title: 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.affiliation: Institute of Cardiology, Catholic University, Rome, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Pedicino
authors.affiliation: Institute of Cardiology, Catholic University, Rome, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Severino
authors.affiliation: Institute of Cardiology, Catholic University, Rome, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Ucci
authors.affiliation: Microbiology, Catholic University, Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Bugli
authors.affiliation: Institute of Cardiology, Catholic University, Rome, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Flego
authors.affiliation: Institute of Cardiology, Catholic University, Rome, Italy.
authors.forename: Ada F
authors.initials: AF
authors.lastname: Giglio
authors.affiliation: Institute of Cardiology, Catholic University, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Trotta
authors.affiliation: Institute of Cardiology, Catholic University, Rome, Italy.
authors.forename: Aureliano
authors.initials: A
authors.lastname: Ruggio
authors.affiliation: Institute of Cardiology, Catholic University, Rome, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Lucci
authors.affiliation: Institute of Cardiology, Catholic University, Rome, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Iaconelli
authors.affiliation: Microbiology, Catholic University, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Paroni Sterbini
authors.affiliation: Institute of Cardiology, Catholic University, Rome, Italy.
authors.forename: Luigi M
authors.initials: LM
authors.lastname: Biasucci
authors.affiliation: Microbiology, Catholic University, Rome, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Sanguinetti
authors.affiliation: Institute of Cardiac Surgery, Catholic University, Rome, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Glieca
authors.affiliation: Institute of Cardiac Surgery, Catholic University, Rome, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Luciani
authors.affiliation: Institute of Cardiac Surgery, Catholic University, Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Massetti
authors.affiliation: Institute of Cardiology, Catholic University, Rome, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Crea
authors.affiliation: Institute of Cardiology, Catholic University, Rome, Italy. Electronic address: giovanna.liuzzo@gmail.com.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Liuzzo
mesh_terms: D054058:Acute Coronary Syndrome / Q000175:diagnosis / Q000276:immunology / Q000601:surgery; D000273:Adipose Tissue / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D000368:Aged; D015169:Colony Count, Microbial / Q000379:methods; D001026:Coronary Artery Bypass / Q000379:methods*; D003331:Coronary Vessels / Q000473:pathology; D004269:DNA, Bacterial / Q000302:isolation & purification; D005260:Female; D006801:Humans; D058847:Inflammasomes / Q000502:physiology*; D053583:Interleukin-1beta / Q000032:analysis; D007558:Italy; D008297:Male; D064307:Microbiota / Q000502:physiology*; D008875:Middle Aged; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000032:analysis; D010496:Pericardium / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D013223:Statistics as Topic
chemical_list: D004269:DNA, Bacterial; D058847:Inflammasomes; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein
keywords: Acute coronary syndrome; Atherosclerosis; Epicardial adipose tissue; Inflammasome; Inflammation; Microbiome