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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1995;15:2010-2018.)
© 1995 American Heart Association, Inc.

Articles

Osteopontin Is Not a Marker for Proliferating Human Vascular Smooth Muscle Cells

Christopher M. Newman; Birgitte C. Bruun; Karen E. Porter; Pramod K. Mistry; Catherine M. Shanahan; Peter L. Weissberg

From the Department of Medicine (C.M.N., B.C.B., P.K.M., C.M.S., P.L.W.), University of Cambridge, Addenbrooke's Hospital, Cambridge, UK, and the Department of Surgery (K.E.P.), University of Leicester, Leicester Royal Infirmary, Leicester, UK.

Correspondence to Dr C. Newman, Section of Cardiology, Clinical Sciences Centre, Northern General Hospital, Sheffield S5 7AU, UK. E-mail c.newman@sheffield.ac.uk.

Abstract Osteopontin (OP) is a secreted glycoprotein that contains the Arg-Gly-Asp (RGD) cell-binding sequence that binds calcium and is chemotactic and adhesive for rat vascular smooth muscle cells (VSMCs). OP gene expression is upregulated in cultured rat VSMCs in vitro and after balloon carotid injury in vivo, suggesting that OP may be a marker for proliferating VSMCs in vivo and in vitro. Our in situ hybridization studies of human atherosclerotic coronary vessels, however, have shown OP mRNA expression in plaque macrophages but not in VSMCs. The current study investigated OP mRNA expression in cultured human VSMCs and macrophages and in an organ culture model of neointima formation in human saphenous vein. OP mRNA expression was not detected by Northern blot analysis of total RNA from subconfluent or confluent cultures of human VSMCs of any passage maintained in normal growth medium or after stimulation with TGFß₁ (20 ng/mL), angiotensin II (1 µmol/L), or basic fibroblast growth factor (10 ng/mL) but was just detectable after stimulation with activated vitamin D₃ (1 µmol/L). In contrast, cultured human macrophages expressed high levels of OP mRNA that were not dependent on lipid loading. OP mRNA was detected in isolated foci in all layers of saphenous veins maintained in organ culture for 14 days, including <2% of neointimal cells, a distribution that paralleled that of tissue macrophages. These results suggest that OP gene expression is not a marker for proliferation of human VSMCs in vitro and highlight a fundamental difference in the biology of human and rodent VSMCs.

Key Words: osteopontin • atherosclerosis • cells, vascular smooth muscle • macrophages • proliferation

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