mediate harmful effects related to coronary artery disease (CAD).

Objective: We explored the regional differences between adipose stores surrounding diseased and non-diseased segments of coronary arteries in patients with advanced CAD.

Methods: We enrolled 32 patients with known CAD who underwent coronary artery bypass graft (CABG) surgery. Inflammatory mediators were measured in EAT biopsies collected from a region of the left anterior descending artery (LAD) with severe stenosis (diseased segment) and without stenosis (non-diseased segment).

Results: Mean age was 64.3±11.1 years, and mean EAT thickness was 7.4±1.9 mm. Dyslipidemia was the most prevalent comorbidity (81% of the patients). Out of a total of 11 cytokines, resistin (p=0.039), matrix metallopeptidase 9 (MMP-9) (p=0.020), C-C motif chemokine ligand 5 (CCL-5) (p=0.021), and follistatin (p=0.038) were significantly increased in the diseased compared with the non-diseased EAT segments. Indexed tumor necrosis factor-alpha (TNF-α), defined as the diseased to non-diseased cytokine levels ratio, was significantly correlated with increased EAT thickness both in the whole cohort (p=0.043) and in a subpopulation of patients with dyslipidemia (p=0.009). Treatment with lipid-lowering agents significantly decreased indexed TNF-α levels (p=0.015). No significant alterations were observed in the circulating levels of these cytokines with respect to CAD-associated comorbidities.

Conclusion: Perivascular EAT is a source of cytokine secretion in distinct areas surrounding the coronary arteries in patients with advanced CAD. Adipocyte-derived TNF-α is a prominent mediator of local inflammation.

Keywords:

Epicardial adipose tissue, coronary artery disease, coronary artery bypass graft surgery, inflammation, TNF-α, IL-1α.

Affiliation:

Laboratory for Experimental Surgery and Surgical Research “N.S Christeas”, National and Kapodistrian University of Athens, School of Medicine, Athens, Laboratory for Experimental Surgery and Surgical Research “N.S Christeas”, National and Kapodistrian University of Athens, School of Medicine, Athens, Laboratory for Experimental Surgery and Surgical Research “N.S Christeas”, National and Kapodistrian University of Athens, School of Medicine, Athens, Laboratory for Experimental Surgery and Surgical Research “N.S Christeas”, National and Kapodistrian University of Athens, School of Medicine, Athens, ProtATonce Ltd, Athens, ProtATonce Ltd, Athens, ProtATonce Ltd, Athens, First Department of Cardiology, “Hippokration” General Hospital, National and Kapodistrian University of Athens, School of Medicine, Athens, ProtATonce Ltd, Athens, Laboratory for Experimental Surgery and Surgical Research “N.S Christeas”, National and Kapodistrian University of Athens, School of Medicine, Athens, ProtATonce Ltd, Athens, Laboratory for Experimental Surgery and Surgical Research “N.S Christeas”, National and Kapodistrian University of Athens, School of Medicine, Athens, Third Department of Surgery, Attikon University General Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Department of Cardiac Surgery, Euroclinic of Athens, Athens



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