Distinct Longitudinal Associations of MBL, MASP-1, MASP-2, MASP-3, and MAp44 With Endothelial Dysfunction and Intima-Media Thickness The Cohort on Diabetes and Atherosclerosis Maastricht (CODAM) Study

Elisabeth Hertle*, Ilja C. W. Arts, Carla J. H. van der Kallen, Edith J. M. Feskens, Casper G. Schalkwijk, Ingeborg T. Hoffmann-Petersen, Steffen Thiel, Coen D. A. Stehouwer, Marleen M. J. van Greevenbroek

*Corresponding author for this work

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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) of MBL, that is, T-Middle was 0.19 SD (0.03 to 0.34) lower than T-Low, and 0.15 SD (-0.02 to 0.31) lower than T-High. cIMT was 28 mu m (-50 to -5) lower in the highest MBL tertile (T-High) than in T-Middle and did not differ between T-Low and T-Middle. MBL was not associated with endothelial dysfunction or CVD. MASP-1 and MASP-2 were not associated with any cardiovascular outcomes. MASP-3 and MAp44 were, independently of MBL levels, associated with endothelial dysfunction (per 1 SD higher MASP-3: beta=0.10 SD [0.02 to 0.18]; per 1 SD higher MAp44 beta=0.12 SD [0.04 to 0.20]) but not with low-grade inflammation, cIMT, or CVD. Conclusions-High MBL may contribute to low cIMT, whereas the association of MBL with low-grade inflammation was nonlinear. MASP-1 and MASP-2 were not associated with adverse cardiovascular outcomes. MASP-3 and MAp44 may play a role in endothelial dysfunction, potentially independent of lectin-pathway activation.
Original languageEnglish
Pages (from-to)1278-1285
Number of pages28
JournalArteriosclerosis Thrombosis and Vascular Biology
Issue number6
Publication statusPublished - Jun 2016


  • carotid intima-media thickness
  • complement system proteins
  • inflammation
  • lectin-complement pathway
  • RISK

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