Publications

Authors:

Lunghi, Barbara; Castagna, Annalisa; Branchini, Alessio; Baroni, Marcello; Marchetti, Giovanna; Mazzoni, Gianni; Legnani, Cristina; Spizzo, Marianna; Mango, Gabriele; Friso, Simonetta; Martinelli, Nicola; Bernardi, Francesco

Title:

Selected cell receptor genotypes differentially modulate the ABO blood group influence on Factor VIII levels in severe aortic stenosis

Year:

2025

Type of item:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Language:

Inglese

Format:

Elettronico

Referee:

Sì

Name of journal:

Thrombosis Research

ISSN of journal:

0049-3848

N° Volume:

251

Page numbers:

1-9

Keyword:

ABO blood-group; ASGR2; Aortic valve stenosis; CLEC4M; Factor VIII; LDLR; STAB2

Short description of contents:

Background: Altered blood flow, which characterizes aortic stenosis (AS), influences von Willebrand factor (VWF) conformation and enhances ADAMTS13 cleavage, potentially influencing factor VIII (FVIII) clearance and plasma levels. Aim: To investigate whether ABO blood group and genetic variants of cellular receptors involved in VWF/FVIII clearance may interact with AS in determining genotype-driven FVIII levels. Patients/methods: FVIII:c levels were analyzed in patients with severe AS (SAS, n = 115), with coronary artery disease and without valvular heart disease (CAD, n = 300), and healthy subjects (HS, n = 172), clustered according to ABO and receptor genotypes. Variants with functional association with receptor mRNA and/or FVIII levels, localized in 5 receptors (LDLR, STAB2, SCARA5, ASGR2, CLEC4M) with different VWF/FVIII binding properties, were selected. Results: In SAS group, a significant interaction between ABO and receptor genotypes in modulating FVIII:c levels was observed with positive B values for lectins (ASGR2 and CLEC4M) and negative for LDLR and STAB2. The lectin variants, as well as their combinations, showed significantly lower FVIII levels in the non-O group with high glycan expression and potentially improved FVIII binding and increased clearance. Differently, the non-lectin LDLR and STAB2 variants, and their combinations, were associated with genotype-driven high FVIII levels, particularly in the O group. All these patterns were not observed in CAD or HS groups. Conclusion: These observations suggest that differential interaction between genotypes of specific cellular receptors and ABO blood group may contribute to high/low FVIII:c levels in O/non-O blood group subjects, respectively, and to the large inter-individual variability of FVIII levels in SAS.

Web page:

https://doi.org/10.1016/j.thromres.2025.109356

Product ID:

146248

Handle IRIS:

11562/1164809

Last Modified:

June 14, 2025

Bibliographic citation:

Lunghi, Barbara; Castagna, Annalisa; Branchini, Alessio; Baroni, Marcello; Marchetti, Giovanna; Mazzoni, Gianni; Legnani, Cristina; Spizzo, Marianna; Mango, Gabriele; Friso, Simonetta; Martinelli, Nicola; Bernardi, Francesco, Selected cell receptor genotypes differentially modulate the ABO blood group influence on Factor VIII levels in severe aortic stenosis «Thrombosis Research» , vol. 251 , 2025 , pp. 1-9

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