Vitamin D Supplementation Reduces Intimal Hyperplasia and Restenosis following Coronary Intervention in Atherosclerotic Swine

• Published in: PloS one Vol. 11; no. 6; p. e0156857
• Main Authors: Gupta, Gaurav K, Agrawal, Tanupriya, Rai, Vikrant, Del Core, Michael G, Hunter, 3rd, William J, Agrawal, Devendra K
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 06.06.2016; Public Library of Science (PLoS)
• Subjects: Animals; Arteries; Arteriosclerosis; Atherosclerosis; Biology and Life Sciences; Cardiovascular diseases; Cholesterol; Coronary Artery Disease - pathology; Coronary Artery Disease - surgery; Coronary Restenosis - etiology; Coronary Restenosis - prevention & control; Data processing; Dietary Supplements; Disease Models, Animal; Health risks; High cholesterol diet; Hyperplasia; Hyperplasia - prevention & control; Interferon; Interleukin 10; Interleukin 6; Intervention; Livestock; Medicine and Health Sciences; Nutrient deficiency; Optical Coherence Tomography; Percutaneous Coronary Intervention - adverse effects; Physical sciences; Physiological aspects; Prevention; Prognosis; Restenosis; Risk factors; Serum levels; Signaling; Stenosis; Supplementation; Swine; Transcription; Tumor necrosis factor-α; Tunica Intima - drug effects; Tunica Intima - pathology; Vitamin D; Vitamin D - therapeutic use; Vitamin D Deficiency - complications; Vitamin D Deficiency - drug therapy; Vitamin D Deficiency - pathology; Vitamin D3; γ-Interferon; United States
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0156857

Vitamin D is a fat-soluble steroid hormone that activates vitamin D receptor to regulate multiple downstream signaling pathways and transcription of various target genes. There is an association between vitamin D deficiency and increased risk for cardiovascular disease. However, most of the studies are observational and associative in nature with limited data on clinical application. Thus, there is a need for more prospective randomized controlled studies to determine whether or not vitamin D supplementation provides cardiovascular protection. In this study, we examined the effects of the deficiency and supplementation of vitamin D on coronary restenosis following coronary intervention in atherosclerotic Yucatan microswine. Twelve Yucatan microswine were fed vitamin D-deficient (n = 4) or -sufficient (n = 8) high cholesterol diet for 6-months followed by coronary intervention. Post-intervention, swine in the vitamin D-sufficient high cholesterol diet group received daily oral supplementation of either 1,000 IU (n = 4) or 3,000 IU (n = 4) vitamin D3. Six months later, optical coherence tomography (OCT) was performed to monitor the development of intimal hyperplasia and restenosis. Animals were euthanized to isolate arteries for histomorphometric and immunohistochemical studies. Animals had graded levels of serum 25(OH)D; vitamin D-deficient (15.33 ± 1.45 ng/ml), vitamin D-sufficient + 1,000 IU oral vitamin D post-intervention (32.27 ± 1.20 ng/ml), and vitamin D-sufficient + 3,000 IU oral vitamin D post-intervention (51.00 ± 3.47 ng/ml). Findings from the OCT and histomorphometric studies showed a decrease in intimal hyperplasia and restenosis in vitamin D-supplemented compared to vitamin D-deficient swine. Vitamin D supplementation significantly decreased serum levels of TNF-α and IFN-γ, upregulated serum levels of IL-10, and had no effect on serum IL-6 levels. These findings suggest that vitamin D supplementation limits neointimal formation following coronary intervention in atherosclerotic swine and provide the support for vitamin D supplementation to protect against the development of coronary restenosis.