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Are circulating endothelial cells the next target for transcriptome-level pathway analysis in ARDS?

Ana C Costa Monteiro1, Michael A Matthay2

  • 1Department of Medicine, Division of Pulmonary and Critical Care, University of California, Los Angeles, California, United States.

American Journal of Physiology. Lung Cellular and Molecular Physiology
|February 7, 2023
PubMed
Summary

Acute respiratory distress syndrome (ARDS) research needs better patient subgroup definitions. Querying circulating endothelial cell (CEC) transcriptomes offers a novel approach to understand ARDS heterogeneity and mechanisms.

Keywords:
ARDSacute respiratory distress syndromecirculating endothelial cellstranscriptomics

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Area of Science:

  • Pulmonary Medicine
  • Critical Care Medicine
  • Translational Research

Background:

  • Acute respiratory distress syndrome (ARDS) research has been hampered by patient heterogeneity, leading to a lack of effective mortality-improving pharmacological interventions despite extensive investigation.
  • Current soluble biomarkers aid in clinical trial recruitment but lack organ specificity and mechanistic insights into ARDS pathophysiology.
  • Advancing ARDS research requires refined definitions of patient subgroups that exhibit more uniform responses to therapeutic interventions.

Discussion:

  • Circulating endothelial cells (CECs) shed from damaged vasculature serve as indicators of site-specific inflammatory injury.
  • CEC quantification has shown associations with disease severity across various conditions, including myocardial infarction, vasculitides, cancer, and ARDS.
  • Analyzing CECs offers a promising avenue to elucidate the specific cellular contributions to disease mechanisms and identify factors driving CEC shedding in ARDS.

Key Insights:

  • The transcriptome of circulating endothelial cells (CECs) presents a novel approach to dissecting ARDS heterogeneity.
  • CEC analysis can provide organ-specific information and mechanistic insights currently lacking in plasma-soluble biomarker studies.
  • Single-cell RNA transcriptomics of CECs holds potential for uncovering novel signals contributing to ARDS pathophysiology.

Outlook:

  • Future research should focus on leveraging CEC transcriptomics to identify ARDS subgroups with distinct biological mechanisms and therapeutic responses.
  • Developing targeted therapies based on CEC-derived insights could improve outcomes for patients with ARDS.
  • This approach may pave the way for personalized medicine strategies in critical care settings for ARDS management.