Unfractionated heparin and low molecular weight heparin do not inhibit the growth of proliferating human arterial smooth muscle cells in culture

Objectives:To clarify the effects of unfractionated heparin (UH) and low molecular weight heparin (LMWH) on proliferating human smooth muscle cells (SMC) compared to growth arrested SMC.Design:A cell culture study where proliferating SMC were exposed to different concentrations of UH and LMWH and the effect on proliferation and collagen secretion was studied. Growth arrested SMC were stimulated with serum and the effect of UH on proliferation was measured.Setting:Sections of Medical Angiology and Vascular Surgery, Malmö General Hospital, Sweden.Materials:Human SMC were established from arterial tissue obtained at vascular surgery or at organ donation.Chief outcome measures:Effects of UH and LMWH on total cellular DNA, 3H-thymidine incorporation and collagen secretion using proliferating and growth arrested human SMC in culture.Main results:In proliferating SMC that had not been growth arrested, 1 and 10 IU/ml UH and LMWH significantly increased total cellular DNA compared to controls while DNA synthesis was not influenced. The higher cellular DNA was probably not a consequence of increased proliferation as DNA synthesis was not affected by UH or LMWH. The increased total cellular DNA could instead be due to reduced cell death. Higher concentrations (10 IU/ml) of UH and LMWH also increased collagen secretion. In control experiments with UH DNA, synthesis was decreased in stimulated human SMC that had been growth arrested previously to heparin exposure.Conclusions:The effects of UH and LMWH on SMC proliferation will depend on the proliferative state of the SMC. The results might be of relevance for the understanding of the atherosclerotic process and for pharmacologic interventions to prevent restenosis after angioplasty or surgery