title: Soluble CD93 Is Involved in Metabolic Dysregulation but Does Not Influence Carotid Intima-Media Thickness.
abstract: Type 2 diabetes and cardiovascular disease are complex disorders involving metabolic and inflammatory mechanisms. Here we investigated whether sCD93, a group XIV c-type lectin of the endosialin family, plays a role in metabolic dysregulation or carotid intima-media thickness (IMT). Although no association was observed between sCD93 and IMT, sCD93 levels were significantly lower in subjects with type 2 diabetes (n = 901, mean ± SD 156.6 ± 40.0 ng/mL) compared with subjects without diabetes (n = 2,470, 164.1 ± 44.8 ng/mL, P < 0.0001). Genetic variants associated with diabetes risk (DIAGRAM Consortium) did not influence sCD93 levels (individually or combined in a single nucleotide polymorphism score). In a prospective cohort, lower sCD93 levels preceded the development of diabetes. Consistent with this, a cd93-deficient mouse model (in addition to apoe deficiency) demonstrated no difference in atherosclerotic lesion development compared with apoe(-/-) cd93-sufficient littermates. However, cd93-deficient mice showed impaired glucose clearance and insulin sensitivity (compared with littermate controls) after eating a high-fat diet. The expression of cd93 was observed in pancreatic islets, and leaky vessels were apparent in cd93-deficient pancreases. We further demonstrated that stress-induced release of sCD93 is impaired by hyperglycemia. Therefore, we propose CD93 as an important component in glucometabolic regulation.
authors.affiliation: Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden rona.strawbridge@ki.se.
authors.forename: Rona J
authors.initials: RJ
authors.lastname: Strawbridge
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Agneta
authors.initials: A
authors.lastname: Hilding
authors.affiliation: Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Angela
authors.initials: A
authors.lastname: Silveira
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden Cell Therapy Institute, Nova Southeastern University, Fort Lauderdale, FL.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Österholm
authors.affiliation: Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Bengt
authors.initials: B
authors.lastname: Sennblad
authors.affiliation: Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Olga
authors.initials: O
authors.lastname: McLeod
authors.affiliation: Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Panagiota
authors.initials: P
authors.lastname: Tsikrika
authors.affiliation: Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Fariba
authors.initials: F
authors.lastname: Foroogh
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Milan, Italy Centro Cardiologico Monzino, Istituto di Ricovero e Cura a Carattere Scientifico, Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Tremoli
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Milan, Italy Centro Cardiologico Monzino, Istituto di Ricovero e Cura a Carattere Scientifico, Milan, Italy.
authors.forename: Damiano
authors.initials: D
authors.lastname: Baldassarre
authors.affiliation: Centro Cardiologico Monzino, Istituto di Ricovero e Cura a Carattere Scientifico, Milan, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Veglia
authors.affiliation: Foundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine, Kuopio, Finland Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Rainer
authors.initials: R
authors.lastname: Rauramaa
authors.affiliation: Department of Medicine, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Andries J
authors.initials: AJ
authors.lastname: Smit
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Service Endocrinologie-Métabolisme, Groupe Hospitalier Pitié-Salpétrière, Unités de Prévention Cardiovasculaire, Paris, France.
authors.forename: Phillipe
authors.initials: P
authors.lastname: Giral
authors.affiliation: Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio Campus, Kuopio, Finland.
authors.forename: Sudhir
authors.initials: S
authors.lastname: Kurl
authors.affiliation: Department of Clinical and Experimental Medicine, Internal Medicine, Angiology and Arteriosclerosis Diseases, University of Perugia, Perugia, Italy.
authors.forename: Elmo
authors.initials: E
authors.lastname: Mannarino
authors.affiliation: Bracco Medical Department, Milan, Italy.
authors.forename: Enzo
authors.initials: E
authors.lastname: Grossi
authors.affiliation: Department of Medical Sciences, Molecular Medicine and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Ann-Christine
authors.initials: AC
authors.lastname: Syvänen
authors.affiliation: Centre for Cardiovascular Genetics, University College London, London, U.K.
authors.forename: Steve E
authors.initials: SE
authors.lastname: Humphries
authors.affiliation: Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Ulf
authors.initials: U
authors.lastname: de Faire
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Claes-Göran
authors.initials: CG
authors.lastname: Östenson
authors.affiliation: Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Maegdefessel
authors.affiliation: Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Hamsten
authors.affiliation: Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Bäcklund
mesh_terms: D000818:Animals; D001057:Apolipoproteins E; D050197:Atherosclerosis / Q000378:metabolism; D059168:Carotid Intima-Media Thickness; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010179:Pancreas / Q000378:metabolism; D011951:Receptors, Complement / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D001057:Apolipoproteins E; D008562:Membrane Glycoproteins; D011951:Receptors, Complement; C032402:complement 1q receptor