PT  - JOURNAL ARTICLE
AU  - Jen Erh Jaw
AU  - Masashi Tsuruta
AU  - Yeni Oh
AU  - John Schipilow
AU  - Yuki Hirano
AU  - David A. Ngan
AU  - Koichi Suda
AU  - Yuexin Li
AU  - Jin Young Oh
AU  - Konosuke Moritani
AU  - Sheena Tam
AU  - Nancy Ford
AU  - Stephan van Eeden
AU  - Joanne L. Wright
AU  - S.F. Paul Man
AU  - Don D. Sin
TI  - Lung exposure to lipopolysaccharide causes atherosclerotic plaque destabilisation
AID  - 10.1183/13993003.00972-2015
DP  - 2016 Jul 01
TA  - European Respiratory Journal
PG  - 205--215
VI  - 48
IP  - 1
4099  - http://erj.ersjournals.com/content/48/1/205.short
4100  - http://erj.ersjournals.com/content/48/1/205.full
SO  - Eur Respir J2016 Jul 01; 48
AB  - 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.Neutrophils play an important role in atherosclerotic plaque vulnerability related to LPS-induced lung inflammation http://ow.ly/Y7dWW