Key result
Heparin inhibited DNA synthesis in cultured human aortic smooth muscle cells to 64% of control, whereas it stimulated DNA synthesis in venous smooth muscle cells to 136% (p=0.01).
p-value: p=0.01
Heparin inhibits DNA synthesis in aortic smooth muscle cells but stimulates it in venous smooth muscle cells, potentially explaining its failure to prevent vein graft stenosis.
Differential effects urge caution extrapolating heparin data across vessel types; leaves open targeted research on graft-specific responses.
The mechanisms resulting in the high incidence of stenoses of coronary venous bypass grafts are still unclear. Heparin, a potential inhibitor of cellular proliferation, neither inhibits intimal hyperplasia in animal models of vein-to-artery grafting nor prevents graft stenosis when administered to patients. We studied the effects of heparin on cultured pairs of human aortic and venous smooth muscle cells (SMC) obtained during coronary bypass surgery from patients with no history of previous restenosis or graft failure. DNA synthesis was measured as [3H]thymidine incorporation after stimulation with 10% fetal calf serum (FCS). Heparin (100 micrograms/ml) inhibited DNA synthesis of aortic SMC to 64 +/- 14% (mean +/- SEM), whereas it stimulated DNA synthesis of venous SMC to 136 +/- 23% (10% FCS alone = 100%; p = 0.01, Wilcoxon signed-rank test, n = 7). Binding studies with [3H]heparin showed no significant differences of Kd values and number of binding sites per cell between SMC derived from aorta or vein that could account for the lack of heparin inhibition of venous SMC DNA synthesis. These data suggest an inherent difference in the heparin susceptibility that may explain the failure of heparin to inhibit intimal proliferation in vein grafts.
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Stöhr et al. (1995) studied Coronary bypass surgery (n=7). Heparin vs. 10% fetal calf serum alone was evaluated on DNA synthesis measured as [3H]thymidine incorporation (p=0.01). Heparin inhibited DNA synthesis in cultured human aortic smooth muscle cells to 64% of control, whereas it stimulated DNA synthesis in venous smooth muscle cells to 136% (p=0.01).
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