Osteoprotegerin Is Associated With Aneurysm Diameter and Proteolysis in Abdominal Aortic Aneurysm Disease

Dave Koole; Rob Hurks; Arjan Schoneveld; Aryan Vink; Jonathan Golledge; Corey S. Moran; Dominique P. de Kleijn; Joost A. van Herwaarden; Jean-Paul de Vries; Jon D. Laman; Ruth Huizinga; Gerard Pasterkamp; Frans L. Moll

doi:10.1161/ATVBAHA.111.243592

Osteoprotegerin Is Associated With Aneurysm Diameter and Proteolysis in Abdominal Aortic Aneurysm Disease

Dave Koole^*, Rob Hurks, Arjan Schoneveld, Aryan Vink, Jonathan Golledge, Corey S. Moran, Dominique P. de Kleijn, Joost A. van Herwaarden, Jean-Paul de Vries, Jon D. Laman, Ruth Huizinga, Gerard Pasterkamp, Frans L. Moll

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

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 (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

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. (Arterioscler Thromb Vasc Biol. 2012;32:1497-1504.)

Original language	English
Pages (from-to)	1497-+
Number of pages	21
Journal	Arteriosclerosis thrombosis and vascular biology
Volume	32
Issue number	6
DOIs	https://doi.org/10.1161/ATVBAHA.111.243592
Publication status	Published - Jun-2012
Externally published	Yes

Keywords

abdominal aortic aneurysm
diameter
proteolysis
osteoprotegerin
LYSOSOMAL CYSTEINE PROTEASES
CORONARY-ARTERY-DISEASE
SMOOTH-MUSCLE-CELLS
KAPPA-B LIGAND
VASCULAR CALCIFICATION
CARDIOVASCULAR-DISEASE
ANTIGEN PRESENTATION
PRACTICE GUIDELINES
RECEPTOR ACTIVATOR
IMMUNE-RESPONSES

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Osteoprotegerin Is Associated With Aneurysm Diameter and Proteolysis in Abdominal Aortic Aneurysm DiseaseFinal publisher's version, 7.64 MBLicence: Taverne

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Koole, D., Hurks, R., Schoneveld, A., Vink, A., Golledge, J., Moran, C. S., de Kleijn, D. P., van Herwaarden, J. A., de Vries, J.-P., Laman, J. D., Huizinga, R., Pasterkamp, G., & Moll, F. L. (2012). Osteoprotegerin Is Associated With Aneurysm Diameter and Proteolysis in Abdominal Aortic Aneurysm Disease. Arteriosclerosis thrombosis and vascular biology, 32(6), 1497-+. https://doi.org/10.1161/ATVBAHA.111.243592

@article{7b52a3434eb44145a089aa4aea5c5fe9,

title = "Osteoprotegerin Is Associated With Aneurysm Diameter and Proteolysis in Abdominal Aortic Aneurysm Disease",

abstract = "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 (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, PConclusion-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. (Arterioscler Thromb Vasc Biol. 2012;32:1497-1504.)",

keywords = "abdominal aortic aneurysm, diameter, proteolysis, osteoprotegerin, LYSOSOMAL CYSTEINE PROTEASES, CORONARY-ARTERY-DISEASE, SMOOTH-MUSCLE-CELLS, KAPPA-B LIGAND, VASCULAR CALCIFICATION, CARDIOVASCULAR-DISEASE, ANTIGEN PRESENTATION, PRACTICE GUIDELINES, RECEPTOR ACTIVATOR, IMMUNE-RESPONSES",

author = "Dave Koole and Rob Hurks and Arjan Schoneveld and Aryan Vink and Jonathan Golledge and Moran, {Corey S.} and {de Kleijn}, {Dominique P.} and {van Herwaarden}, {Joost A.} and {de Vries}, Jean-Paul and Laman, {Jon D.} and Ruth Huizinga and Gerard Pasterkamp and Moll, {Frans L.}",

year = "2012",

month = jun,

doi = "10.1161/ATVBAHA.111.243592",

language = "English",

volume = "32",

pages = "1497--+",

journal = "Arteriosclerosis thrombosis and vascular biology",

issn = "1079-5642",

publisher = "LIPPINCOTT WILLIAMS & WILKINS",

number = "6",

}

Koole, D, Hurks, R, Schoneveld, A, Vink, A, Golledge, J, Moran, CS, de Kleijn, DP, van Herwaarden, JA, de Vries, J-P , Laman, JD, Huizinga, R, Pasterkamp, G & Moll, FL 2012, 'Osteoprotegerin Is Associated With Aneurysm Diameter and Proteolysis in Abdominal Aortic Aneurysm Disease', Arteriosclerosis thrombosis and vascular biology, vol. 32, no. 6, pp. 1497-+. https://doi.org/10.1161/ATVBAHA.111.243592

TY - JOUR

T1 - Osteoprotegerin Is Associated With Aneurysm Diameter and Proteolysis in Abdominal Aortic Aneurysm Disease

AU - Koole, Dave

AU - Hurks, Rob

AU - Schoneveld, Arjan

AU - Vink, Aryan

AU - Golledge, Jonathan

AU - Moran, Corey S.

AU - de Kleijn, Dominique P.

AU - van Herwaarden, Joost A.

AU - de Vries, Jean-Paul

AU - Laman, Jon D.

AU - Huizinga, Ruth

AU - Pasterkamp, Gerard

AU - Moll, Frans L.

PY - 2012/6

Y1 - 2012/6

N2 - 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 (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, PConclusion-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. (Arterioscler Thromb Vasc Biol. 2012;32:1497-1504.)

AB - 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 (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, PConclusion-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. (Arterioscler Thromb Vasc Biol. 2012;32:1497-1504.)

KW - abdominal aortic aneurysm

KW - diameter

KW - proteolysis

KW - osteoprotegerin

KW - LYSOSOMAL CYSTEINE PROTEASES

KW - CORONARY-ARTERY-DISEASE

KW - SMOOTH-MUSCLE-CELLS

KW - KAPPA-B LIGAND

KW - VASCULAR CALCIFICATION

KW - CARDIOVASCULAR-DISEASE

KW - ANTIGEN PRESENTATION

KW - PRACTICE GUIDELINES

KW - RECEPTOR ACTIVATOR

KW - IMMUNE-RESPONSES

U2 - 10.1161/ATVBAHA.111.243592

DO - 10.1161/ATVBAHA.111.243592

M3 - Article

SN - 1079-5642

VL - 32

SP - 1497-+

JO - Arteriosclerosis thrombosis and vascular biology

JF - Arteriosclerosis thrombosis and vascular biology

IS - 6

ER -

Osteoprotegerin Is Associated With Aneurysm Diameter and Proteolysis in Abdominal Aortic Aneurysm Disease

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Keywords

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