Osteoprotegerin is associated with aneurysm diameter and proteolysis in abdominal aortic aneurysm disease
Koole, Dave, Hurks, Rob, Schoneveld, Arjan, Vink, Aryan, Golledge, Jonathan, Moran, Corey S., de Kleijn, Dominique P., van Herwaarden, Joost A., de Vries, Jean-Paul, Laman, Jon D., Huizinga, Ruth, Pasterkamp, Gerard, and Moll, Frans L. (2012) Osteoprotegerin is associated with aneurysm diameter and proteolysis in abdominal aortic aneurysm disease. Arteriosclerosis, Thrombosis and Vascular Biology, 32 (6). pp. 1497-1504.
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Objective: Serum osteoprotegerin (OPG) concentrations have previously been associated with growth of abdominal aortic aneurysms (AAAs). In vitro experiments showed that OPG promotes matrix metalloprotease (MMP) release from monocytes and vascular smooth muscle cells. We hypothesized that OPG expression is increased in human AAAs and is associated with proteolysis. Methods and Results: AAA biopsies were collected from 329 patients. We assessed the concentrations of OPG, cathepsins A, B, and S as well as the activity of MMP-2 and MMP-9. The AAA wall infiltration by macrophages, lymphocytes, and plasma cells was estimated by immunohistochemistry. The concentration of OPG correlated positively with aortic diameter (<55 mm: 16.1 [5.8–28.7], 55–70 mm: 21.9 [10.2–36.0], >70 mm: 24.0 [13.5–52.9] ng OPG/mg total amount of protein, P=0.020), cathepsin A (r=0.221, P=0.005), B (r=0.384, P<0.001), and S (r=0.467, P<0.001), MMP-2 (r=0.180, P<0.001), MMP-9 (r=0.178, P<0.001), and the number of lymphocytes (P<0.001) and plasma cells (P=0.001). OPG immunostaining was predominantly demonstrated in plasma cells. Conclusion: The concentration of aortic wall OPG is positively associated with established markers of AAA severity and pathogenesis. OPG appeared to be associated with lymphocytes and plasma cells. These human data support previous experimental data suggesting a role for OPG in AAA pathogenesis.
|Item Type:||Article (Refereed Research - C1)|
|Keywords:||abdominal aortic aneurysm, diameter, proteolysis, osteoprotegerin|
|FoR Codes:||11 MEDICAL AND HEALTH SCIENCES > 1102 Cardiovascular Medicine and Haematology > 110201 Cardiology (incl Cardiovascular Diseases) @ 100%|
|SEO Codes:||92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920103 Cardiovascular System and Diseases @ 100%|
|Deposited On:||06 Aug 2012 12:36|
|Last Modified:||18 Oct 2013 01:29|
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