Intracoronary stenting is a common procedure in patients with coronary artery disease (CAD). Stent deployment stretches and denudes the endothelial layer, promoting a local inflammatory response, resulting in neointimal hyperplasia. Vitamin D deficiency associates with CAD. In this study, we examined the association of vitamin D status with high mobility group box 1 (HMGB1)-mediated pathways (HMGB1, receptor for advanced glycation end products [RAGE], and Toll-like receptor-2 and -4 [TLR2 and TLR4]) in neointimal hyperplasia in atherosclerotic swine following bare metal stenting. Yucatan microswine fed with a high-cholesterol diet were stratified to receive vitamin D-deficient (VD-DEF), vitamin D-sufficient (VD-SUF), and vitamin D-supplemented (VD-SUP) diet. After 6 months, PTCA (percutaneous transluminal balloon angioplasty) followed by bare metal stent implantation was performed in the left anterior descending (LAD) artery of each swine. Four months following coronary intervention, angiogram and optical coherence tomography (OCT) were performed and swine euthanized. Histology and immunohistochemistry were performed in excised LAD to evaluate the expression of HMGB1, RAGE, TLR2, and TLR4. OCT analysis revealed the greatest in-stent restenosis area in the LAD of VD-DEF compared to VD-SUF or VD-SUP swine. The protein expression of HMGB1, RAGE, TLR2, and TLR4 was significantly higher in the LAD of VD-DEF compared to VD-SUF or VD-SUP swine. Vitamin D deficiency was associated with both increased in-stent restenosis and increased HMGB1-mediated inflammation noted in coronary arteries following intravascular stenting. Inversely, vitamin D supplementation was associated with both a decrease in this inflammatory profile and in neointimal hyperplasia, warranting further investigation for vitamin D as a potential adjunct therapy following coronary intervention.

冠状动脉内支架置入术是冠状动脉疾病 (CAD) 患者的常见手术。支架部署拉伸并剥脱内皮层，促进局部炎症反应，导致新生内膜增生。维生素 D 缺乏与 CAD 相关。在这项研究中，我们检查了维生素 D 状态与高迁移率族框 1 (HMGB1) 介导的通路（HMGB1，晚期糖基化终产物受体 [RAGE]，以及 Toll 样受体 2 和 -4 [TLR2 和TLR4]) 在裸金属支架植入后动脉粥样硬化猪的新生内膜增生中的作用。用高胆固醇日粮喂养的尤卡坦小型猪被分层接受维生素 D 缺乏 (VD-DEF)、维生素 D 充足 (VD-SUF) 和维生素 D 补充 (VD-SUP) 日粮。6个月后，在每头猪的左前降支 (LAD) 动脉中进行 PTCA（经皮腔内球囊血管成形术），然后进行裸金属支架植入。冠状动脉介入治疗后四个月，进行血管造影和光学相干断层扫描 (OCT) 并对猪实施安乐死。在切除的 LAD 中进行组织学和免疫组织化学以评估 HMGB1、RAGE、TLR2 和 TLR4 的表达。OCT 分析显示，与 VD-SUF 或 VD-SUP 猪相比，VD-DEF 的 LAD 中支架内再狭窄区域最大。与 VD-SUF 或 VD-SUP 猪相比，VD-DEF 的 LAD 中 HMGB1、RAGE、TLR2 和 TLR4 的蛋白质表达显着更高。维生素 D 缺乏与支架内再狭窄增加和血管内支架置入后冠状动脉中 HMGB1 介导的炎症增加有关。