© 1995 American Heart Association, Inc.
Articles |
Combination of Vitamins C and E Alters the Response to Coronary Balloon Injury in the Pig
From the Departments of Medicine (Cardiology Division, Andreas Gruentzig Cardiovascular Center) (G.L.N., R.A.R., S.R.S., S.B.K.) and Pathology (D.S.S., M.B.G.), Emory University School of Medicine, Atlanta, Ga, and the Department of Medicine (Cardiology Division), University of Washington School of Medicine (B.C.B), Seattle.
Correspondence to Bradford C. Berk, MD, PhD, Cardiology Division, Department of Medicine, RG-22, University of Washington, Seattle, WA 98195.
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 
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.
Key Words: antioxidant • restenosis • reactive oxygen species • vascular remodeling
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