Imbalance Between Interleukin-1β and Interleukin-1 Receptor Antagonist in Epicardial Adipose Tissue Is Associated With Non ST-Segment Elevation Acute Coronary Syndrome

Valentina Parisi; Laura Petraglia; Serena Cabaro; Vittoria D'Esposito; Dario Bruzzese; Giusy Ferraro; Andrea Urbani; Fabrizio Vincenzo Grieco; Maddalena Conte; Aurelio Caruso; Maria Gabriella Grimaldi; Antonio de Bellis; Salvatore Severino; Pasquale Campana; Emanuele Pilato; Giuseppe Comentale; Maddalena Raia; Giulia Scalia; Giuseppe Castaldo; Pietro Formisano; Dario Leosco

doi:10.3389/fphys.2020.00042

Imbalance Between Interleukin-1β and Interleukin-1 Receptor Antagonist in Epicardial Adipose Tissue Is Associated With Non ST-Segment Elevation Acute Coronary Syndrome

Front Physiol. 2020 Feb 5:11:42. doi: 10.3389/fphys.2020.00042. eCollection 2020.

Authors

Valentina Parisi¹, Laura Petraglia¹, Serena Cabaro^{1

2}, Vittoria D'Esposito^{1

2}, Dario Bruzzese³, Giusy Ferraro^{1

2}, Andrea Urbani¹, Fabrizio Vincenzo Grieco¹, Maddalena Conte¹, Aurelio Caruso⁴, Maria Gabriella Grimaldi⁴, Antonio de Bellis⁴, Salvatore Severino⁴, Pasquale Campana¹, Emanuele Pilato⁵, Giuseppe Comentale⁵, Maddalena Raia⁶, Giulia Scalia⁶, Giuseppe Castaldo^{6

7}, Pietro Formisano^{1

2}, Dario Leosco¹

Affiliations

¹ Department of Translational Medical Science, University of Naples Federico II, Naples, Italy.
² Institute of Experimental Endocrinology and Oncology, National Research Council, Naples, Italy.
³ Department of Public Health, University of Naples Federico II, Naples, Italy.
⁴ Casa di Cura San Michele, Maddaloni, Italy.
⁵ DAI Emergenze Cardiovascolari, Medicina Clinica e dell'Invecchiamento, Università degli Studi di Napoli Federico II, Naples, Italy.
⁶ Ceinge Biotecnologie Avanzate s.c. a r.l., Naples, Italy.
⁷ Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Naples, Italy.

Abstract

Introduction: Interleukin-1beta (IL-1β) is crucially involved in the pathogenesis of coronary atherosclerotic diseases (CAD) and its inhibition has proven cardiovascular benefits. Epicardial adipose tissue (EAT) is a local source of inflammatory mediators which may negatively affect the surrounding coronary arteries. In the present study, we explored the relationship between serum and EAT levels of IL-1β and IL-1 receptor antagonist (IL-1ra) in patients with chronic coronary syndrome (CCS) and recent acute coronary syndrome (ACS).

Methods: We obtained EAT biopsies in 54 CCS (Group 1) and 33 ACS (Group 2) patients undergoing coronary artery bypass grafting. Serum and EAT levels of IL-1β and IL-1ra were measured in all patients. An immunophenotypic study was carried out on EAT biopsies and the CD86 events were studied as markers of M1 macrophages.

Results: Circulating levels of IL-1β were significantly higher in the overall CAD population compared to a control group [7.64 pg/ml (6.86; 8.57) vs. 1.89 pg/ml (1.81; 2.29); p < 0.001]. In contrast, no differences were observed for serum IL-1ra levels between CAD and controls. Comparable levels of serum IL-1β were found between Groups 1 and 2 [7.6 pg/ml (6.9; 8.7) vs. 7.9 pg/ml (7.2; 8.6); p = 0.618]. In contrast, significantly lower levels of serum IL-1ra were found in Group 2 compared to Group 1 [274 pg/ml (220; 577) vs. 603 pg/ml (334; 1022); p = 0.035]. No differences of EAT levels of IL-1β were found between Group 2 and Group 1 [3.4 pg/ml (2.3; 8.4) vs. 2.4 pg/ml (1.9; 8.0); p = 0.176]. In contrast, significantly lower EAT levels of IL-1ra were found in Group 2 compared to Group 1 [101 pg/ml (40; 577) vs. 1344 pg/ml (155; 5327); p = 0.002]. No correlation was found between EAT levels of IL-1β and CD86 and CD64 events.

Conclusion: The present study explores the levels of IL-1β and IL-1ra in the serum and in EAT of CCS and ACS patients. ACS seems to be associated to a loss of the counter-regulatory activity of IL-1ra against the pro-inflammatory effects related to IL-1β activation.

Keywords: IL-1; IL1-ra; acute coronary syndrome; epicardial adipose tissue; inflammation.

Copyright © 2020 Parisi, Petraglia, Cabaro, D’Esposito, Bruzzese, Ferraro, Urbani, Grieco, Conte, Caruso, Grimaldi, de Bellis, Severino, Campana, Pilato, Comentale, Raia, Scalia, Castaldo, Formisano and Leosco.