Differentiating agent, hexamethylene bisacetamide, inhibits neointimal formation after vascular injury

Background: Hexamethylene bisacetamide (HMBA), a potent differentiating agent of transformed cell lines, has been reported to affect phenotypic modulation and suppress proliferation of vascular smooth muscle cells (VSMCs). The effects of HMBA on the growth of VSMCs were studied in the rat carotid injury model. Methods: HMBA was added to culture medium of VSMCs explanted from aorta of Sprague Dawley rats and the cell number was counted after 5 days of incubation. The carotid artery of Sprague Dawley rats was denuded with a balloon embolectomy catheter. The rats were treated with continuous infusion of HMBA (1 g/day) or saline for 7 days after injury. Results: HMBA inhibited VSMC proliferation in a dose-dependent manner (at a HMBA concentration of 1-5 mM). Plasma concentration of HMBA during continuous infusion was in the range 0.8-1.0 mM. Immunohistochemistry of proliferating cell nuclear antigan showed that HMBA inhibited VSMC proliferation after vascular injury. Cell number in the intima and neointimal thickening were significantly reduced in HMBA-treated rats at 14 days after injury. Conclusions: Systemic administration of HMBA inhibited VSMC proliferation in the rat carotid injury model.