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Jan Nilsson

Professor

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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

Summary, in 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.

Department/s

  • Cardiovascular Research - Immunity and Atherosclerosis
  • Medicine, Lund

Publishing year

2002

Language

English

Pages

4505-4511

Publication/Series

Journal of Biological Chemistry

Volume

277

Issue

6

Document type

Journal article

Publisher

ASBMB

Topic

  • Other Clinical Medicine

Keywords

  • Animal
  • Pathology
  • Ultrastructure
  • Arteriosclerosis
  • Disease Models
  • Transgenes
  • Aorta

Status

Published

Research group

  • Cardiovascular Research - Immunity and Atherosclerosis

ISBN/ISSN/Other

  • ISSN: 1083-351X