Galectin-3 and Blood Group: Binding Properties, Effects on Plasma Levels, and Consequences for Prognostic Performance

Carolin Pozder; Elles M Screever; A Rogier van der Velde; Herman H Silljé; Janne Suwijn; Saskia de Rond; Marcus E Kleber; Graciela Delgado; Jan Jacob Schuringa; Wiek H van Gilst; Wouter C Meijers; Winfried März; Rudolf A de Boer

doi:10.3390/ijms24054415

Galectin-3 and Blood Group: Binding Properties, Effects on Plasma Levels, and Consequences for Prognostic Performance

Int J Mol Sci. 2023 Feb 23;24(5):4415. doi: 10.3390/ijms24054415.

Authors

Carolin Pozder¹, Elles M Screever^{1

2}, A Rogier van der Velde¹, Herman H Silljé¹, Janne Suwijn^{3

4}, Saskia de Rond^{3

4}, Marcus E Kleber^{3

4}, Graciela Delgado³, Jan Jacob Schuringa⁵, Wiek H van Gilst¹, Wouter C Meijers^{1

2}, Winfried März^{3

6}, Rudolf A de Boer^{1

2}

Affiliations

¹ Department of Cardiology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
² Department of Cardiology, Thorax Center, Erasmus University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
³ Mannheim Medical Faculty, Medical Clinic V (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), University of Heidelberg, 68167 Mannheim, Germany.
⁴ SYNLAB MVZ Humangenetik Mannheim, 68163 Mannheim, Germany.
⁵ Department of Experimental Hematology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
⁶ Synlab Academy, SYNLAB Holding Deutschland GmbH, 68159 Mannheim, Germany.

Abstract

Previous studies have reported an association between ABO type blood group and cardiovascular (CV) events and outcomes. The precise mechanisms underpinning this striking observation remain unknown, although differences in von Willebrand factor (VWF) plasma levels have been proposed as an explanation. Recently, galectin-3 was identified as an endogenous ligand of VWF and red blood cells (RBCs) and, therefore, we aimed to explore the role of galectin-3 in different blood groups. Two in vitro assays were used to assess the binding capacity of galectin-3 to RBCs and VWF in different blood groups. Additionally, plasma levels of galectin-3 were measured in different blood groups in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study (2571 patients hospitalized for coronary angiography) and validated in a community-based cohort of the Prevention of Renal and Vascular End-stage Disease (PREVEND) study (3552 participants). To determine the prognostic value of galectin-3 in different blood groups, logistic regression and cox regression models were used with all-cause mortality as the primary outcome. First, we demonstrated that galectin-3 has a higher binding capacity for RBCs and VWF in non-O blood groups, compared to blood group O. Additionally, LURIC patients with non-O blood groups had substantially lower plasma levels of galectin-3 (15.0, 14.9, and 14.0 μg/L in blood groups A, B, and AB, respectively, compared to 17.1 μg/L in blood group O, p < 0.0001). Finally, the independent prognostic value of galectin-3 for all-cause mortality showed a non-significant trend towards higher mortality in non-O blood groups. Although plasma galectin-3 levels are lower in non-O blood groups, the prognostic value of galectin-3 is also present in subjects with a non-O blood group. We conclude that physical interaction between galectin-3 and blood group epitopes may modulate galectin-3, which may affect its performance as a biomarker and its biological activity.

Keywords: biomarker; blood group; galectin-3; prognosis; von Willebrand factor.

MeSH terms

ABO Blood-Group System
Galectin 3*
Humans
Kidney / metabolism
Prognosis
von Willebrand Factor* / metabolism

Substances

von Willebrand Factor
Galectin 3
ABO Blood-Group System

Grants and funding

This work was supported by grants from the Dutch Heart Foundation (CVON SHE-PREDICTS-HF, Grant 2017-21; CVON RED-CVD, Grant 2017-11; CVON PREDICT2, grant 2018-30; CVON DOUBLE DOSE, grant 2020B005; and grant 2000Z003), by a grant from the leDucq Foundation (Cure PhosphoLambaN induced Cardiomyopathy (Cure-PLaN)), and by a grant from the European Research Council (ERC CoG 818715, SECRETE-HF). Dr. Meijers is supported by the Mandema-Stipendium of the Junior Scientific Masterclass 2020-10 of the University Medical Center Groningen and by the Dutch Heart Foundation (Dekker grant 03-005-2021-T005). The funders had no role in the design and conduct of the study; collection, analysis, and interpretation of data; writing of the manuscript; and decision to submit the manuscript for publication.