Pentoxifylline inhibits neointimal formation and stimulates constrictive vascular remodeling after arterial injury

Pentoxifylline (PTX) is a phosphodiesterase inhibitor used in the treatment of peripheral vascular disease, and this agent can suppress inflammatory v ascular damage. Inflammation has been implicated in vascular lesion formati on, and we examined the effects of PTX in a model of arterial injury. Sprag ue-Dawley rats were treated with intraperitoneal PTX (75 mg/kg/day) or sali ne starting 3 days before carotid balloon injury, and killed 24 h or 14 day s later. Carotid arteries were analyzed by cross-sectional morphometry, imm unostaining for proliferating cell nuclear antigen (PCNA) and subjected to terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelin g (TUNEL). Moreover, the effects of PTX on vascular smooth-muscle cell (VSM C) migration and production of collagen types I, IV, and VI were examined i n vitro. At 14 days after balloon injury, PTX reduced the neointimal area ( 0.074 +/- 0.001 us. 0.172 +/- 0.003 mm(2); p < 0.001), media area (0.143 +/ - 0.001 vs. 0.176 +/- 0.001 mm(2); p < 0.01), intima/media ratio (0.50 +/- 0.02 vs. 0.99 +/- 0.12; p < 0.001), and total vessel area (0.601 +/- 0.010 vs. 0.744 +/- 0.011 mm(2); p < 0.01). The lumen area, PCNA expression, and TUNEL were similar in the two treatment groups, whereas the neointimal cell density was increased by PTX (3,476 +/- 504 cells/mm(2) vs. 2,215 +/- 232 cells/mm(2); p < 0.05). In vitro, PTX inhibited VSMC production of collagen type I in a concentration-dependent manner and did not influence VSMC migr ation. We conclude that PTX inhibits neointimal formation and induces const rictive vascular remodeling in the rat model of balloon injury by mechanism s involving decreased VSMC collagen type I production.