Systemic dilation diathesis in patients with abdominal aortic aneurysms: a role for matrix metalloproteinase-9?
BACKGROUND
Accumulating evidence suggests that patients with abdominal aortic aneurysm (AAA) suffer from a systemic dilating condition affecting all arteries. Matrix metalloproteinases (MMPs) and their natural inhibitors, the tissue inhibitors of metalloproteinases (TIMPs), appear to be involved in aneurysm formation, as evidenced by increased aortic tissue MMP activity and plasma MMP levels in patients with AAA. Hypothesizing that an imbalance in plasma MMP/TIMP level might be associated with a systemic dilation diathesis, we studied mechanical vessel wall properties of non-affected arteries of patients with either AAA or aorto-iliac obstructive lesions in association with plasma MMP-9 and TIMP-1 levels.


METHODS
Twenty-two patients with AAA and 12 with aorto-iliac occlusive disease (AOD) were included. Diastolic diameter (d) and distension (Deltad) were measured at the level of the common carotid artery (CCA) and suprarenal aorta (SA) using ultrasonography. Distensibility (DC) and compliance (CC) were calculated from d, Deltad and brachial pulse pressure. Plasma MMP-9 and TIMP-1 were determined with specific immunoassays.


RESULTS
The average (+/-SD) age was 72.3+/-5.6 and 65.0+/-8.2 years for the AAA and AOD patients, respectively, (P=0.005). CCA diameter was 9.1+/-1.3mm in AAA patients and AOD 7.8+/-1.4mm in AOD patients, P=0.009. This difference persisted after correction for age. Plasma MMP-9 and TIMP-1 did not differ significantly between AAA and AOD patients. In the total 34 patients, the MMP-9/TIMP-1 ratio was correlated inversely with distensibility (r=-0.74, P=0.002) and to compliance (r=-0.58, P=0.024) of the suprarenal aorta.


CONCLUSIONS
The CCA diameter was larger in AAA patients compared to AOD patients. MMP-9/TIMP-1 ratio was associated with decreased distensibility and compliance of the suprarenal aorta. These data support the idea that AAA patients exhibit a systemic dilation diathesis, which might be attributable to MMP/TIMP imbalances.
van Laake
L W
LW
Department of Surgery, University Hospital Maastricht, 6202 AZ Maastricht, The Netherlands.
Vainas
T
T
Dammers
R
R
Kitslaar
P J E H M
PJ
Hoeks
A P G
AP
Schurink
G W H
GW
D000368:Aged; D000704:Analysis of Variance; D001012:Aorta, Abdominal / Q000000981:diagnostic imaging / Q000473:pathology*; D017544:Aortic Aneurysm, Abdominal / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000473:pathology; D001157:Arterial Occlusive Diseases / Q000000981:diagnostic imaging / Q000201:enzymology / Q000473:pathology; D017536:Carotid Artery, Common / Q000000981:diagnostic imaging / Q000473:pathology*; D016022:Case-Control Studies; D004108:Dilatation, Pathologic; D004198:Disease Susceptibility; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D018709:Statistics, Nonparametric; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*; D014463:Ultrasonography
D019715:Tissue Inhibitor of Metalloproteinase-1; D020780:Matrix Metalloproteinase 9