Microvesicles as new therapeutic targets for the treatment of the acute respiratory distress syndrome (ARDS)

ABSTRACT

Introduction: Acute respiratory distress syndrome (ARDS) is a heterogeneous and multifactorial disease; it is a common and devastating condition that has a high mortality. Treatment is limited to supportive measures hence novel pharmacological approaches are necessary. We propose a new direction in ARDS research; this means moving away from thinking about individual inflammatory mediators and instead investigating how packaged information is transmitted between cells. Microvesicles (MVs) represent a novel vehicle for inter-cellular communication with an emerging role in ARDS pathophysiology.

Areas covered: This review examines current approaches to ARDS and emerging MV research. We describe advances in our understanding of microvesicles and focus on their pro-inflammatory roles in airway and endothelial signaling. We also offer reasons for why MVs are attractive therapeutic targets.

Expert opinion: MVs have a key role in ARDS pathophysiology. Preclinical studies must move away from simple models toward more realistic scenarios while clinical studies must embrace patient heterogeneity. Microvesicles have the potential to aid identification of patients who may benefit from particular treatments and act as biomarkers of cellular status and disease progression. Understanding microvesicle cargoes and their cellular interactions will undoubtedly uncover new targets for ARDS.

KEYWORDS:

• Acute lung injury
• acute respiratory distress syndrome
• cellular communication
• extracellular vesicles
• microvesicles

Article Highlights

• ARDS is a heterogeneous and multifactorial disease that develops following exposure to numerous factors that include pneumonia and sepsis.

• There are no specific pharmacological therapies for ARDS; treatment is restricted to supportive measures, hence there is an urgent need for novel pharmacological therapies.

• Microvesicles (MVs) are novel mediators of intercellular communication; they carry biological mediators and cargo between cells and have an important role in the pathophysiology of ARDS, including crucial roles in airway and endothelial signalling during inflammation.

• Because of the ‘packaged’ nature of their cargo, manipulation of microvesicles is likely to lead to more substantive outcomes than manipulation/targeting of single mediators, and thus may succeed where previous approaches have failed.

• Microvesicles have the potential to provide information on the status of cells that cannot otherwise be interrogated, allowing novel insights into pathophysiology and theoretically, disease progression and treatment responses.

• Microvesicles are potential therapeutic targets. Understanding the mechanisms of MV production in ARDS, particularly from pulmonary microvascular inflammation resulting in systemic release of MVs into the circulation, could provide crucial insights for developing targeted therapies to patients.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

The work of the authors has been supported by grants from GlaxoSmithKline, Medical Research Council, British Journal of Anaesthesia, Biotechnology and Biological Sciences Research Council and Chelsea and Westminster Health Charity.