Matrix proteins associated with bone calcification are present in human vascular smooth muscle cells grownin vitro

Abstract

Atherosclerotic lesions are composed of cellular elements that have migrated from the vessel lumen and wall to form the cellular component of the developing plaque. The cellular elements are influenced by various growth-regulatory molecules, cytokines, chemoattractants, and vasoregulatory molecules that regulate the synthesis of the extracellular matrix composing the plaque. Because vascular smooth muscle cells (VSMC) constitute the major cellular elements of the atherosclerotic plaque and are thought to be responsible for the extracellular matrix that becomes calcified in mature plaques, immunostaining for collagenous and noncollagenous proteins typically associated with bone matrix was conducted on VSMC grown in vitro. VSMC obtained from human aorta were grown in chambers on glass slides and immunostained for procollagen type I, bone sialoprotein, osteonectin, osteocalcin, osteopontin, decorin, and biglycan. VSMC demonstrated an intense staining for procollagen type I, and a moderately intense staining for the noncollagenous proteins, bone sialoprotein and osteonectin, two proteins closely associated with bone mineralization. Minimal immunostaining was noted for osteocalcin, osteopontin, decorin, and biglycan. The presence in VSMC of collagenous and noncollagenous proteins associated with bone mineralization suggest that the smooth muscle cells in the developing atherosclerotic plaque play an important role in the deposition of the extracellular matrix involved in calcification of developing lesions.

Increased cellular expression of matrix proteins that regulate mineralization is associated with calcification of native human and porcine xenograft bioprosthetic heart valves.

“…Monocyte-macrophages and smooth muscle cells synthesize osteopontin (18,22,(40)(41)(42)(43)(44)(45)(46), matrix Gla protein (43,46) and osteonectin (43) in cell culture, atherosclerotic plaques (41,42,45), or restenotic neointima (22,42,47). Vascular pericyte-like cells (23,48), monocytes (49), and endothelial cells (45) also express osteopontin.…”

“…Such a concept is in keeping with the idea that the mineralization of extraskeletal tissues passively termed "dystrophic mineralization" is, in fact, a coordinated cell-mediated process. There is emerging evidence that other related reparative processes such as atherosclerotic calcification and coronary restenosis also involve cell-mediated, coordinated matrix protein expression (18,(22)(23)(24)(43)(44)(45)(46)(47)(48). Studies in different species have shown that both mRNA and protein for osteopontin are closely associated with osteoblasts, osteocytes, osteoclasts, smooth muscle cells, endothelial cells, foam cells, macrophages, and pericyte-like cells around zones of calcification (18,19,(22)(23)(24)50).…”

Time Course of Osteopontin, Osteocalcin, and Osteonectin Accumulation and Calcification After Acute Vessel Wall Injury

“…ON is detected in cultured SMCs (Severson et al 1995) and is strongly expressed in young but not in healthy adult vessel walls. However, a few ON-expressing cells were scattered throughout the atherosclerosic lesions in humans (Hirota et al 1993).…”

Calcification of Aortic Smooth Muscle Cells Isolated From Spontaneously Hypertensive Rats

“…Due to the presence of collagenous and noncollagenous proteins associated with bone mineralization in vascular smooth muscle cells (SMCs), vascular SMCs within developing atherosclerotic plaques play an important role in the deposition of extracellular matrix, resulting in vascular calcification (8). During vascular calcification, various vascular cells, including vascular SMCs, pericytes, fibroblasts, and macrophages, are transformed into osteoblast-like phenotypes, exhibit increased alkaline phosphatase (ALP) activity, and matrix vesicle formation, and show significant expressions of the genes for bone morphogenetic protein 2 (BMP2) and bone matrix proteins such as osteocalcin and osteopontin (9,10).…”