Advanced glycation of apolipoprotein A-I impairs its anti-atherogenic properties

Hoang, A., Murphy, A. J., Coughlan, M. T., Thomas, M. C., Forbes, J. M., O'Brien, R., Cooper, M. E., Chin-Dusting, J. P. F. and Sviridov, D. (2007) Advanced glycation of apolipoprotein A-I impairs its anti-atherogenic properties. Diabetologia, 50 8: 1770-1779. doi:10.1007/s00125-007-0718-9


Author Hoang, A.
Murphy, A. J.
Coughlan, M. T.
Thomas, M. C.
Forbes, J. M.
O'Brien, R.
Cooper, M. E.
Chin-Dusting, J. P. F.
Sviridov, D.
Title Advanced glycation of apolipoprotein A-I impairs its anti-atherogenic properties
Journal name Diabetologia   Check publisher's open access policy
ISSN 0012-186X
1432-0428
Publication date 2007-08
Sub-type Article (original research)
DOI 10.1007/s00125-007-0718-9
Open Access Status Not yet assessed
Volume 50
Issue 8
Start page 1770
End page 1779
Total pages 10
Place of publication Heidelberg, Germany
Publisher Springer
Language eng
Formatted abstract
Aims/hypothesis: AGE contribute to the pathogenesis of diabetic complications, including dyslipidaemia and atherosclerosis. However, the precise mechanisms remain to be established. In the present study, we examined whether AGE modification of apolipoprotein A-I (apoA-I) affects its functionality, thus altering its cardioprotective profile.

Materials and methods: The ability of AGE-modified apoA-I to facilitate cholesterol and phospholipid efflux, stabilise ATP-binding cassette transporter A1 (ABCA1) and inhibit expression of adhesion molecules in human macrophages and monocytes was studied.

Results: The ability of AGE-modified apoA-I to promote cholesterol efflux from THP-1 macrophages, isolated human monocytes and from ABCA1-transfected HeLa cells was significantly reduced (>70%) compared with unmodified apoA-I. This effect was reversed by preventing AGE formation with aminoguanidine or reversing AGE modification using the cross-link breaker alagebrium chloride. AGE-modification of HDL also reduced its capacity to promote cholesterol efflux. AGE-apoA-I was also less effective than apoA-I in stabilising ABCA1 in THP-1 cells as well as in inhibiting expression of CD11b in human monocytes.

Conclusions/interpretation: AGE modification of apoA-I considerably impairs its cardioprotective, antiatherogenic properties, including the ability to promote cholesterol efflux, stabilise ABCA1 and inhibit the expression of adhesion molecules. These findings provide a rationale for targeting AGE in the management of diabetic dyslipidaemia.
Keyword AGE
Atherosclerosis
Diabetes
High-density lipoprotein
Inflammation
Reverse cholesterol transport
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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