Matrix metalloproteinase-9 might affect adaptive immunity in non-ST segment elevation acute coronary syndromes by increasing CD31 cleavage on CD4+ T-cells

Angelini, Giulia; Flego, Davide; Vinci, Ramona; Pedicino, Daniela; Trotta, Francesco; Ruggio, Aureliano; Piemontese, Giuseppe Pio; Galante, Domenico; Ponzo, Myriana; Biasucci, Luigi M.; Liuzzo, Giovanna; Crea, Filippo

doi:10.1093/eurheartj/ehx684

Cited by 29 publications

(20 citation statements)

References 30 publications

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“…To date, interventional trials designed to investigate whether periodontal treatment results in overall improvement of cardiovascular parameters have yet to demonstrate any causal relationships between these two disease groups, and thus additional more precisely designed studies are needed (14). Increased (blood) levels of matrix metalloproteinases (MMP) are associated with an increase in the incidence of MI and may be a predictive marker for future CAD (18). Eventually it might be possible to use OIL in a predictive way to help identify individuals at risk for CAD and the subsequent development of other cardiovascular disease conditions.…”

Section: Discussionmentioning

confidence: 99%

Oral inflammatory load in patients with coronary artery disease

et al. 2019

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Periodontitis is an oral inflammatory disease that may have an association with coronary artery disease (CAD). Oral inflammatory load (OIL) can be quantified by assesment of oral polymorphonucleocytes (oPMN) in an oral rinse assay. The aim of the present study was to prospectively correlate OIL with CAD on angiography assessed in terms of SYNTAX score in patients presenting with stable angina or acute coronary syndrome (ACS). Consecutive eligible patients at a cardiac center were prospectively recruited. Two sets of oral rinse samples were collected before and after angiography, and the relationship between oPMN and SYNTAX score was assessed. Of the 137 patients recruited, 32.8% (n = 45) were female and 34.3% (n = 47) had diabetes mellitus. The overall mean oPMN count was low (mean 1.3 × 10 5 cells/mL), and the mean SYNTAX score was 7.4 ± 8.5. Most of the patients presented with stable angina (89.8%, n =123). Patients with oPMN ≥1.45 × 10 5 (periodontitis threshold) were more likely to be elderly males presenting with stable angina. No significant correlation was established between oPMN and SYNTAX score. Although this prospective study did not demonstrate a correlation between OIL and the severity of CAD, most patients had low mean oPMN values. Larger studies are required before definite conclusions can be drawn.

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Section: Discussionmentioning

confidence: 99%

Oral inflammatory load in patients with coronary artery disease

et al. 2019

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“…Interestingly, higher serum levels of MMP-9 have been observed in acute coronary syndrome. 19 The ratio between the domains was significantly lower in ACS than in stable angina or in controls.…”

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confidence: 89%

Acute coronary syndromes: the tipping point of coronary artery disease

Lüscher

2018

European Heart Journal

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For the podcast associated with this article, please visit https://academic. oup.com/eurheartj/pages/Podcasts.Heart attacks are the tipping point, from the nuisance of exerciseinduce angina to a potentially lethal outcome. In spite of enormous progress made since Eisenhower's famous heart attack on 25 September 1955, 1,2 acute coronary syndromes remain the major cause of mortality in Western countries, as again documented in the most recent ESC Atlas published earlier this year. showed that overall mortality related to this condition declined impressively, but patients presenting in cardiogenic shock or after cardiopulmonary resuscitation still have an unacceptable fatality rate. The most recent ESC guidelines in the management of ST-segment elevation myocardial infarction 6 are summarized and includeamong others-an upgrade on the recommendation of radial access, 7,8 of drug-eluting over bare metal stents, complete revascularization, enoxaparin, and early discharge, while thrombus aspiration and bivalirudin utilization have been downgraded, particularly as with radial access there seems to be no benefit over heparin.

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“…Of interest, CD31 extracellular domain is shed from the lymphocyte surface during ACS and this contributes to the over activation of adaptive immunity[ 19 ]. In their recent article, Angelini et al[ 10 ] added one more piece to this puzzle by showing matrix metalloproteinase (MMP)-9 to be involved in CD31 cleavage in lymphocytes from ACS patients. Firstly, they confirm CD31 shedding to be a specific feature of lymphocytes in ACS, as compared to samples from healthy subjects but also patients with stable angina (SA).…”

Section: Mmp-9 and Cd31: A Dangerous Associationmentioning

confidence: 99%

“…Finally, after observing CD31 to be a possible substrate for MMP-9 by using an dedicated software predicting novel substrates and their cleavage sites, the authors show lymphocytes from ACS patients to produce higher enzyme levels after stimulation and CD31 active domain to be preserved by MMP-9 inhibition. Based on these results, the authors propose a new sequence of events that might characterize ACS onset in which the increased release of MMP-9 causes CD31 cleavage, thus affecting TCR-dependent T-cell activation and causing T-cell hyperactivity[ 10 ].…”

Section: Mmp-9 and Cd31: A Dangerous Associationmentioning

confidence: 99%

“…Afterward, the same immune-mediated tissue injury supplies the amount of autoantigens necessary to maintain the auto-reactivity thus sustaining the dysfunctional immune cardiac process[ 9 ]. This editorial refers to the outstanding research article entitled “matrix metalloproteinases-9 might affect adaptive immunity in non-ST segment elevation ACS by increasing CD31 cleavage on CD4+ cells”, recently published by Angelini et al[ 10 ] in European Heart Journal.…”

Section: Introductionmentioning

confidence: 99%

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T-cells in myocardial infarction: Culprit instigators or mere effectors?

Liberale¹,

Bonaventura²,

Montecucco³

2018

WJC

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Immune system activation and dysfunction characterize the early phase of reperfusion after a myocardial infarction (MI). Despite initially neglected, adaptive immunity has been recently showed to play an important role in this setting. In fact, the immune system can recognize sequestered antigens released by the necrotic tissue, initiating a deleterious autoimmune vicious circle leading to worse outcome. In their recent work, Angelini et al shed the light on a new feature of post-MI which involves two “old players” of post-ischemic myocardial injury: CD31 and matrix metalloproteinase (MMP)-9. Specifically, the authors showed that an enhancement of MMP-9 release could determine the cleavage of inhibitory CD31 from CD4+ T-cells surface in patients with Acute Coronary Syndromes (ACS). These findings open the room for new studies investigating the role of MMP9 in other pathological processes associated with a reduction of CD31 functionality, such as plaque instability and rupture. Of interest, in the case of a causative role for CD31 shedding in ACS would be confirmed, there might be a potential role for the administration of CD31 protein or analogue compounds to blunt post-ischemic cardiac inflammation and improve ACS outcome.

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Matrix metalloproteinase-9 might affect adaptive immunity in non-ST segment elevation acute coronary syndromes by increasing CD31 cleavage on CD4+ T-cells

Cited by 29 publications

References 30 publications

Oral inflammatory load in patients with coronary artery disease

Oral inflammatory load in patients with coronary artery disease

Acute coronary syndromes: the tipping point of coronary artery disease

T-cells in myocardial infarction: Culprit instigators or mere effectors?

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