The Effect of Ascorbic Acid on Proliferation of Vascular Smooth Muscle Cells and Intimal Hyperplasia

Objective: Proliferation of smooth muscle cells leading to intimal hyperplasia developing at vascular intervention sites plays a major role in the development of restenosis. Ascorbic acid is a potent anti-oxidant with antiproliferative properties. The aim of this study was to investigate such effect of ascorbic acid on intimal hyperplasia. Material and Methods: Twenty-one male white New Zealand rabbits weighing 2-3 kg were selected. The animals were allocated to three groups each consisting of seven rabbits. Group 1 was the sham group. Group 2 was the control group and Group 3 consisted of rabbits receiving ascorbic acid. The right carotid arteries of the subjects in Groups 2 and 3 were transected and re-anastomosed. A daily dose of 100 mg ascorbic acid per kg body weight was administered intraperitoneally for 14 days to rabbits in Group 3. Rabbits in Group 2 were not subject to any pharmaceutical agent. All the subjects were sacrificed at the end of postoperative day 28. Their right carotid arteries were resected and were subject to histopathologic examination for smooth muscle cell proliferation and intimal hyperplasia. The arterial segments were fixed in 10% buffered formalin solution until the time of histological analysis. Each vessel was sectioned serially in 2-mm increments from the prepared paraffin blocks. Sections of 5 µm thickness were stained with hematoxylin and eosin (H&E) and Masson Trichrome. The diameters of vessels and their luminal areas, and the areas of tunica intima and tunica media were measured with 10X magnification. The thicknesses of tunica intima and tunica media were measured with 20X magnification. The morphometric measurements were then compared between groups. Results: Intimal thickness and intimal area were significantly lower in Group 1 when compared with the other groups (p=0.004, p=0.003). In Group 3, the ratios of tunica intima thickness/tunica media thickness and area of tunica intima/area of tunica media were significantly lower than those of Group 2 (p=0.015, p=0.046). Conclusion: Ascorbic acid reduces the intimal hyperplasia developing after vascular anastomoses.