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Updated: Dec 13, 2025
A Murine Model of Stent Implantation in the Carotid Artery for the Study of Restenosis
Published on: May 14, 2013
Vitamin D attenuates HMGB1-mediated neointimal hyperplasia after percutaneous coronary intervention in swine
Mohan Satish1, Palanikumar Gunasekar1, Juan A Asensio1
1Department of Clinical & Translational Science, Creighton University School of Medicine, 2500 California Plaza, Omaha, NE, 68178, USA.
Insights
Vitamin D deficiency worsens in-stent restenosis and inflammation after coronary stenting by increasing high mobility group box 1 (HMGB1) pathways. Supplementation may reduce neointimal hyperplasia and inflammation.
Area of Science:
- Cardiovascular Research
- Nutritional Science
- Immunology
Background:
- Coronary artery disease (CAD) is prevalent, with intracoronary stenting a common treatment.
- Stent deployment can cause neointimal hyperplasia (NIH) due to endothelial injury and inflammation.
- Vitamin D deficiency is linked to CAD and may influence post-stenting outcomes.
Purpose of the Study:
- To investigate the association between vitamin D status and HMGB1-mediated inflammatory pathways in NIH after bare metal stenting.
- To evaluate the impact of vitamin D deficiency and supplementation on in-stent restenosis and specific inflammatory markers.
Main Methods:
- Yucatan microswine on a high-cholesterol diet were divided into vitamin D-deficient, sufficient, and supplemented groups.
- Percutaneous transluminal coronary angioplasty (PTCA) with bare metal stenting was performed in the LAD artery.
- In-stent restenosis was assessed by angiography and OCT; protein expression of HMGB1, RAGE, TLR2, and TLR4 was analyzed via histology and immunohistochemistry.
Main Results:
- Vitamin D-deficient swine exhibited significantly greater in-stent restenosis area compared to sufficient or supplemented groups.
- Protein expression of HMGB1, RAGE, TLR2, and TLR4 was markedly elevated in vitamin D-deficient swine.
- Vitamin D supplementation was associated with reduced neointimal hyperplasia and a less pronounced inflammatory profile.
Conclusions:
- Vitamin D deficiency is associated with increased in-stent restenosis and HMGB1-mediated inflammation following coronary stenting.
- Vitamin D supplementation appears to mitigate neointimal hyperplasia and associated inflammatory responses.
- Vitamin D may hold potential as an adjunctive therapy to improve outcomes after coronary interventions.
Abstract:
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.
