Epicardial adipose tissue microbial colonization and inflammasome activation in acute coronary syndrome.

Abstract

BACKGROUND:

Epicardial adipose tissue (EAT) has a close functional and anatomic relationship with epicardial coronary arteries. Accumulating evidence suggests that host microbiome alterations may play a role in several inflammatory/immune disorders, triggering a robust proinflammatory response also involving interleukin-1β (IL-1β) and the NALP3 inflammasome. In the current study, we explore the hypothesis that in patients with non-ST elevation acute coronary syndrome (ACS), EAT contains potentially pro-atherosclerotic bacteria that might elicit inflammasome activation.

METHODS:

EAT samples were obtained during coronary artery bypass grafting from ACS (n=18) and effort stable angina (SA; n=16) patients, and as controls, from patients with angiographically normal coronary arteries undergoing surgery for mitral insufficiency (MVD; n=13). In all patients, NALP3 and proIL-1β mRNA expressions were evaluated with qRT-PCR. In 3 patients from each group, EAT microbiota composition was determined using next-generation sequencing technologies.

RESULTS:

In EAT, mRNA expression of both NALP3 and pro-IL1β was significantly higher in ACS than in SA and MVD (P=0.028 and P=0.005, respectively). A broad range of bacterial species (n=76) was identified in both ACS and SA, with different predominant species. In contrast, microbial DNA was barely observed in MVD.

CONCLUSIONS:

Our study demonstrated the presence of bacterial DNA directly into EAT, surrounding diseased coronary arteries, of patients with ACS. Furthermore, ACS is associated with NALP3/inflammasome pathway activation in EAT. Our data suggest that the EAT environment is susceptible to microbial colonization that might stimulate a proinflammatory response. These findings add new elements to the pathogenesis of ACS and suggest novel therapeutic targets.

• Authors: Daniela Pedicino, Anna Severino, Sara Ucci, Francesca Bugli, Davide Flego, Ada F Giglio, Francesco Trotta, Aureliano Ruggio, Claudia Lucci, Antonio Iaconelli, Francesco Paroni Sterbini, Luigi M Biasucci, Maurizio Sanguinetti, Franco Glieca, Nicola Luciani, Massimo Massetti, Filippo Crea, Giovanna Liuzzo
• Journal: International journal of cardiology (Int J Cardiol) Vol. 236 Pg. 95-99 (Jun 01 2017) ISSN: 1874-1754 [Electronic] Netherlands
• PMID: 28268083 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier B.V. All rights reserved.

Chemical References

• DNA, Bacterial
• Inflammasomes
• Interleukin-1beta
• NLR Family, Pyrin Domain-Containing 3 Protein

Topics

• Acute Coronary Syndrome (diagnosis, immunology, surgery)
• Adipose Tissue (immunology, microbiology, pathology)
• Aged
• Colony Count, Microbial (methods)
• Coronary Artery Bypass (methods)
• Coronary Vessels (pathology)
• DNA, Bacterial (isolation & purification)
• Female
• Humans
• Inflammasomes (physiology)
• Interleukin-1beta (analysis)
• Italy
• Male
• Microbiota (physiology)
• Middle Aged
• NLR Family, Pyrin Domain-Containing 3 Protein (analysis)
• Pericardium (immunology, microbiology, pathology)
• Statistics as Topic