Association between endogenous complement inhibitor and myocardial salvage in patients with myocardial infarction

Holt, Charlotte B.; Thiel, Steffen; Munk, Kim; Østergaard, Jakob Appel; Bøtker, Hans Erik; Hansen, Troels Krarup

doi:10.1177/2048872613507004

Cited by 13 publications

(19 citation statements)

References 34 publications

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“…This finding has later been confirmed (Frauenknecht et al, 2013). The latter group also measured an increase in plasma MASP-1 in acute myocardial infarction, a finding recently reproduced by others (Frauenknecht et al, 2013;Holt et al, 2014). Collectively these data indicate that genetic low MBL is beneficial by reduced activation potential of the lectin pathway, whereas the consequences of the changes in MASPs are more uncertain.…”

Section: Evidence For Complement Activation In Coronary Heart Diseasesupporting

confidence: 59%

A vital role for complement in heart disease

Lappegård

Garred

Jonasson

et al. 2014

Molecular Immunology

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Heart diseases are common and significant contributors to worldwide mortality and morbidity. During recent years complement mediated inflammation has been shown to be an important player in a variety of heart diseases. Despite some negative results from clinical trials using complement inhibitors, emerging evidence points to an association between the complement system and heart diseases. Thus, complement seems to be important in coronary heart disease as well as in heart failure, where several studies underscore the prognostic importance of complement activation. Furthermore, patients with atrial fibrillation often share risk factors both with coronary heart disease and heart failure, and there is some evidence implicating complement activation in atrial fibrillation. Moreover, Chagas heart disease, a protozoal infection, is an important cause of heart failure in Latin America, and the complement system is crucial for the protozoa-host interaction. Thus, complement activation appears to be involved in the pathophysiology of a diverse range of cardiac conditions. Determination of the exact role of complement in the various heart diseases will hopefully help to identify patients that might benefit from therapeutic complement intervention.

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Section: Evidence For Complement Activation In Coronary Heart Diseasesupporting

confidence: 59%

A vital role for complement in heart disease

Lappegård

Garred

Jonasson

et al. 2014

Molecular Immunology

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“…This support our previous finding, that even though the lectin pathway components are elevated in patients with MI, they are not directly associated with the extent of cardiac damage [14]. Our study shows no correlation between levels of the initiating molecules of the lectin pathway, nor the final complement activation end-product and the magnitude of the cardiac damage.…”

Section: Discussionsupporting

confidence: 91%

“…On one hand, MBL is shown to be protective in the development of coronary artery disease, but on the other hand it is suggested to be harmful [11,12]. We showed that proteins involved in regulation of the lectin pathway, MAp44, MASP-1 and MASP-3, are found at higher concentrations in patients with acute MI compared to healthy controls, but these proteins had no association with infarct size [14]. We showed that proteins involved in regulation of the lectin pathway, MAp44, MASP-1 and MASP-3, are found at higher concentrations in patients with acute MI compared to healthy controls, but these proteins had no association with infarct size [14].…”

Section: Introductionmentioning

confidence: 73%

Circulating lectin pathway proteins do not predict short-term cardiac outcomes after myocardial infarction

Holt

Østergaard

Thiel

et al. 2019

Clinical and Experimental Immunology

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Despite improvements in treatment, coronary artery disease is still responsible for one-third of all deaths globally, due predominantly to myocardial infarction (MI) and stroke. There is an important potential in developing new strategies for treatment of patients with these conditions. Inflammation, and in particular the actions of the complement system, has emerged as part of the pathogenesis in reperfusion injury in patients with MI. To further qualify this, we examined the association between the plasma levels of lectin pathway proteins and myocardial end-points, left ventricular ejection fraction (LVEF) and infarct size in a cohort of patients with ST-elevation myocardial infarction (STEMI). A blood sample was drawn the day after percutaneous coronary intervention from 73 patients with STEMI. The primary end-points, LVEF and infarct size, were measured with magnetic resonance imaging 6-9 days after the infarct. Complement pattern-recognition molecules of the lectin pathway (mannanbinding lectin, H-ficolin, L-ficolin and M-ficolin) were analysed along with soluble membrane attack complex (sMAC) and C-reactive protein (CRP)in plasma with immunofluorometric assays <50%. CRP correlated negatively with LVEF, regression coefficient = -0·17 (P = 0·01). None of the lectin pathway proteins correlated to LVEF or infarct size, nor did soluble membrane attack complex (sMAC). There were no differences in plasma levels of these complement proteins when comparing patients with ejection fraction <50% to patients with ejection fraction <50%. Pattern-recognition molecules of the lectin pathway and sMAC do not predict shortterm cardiac outcomes after MI.

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“…The few previous studies on MASPs in CVD were case-control studies, 19 or measured MASPs at admission for an acute CVE, 20 or measured only a single MASP (MASP-2). 21 During the 7-year follow-up period, the CODAM participants with plasma MBL levels in the lowest tertile were characterized by more inflammation than those in the middle tertile.…”

Section: Discussionmentioning

confidence: 99%

“…MBL circulates in plasma as a complex with MBL-associated proteases (MASPs) and MBL-associated proteins (MAps) that mediate or regulate downstream complement activation. 7,17,18 In humans, MASPs and MAps have been measured in case-control studies or during acute cardiovascular events (CVEs), [19][20][21] but longitudinal studies on the role of MASPs and MAps in CVD are not yet available.…”

mentioning

confidence: 99%

Distinct Longitudinal Associations of MBL, MASP-1, MASP-2, MASP-3, and MAp44 With Endothelial Dysfunction and Intima–Media Thickness

Hertle

Arts

Kallen

et al. 2016

ATVB

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12associations with future CVD. When the effect of MBL on complications of established CVD was investigated, low MBL was in fact protective in most studies. [13][14][15] Thus, considerable discrepancy remains in the literature on whether MBL has beneficial or adverse effects in CVD.This reported discrepancy might be explained by a dual role of MBL in different etiologic aspects of CVD. Objective-Previous studies suggested that the lectin-complement pathway plays a complex role in cardiovascular disease (CVD). To date, no prospective human studies have investigated the relationship between the initiating factor of the lectin pathway, that is, mannose-binding lectin (MBL), and low-grade inflammation, endothelial dysfunction, or carotid intima-media thickness (cIMT). Moreover, MBL-associated proteases (MASPs) and MBL-associated proteins (MAps), which mediate downstream complement activation, have not been studied in the development of CVD. Approach and Results-In a prospective cohort (n=574; age 60±7 years; 7-year follow-up), we investigated longitudinal associations of plasma MBL, MASP-1, MASP-2, MASP-3, and MAp44 with biomarker scores that reflect low-grade inflammation and endothelial dysfunction, respectively, and with cIMT. We also investigated their associations with incident CVD (n=73). In adjusted analyses, low-grade inflammation was lowest in the middle tertile (T Middle )

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Association between endogenous complement inhibitor and myocardial salvage in patients with myocardial infarction

Abstract: Plasma levels of MAp44, MASP-1, and MASP-3 are significantly higher in patients with MI compared to healthy control persons, but are not associated with short-term outcome measured as salvage index and final infarct.

Cited by 13 publications

References 34 publications

A vital role for complement in heart disease

A vital role for complement in heart disease

Circulating lectin pathway proteins do not predict short-term cardiac outcomes after myocardial infarction

Distinct Longitudinal Associations of MBL, MASP-1, MASP-2, MASP-3, and MAp44 With Endothelial Dysfunction and Intima–Media Thickness

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