TY - JOUR
T1 - Differential expression of bone matrix regulatory proteins in human atherosclerotic plaques
AU - Dhore, Cherida R.
AU - Cleutjens, Jack P.M.
AU - Lutgens, Esther
AU - Cleutjens, Kitty B.J.M.
AU - Geusens, Piet P.M.
AU - Kitslaar, Peter J.E.H.M.
AU - Tordoir, Jan H.M.
AU - Spronk, Henri M.H.
AU - Vermeer, Cees
AU - Daemen, Mat J.A.P.
PY - 2001
Y1 - 2001
N2 - In the present study, we examined the expression of regulators of bone formation and osteoclastogenesis in human atherosclerosis because accumulating evidence suggests that atherosclerotic calcification shares features with bone calcification. The most striking finding of this study was the constitutive immunoreactivity of matrix G1a protein, osteocalcin, and bone sialoprotein in nondiseased aortas and the absence of bone morphogenetic protein (BMP)-2, BMP-4, osteopontin, and osteonectin in nondiseased aortas and early atherosclerotic lesions. When atherosclerotic plaques demonstrated calcification or bone formation, BMP-2, BMP-4, osteopontin, and osteonectin were upregulated. Interestingly, this upregulation was associated with a sustained immunoreactivity of matrix G1a protein, osteocalcin, and bone sialoprotein. The 2 modulators of osteoclastogenesis (osteoprotegerin [OPG] and its ligand, OPGL) were present in the nondiseased vessel wall and in early atherosclerotic lesions. In advanced calcified lesions, OPG was present in bone structures, whereas OPGL was only present in the extracellular matrix surrounding calcium deposits. The observed expression patterns suggest a tight regulation of the expression of bone matrix regulatory proteins during human atherogenesis. The expression pattern of both OPG and OPGL during atherogenesis might suggest a regulatory role of these proteins not only in osteoclastogenesis but also in atherosclerotic calcification.
AB - In the present study, we examined the expression of regulators of bone formation and osteoclastogenesis in human atherosclerosis because accumulating evidence suggests that atherosclerotic calcification shares features with bone calcification. The most striking finding of this study was the constitutive immunoreactivity of matrix G1a protein, osteocalcin, and bone sialoprotein in nondiseased aortas and the absence of bone morphogenetic protein (BMP)-2, BMP-4, osteopontin, and osteonectin in nondiseased aortas and early atherosclerotic lesions. When atherosclerotic plaques demonstrated calcification or bone formation, BMP-2, BMP-4, osteopontin, and osteonectin were upregulated. Interestingly, this upregulation was associated with a sustained immunoreactivity of matrix G1a protein, osteocalcin, and bone sialoprotein. The 2 modulators of osteoclastogenesis (osteoprotegerin [OPG] and its ligand, OPGL) were present in the nondiseased vessel wall and in early atherosclerotic lesions. In advanced calcified lesions, OPG was present in bone structures, whereas OPGL was only present in the extracellular matrix surrounding calcium deposits. The observed expression patterns suggest a tight regulation of the expression of bone matrix regulatory proteins during human atherogenesis. The expression pattern of both OPG and OPGL during atherogenesis might suggest a regulatory role of these proteins not only in osteoclastogenesis but also in atherosclerotic calcification.
KW - Atherosclerosis
KW - Bone matrix proteins
KW - Osteoclastogenesis
KW - Osteogenesis
KW - Vascular calcification
UR - http://www.scopus.com/inward/record.url?scp=0035571591&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035571591&partnerID=8YFLogxK
U2 - 10.1161/hq1201.100229
DO - 10.1161/hq1201.100229
M3 - Article
C2 - 11742876
AN - SCOPUS:0035571591
SN - 1079-5642
VL - 21
SP - 1998
EP - 2003
JO - Arteriosclerosis, thrombosis, and vascular biology
JF - Arteriosclerosis, thrombosis, and vascular biology
IS - 12
ER -