RT Journal Article
SR Electronic
T1 Lung exposure to lipopolysaccharide causes atherosclerotic plaque destabilisation
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 205
OP 215
DO 10.1183/13993003.00972-2015
VO 48
IS 1
A1 Jen Erh Jaw
A1 Masashi Tsuruta
A1 Yeni Oh
A1 John Schipilow
A1 Yuki Hirano
A1 David A. Ngan
A1 Koichi Suda
A1 Yuexin Li
A1 Jin Young Oh
A1 Konosuke Moritani
A1 Sheena Tam
A1 Nancy Ford
A1 Stephan van Eeden
A1 Joanne L. Wright
A1 S.F. Paul Man
A1 Don D. Sin
YR 2016
UL http://erj.ersjournals.com/content/48/1/205.abstract
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