Lung exposure to lipopolysaccharide causes atherosclerotic plaque destabilisation

Jen Erh Jaw, Masashi Tsuruta, Yeni Oh, John Schipilow, Yuki Hirano, David A. Ngan, Koichi Suda, Yuexin Li, Jin Young Oh, Konosuke Moritani, Sheena Tam, Nancy Ford, Stephan Van Eeden, Joanne L. Wright, S. F.Paul Man, Don D. Sin

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)205-215
Number of pages11
JournalEuropean Respiratory Journal
Volume48
Issue number1
DOIs
Publication statusPublished - 01-07-2016

All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine

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    Jaw, J. E., Tsuruta, M., Oh, Y., Schipilow, J., Hirano, Y., Ngan, D. A., Suda, K., Li, Y., Oh, J. Y., Moritani, K., Tam, S., Ford, N., Van Eeden, S., Wright, J. L., Man, S. F. P., & Sin, D. D. (2016). Lung exposure to lipopolysaccharide causes atherosclerotic plaque destabilisation. European Respiratory Journal, 48(1), 205-215. https://doi.org/10.1183/13993003.00972-2015