This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Refson, J. S. Articles by Sever, P. S. Search for Related Content PubMed PubMed Citation Articles by Refson, J. S. Articles by Sever, P. S. Pubmed/NCBI databases Substance via MeSH Hazardous Substances DB HEPARIN

(Circulation. 1998;97:2506-2510.)
© 1998 American Heart Association, Inc.

Clinical Investigation and Reports

Vein Graft Stenosis and the Heparin Responsiveness of Human Vascular Smooth Muscle Cells

Jonathan S. Refson, MB; Michael Schachter, MB, BSc; Mahendra K. Patel, PhD; Alun D. Hughes, MB, PhD; Euan Munro, MD; Philip Chan, MD; John H. N. Wolfe, MS; ; Peter S. Sever, MB, PhD

From the Department of Clinical Pharmacology, Imperial College School of Medicine, St Mary's Hospital (J.S.R., M.S., M.K.P., A.D.H., P.C., P.S.S.), and the Regional Vascular Unit (J.S.R., E.M., J.H.N.W.), St Mary's Hospital, London, UK.

Correspondence to Dr Michael Schachter, Department of Clinical Pharmacology, St Mary's Hospital, London W2 1NY UK. E-mail m.schachter{at}ic.ac.uk

Background—Vascular smooth muscle cell (VMSC) proliferation is an essential component of myointimal hyperplasia, which is implicated in the failure of 30% to 50% of vascular interventions, such as coronary angioplasty and peripheral vein grafting. We have shown that cells derived from stenotic lesions in infrainguinal vein grafts were significantly more resistant than controls to growth inhibition by heparin.

Methods and Results—In a prospective study, we correlated antiproliferative responses to heparin in vitro with graft patency after 1 year. Sixty-two patients with infrainguinal vein grafts were entered into a graft surveillance program for 1 year. At operation, saphenous vein segments were explanted for VSMC culture. Cell proliferation in response to fetal calf serum was later determined in the presence and absence of heparin. In 35 cell cultures, including 13 from the above-mentioned patients, [³H]heparin binding was also estimated. VSMCs from patients with patent grafts were significantly more sensitive to growth inhibition by heparin than cells from patients with stenoses (median, 54% versus 20.9%, P<0.001), and [³H]heparin binding was strongly correlated with inhibition of proliferation (r=0.81).

Conclusions—Responsiveness to heparin in cultured VSMCs is a strong predictor of outcome for infrainguinal vein grafts, and reduced sensitivity to heparin is correlated with decreased heparin binding. Relative resistance to the antiproliferative action of heparin may be a marker for aberrant regulation of VSMC growth.

Key Words: veins • grafting • stenosis • heparin

This article has been cited by other articles:

				E. Millette, B. H. Rauch, O. Defawe, R. D. Kenagy, G. Daum, and A. W. Clowes Platelet-Derived Growth Factor-BB-Induced Human Smooth Muscle Cell Proliferation Depends on Basic FGF Release and FGFR-1 Activation Circ. Res., February 4, 2005; 96(2): 172 - 179. [Abstract] [Full Text] [PDF]

				P.A. Underwood and S. M. Mitchell Low density lipoproteins in human plasma make vascular smooth muscle cells resistant to growth inhibition by heparin Cardiovasc Res, September 1, 2000; 47(4): 749 - 758. [Abstract] [Full Text] [PDF]

				J. R. Sindermann and K. L. March Heparin Responsiveness In Vitro as a Prognostic Tool for Vascular Graft Stenosis : A Tale of Two Cell Types? Circulation, June 30, 1998; 97(25): 2486 - 2490. [Full Text] [PDF]