title: C-peptide promotes lesion development in a mouse model of arteriosclerosis.
abstract: Patients with insulin resistance and early type 2 diabetes exhibit an increased propensity to develop a diffuse and extensive pattern of arteriosclerosis. Typically, these patients show elevated serum levels of the proinsulin cleavage product C-peptide and immunohistochemical data from our group revealed C-peptide deposition in early lesions of these individuals. Moreover, in vitro studies suggest that C-peptide could promote atherogenesis. This study examined whether C-peptide promotes vascular inflammation and lesion development in a mouse model of arteriosclerosis. ApoE-deficient mice on a high fat diet were treated with C-peptide or control injections for 12 weeks and the effect on lesion size and plaque composition was analysed. C-peptide treatment significantly increased C-peptide blood levels by 4.8-fold without having an effect on glucose or insulin levels, nor on the lipid profile. In these mice, C-peptide deposition in atherosclerotic plaques was significantly increased compared with controls. Moreover, lesions of C-peptide-treated mice contained significantly more macrophages (1.6 ± 0.3% versus 0.7 ± 0.2% positive area; P < 0.01) and more vascular smooth muscle cells (4.8 ± 0.6% versus 2.4 ± 0.3% positive area; P < 0.01). Finally, lipid deposition measured by Oil-red-O staining in the aortic arch was significantly higher in the C-peptide group compared with controls. Our results demonstrate that elevated C-peptide levels promote inflammatory cell infiltration and lesion development in ApoE-deficient mice without having metabolic effects. These data obtained in a mouse model of arteriosclerosis support the hypothesis that C-peptide may have an active role in atherogenesis in patients with diabetes and insulin resistance.
authors.affiliation: Department of Internal Medicine II - Cardiology, University of Ulm, Ulm, Germany.
authors.forename: Dusica
authors.initials: D
authors.lastname: Vasic
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Marx
authors.forename: Galina
authors.initials: G
authors.lastname: Sukhova
authors.forename: Helga
authors.initials: H
authors.lastname: Bach
authors.forename: Renate
authors.initials: R
authors.lastname: Durst
authors.forename: Miriam
authors.initials: M
authors.lastname: Grüb
authors.forename: Angelina
authors.initials: A
authors.lastname: Hausauer
authors.forename: Vinzenz
authors.initials: V
authors.lastname: Hombach
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Rottbauer
authors.forename: Daniel
authors.initials: D
authors.lastname: Walcher
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D001161:Arteriosclerosis / Q000378:metabolism / Q000473:pathology*; D002096:C-Peptide / Q000378:metabolism / Q000502:physiology*; D004195:Disease Models, Animal; D066298:In Vitro Techniques; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data
chemical_list: D001057:Apolipoproteins E; D002096:C-Peptide