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Insulin-like growth factor II plays a central role in atherosclerosis in a mouse model.

Author:
  • Silvio Zaina
  • Linda Pettersson
  • Bo Ahrén
  • Lena Brånén
  • A Bassim Hassan
  • Marie Lindholm
  • Ragnar Mattsson
  • Johan Thyberg
  • Jan Nilsson
Publishing year: 2002
Language: English
Pages: 4505-4511
Publication/Series: Journal of Biological Chemistry
Volume: 277
Issue: 6
Document type: Journal article
Publisher: ASBMB

Abstract english

Insulin-like growth factor II is a fetal promoter of cell proliferation that is involved in some forms of cancer and overgrowth syndromes in humans. Here, we provide two sources of genetic evidence for a novel, pivotal role of locally produced insulin-like growth factor II in the development of atherosclerosis. First, we show that homozygosity for a disrupted insulin-like growth factor II allele in mice lacking apolipoprotein E, a widely used animal model of atherosclerosis, results in aortic lesions that are approximately 80% smaller and contain approximately 50% less proliferating cells compared with mice lacking only apolipoprotein E. Second, targeted expression of an insulin-like growth factor II transgene in smooth muscle cells, but not the mere elevation of circulating levels of the peptide, causes per se aortic focal intimal thickenings. The insulin-like growth factor II transgenics presented here are the first viable mutant mice spontaneously developing intimal masses. These observations provide the first direct evidence for an atherogenic activity of insulin-like growth factor II in vivo.

Keywords

  • Other Clinical Medicine
  • Animal
  • Pathology
  • Ultrastructure
  • Arteriosclerosis
  • Disease Models
  • Transgenes
  • Aorta

Other

Published
  • Cardiovascular Research - Immunity and Atherosclerosis
  • ISSN: 1083-351X
E-mail: jan [dot] nilsson [at] med [dot] lu [dot] se

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