Abstract
Introduction:
Vitamin D is a sectosteroid that functions through vitamin D receptor (VDR), a transcription factor, which regulates various downstream signaling pathways and controls the transcription of many targets genes. Vitamin D deficiency is associated increased risk of incident congestive heart failure, myocardial infarction, and cardiovascular disease mortality. However, most of the studies which identified an association between lower vitamin D intake or lower 25-hydroxyvitamin D and increased risk of cardiovascular disease are observational or cross-sectional studies. There has been no careful study evaluating the effect of vitamin D supplementation on coronary artery disease outcome following coronary intervention.
Objective:
The purpose of this study was to examine the effect of vitamin D deficiency and vitamin D supplementation on coronary artery restenosis following balloon angioplasty in hypercholesterolemic Yucatan microswine.
Methods:
Twelve female microswine were fed vitamin D-deficient or vitamin D-sufficient high cholesterol diet. At six months, animals underwent coronary angioplasty. Following coronary intervention swine in the vitamin D-sufficient high cholesterol diet group received supplementation of 1,000 IU or 3,000 IU of vitamin D3. Six months later, angiogram was performed followed by optical coherence tomography to monitor the development of intimal hyperplasia and restenosis. At the end of 12 months animals were euthanized, coronary arteries were harvested and morphological and histological studies were performed.
Results:
Findings from the optical coherence tomography and histomorphometric studies showed a significant decrease in neointimal hyperplasia, increase in in-segment lumen diameter, and decrease in the intima-media ratio in coronary arteries following balloon angioplasty in swine with vitamin D supplementation compared to the animals with vitamin D-deficient status. In the in-vitro studies, calcitriol inhibited proliferation of coronary artery smooth muscle cells.
Conclusion:
These data suggest that vitamin D deficiency increases intimal hyperplasia and restenosis following coronary balloon angioplasty in hypercholesterolemic swine. Since vitamin D inhibits smooth muscle cell proliferation, supplementation of non-secosteroidal VDR ligands prior to coronary intervention could help in preventing the neointimal formation and restenosis.