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01-07-2017 | Original Article

Interleukin-1β is associated with coronary endothelial dysfunction in patients with mTOR-inhibitor-eluting stent implantation

Authors: Hidetoshi Chibana, Hidemi Kajimoto, Takafumi Ueno, Shinji Yokoyama, Ken-ichiro Sasaki, Masanori Ohtsuka, Hiroshi Koiwaya, Takaharu Nakayoshi, Yoshiaki Mitsutake, Naoki Itaya, Masahiro Sasaki, Yoshihiro Fukumoto

Published in: Heart and Vessels | Issue 7/2017

Abstract

Implantation of mammalian target of rapamycin (mTOR)-inhibitor drug-eluting stents (DESs) impairs coronary endothelial function. There are no known non-invasive biomarkers of coronary endothelial dysfunction. We aimed to assess the association between serum interleukin-1beta (IL-1β) and coronary endothelial dysfunction in patients with mTOR-inhibitor DES implantation and to investigate the association between the mTOR pathway and IL-1β. We enrolled 35 patients who had implanted DESs for coronary artery disease. At a 10-month follow-up, peripheral venous blood samples were collected to measure IL-1β levels. Coronary endothelial dysfunction was evaluated by intracoronary infusion of incremental doses of acetylcholine. Serum IL-1β levels were significantly associated with the magnitude of vasoconstriction to acetylcholine at the segment distal (P < 0.05) but not proximal to the stent. Serum IL-1β levels were positively correlated with stent length (P < 0.05). To examine the direct effects of mTOR inhibition on IL-1β release, sirolimus was incubated in cultured human umbilical vein endothelial cells (HUVECs) or coronary artery smooth muscle cells (CASMCs). Sirolimus directly increased IL-1β mRNA expression (P < 0.01) and enhanced IL-1β release into the culture media (P < 0.01) in CASMCs, but not in HUVECs. Inhibition of mTOR triggers IL-1β release through transcriptional activation in CASMCs. Serum IL-1β levels are a potential biomarker for mTOR-inhibitor DES-associated coronary endothelial dysfunction.

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Title: Interleukin-1β is associated with coronary endothelial dysfunction in patients with mTOR-inhibitor-eluting stent implantation
Authors: Hidetoshi Chibana
Hidemi Kajimoto
Takafumi Ueno
Shinji Yokoyama
Ken-ichiro Sasaki
Masanori Ohtsuka
Hiroshi Koiwaya
Takaharu Nakayoshi
Yoshiaki Mitsutake
Naoki Itaya
Masahiro Sasaki
Yoshihiro Fukumoto
Publication date: 01-07-2017
Publisher: Springer Japan
Published in: Heart and Vessels / Issue 7/2017
Print ISSN: 0910-8327
Electronic ISSN: 1615-2573
DOI: https://doi.org/10.1007/s00380-017-0947-x

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