© 1996 American Heart Association, Inc.
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Osteopontin Expression in Platelet-Derived Growth Factor–Stimulated Vascular Smooth Muscle Cells and Carotid Artery After Balloon Angioplasty
the Departments of Cardiovascular Pharmacology and Experimental Pathology (C.L.), SmithKline Beecham Pharmaceuticals, King of Prussia, Pa.
Correspondence to Xinkang Wang, PhD, Department of Cardiovascular Pharmacology, SmithKline Beecham Pharmaceuticals, 709 Swedeland Rd, PO Box 1539, UW 2511, King of Prussia, PA 19406. E-mail Xinkang _Wang-1@SBPHRD.com.
Osteopontin (OPN), an arginine-glycine-aspartate (RGD)–containing adhesive glycoprotein, is constitutively expressed in rat aorta and carotid arteries and is markedly elevated in response to vascular injury. OPN is chemotactic for vascular smooth muscle cells (SMCs), suggesting a role in vascular remodeling. However, the mechanism for the regulation of OPN expression is poorly understood. In the present study, the effect of platelet-derived growth factor (PDGF) on OPN mRNA expression was investigated in cultured rat aortic SMCs (RASMCs). When RASMCs were stimulated with 1 nmol/L PDGF, a 2.4-fold increase in OPN mRNA expression was observed at 3 hours (P<.05) that peaked at 14 hours with a 6.7-fold increase (P<.001). This induction was blocked by a monoclonal anti-PDGF antibody. Further studies revealed that OPN mRNA expression was induced by PDGF-AB or PDGF-BB but not by PDGF-AA, indicating that only the ß-type PDGF receptor mediates this response. Compared with basic fibroblast growth factor, epidermal growth factor, transforming growth factor-ß, and interleukin-1ß, PDGF was the most potent factor studied to induce OPN mRNA expression in RASMCs. Immunohistochemical studies demonstrated the elevation of OPN protein in PDGF-stimulated RASMCs. The temporal expression of OPN mRNA after rat carotid artery balloon angioplasty as assessed by both reverse transcription–polymerase chain reaction and Northern blot analysis revealed a 1.5-fold increase at 6 hours (P<.01) that peaked at 1 and 3 days with a 3.1-fold increase (P<.001). Immunohistochemical studies of carotid artery after angioplasty localized OPN expression in the medial SMCs at 1 day, ie, at a time of significant platelet adherence to the injured vessel, and thereafter to the intimal lesion during neointimal formation. These data suggest that OPN expression in vascular SMCs is regulated by PDGF through the ß-type PDGF receptor in vitro, and possibly in vivo, in situations that involve PDGF released from platelets or other cellular sources, such as blood vessels after angioplasty injury.
Key Words: osteopontin • platelet-derived growth factor • smooth muscle cell • balloon angioplasty
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