Pentraxin 3, ficolin-2 and lectin pathway associated serine protease MASP-3 as early predictors of myocardial infarction - the HUNT2 study

Abstract

The lectin complement pathway is suggested to play a role in atherogenesis. Pentraxin-3 (PTX3), ficolin-1, ficolin-2, ficolin-3, MBL/ficolin/collectin-associated serine protease-3 (MASP-3) and MBL/ficolin/collectin-associated protein-1 (MAP-1) are molecules related to activation of the lectin complement pathway. We hypothesized that serum levels of these molecules may be associated with the incidence of myocardial infarction (MI). In a Norwegian population-based cohort (HUNT2) where young to middle-aged relatively healthy Caucasians were followed up for a first-time MI from 1995–1997 through 2008, the 370 youngest MI patients were matched by age (range 29–62 years) and gender to 370 controls. After adjustments for traditional risk factors, the two highest tertiles of PTX3 and the highest tertiles of ficolin-2 and MASP-3 were associated with MI, with odds ratios (95% confidence interval) of 1.65 (1.10–2.47) and 2.79 (1.83–4.24) for PTX3, 1.55 (1.04–2.30) for ficolin-2, and 0.63 (0.043–0.94) for MASP-3. Ficolin-1, ficolin-3 and MAP-1 were not associated with MI. In a multimarker analysis of all associated biomarkers, only PTX3 and MASP-3 remained significant. PTX-3 and MASP-3 enhanced prediction of MI compared to the traditional Framingham risk score alone (AUC increased from 0.64 to 0.68, p = 0.006). These results support the role of complement-dependent inflammation in the pathophysiology of cardiovascular disease.

Local complement activation is associated with primary graft dysfunction after lung transplantation

“…The following lectin pathway pattern recognition molecules were measured in both plasma and BAL in duplicate: MBL, PTX3, FCN-1, FCN-2, and FCN-3 were quantified in specific sandwich ELISAs with monoclonal antibodies for each marker developed in the Laboratory of Molecular Medicine, Rigshospitalet, according to previously described procedures ( 57 – 61 ). All assays were optimized for automated analysis in a 384-well format on the Biomek FX robotic system (Beckman Coulter) ( 62 ). Alternative assays for C4 activation, i.e., C4c and sC5b-9 (TCC) were measured in ELISAs based on monoclonal antibodies against neoepitopes on the C4c fragment and C9 not exposed on the native molecules as described previously ( 63 , 64 ).…”

Pentraxin 3 in Cardiovascular Disease

“…These two studies illustrated a significant relation between PTX3 levels and cardiovascular mortality and all-cause death (60, 61). In addition, it was recently shown that higher PTX3 levels predicted occurrence of MI in a cohort of young or middle-aged individuals followed for a first-time MI (62).…”

The prognostic significance of heart-type fatty acid binding protein in patients with stable coronary heart disease

“…Ischemic heart disease and stroke have been the leading causes of death globally in the past decades, and the mortality rate from these diseases is gradually increasing. In addition to traditional cardiovascular (CV) risk factors such as smoking, type 2 diabetes mellitus (T2DM), hypertension (HTN) and dyslipidemia, researchers have investigated potential novel biomarkers, for instance, copeptin 1 , pentraxin-3 2 and heart-type fatty acid binding protein (H-FABP) to predict the clinical course and CV outcomes. In particular, H-FABP has been widely studied in patients with acute coronary syndrome (ACS), and it has been suggested to increase diagnostic sensitivity and possibly predict long-term survival 3 .…”