title: Lung exposure to lipopolysaccharide causes atherosclerotic plaque destabilisation.
abstract: Epidemiological studies have implicated lung inflammation as a risk factor for acute cardiovascular events, but the underlying mechanisms linking lung injury with cardiovascular events are largely unknown.Our objective was to develop a novel murine model of acute atheromatous plaque rupture related to lung inflammation and to investigate the role of neutrophils in this process.Lipopolysaccharide (LPS; 3 mg·kg(-1)) or saline (control) was instilled directly into the lungs of male apolipoprotein E-null C57BL/6J mice following 8 weeks of a Western-type diet. 24 h later, atheromas in the right brachiocephalic trunk were assessed for stability ex vivo using high-resolution optical projection tomography and histology. 68% of LPS-exposed mice developed vulnerable plaques, characterised by intraplaque haemorrhage and thrombus, versus 12% of saline-exposed mice (p=0.0004). Plaque instability was detectable as early as 8 h post-intratracheal LPS instillation, but not with intraperitoneal instillation. Depletion of circulating neutrophils attenuated plaque rupture.We have established a novel plaque rupture model related to lung injury induced by intratracheal exposure to LPS. In this model, neutrophils play an important role in both lung inflammation and plaque rupture. This model could be useful for screening therapeutic targets to prevent acute vascular events related to lung inflammation.
authors.affiliation: Centre for Heart Lung Innovation, University of British Columbia and St Paul's Hospital, Vancouver, Canada Dept of Medicine, Division of Respirology, University of British Columbia, Vancouver, Canada.
authors.forename: Jen Erh
authors.identifier: 0000-0002-4065-9876
authors.initials: JE
authors.lastname: Jaw
authors.affiliation: Centre for Heart Lung Innovation, University of British Columbia and St Paul's Hospital, Vancouver, Canada Dept of Surgery, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Tsuruta
authors.affiliation: Centre for Heart Lung Innovation, University of British Columbia and St Paul's Hospital, Vancouver, Canada.
authors.forename: Yeni
authors.initials: Y
authors.lastname: Oh
authors.affiliation: Centre for High-Throughput Phenogenomics, Oral Biological and Medical Sciences, University of British Columbia, Vancouver, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Schipilow
authors.affiliation: Centre for Heart Lung Innovation, University of British Columbia and St Paul's Hospital, Vancouver, Canada Dept of Surgery, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hirano
authors.affiliation: Centre for Heart Lung Innovation, University of British Columbia and St Paul's Hospital, Vancouver, Canada.
authors.forename: David A
authors.initials: DA
authors.lastname: Ngan
authors.affiliation: Centre for Heart Lung Innovation, University of British Columbia and St Paul's Hospital, Vancouver, Canada Division of Upper GI, Dept of Surgery, Fujita Health University, Aichi, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Suda
authors.affiliation: Centre for Heart Lung Innovation, University of British Columbia and St Paul's Hospital, Vancouver, Canada.
authors.forename: Yuexin
authors.initials: Y
authors.lastname: Li
authors.affiliation: Centre for Heart Lung Innovation, University of British Columbia and St Paul's Hospital, Vancouver, Canada Dept of Internal Medicine, Division of Pulmonology, Dongguk University Ilsan Hospital, Goyang, South Korea.
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Oh
authors.affiliation: Centre for Heart Lung Innovation, University of British Columbia and St Paul's Hospital, Vancouver, Canada Dept of Surgery, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Konosuke
authors.initials: K
authors.lastname: Moritani
authors.affiliation: Centre for Heart Lung Innovation, University of British Columbia and St Paul's Hospital, Vancouver, Canada.
authors.forename: Sheena
authors.initials: S
authors.lastname: Tam
authors.affiliation: Centre for High-Throughput Phenogenomics, Oral Biological and Medical Sciences, University of British Columbia, Vancouver, Canada.
authors.forename: Nancy
authors.initials: N
authors.lastname: Ford
authors.affiliation: Centre for Heart Lung Innovation, University of British Columbia and St Paul's Hospital, Vancouver, Canada Dept of Medicine, Division of Respirology, University of British Columbia, Vancouver, Canada.
authors.forename: Stephan
authors.initials: S
authors.lastname: van Eeden
authors.affiliation: Dept of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada.
authors.forename: Joanne L
authors.initials: JL
authors.lastname: Wright
authors.affiliation: Centre for Heart Lung Innovation, University of British Columbia and St Paul's Hospital, Vancouver, Canada Dept of Medicine, Division of Respirology, University of British Columbia, Vancouver, Canada.
authors.forename: S F Paul
authors.initials: SF
authors.lastname: Man
authors.affiliation: Centre for Heart Lung Innovation, University of British Columbia and St Paul's Hospital, Vancouver, Canada Dept of Medicine, Division of Respirology, University of British Columbia, Vancouver, Canada don.sin@hli.ubc.ca.
authors.forename: Don D
authors.initials: DD
authors.lastname: Sin
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000166:cytology*; D058226:Plaque, Atherosclerotic / Q000473:pathology*; D041622:Tomography, Optical
chemical_list: D001057:Apolipoproteins E; D016207:Cytokines; D008070:Lipopolysaccharides