title: Interleukin-1β is associated with coronary endothelial dysfunction in patients with mTOR-inhibitor-eluting stent implantation.
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.
authors.affiliation: Division of Cardio-Vascular Medicine, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Chibana
authors.affiliation: Division of Cardio-Vascular Medicine, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan. kajimoto@med.kurume-u.ac.jp.
authors.forename: Hidemi
authors.initials: H
authors.lastname: Kajimoto
authors.affiliation: Division of Cardio-Vascular Medicine, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Ueno
authors.affiliation: Division of Cardio-Vascular Medicine, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Yokoyama
authors.affiliation: Division of Cardio-Vascular Medicine, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan.
authors.forename: Ken-Ichiro
authors.initials: KI
authors.lastname: Sasaki
authors.affiliation: Division of Cardio-Vascular Medicine, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Ohtsuka
authors.affiliation: Division of Cardio-Vascular Medicine, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Koiwaya
authors.affiliation: Division of Cardio-Vascular Medicine, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan.
authors.forename: Takaharu
authors.initials: T
authors.lastname: Nakayoshi
authors.affiliation: Division of Cardio-Vascular Medicine, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Mitsutake
authors.affiliation: Division of Cardio-Vascular Medicine, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Itaya
authors.affiliation: Division of Cardio-Vascular Medicine, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sasaki
authors.affiliation: Division of Cardio-Vascular Medicine, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Fukumoto
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D003324:Coronary Artery Disease / Q000503:physiopathology* / Q000628:therapy; D003331:Coronary Vessels / Q000503:physiopathology*; D054855:Drug-Eluting Stents / Q000009:adverse effects*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology*; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000097:blood*; D007564:Japan; D016014:Linear Models; D008297:Male; D062645:Percutaneous Coronary Intervention; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D015415:Biomarkers; C508585:IL1B protein, human; D053583:Interleukin-1beta; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus
keywords: Biomarker; Coronary artery; Drug-eluting stent; Endothelial dysfunction