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European Heart Journal Advance Access published online on February 9, 2008

European Heart Journal, doi:10.1093/eurheartj/ehm557
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

Reduced expansion rate of abdominal aortic aneurysms in patients with diabetes may be related to aberrant monocyte–matrix interactions

Jonathan Golledge1,*, Mirko Karan1, Corey S. Moran1, Juanita Muller1, Paula Clancy1, Anthony E. Dear2 and Paul E. Norman3

1 Vascular Biology Unit, Department of Surgery, School of Medicine, James Cook University, Townsville, QLD 4811, Australia
2 Department of Vascular Surgery, Monash University, Box Hill Hospital, Box Hill, Melbourne, VIC 3128, Australia
3 School of Surgery and Pathology, University of Western Australia, Fremantle Hospital, Fremantle, WA 6959, Australia

Received 9 July 2007; revised 9 October 2007; accepted 5 November 2007.

* Corresponding author. Tel: +61 7 4796 1417, Fax: +61 7 4796 1401. Email: jonathan.golledge{at}jcu.edu.au

Aims: Diabetes increases the risk of atherothrombosis, but reduces the risk of abdominal aortic aneurysm (AAA). The reason for this difference is unknown. We examined the role of diabetes and glycation on AAA expansion and extracellular matrix–monocyte interactions.

Methods and results: We followed 198 patients (20 with diabetes) who had 30–45 mm AAAs with yearly aortic ultrasound for 3 years. Diabetes was independently associated with reduced AAA growth (β = –0.17, P = 0.01; OR for expansion above median 0.18, 95% confidence interval 0.06–0.57). In vitro incubation of resting human monocytes with glycated bovine serum albumin or monomeric type I collagen increased matrix metalloproteinase (MMP) secretion. In contrast, exposure of activated monocytes to glycated type I collagen lattices induced a marked reduction in MMP and interleukin-6 secretion. This de-activating effect was also demonstrated in cross-linked non-glycated collagen lattices, healthy decellularized aortic media, and decellularized aortic media from diabetes patients with atherosclerosis. In contrast, decellularized aortic media from patients with atherosclerosis, but no diabetes, induced increased MMP secretion.

Conclusion: These findings confirm that the progression of AAA is slower in patients with diabetes and suggest a mechanism by which the aortic media may be protected from degradation in these individuals.

Key Words: Abdominal aortic aneurysm • Diabetes • Glycation • Monocytes • Matrix metalloproteinase


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K. L. Rensing and Th. B. Twickler
Abdominal aorta aneurysm: an exceptional expression of atherosclerotic disease in type II diabetes
Eur. Heart J., March 1, 2008; 29(5): 581 - 582.
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