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


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 (beta = -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.


CONCLUSIONS
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.
Golledge
Jonathan
J
Vascular Biology Unit, Department of Surgery, School of Medicine, James Cook University, Townsville, QLD 4811, Australia. jonathan.golledge@jcu.edu.au
Karan
Mirko
M
Moran
Corey S
CS
Muller
Juanita
J
Clancy
Paula
P
Dear
Anthony E
AE
Norman
Paul E
PE
D000368:Aged; D017544:Aortic Aneurysm, Abdominal / Q000201:enzymology / Q000473:pathology*; D050197:Atherosclerosis / Q000150:complications*; D016207:Cytokines / Q000502:physiology*; D003925:Diabetic Angiopathies / Q000201:enzymology / Q000473:pathology*; D004812:Epidemiologic Methods; D005109:Extracellular Matrix / Q000201:enzymology; D005260:Female; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009000:Monocytes / Q000502:physiology*
D016207:Cytokines; D020782:Matrix Metalloproteinases