Combination of vitamins C and E alters the response to coronary balloon injury in the pig.

Abstract

Restenosis is the major limitation of the long-term success of percutaneous transluminal coronary angioplasty. The process of restenosis involves repair of vascular injury and remodeling of vessel architecture. Therapeutic interventions that improve vascular function may therefore be beneficial in the treatment of restenosis. Antioxidants such as probucol and vitamins C and E have proved effective in improving endothelial function in hypercholesterolemia, inhibiting lipid accumulation in animal models of atherosclerosis, and decreasing cardiovascular mortality in humans. Forty-two female domestic swine were divided into four study groups: control (n = 12); vitamin C (500 mg/d, group C, n = 9); vitamin E (1000 U/d, group E, n = 10); and vitamins C and E (500 mg/d + 1000 U/d, group C+E, n = 11) before oversized balloon injury of the left anterior descending and circumflex coronary arteries. Vitamins were administered 7 days before balloon injury and continued until the swine were killed 14 days after injury. Significant differences in morphometric parameters were present only in group C+E, with increases in vessel and lumen area in the segment with maximal injury. Although there was no decrease in intima area or in maximal intima thickness, the ratio of intima area to vessel area was significantly reduced, consistent with a positive effect in group C+E. Graphic analysis of the relationship between initial vessel injury (using internal elastic lamina fracture length/lumen perimeter) and vessel response to injury (using intima area/vessel area) for all segments showed improved indices for group C+E (P < .005). The beneficial effect of vitamins correlated with changes in lipid redox state. Low-density lipoprotein (LDL) thiobarbituric acid-reactive substances showed an approximately 70% decrease in all treatment groups, and the lag phase for LDL-conjugated diene formation was significantly increased, with group C+E > group E > group C. The combination of vitamins C and E improved vascular response to injury because of an apparent beneficial effect on vascular remodeling. The fact that the combination of vitamins C+E was better than vitamin E or vitamin C alone is consistent with the ability of vitamin C to improve the antioxidant effect of vitamin E, suggesting that the improved vessel response was due to a change in redox state. This study suggests an important role for oxygen radicals in the vascular response to injury and suggests that vascular remodeling and intimal proliferation are important to the restenotic process.