Functional investigation of the coronary artery disease gene SVEP1

• DOI: 10.1007/s00395-020-00828-6
• Publication Date: 2020-11-13T10:02:57Z
• Authors: Michael J. Winkler; Philipp Müller; Amin M. Sharifi; Jana Wobst; Hanna Winter; Michal Mokry; Lijiang Ma; Sander W. van der...; Shichao Pang; Benedikt Miritsch; Julia Hinterdobler; Julia Werner; Barbara Stiller; Ulrich Güldener; Tom R. Webb; Folkert W. Asselb...; Johan L. M. Björk...; Lars Maegdefessel; Heribert Schunkert; Hendrik B. Sager; Thorsten Kessler
• Keywords: 0301 basic medicine; Physiology; Mice, Knockout, ApoE; Chemokine CXCL1; Myocytes, Smooth Muscle; Endothelial Cells/pathology [MeSH] ; Coronary Artery Disease/pathology [MeSH] ; Mice, Inbred C57BL [MeSH] ; Coronary Artery Disease/genetics [MeSH] ; Polymorphism, Single Nucleotide [MeSH] ; Haploinsufficiency [MeSH] ; Original Contribution ; Atherosclerosis ; Genetic Association Studies [MeSH] ; Macrophages/metabolism [MeSH] ; Genetics ; Neutrophils/pathology [MeSH] ; Cell Adhesion Molecules/genetics [MeSH] ; Coronary Artery Disease/metabolism [MeSH] ; Calcium-Binding Proteins/metabolism [MeSH] ; Cell Adhesion Molecules/metabolism [MeSH] ; Disease Models, Animal [MeSH] ; Genetic Predisposition to Disease [MeSH] ; Endothelial Cells/metabolism [MeSH] ; Myocytes, Smooth Muscle/pathology [MeSH] ; Cell Adhesion Molecules/deficiency [MeSH] ; Chemokine CXCL1/genetics [MeSH] ; Humans [MeSH] ; Coronary Vessels/pathology [MeSH] ; Animals [MeSH] ; Coronary Vessels/metabolism [MeSH] ; Chemotaxis, Leukocyte [MeSH] ; Mice, Knockout, ApoE [MeSH] ; Calcium-Binding Proteins/genetics [MeSH] ; Chemokine CXCL1/metabolism [MeSH] ; Myocytes, Smooth Muscle/metabolism [MeSH] ; Neutrophil Infiltration [MeSH] ; Proteins/genetics [MeSH] ; SVEP1 ; Plaque, Atherosclerotic [MeSH] ; Cells, Cultured [MeSH] ; Proteins/metabolism [MeSH] ; Coronary artery disease ; Calcium-Binding Proteins/deficiency [MeSH] ; Antigens, Ly/metabolism [MeSH]; Coronary Artery Disease; Haploinsufficiency; Coronary artery disease; 03 medical and health sciences; Physiology (medical); Genetics; Journal Article; Animals; Antigens, Ly; Humans; Genetic Predisposition to Disease; SVEP1; Cells, Cultured; Genetic Association Studies; Macrophages; Calcium-Binding Proteins; Endothelial Cells; Original Contribution; Atherosclerosis; Coronary Vessels; ddc:; 3. Good health; Mice, Inbred C57BL; Chemotaxis, Leukocyte; Disease Models, Animal; Neutrophil Infiltration; Original Contribution ; SVEP1 ; Atherosclerosis ; Coronary artery disease ; Genetics; Cardiology and Cardiovascular Medicine; Cell Adhesion Molecules

A missense variant of the sushi, von Willebrand factor type A, EGF and pentraxin domain containing protein 1 (SVEP1) is genome-wide significantly associated with coronary artery disease. The mechanisms how SVEP1 impacts atherosclerosis are not known. We found endothelial cells (EC) vascular smooth muscle to represent major cellular source in plaques. Plaques were larger atherosclerosis-prone Svep1 haploinsufficient (ApoE