Differential expression of bone matrix regulatory proteins in human atherosclerotic plaques.
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 Gla 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 Gla 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.
Dhore
C R
CR
Department of Pathology, Cardiovascular Research Institute Maastricht, University of Maastricht, Netherlands.
Cleutjens
J P
JP
Lutgens
E
E
Cleutjens
K B
KB
Geusens
P P
PP
Kitslaar
P J
PJ
Tordoir
J H
JH
Spronk
H M
HM
Vermeer
C
C
Daemen
M J
MJ
D000328:Adult; D000368:Aged; D001012:Aorta, Abdominal / Q000737:chemistry* / Q000473:pathology; D001161:Arteriosclerosis / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D002114:Calcinosis / Q000145:classification* / Q000150:complications / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics; D002352:Carrier Proteins / Q000032:analysis*; D018450:Disease Progression; D016326:Extracellular Matrix Proteins; D005260:Female; D006023:Glycoproteins / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis*; D008875:Middle Aged; D010006:Osteoblasts / Q000737:chemistry; D010010:Osteoclasts / Q000737:chemistry; D010012:Osteogenesis; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger / Q000032:analysis; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000032:analysis*; D018124:Receptors, Tumor Necrosis Factor; D029607:Seminal Vesicle Secretory Proteins / Q000032:analysis; D017539:Tunica Intima / Q000737:chemistry / Q000473:pathology; D014973:Xanthomatosis / Q000473:pathology; D000097568:Matrix Gla Protein
D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; D029607:Seminal Vesicle Secretory Proteins; D000097568:Matrix Gla Protein; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; C424303:seminal vesicle secretory protein 109, Bos taurus