All-trans-retinoic acid limits restenosis after balloon angioplasty in thefocally atherosclerotic rabbit - A favorable effect on vessel remodeling

All-trans-retinoic acid (atRA) has potent in vitro effects on a number of p rocesses involved in vascular injury and repair, such as modulating smooth muscle cell (SMC) proliferation and inducing SMC differentiation, and may p lay an important role in the in vivo response to vascular injury. We hypoth esized that atRA would limit restenosis after balloon angioplasty through S MC-modulated changes in plaque size and vessel geometry. Balloon angioplast y was performed on rabbits with focal femoral atherosclerosis randomized to treatment with atRA or saline. At 28 days after balloon angioplasty, minim al luminal diameter was significantly larger in the atRA group (1.24+/-0.17 versus 1.12+/-0.22 mm, P=0.02). Histomorphometry confirmed a larger lumen area (0.51+/-0.20 versus 0.34+/-0.13 mm(2), P=0.004) in the atRA group, wit h no difference in absolute plaque area. Internal elastic lamina and extern al elastic lamina areas were significantly larger in the atRA group (0.89+/ -0.27 versus 0.66+/-0.24 mm(2), P=0.001, and 1.29+/-0.38 versus 0.98+/-0.32 mm2, P=0.001, respectively). Vessel sections exhibited significantly more alpha-actin and desmin immunostaining (P=0.01) in the atRA-treated group. N o differences in early cellular proliferation and collagen content were det ected with the use of bromodeoxyuridine. In this atherosclerotic model of v ascular injury, atRA limits restenosis after balloon angioplasty by effects secondary to overall vessel segment enlargement at the angioplasty site ra ther than by effects on plaque size or cellular proliferation. Increased al pha-actin and desmin immunostaining suggest a possible role for phenotypic modulation of SMCs in this favorable remodeling effect.