Tacrolimus-eluting stent inhibits neointimal hyperplasia via calcineurin/NFAT signaling in porcine coronary artery model Narisato Hamada, Masaaki Miyata,

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Date of download: 11/12/2016 Copyright © The American College of Cardiology. All rights reserved. From: Formulation of Nanoparticle-Eluting Stents by a.

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Tacrolimus-eluting stent inhibits neointimal hyperplasia via calcineurin/NFAT signaling in porcine coronary artery model Narisato Hamada, Masaaki Miyata, Hideyuki Eto, Takahiro Shirasawa, Yuichi Akasaki, Aya Nagaki, Chuwa Tei Atherosclerosis Volume 208, Issue 1, Pages 97-103 (January 2010) DOI: 10.1016/j.atherosclerosis.2009.07.040 Copyright © 2009 Elsevier Ireland Ltd Terms and Conditions

Fig. 1 Quantitative coronary angiography (QCA). (A) Representative coronary angiography 12 weeks after stent implantation shows implantation of a bare metal stent (BMS) in the left anterior descending coronary artery (LAD) and implantation of a tacrolimus-eluting stent (TES) in the left circumflex coronary artery (LCX). (B) The % diameter stenosis measured by QCA 4 weeks after stent implantation. The % diameter stenosis of the TES was significantly smaller than that of the BMS (n=6). Atherosclerosis 2010 208, 97-103DOI: (10.1016/j.atherosclerosis.2009.07.040) Copyright © 2009 Elsevier Ireland Ltd Terms and Conditions

Fig. 2 Morphometric analysis at 12 weeks after stent implantation. (A and B) HE staining of cross-sections of coronary arteries implanted with a bare metal stent (BMS) (A) and a tacrolimus-eluting stent (TES) (B). (C) The neointimal area was significantly smaller with a TES than with a BMS (n=6). (D) The % area stenosis measured by histomorphometry was significantly smaller in TES compared with BMS (n=6). Atherosclerosis 2010 208, 97-103DOI: (10.1016/j.atherosclerosis.2009.07.040) Copyright © 2009 Elsevier Ireland Ltd Terms and Conditions

Fig. 3 Immunohistochemical staining for calcineurin in porcine coronary arteries after stenting. Calcineurin was up-regulated in the medial and neointimal smooth muscle cells (SMCs) at 2 (A), 4 (C), and 12 (E) weeks after stenting with a bare metal stent (BMS). In contrast, after stenting with a tacrolimus-eluting stent (TES), the expression of calcineurin was suppressed in the medial and neointimal SMCs at 2 (B), 4 (D) and 12 (F) weeks after stenting. Arrows demonstrate the internal elastic lamina, (*) the space of the stent. Bar, 10μm. Atherosclerosis 2010 208, 97-103DOI: (10.1016/j.atherosclerosis.2009.07.040) Copyright © 2009 Elsevier Ireland Ltd Terms and Conditions

Fig. 4 Western blot analysis for calcineurin, nuclear factor of activated T cell (NFAT), interleukin-2 (IL-2), and actin in neointima of porcine coronary arteries at 4 weeks after implantation of a tacrolimus-eluting stent (TES) or a bare metal stent (BMS). (A) Representative Western blot analysis for calcineurin, NFATc4, IL-2, and actin in BMS and TES. (B) Densitometric analysis of Western blotting demonstrated that the expression of calcineurin, NFATc4, and IL-2 with the TES was significantly lower compared with the BMS. Atherosclerosis 2010 208, 97-103DOI: (10.1016/j.atherosclerosis.2009.07.040) Copyright © 2009 Elsevier Ireland Ltd Terms and Conditions

Fig. 5 Cell proliferation at 48h of incubation with or without tacrolimus and Western blotting for calcineurin, nuclear factor of activated T cell (NFAT), and interleukin-2 (IL-2) of cultured vascular smooth muscle cells (SMCs). (A) The cell number of the tacrolimus group was significantly lower than that of the control group. (B) Representative Western blot analysis for calcineurin, NFATc4, IL-2, and actin in the tacrolimus or control group. (C) Densitometric analysis of Western blotting demonstrated that the expression of calcineurin, NFATc4, and IL-2 in the tacrolimus group was significantly lower compared with the control group. Atherosclerosis 2010 208, 97-103DOI: (10.1016/j.atherosclerosis.2009.07.040) Copyright © 2009 Elsevier Ireland Ltd Terms and Conditions