| First Author | Zaina S | Year | 2002 |
| Journal | J Biol Chem | Volume | 277 |
| Issue | 6 | Pages | 4505-11 |
| PubMed ID | 11726660 | Mgi Jnum | J:74530 |
| Mgi Id | MGI:2158589 | Doi | 10.1074/jbc.M108061200 |
| Citation | Zaina S, et al. (2002) Insulin-like growth factor II plays a central role in atherosclerosis in a mouse model. J Biol Chem 277(6):4505-11 |
| abstractText | 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. |
