title: Insulin-regulated increase of soluble vascular adhesion protein-1 in diabetes.
abstract: Vascular adhesion protein-1 (VAP-1) is one of the molecules on the endothelial cell membrane, which may guide inflammatory cells into atherosclerotic lesions. This dual function molecule may also contribute to the pathogenesis of atherosclerosis and other vasculopathies via its enzymatic activity that oxidizes primary amines to produce their corresponding aldehydes, hydrogen peroxide, and ammonium. Because VAP-1 also exists in a soluble form, we analyzed its potential usefulness as a biomarker to monitor and predict the extent of ongoing atherosclerotic processes. Soluble VAP-1 (sVAP-1) levels were determined from the sera of 136 Finnish men with established coronary heart disease and in 275 controls using sandwich enzyme immunoassays and correlated to multiple risk factors for coronary events. Intriguingly, sVAP-1 showed a statistically significant correlation with diabetes in both cohorts. We then collected patients with type 1 diabetes and observed that sVAP-1 levels were highly elevated when the patients were metabolically compromised. On normalization of their blood glucose and ketone body levels by exogenous insulin, their sVAP-1 concentration rapidly decreased to control levels. Intravenous glucose tolerance and hyperinsulinemic clamp tests further showed that elevation of blood glucose per se did not increase sVAP-1 levels, but rather, sVAP-1 was inversely correlated with circulating insulin concentrations. In conclusion insulin appears to regulate shedding or clearance of VAP-1, and an increase in sVAP-1 because of absolute or relative insulin deficiency may be directly involved in the pathogenesis of diabetic angiopathy.
authors.affiliation: MediCity Research Laboratory, University of Turku, Tykistökatu 6A, 20520 Turku, Finland. marko.salmi@utu.fi
authors.forename: Marko
authors.initials: M
authors.lastname: Salmi
authors.forename: Craig
authors.initials: C
authors.lastname: Stolen
authors.forename: Pekka
authors.initials: P
authors.lastname: Jousilahti
authors.forename: Gennady G
authors.initials: GG
authors.lastname: Yegutkin
authors.forename: Päivi
authors.initials: P
authors.lastname: Tapanainen
authors.forename: Tuula
authors.initials: T
authors.lastname: Janatuinen
authors.forename: Mikael
authors.initials: M
authors.lastname: Knip
authors.forename: Sirpa
authors.initials: S
authors.lastname: Jalkanen
authors.forename: Veikko
authors.initials: V
authors.lastname: Salomaa
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D006631:Amine Oxidase (Copper-Containing) / Q000378:metabolism*; D001161:Arteriosclerosis / Q000503:physiopathology; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002648:Child; D015331:Cohort Studies; D003327:Coronary Disease / Q000503:physiopathology; D003920:Diabetes Mellitus / Q000378:metabolism*; D005387:Finland; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D013223:Statistics as Topic
chemical_list: D015815:Cell Adhesion Molecules; D007328:Insulin; C076668:AOC3 protein, human; D006631:Amine Oxidase (Copper-Containing)