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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:1912.)
© 2000 American Heart Association, Inc.

Vascular Biology

Nov Gene Encodes Adhesion Factor for Vascular Smooth Muscle Cells and Is Dynamically Regulated in Response to Vascular Injury

Peter D. Ellis; Qin Chen; Patrick J. Barker; James C. Metcalfe; Paul R. Kemp

From the Section of Cardiovascular Biology (P.D.E., J.C.M., P.R.K.), Department of Biochemistry, and the Physiological Laboratory (Q.C.), University of Cambridge, Cambridge, UK, and the Microchemical Facility (P.J.B.), The Babraham Institute, Cambridge, UK. Dr Chen is now at Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass.

Correspondence to Dr Peter D. Ellis, Section of Cardiovascular Biology, Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QW, UK. E-mail pde1001{at}mole.bio.cam.ac.uk

Abstract—Nephroblastoma overexpressed (NOV) is a member of the CCN family (connective tissue growth factor, CYR61, and NOV) of proteins that are involved in regulating the proliferation, differentiation, and adhesion of a variety of cell types. We have examined the expression of the Nov gene and NOV protein by vascular smooth muscle cells (VSMCs), in vitro and in vivo, and the effects of recombinant NOV on VSMCs. Rat aortic VSMCs were found to express Nov mRNA and NOV protein in vitro and in vivo. Nov expression in adult rat tissues was very high in the aorta and was detected only weakly in the brain and lung by Northern analysis (relative levels 33:3:1). During postnatal development (3 days to 12 weeks), the expression of Nov was correlated with markers of the differentiated smooth muscle cell phenotype (smooth muscle myosin heavy chain and SM22). In the rat carotid artery balloon injury model, Nov was detectable by in situ hybridization and was downregulated in the media of the injured artery compared with the uninjured artery at 7 and 14 days after injury. Expression in the developing intima was barely detectable at 7 days after injury except for strong expression at the luminal surface. At 14 days after injury, Nov expression was substantially increased throughout the intima. In vitro studies of the function of NOV protein showed that it promoted VSMC adhesion via a mechanism that was divalent cation and Arg-Gly-Asp independent but that it did not modulate VSMC proliferation or phenotype. The strong expression and dynamic regulation of Nov in the arterial wall, together with its ability to promote VSMC adhesion, suggest that it may be involved in homeostasis and repair.

Key Words: Nov gene • CCN family • gene expression • balloon injury

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