© 1995 American Heart Association, Inc.
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Balloon Catheterization Induces Arterial Expression of Embryonic Fibronectins
From the Departments of Pathology (D.D., L.F.B., B.L., B.B., S.B., L.V.D.W.) and Surgery (K.C.K.), Beth Israel Hospital and Harvard Medical School, Boston, Mass; the Division of Cardiovascular Medicine and Falk Cardiovascular Research Center (R.E.P., V.J.D.), Stanford University School of Medicine, Stanford, Calif; and the Divisions of Pulmonary Medicine (J.H.P.) and Cardiology (B.C., B.G.S.), Department of Medicine, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, Calif.
Correspondence to Livingston Van De Water, PhD, Department of Pathology, Beth Israel Hospital, 330 Brookline Ave, Boston, MA 02215.
Abstract Fibronectins (FNs) comprise a family of adhesive extracellular matrix proteins that arise by alternative splicing in three regions: V (IIICS), EIIIA (ED-A), and EIIIB (ED-B). FNs bearing the EIIIA and EIIIB segments are prevalent during embryogenesis, expressed to lesser degrees in normal adult tissues, and may be locally reexpressed at sites of adult tissue injury. RNase mapping shows that normal rat arteries express low levels of FNs that are predominantly EIIIA- and EIIIB-. Following balloon injury, arterial walls produce increased total levels of FN transcripts that preferentially include both the EIIIA and EIIIB segments. However, despite inducing increased total FN mRNA, balloon injury does not alter the relative composition of V120+, V95+, and V0 spliced forms. In situ hybridization reveals that as early as 4 days after injury medial cells express increased total FN mRNA, and by 7 days substantial neointimal and focal medial synthesis of EIIIA+, EIIIB+, and V120+ FNs occurs; macrophages do not significantly contribute to this observed vascular FN synthesis. Consistent with the mRNA data, immunofluorescence microscopic analysis reveals increased deposition of EIIIB+ and V+ FN protein forms in injured arterial walls, particularly within the neointima. Our results suggest that local synthesis of specific FN isoforms is important to the neointimal formation that ensues after balloon injury.
Key Words: artery • fibronectins • alternative splicing • neointima • macrophages
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