Abnormal growth regulation of vascular smooth muscle cells by heparin in patients with restenosis

Chan, Pan F.; Patel, M.; Betteridge, L.; Munro, Euan; Schächter, Michael; Sever, Peter; Wolfe, John H.

doi:10.1016/0140-6736(93)90139-8

Cited by 50 publications

(35 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…35 By contrast, in confirmation of earlier observations, we have demonstrated that there is wide interindividual diversity in responses. 18 These findings support the assumption that differences in cellular response are reproducible and significant. In the present study, we have confirmed and extended our earlier observation that VSMCs derived from patients with stenoses are relatively resistant to growth inhibition by heparin and report a highly significant correlation between reduced growth inhibition by heparin in cells cultured from the grafted vessel and the development of stenosis in the subsequent year.…”

Section: Discussionsupporting

confidence: 67%

“…15,16 This is a property shared by heparin. 17 In a previous report, we showed that VSMCs from patients with proven stenoses are relatively resistant to the antiproliferative effect of heparin 18 and that VSMCs obtained from a variety of patients undergoing vein bypass procedures (cardiac or infrainguinal) exhibit a very wide range of responses to this antiproliferative action (0% to 80% inhibition). Among this group, Ϸ30% are likely to develop MIH lesions severe enough to cause clinically significant graft stenoses.…”

Section: See P 2486mentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 1998

View full text Add to dashboard Cite

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 Ն1 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, [ 3 H]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%, PϽ0.001), and [ 3 H]heparin binding was strongly correlated with inhibition of proliferation (rϭ0.81). 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.

show abstract

Section: Discussionsupporting

confidence: 67%

Section: See P 2486mentioning

confidence: 99%

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

et al. 1998

View full text Add to dashboard Cite

show abstract

“…provides the cells limited immunity from the antiproliferative (6) and apoptotic effects of TGF-␤1 (30), and possibly from other regulatory factors that act partially through TGF-␤1, such as heparin (31)(32)(33)(34).…”

Section: Discussionmentioning

confidence: 99%

Genomic instability in the type II TGF-beta1 receptor gene in atherosclerotic and restenotic vascular cells.

McCaffrey¹,

Du²,

Consigli³

et al. 1997

J. Clin. Invest.

172

121

View full text Add to dashboard Cite

Cells proliferating from human atherosclerotic lesions are resistant to the antiproliferative effect of TGF-␤ 1, a key factor in wound repair. DNA from human atherosclerotic and restenotic lesions was used to test the hypothesis that microsatellite instability leads to specific loss of the Type II receptor for TGF-␤ 1 (T ␤ R-II), causing acquired resistance to TGF-␤ 1. High fidelity PCR and restriction analysis was adapted to analyze deletions in an A 10 microsatellite within T ␤ R-II. DNA from lesions, and cells grown from lesions, showed acquired 1 and 2 bp deletions in T ␤ R-II, while microsatellites in the hMSH3 and hMSH6 genes, and hypermutable regions of p53 were unaffected. Sequencing confirmed that these deletions occurred principally in the replication error-prone A 10 microsatellite region, though nonmicrosatellite mutations were observed. The mutations could be identified within specific patches of the lesion, while the surrounding tissue, or unaffected arteries, exhibited the wild-type genotype. This microsatellite deletion causes frameshift loss of receptor function, and thus, resistance to the antiproliferative and apoptotic effects of TGF-␤ 1. We propose that microsatellite instability in T ␤ R-II disables growth inhibitory pathways, allowing monoclonal selection of a disease-prone cell type within some vascular lesions. ( J. Clin. Invest. 1997.

show abstract

“…Cells grow more rapidly from restenotic lesions than from primary atherosclerotic plaques ( 16), and cells cultured from restenotic sites are resistant to inhibition by heparin (17), which is a well-established inhibitor in normal arterial SMC. Cells grown from vascular lesions also produce greater amounts of extracellular matrix proteins than normal SMC (3).…”

Section: Responsiveness Of Vascular Cells To Tgf-p1 Is Demonstrated Bymentioning

confidence: 99%

Decreased type II/type I TGF-beta receptor ratio in cells derived from human atherosclerotic lesions. Conversion from an antiproliferative to profibrotic response to TGF-beta1.

McCaffrey

Consigli²,

Du³

et al. 1995

J. Clin. Invest.

169

105

View full text Add to dashboard Cite

Abnormal growth regulation of vascular smooth muscle cells by heparin in patients with restenosis

Cited by 50 publications

References 8 publications

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

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

Genomic instability in the type II TGF-beta1 receptor gene in atherosclerotic and restenotic vascular cells.

Decreased type II/type I TGF-beta receptor ratio in cells derived from human atherosclerotic lesions. Conversion from an antiproliferative to profibrotic response to TGF-beta1.

Contact Info

Product

Resources

About