Platelet-mediated vascular dysfunction during acute lung injury

Abstract

Context: Platelets have significant roles in initiating and mediating reduced alveolar blood flow, microvascular leak, and ventilation/perfusion mismatch caused by metabolic changes and altered signal transduction caused by ischemia-reperfusion.

Objective: This review focuses on platelet mechanisms of vascular dysfunction in the lung and presents a hypothesis for interplay between platelet activation, endothelial damage and fibrinogen. The purpose is to discuss current knowledge regarding mechanisms of platelet-mediated endothelial injury and implications for new strategies to treat vascular dysfunction associated with acute lung injury (ALI).

Methods: Literature from a number of fields was searched using Medline and Google Scholar.

Results: Activated platelets contribute to redox imbalance through reactive oxygen species production, pro-leak molecules such as PAF and serotonin, and recruitment of inflammatory cytokines and leukocytes to the damaged endothelium.

Conclusion: Platelets are a critical component of pulmonary ALI, acting in conjunction with fibrinogen to mediate endothelial damage through multiple signal transduction pathways.

Keywords::

• Ischemia-reperfusion
• oxidative stress
• nitric oxide synthase
• fibrinogen

Acknowledgements

The authors thank David Lominadze, PhD, for his many helpful discussions regarding involvement of fibrinogen and platelets in inflammatory disorders and signalling pathways that mediate endothelial dysfunction.

Declaration of interest

The authors declare no conflict of interest.