From the Department of Physiology, Medical College of Wisconsin,
Milwaukee (J.M.M., L.A.K., T.A.N.), and the Institute of Human Nutrition,
Columbia University, New York, NY (C.A.A., R.P., W.S.B.).
Correspondence to Joseph M. Miano, PhD, Department of Physiology, Cardiovascular Research Center, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226. E-mail jmiano{at}mcw.edu
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 in 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.
© 1998 American Heart Association, Inc.
Basic Science Reports
all-Trans-Retinoic Acid Reduces Neointimal Formation and Promotes Favorable Geometric Remodeling of the Rat Carotid Artery After Balloon Withdrawal Injury
Key Words: retinoids • actins • restenosis • muscle, smooth • cells • revascularization
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