Insulin-like growth factor II plays a central role in atherosclerosis in a mouse model.
(2002) In Journal of Biological Chemistry 277(6). p.4505-4511- Abstract
- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/107055
- author
- Zaina, Silvio LU ; Pettersson, Linda ; Ahrén, Bo LU ; Brånén, Lena LU ; Hassan, A Bassim ; Lindholm, Marie LU ; Mattsson, Ragnar ; Thyberg, Johan and Nilsson, Jan LU
- organization
- publishing date
- 2002
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Animal, Pathology, Ultrastructure, Arteriosclerosis, Disease Models, Transgenes, Aorta
- in
- Journal of Biological Chemistry
- volume
- 277
- issue
- 6
- pages
- 4505 - 4511
- publisher
- American Society for Biochemistry and Molecular Biology
- external identifiers
-
- wos:000173813900093
- pmid:11726660
- scopus:0037040247
- ISSN
- 1083-351X
- DOI
- 10.1074/jbc.M108061200
- language
- English
- LU publication?
- yes
- id
- 2ab13cba-2b44-4f20-9b7c-bc6d382b29b6 (old id 107055)
- alternative location
- http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11726660&dopt=Abstract
- date added to LUP
- 2016-04-01 11:41:57
- date last changed
- 2024-01-07 17:07:22
@article{2ab13cba-2b44-4f20-9b7c-bc6d382b29b6, abstract = {{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.}}, author = {{Zaina, Silvio and Pettersson, Linda and Ahrén, Bo and Brånén, Lena and Hassan, A Bassim and Lindholm, Marie and Mattsson, Ragnar and Thyberg, Johan and Nilsson, Jan}}, issn = {{1083-351X}}, keywords = {{Animal; Pathology; Ultrastructure; Arteriosclerosis; Disease Models; Transgenes; Aorta}}, language = {{eng}}, number = {{6}}, pages = {{4505--4511}}, publisher = {{American Society for Biochemistry and Molecular Biology}}, series = {{Journal of Biological Chemistry}}, title = {{Insulin-like growth factor II plays a central role in atherosclerosis in a mouse model.}}, url = {{http://dx.doi.org/10.1074/jbc.M108061200}}, doi = {{10.1074/jbc.M108061200}}, volume = {{277}}, year = {{2002}}, }