A multiomics approach reveals novel regulators of plasma factor V levels, highlighting CLEC4M as a clearance receptor
Abstract
Abstract Coagulation factor V (FV) is a key protein in maintaining the hemostatic balance, with abnormal plasma levels associated with both thrombotic and hemorrhagic conditions. We propose a comprehensive bioinformatic analysis integrating large-scale proteogenomics and transcriptomic data from original and public data sets. We identify a biological fingerprint of 26 new proteins and loci involved in the regulation of plasma FV levels. Furthermore, the messenger RNA expression levels of 10 of these components demonstrate strong correlation in the liver. In addition, we provide experimental evidence for the involvement of one of the newly identified players (CLEC4M) in the clearance of FV. This work opens new avenues for a better understanding of the physiological processes involved in thrombotic and bleeding disorders.
Article Details
Authors (26)
Gaëlle Munsch
1University of Bordeaux, INSERM, Bordeaux Population Health Research Center, UMR 1219, Bordeaux, France
Adarsh K. Mohapatra
2Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, The Netherlands
Astrid van Hylckama Vlieg
6Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
Marcus E. Kleber
Angel Martinez-Perez
Ngoc-Quynh Le
7Unit of Genomics of Complex Disease, Institut de Recerca Sant Pau, Barcelona, Spain
Kristian Dalsbø Hindberg
9Thrombosis Research Center, Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway
Philip Dusart
10Department of Protein Science, Science for Life Laboratory, Royal Institute of Technology, Stockholm, Sweden
Marine Germain
1University of Bordeaux, INSERM, Bordeaux Population Health Research Center, UMR 1219, Bordeaux, France
Florian Thibord
INSERM UMR 1219, Bordeaux Population Health Research Center, Bordeaux, France (F.T.).
Jean-François Deleuze
Graciela E. Delgado
Louisa Goumidi
8Cardiovascular and Nutrition Research Center, INSERM, Institut national de recherche pour l'agriculture, l'alimentation et l'environnement, Aix-Marseille University, Marseille, France
Pierre Suchon
8Cardiovascular and Nutrition Research Center, INSERM, Institut national de recherche pour l'agriculture, l'alimentation et l'environnement, Aix-Marseille University, Marseille, France
Noémie Saut
8Cardiovascular and Nutrition Research Center, INSERM, Institut national de recherche pour l'agriculture, l'alimentation et l'environnement, Aix-Marseille University, Marseille, France
Juan-Carlos Souto
7Unit of Genomics of Complex Disease, Institut de Recerca Sant Pau, Barcelona, Spain
Lynn M. Butler
14Clinical Chemistry and Blood Coagulation Research, Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden
Jose-Manuel Soria
7Unit of Genomics of Complex Disease, Institut de Recerca Sant Pau, Barcelona, Spain
John-Bjarne Hansen
Winfried März
Frits R. Rosendaal
Elisabetta Castoldi
2Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, The Netherlands
Franck Peiretti
3Aix Marseille Université, INSERM, Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement, Centre de Recherche en CardioVasculaire et Nutrition, Marseille, France
Maria Sabater-Lleal
Unit of Genomics of Complex Diseases, Institut de Recerca Sant Pau (IR SANT PAU), Barcelona, Spain (M.S.-L.).
David-Alexandre Trégouët
Pierre-Emmanuel Morange