Vitamin D attenuates HMGB1-mediated neointimal hyperplasia after percutaneous coronary intervention in swine
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Vitamin D attenuates HMGB1‑mediated neointimal hyperplasia after percutaneous coronary intervention in swine Mohan Satish1 · Palanikumar Gunasekar1 · Juan A. Asensio1 · Devendra K. Agrawal2 Received: 6 May 2020 / Accepted: 20 July 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
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 instent 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. Keywords Toll-like receptors · High mobility group box1 · Vitamin D · Intimal hyperplasia · Restenosis · Intravascular stenting
Introduction Coronary artery disease (CAD) remains a major cause of morbidity and mortality in the developed world [1]. While the advent of percutaneous coronary transluminal angioplasty (PTCA) has been a viable approach to revascularization, increased incidence of restenosis in 30–50% of patients within 3–5 years remains a major drawback [2, 3]. * Devendra K. Agrawal [email protected] 1
Department of Clinical & Translational Science, Creighton University School of Medicine, 2500 California Plaza, Omaha, NE 68178, USA
Department of Translational Research, Western University of Health Sciences, 309 E. Second Street, Pomona, CA 91766, USA
2
Furthermore, while the additional use of bare metal stents (BMS) or drug-elut
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