Lung exposure to lipopolysaccharide causes atherosclerotic plaque destabilisation.

Autor:	Jaw JE; 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., Tsuruta M; 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., Oh Y; Centre for Heart Lung Innovation, University of British Columbia and St Paul's Hospital, Vancouver, Canada., Schipilow J; Centre for High-Throughput Phenogenomics, Oral Biological and Medical Sciences, University of British Columbia, Vancouver, Canada., Hirano Y; 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., Ngan DA; Centre for Heart Lung Innovation, University of British Columbia and St Paul's Hospital, Vancouver, Canada., Suda K; 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., Li Y; Centre for Heart Lung Innovation, University of British Columbia and St Paul's Hospital, Vancouver, Canada., Oh JY; 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., Moritani K; 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., Tam S; Centre for Heart Lung Innovation, University of British Columbia and St Paul's Hospital, Vancouver, Canada., Ford N; Centre for High-Throughput Phenogenomics, Oral Biological and Medical Sciences, University of British Columbia, Vancouver, Canada., van Eeden S; 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., Wright JL; Dept of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada., Man SF; 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., Sin DD; 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.
Jazyk:	angličtina
Zdroj:	The European respiratory journal [Eur Respir J] 2016 Jul; Vol. 48 (1), pp. 205-15. Date of Electronic Publication: 2016 Mar 23.
DOI:	10.1183/13993003.00972-2015
Abstrakt:	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. (Copyright ©ERS 2016.)
Databáze:	MEDLINE
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