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

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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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Abbreviations

DES:

Drug-eluting stent

IL-1β:

Interleukin-1 beta

Ach:

Acetylcholine

CASMCs:

Coronary artery smooth muscle cells

BMS:

Bare-metal stent

mTOR:

Mammalian target of rapamycin

NTG:

Nitroglycerin

HUVECs:

Human umbilical vein endothelial cells

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Acknowledgements

The authors gratefully acknowledge the technical assistance of Eiko Ogura, Katsue Shiramizu, and Makiko Kiyohiro. We also thank the staff in the Cardiac Catheterization Laboratory in Kurume University Hospital for technical assistance.

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Authors and Affiliations

  1. Division of Cardio-Vascular Medicine, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan

    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

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  1. Hidetoshi Chibana
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  2. Hidemi Kajimoto
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  3. Takafumi Ueno
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  4. Shinji Yokoyama
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  5. Ken-ichiro Sasaki
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  6. Masanori Ohtsuka
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  9. Yoshiaki Mitsutake
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  10. Naoki Itaya
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  11. Masahiro Sasaki
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  12. Yoshihiro Fukumoto
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Correspondence to Hidemi Kajimoto.

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This study was supported, in part, by a Grant from the Science Frontier Research Promotion Centers (Cardiovascular Research Institute, Kurume University).

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Chibana, H., Kajimoto, H., Ueno, T. et al. Interleukin-1β is associated with coronary endothelial dysfunction in patients with mTOR-inhibitor-eluting stent implantation. Heart Vessels 32, 823–832 (2017). https://doi.org/10.1007/s00380-017-0947-x

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  • DOI: https://doi.org/10.1007/s00380-017-0947-x

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