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Interleukin-10 deficiency increases atherosclerosis, thrombosis, and low-density lipoproteins in apolipoprotein E knockout mice.

Authors
  • Caligiuri, Giuseppina
  • Rudling, Mats
  • Ollivier, Véronique
  • Jacob, Marie-Paule
  • Michel, Jean-Baptiste
  • Hansson, Göran K
  • Nicoletti, Antonino
Type
Published Article
Journal
Molecular medicine (Cambridge, Mass.)
Publication Date
Jan 01, 2003
Volume
9
Issue
1-2
Pages
10–17
Identifiers
PMID: 12765335
Source
Medline
License
Unknown

Abstract

Interleukin (IL)-10 is an anti-inflammatory cytokine that may play a protective role in atherosclerosis. The aim of this study was to assess the effect of IL-10 deficiency in the apolipoprotein E knockout mouse. Apolipoprotein E deficient (E-/-) and IL-10 deficient (-/-) mice were crossed to generate E-/- x IL-10-/- double knockout mice. By 16 wk, cholesterol and triglycerides were similar in double and single knockouts but the lack of IL-10 led to increased low-density lipoprotein cholesterol whereas very-low-density lipoprotein was reduced. In parallel, T-helper 1 responses and lesion size were dramatically increased in double knockout compared with E-/- controls. At 48 wk, matrix metalloproteinases and tissue factor activities were increased in lesions of double-knockout mice. Furthermore, markers of systemic coagulation were increased, and vascular thrombosis in response to i.v. thrombin occurred more frequently in E-/- x IL-10-/- than in E-/- mice. Our findings suggest that IL-10 deficiency plays a deleterious role in atherosclerosis. The early phase of lesion development was increased, and the proteolytic and procoagulant activity was elevated in advanced lesions. These data show that IL-10 may reduce atherogenesis and improve the stability of plaques.

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