Loss of Insulin Signaling in Vascular Endothelial Cells Accelerates Atherosclerosis in Apolipoprotein E Null Mice
View/ Open
RaskMadsen et al 2010.pdf (1.222Mb)
Access Status
Full text of the requested work is not available in DASH at this time ("restricted access"). For more information on restricted deposits, see our FAQ.Author
Freund, Bryn
Feather, Danielle
Abramov, Roman
Wu, I-Hsien
Chen, Kai
Yamamoto-Hiraoka, Junko
Goldenbogen, Jan
Sotiropoulos, Konstantinos B.
Geraldes, Pedro
Dall, Claudia
Rekhter, Mark
Scalia, Rosario
Note: Order does not necessarily reflect citation order of authors.
Published Version
https://doi.org/10.1016/j.cmet.2010.03.013Metadata
Show full item recordCitation
Rask-Madsen, Christian, Qian Li, Bryn Freund, Danielle Feather, Roman Abramov, I-Hsien Wu, Kai Chen, et al. 2010. “Loss of Insulin Signaling in Vascular Endothelial Cells Accelerates Atherosclerosis in Apolipoprotein E Null Mice.” Cell Metabolism 11 (5) (May): 379–389. doi:10.1016/j.cmet.2010.03.013.Abstract
To determine whether insulin action on endothelial cells promotes or protects against atherosclerosis, we generated apolipoprotein E null mice in which the insulin receptor gene was intact or conditionally deleted in vascular endothelial cells. Insulin sensitivity, glucose tolerance, plasma lipids, and blood pressure were not different between the two groups, but atherosclerotic lesion size was more than 2-fold higher in mice lacking endothelial insulin signaling. Endothelium-dependent vasodilation was impaired and endothelial cell VCAM-1 expression was increased in these animals. Adhesion of mononuclear cells to endothelium in vivo was increased 4-fold compared with controls but reduced to below control values by a VCAM-1-blocking antibody. These results provide definitive evidence that loss of insulin signaling in endothelium, in the absence of competing systemic risk factors, accelerates atherosclerosis. Therefore, improving insulin sensitivity in the endothelium of patients with insulin resistance or type 2 diabetes may prevent cardiovascular complications.Citable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:33172628
Collections
- FAS Scholarly Articles [18304]
Contact administrator regarding this item (to report mistakes or request changes)