Abstract
Event Abstract Back to Event Specific oligoclonal T-cell recruitment within epicardial adipose tissue of patients with acute coronary syndrome: evidence for a local, immune-mediated, pathogenetic mechanism Gabriele Di Sante1*, Giovanna Liuzzo2, Anna Severino2, Vincenzo Pazzano2, Daniela Pedicino2, Franco Glieca3, Luciani Nicola3, Francesco Ria1 and Filippo Crea2 1 Università Cattolica del Sacro Cuore - Policlinico Gemelli, General Pathology, Italy 2 Università Cattolica del Sacro Cuore, Cardiovascular Disease, Italy 3 Università Cattolica del Sacro Cuore, Cardiosurgery, Italy Epicardial adipose tissue (EAT) has a close functional and anatomic relationship with epicardial coronary arteries (1). Release of proinflammatory cytokines, associated with macrophage infiltration, have been demonstrated in EAT of patients with coronary artery disease (CAD), although without any distinction between chronic and acute manifestations of the disease. The present study aims to address whether a specific, immune-driven T-lymphocyte recruitment within EAT might be implicated in acute coronary syndrome (ACS) (1-3). We examined the T-cell receptor (TCR) repertoire using CDR3 BV-BC spectratyping (4-6) both in EAT samples (obtained during coronary artery bypass grafting) and in peripheral blood mononuclear cells of patients with either ACS (n=27) or CAD as chronic stable angina (n=26). Patients undergoing cardiac surgery for mitral insufficiency, with angiographically normal coronary arteries, served as control group (controls; n=10). We found T-cell clonotype expansions in EAT as compared with peripheral blood from each patient with ACS. The TCR repertoire in EAT samples of ACS patients was restricted, involving 6/21 (24%) analyzed TCR-BV families (BV3, BV6.2, BV7, BV9, BV10, BV12). In particular, we observed a disproportionately high expression of TCR-BV10 and BV6.2, as they were found in 12 (44%) and in 7 (26%) out of 27 EAT samples, respectively. Intriguingly, TCR-BV10 was strongly associated with the first clinical manifestation of ACS, as 11/18 (61%) patients at their first manifestation of ACS and 1/9 (11%) of those with previous acute coronary events expressed BV10 (P=0.019). Although the size of the repertoire used by CAD and control was comparable to that of ACS patients (7), it was characterized by different T-cell receptors. CAD patients expressed preferentially TCR-BV3 that was observed in 16/26 (62%) EAT samples, while BV10 and BV6.2 (both 8%) were less frequent (P<0.01 vs ACS). Controls expressed BV3 (30%) and BV9 (20%), but none had BV10 or BV6.2 (P<0.01 vs ACS). Thus, TCR-BV10 and BV6.2 usage was almost exclusively observed in patients at their first clinical manifestation of ACS, while TCR-BV3 was a prerogative of chronic CAD. For the first time, T-cell receptor repertoire was investigated directly into epicardial adipose tissue surrounding diseased coronary arteries. Using this approach, we demonstrated that coronary plaque instability in the setting of ACS is associated with immune-driven T-cell recruitment, not only within the plaque, but also in the surrounding adipose tissue, and that T-cells bearing selected TCRs might be involved in the pathogenesis of ACS. Figure 1 Figure 2 Figure 3 Figure 4 Figure 5
Highlights
Potential role of Epicardial Adipose Tissue (EAT) in acute coronary syndromes (ACS)T-cell receptor (TCR)-BV10 was strongly associated with the first clinical manifestation of ACSA total of 24 TCR BV-BC rearrangement were assessed and 620 spectra were examined in EAT samples
We found T-cell clonotype expansions in EAT as compared with peripheral blood from each ACS patient
The present study aims to address whether a specific, immune-driven T-lymphocyte recruitment within EAT might be implicated in acute coronary syndrome (ACS)
Summary
Potential role of Epicardial Adipose Tissue (EAT) in acute coronary syndromes (ACS)TCR-BV10 was strongly associated with the first clinical manifestation of ACSA total of 24 TCR BV-BC rearrangement were assessed and 620 spectra were examined in EAT samples. Potential role of Epicardial Adipose Tissue (EAT) in acute coronary syndromes (ACS). TCR-BV10 was strongly associated with the first clinical manifestation of ACS. A total of 24 TCR BV-BC rearrangement were assessed and 620 spectra were examined in EAT samples. (Relative Enrichment Index = normalized peak area obtained from EAT/. Normalized peak area of PBMC), with R.E.I. 11/18 (61%) patients at their first manifestation of ACS and in 1/12. (8%) of those with previous acute coronary events (P=0.007) (Figure 4). EAT has a close functional and anatomic relationship with epicardial coronary arteries. EAT is different from other fat depots (smaller adipocytes size, different fatty acid composition, high protein content)
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