Journal
CLINICAL SCIENCE
Volume 127, Issue 7-8, Pages 485-497Publisher
PORTLAND PRESS LTD
DOI: 10.1042/CS20140045
Keywords
atherosclerosis; bone marrow transplantation; diabetes mellitus; mouse model; receptor for advanced glycation end-products (RAGE)
Categories
Funding
- National Health and Medical Research Council (NHMRC) Australia
- National Heart Foundation (NHF)
- Diabetes Australia Research Trust (DART)
- NHMRC
- Victorian Government's OIS (Operational Infrastructure Program)
- DART
Ask authors/readers for more resources
RAGE (receptor for advanced glycation end-products) is expressed on multiple cell types implicated in the progression of atherosclerosis and plays a role in DAA (diabetes-associated atherosclerosis). The aim of the present study was to determine the relative role of either BM (bone marrow)- or non-BM-derived RAGE in the pathogenesis of STZ (streptozotocin)-induced DAA. Male ApoE (apolipoprotein E)-null (ApoE(-/-) :RAGE(+/+)) and ApoE:RAGE-null (ApoE(-/-):RAGE(-/-)) mice at 7 weeks of age were rendered diabetic with STZ. At 8 weeks of age, ApoE(-/-) and ApoE(-/-):RAGE(-/-) control and diabetic mice received BM from either RAGE-null or RAGE-bearing mice, generating various chimaeras. After 10 and 20 weeks of diabetes, mice were killed and gene expression and atherosclerotic lesion formation were evaluated respectively. Deletion of RAGE in either the BM cells or non-BM cells both resulted in a significant attenuation in DAA, which was associated with reduced VCAM-1 (vascular cell adhesion molecule-1) expression and translated into reduced adhesion in vitro. In conclusion, the results of the present study highlight the importance of both BM- and non-BM-derived RAGE in attenuating the development of DAA.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available