all-Trans-retinoic acid reduces neointimal formation and promotes favorable geometric remodeling of the rat carotid artery after balloon withdrawal injury

Abstract

Background - The multifactorial and unpredictable nature of human restenosis will probably necessitate interventional strategies that target multiple processes involved in acute vascular narrowing. Retinoids (eg, all- trans-retinoic acid, atRA) represent a growing class of pleiotropic biological response modifiers with demonstrable efficacy managing several pathological conditions. In this report, we have initiated studies to examine the hypothesis that atRA limits neointimal formation after experimental vascular injury. Methods and Results - Rats were predosed with atRA (30 mg·kg-1·d-1 PO) or corn oil 4 days before balloon withdrawal injury (BWI) of the left common carotid artery and continued on this drug regimen for an additional 14 days. High-performance liquid chromatographic analysis documented therapeutic levels of atRA in serum and vascular tissue. atRA depressed peak DNA synthesis in the tunica media of BWI vessels (P<0.05). Histomorphometry revealed atRA-mediated reductions in neointimal area, neointimal cell number, and intimal/medial area ratio as well as significant increases in vessel wall perimeter (P<0.05). Such changes in vascular architecture contributed to a 35% to 37% increase in the luminal area of BWI vessels exposed to atRA (P<0.005 compared with controls). Conclusions - atRA reduces neointimal mass and elicits favorable geometric remodeling of the injured rat carotid artery.