PMID- 35880176
OWN - NLM
STAT- MEDLINE
DCOM- 20220727
LR  - 20220804
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 13
DP  - 2022
TI  - Restricted T-Cell Repertoire in the Epicardial Adipose Tissue of Non-ST Segment 
      Elevation Myocardial Infarction Patients.
PG  - 845526
LID - 10.3389/fimmu.2022.845526 [doi]
LID - 845526
AB  - AIMS: Human epicardial adipose tissue, a dynamic source of multiple bioactive 
      factors, holds a close functional and anatomic relationship with the epicardial 
      coronary arteries and communicates with the coronary artery wall through 
      paracrine and vasocrine secretions. We explored the hypothesis that T-cell 
      recruitment into epicardial adipose tissue (EAT) in patients with non-ST segment 
      elevation myocardial infarction (NSTEMI) could be part of a specific 
      antigen-driven response implicated in acute coronary syndrome onset and 
      progression. METHODS AND RESULTS: We enrolled 32 NSTEMI patients and 34 chronic 
      coronary syndrome (CCS) patients undergoing coronary artery bypass grafting 
      (CABG) and 12 mitral valve disease (MVD) patients undergoing surgery. We 
      performed EAT proteome profiling on pooled specimens from three NSTEMI and three 
      CCS patients. We performed T-cell receptor (TCR) spectratyping and CDR3 
      sequencing in EAT and peripheral blood mononuclear cells of 29 NSTEMI, 31 CCS, 
      and 12 MVD patients. We then used computational modeling studies to predict 
      interactions of the TCR beta chain variable region (TRBV) and explore sequence 
      alignments. The EAT proteome profiling displayed a higher content of 
      pro-inflammatory molecules (CD31, CHI3L1, CRP, EMPRINN, ENG, IL-17, IL-33, MMP-9, 
      MPO, NGAL, RBP-4, RETN, VDB) in NSTEMI as compared to CCS (P < 0.0001). CDR3-beta 
      spectratyping showed a TRBV21 enrichment in EAT of NSTEMI (12/29 patients; 41%) 
      as compared with CCS (1/31 patients; 3%) and MVD (none) (ANOVA for trend P < 
      0.001). Of note, 11/12 (92%) NSTEMI patients with TRBV21 perturbation were at 
      their first manifestation of ACS. Four patients with the first event shared a 
      distinctive TRBV21-CDR3 sequence of 178 bp length and 2/4 were carriers of the 
      human leukocyte antigen (HLA)-A*03:01 allele. A 3D analysis predicted the most 
      likely epitope able to bind HLA-A3*01 and interact with the TRBV21-CDR3 sequence 
      of 178 bp length, while the alignment results were consistent with microbial DNA 
      sequences. CONCLUSIONS: Our study revealed a unique immune signature of the 
      epicardial adipose tissue, which led to a 3D modeling of the TCRBV/peptide/HLA-A3 
      complex, in acute coronary syndrome patients at their first event, paving the way 
      for epitope-driven therapeutic strategies.
CI  - Copyright (c) 2022 Pedicino, Severino, Di Sante, De Rosa, Pirolli, Vinci, Pazzano, 
      Giglio, Trotta, Russo, Ruggio, Pisano, d'Aiello, Canonico, Ciampi, Cianflone, 
      Cianfanelli, Grimaldi, Filomia, Luciani, Glieca, Bruno, Massetti, Ria, Crea and 
      Liuzzo.
FAU - Pedicino, Daniela
AU  - Pedicino D
AD  - Dipartimento di Scienze Cardiovascolari, Fondazione Policlinico Universitario A. 
      Gemelli Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy.
FAU - Severino, Anna
AU  - Severino A
AD  - Dipartimento di Scienze Cardiovascolari, Fondazione Policlinico Universitario A. 
      Gemelli Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy.
AD  - Dipartimento di Scienze Cardiovascolari e Pneumologiche, Universita Cattolica del 
      Sacro Cuore, Rome, Italy.
FAU - Di Sante, Gabriele
AU  - Di Sante G
AD  - Dipartimento di Medicina e Chirurgia traslazionale, Universita Cattolica del 
      Sacro Cuore, Rome, Italy.
AD  - Dipartimento di Medicina e Chirurgia, Sezione di Anatomia Umana, Clinica e 
      Forense, Universita di Perugia, Perugia, Italy.
FAU - De Rosa, Maria Cristina
AU  - De Rosa MC
AD  - Istituto di Scienze e Tecnologie Chimiche "Giulio Natta" (SCITEC) - Consiglio 
      Nazionale delle Ricerche (CNR), Rome, Italy.
FAU - Pirolli, Davide
AU  - Pirolli D
AD  - Istituto di Scienze e Tecnologie Chimiche "Giulio Natta" (SCITEC) - Consiglio 
      Nazionale delle Ricerche (CNR), Rome, Italy.
FAU - Vinci, Ramona
AU  - Vinci R
AD  - Dipartimento di Scienze Cardiovascolari, Fondazione Policlinico Universitario A. 
      Gemelli Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy.
AD  - Dipartimento di Scienze Cardiovascolari e Pneumologiche, Universita Cattolica del 
      Sacro Cuore, Rome, Italy.
FAU - Pazzano, Vincenzo
AU  - Pazzano V
AD  - Paediatric Cardiology and Cardiac Arrhythmia/Syncope Unit, Bambino Gesu 
      Children's Hospital Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 
      Rome, Italy.
FAU - Giglio, Ada F
AU  - Giglio AF
AD  - Dipartimento di Cardiologia, Aziende Socio Sanitarie Territoriali (ASST) 
      Fatebenefratelli Sacco, Milano, Italy.
FAU - Trotta, Francesco
AU  - Trotta F
AD  - Cardiology Unit "F. Perinei" Hospital, Bari, Italy.
FAU - Russo, Giulio
AU  - Russo G
AD  - Dipartimento di Scienze Cardiovascolari e Pneumologiche, Universita Cattolica del 
      Sacro Cuore, Rome, Italy.
FAU - Ruggio, Aureliano
AU  - Ruggio A
AD  - Dipartimento di Scienze Cardiovascolari, Fondazione Policlinico Universitario A. 
      Gemelli Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy.
FAU - Pisano, Eugenia
AU  - Pisano E
AD  - Dipartimento di Scienze Cardiovascolari e Pneumologiche, Universita Cattolica del 
      Sacro Cuore, Rome, Italy.
FAU - d'Aiello, Alessia
AU  - d'Aiello A
AD  - Dipartimento di Scienze Cardiovascolari, Fondazione Policlinico Universitario A. 
      Gemelli Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy.
FAU - Canonico, Francesco
AU  - Canonico F
AD  - Dipartimento di Scienze Cardiovascolari, Fondazione Policlinico Universitario A. 
      Gemelli Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy.
AD  - Dipartimento di Scienze Cardiovascolari e Pneumologiche, Universita Cattolica del 
      Sacro Cuore, Rome, Italy.
FAU - Ciampi, Pellegrino
AU  - Ciampi P
AD  - Dipartimento di Scienze Cardiovascolari e Pneumologiche, Universita Cattolica del 
      Sacro Cuore, Rome, Italy.
FAU - Cianflone, Domenico
AU  - Cianflone D
AD  - Cardiac Rehabilitation Unit, Istituto di Ricovero e Cura a Carattere Scientifico 
      (IRCCS) Ospedale San Raffaele, Universita Vita-Salute San Raffaele, Milan, Italy.
FAU - Cianfanelli, Lorenzo
AU  - Cianfanelli L
AD  - Cardiac Rehabilitation Unit, Istituto di Ricovero e Cura a Carattere Scientifico 
      (IRCCS) Ospedale San Raffaele, Universita Vita-Salute San Raffaele, Milan, Italy.
FAU - Grimaldi, Maria Chiara
AU  - Grimaldi MC
AD  - Dipartimento di Scienze Cardiovascolari e Pneumologiche, Universita Cattolica del 
      Sacro Cuore, Rome, Italy.
FAU - Filomia, Simone
AU  - Filomia S
AD  - Dipartimento di Scienze Cardiovascolari e Pneumologiche, Universita Cattolica del 
      Sacro Cuore, Rome, Italy.
FAU - Luciani, Nicola
AU  - Luciani N
AD  - Dipartimento di Scienze Cardiovascolari, Fondazione Policlinico Universitario A. 
      Gemelli Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy.
AD  - Dipartimento di Scienze Cardiovascolari e Pneumologiche, Universita Cattolica del 
      Sacro Cuore, Rome, Italy.
FAU - Glieca, Franco
AU  - Glieca F
AD  - Dipartimento di Scienze Cardiovascolari, Fondazione Policlinico Universitario A. 
      Gemelli Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy.
AD  - Cardiac Rehabilitation Unit, Istituto di Ricovero e Cura a Carattere Scientifico 
      (IRCCS) Ospedale San Raffaele, Universita Vita-Salute San Raffaele, Milan, Italy.
FAU - Bruno, Piergiorgio
AU  - Bruno P
AD  - Dipartimento di Scienze Cardiovascolari, Fondazione Policlinico Universitario A. 
      Gemelli Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy.
AD  - Dipartimento di Scienze Cardiovascolari e Pneumologiche, Universita Cattolica del 
      Sacro Cuore, Rome, Italy.
FAU - Massetti, Massimo
AU  - Massetti M
AD  - Dipartimento di Scienze Cardiovascolari, Fondazione Policlinico Universitario A. 
      Gemelli Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy.
AD  - Dipartimento di Scienze Cardiovascolari e Pneumologiche, Universita Cattolica del 
      Sacro Cuore, Rome, Italy.
FAU - Ria, Francesco
AU  - Ria F
AD  - Dipartimento di Medicina e Chirurgia traslazionale, Universita Cattolica del 
      Sacro Cuore, Rome, Italy.
AD  - Dipartimento di Scienze di Laboratorio ed Infettivologiche, Fondazione 
      Policlinico Universitario A. Gemelli Istituto di Ricovero e Cura a Carattere 
      Scientifico (IRCCS), Rome, Italy.
FAU - Crea, Filippo
AU  - Crea F
AD  - Dipartimento di Scienze Cardiovascolari, Fondazione Policlinico Universitario A. 
      Gemelli Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy.
AD  - Dipartimento di Scienze Cardiovascolari e Pneumologiche, Universita Cattolica del 
      Sacro Cuore, Rome, Italy.
FAU - Liuzzo, Giovanna
AU  - Liuzzo G
AD  - Dipartimento di Scienze Cardiovascolari, Fondazione Policlinico Universitario A. 
      Gemelli Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy.
AD  - Dipartimento di Scienze Cardiovascolari e Pneumologiche, Universita Cattolica del 
      Sacro Cuore, Rome, Italy.
LA  - eng
SI  - figshare/10.6084/m9.figshare.19932182
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220708
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Epitopes)
RN  - 0 (HLA-A3 Antigen)
RN  - 0 (Proteome)
SB  - IM
MH  - *Acute Coronary Syndrome
MH  - Adipose Tissue
MH  - Epitopes
MH  - HLA-A3 Antigen
MH  - Humans
MH  - Leukocytes, Mononuclear
MH  - *Non-ST Elevated Myocardial Infarction
MH  - Proteome
MH  - T-Lymphocytes
PMC - PMC9307872
OTO - NOTNLM
OT  - NSTE ACS
OT  - T-cell receptor (TCR)
OT  - antigen-driven immunity
OT  - computational modeling
OT  - epicardial adipose tissue (EAT)
OT  - first acute myocardial infarction
OT  - immune response
OT  - precision medicine
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/07/27 06:00
MHDA- 2022/07/28 06:00
PMCR- 2022/01/01
CRDT- 2022/07/26 02:05
PHST- 2021/12/29 00:00 [received]
PHST- 2022/05/31 00:00 [accepted]
PHST- 2022/07/26 02:05 [entrez]
PHST- 2022/07/27 06:00 [pubmed]
PHST- 2022/07/28 06:00 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2022.845526 [doi]
PST - epublish
SO  - Front Immunol. 2022 Jul 8;13:845526. doi: 10.3389/fimmu.2022.845526. eCollection 
      2022.