Transcriptional signatures of endothelial cells shape immune responses in cardiopulmonary health and disease

The cardiopulmonary vasculature and its associated endothelial cells (ECs) play an essential role in
sustaining life by ensuring the delivery of oxygen and nutrients. Beyond these foundational functions,
ECs serve as key regulators of immune responses. Recent advances in single-cell RNA-sequencing have
revealed that the cardiopulmonary vasculature is composed of diverse EC subpopulations, some of
which exhibit specialized immunomodulatory properties. Evidence for immunomodulation includes
distinct expression profiles associated with antigen presentation, cytokine secretion, immune cell
recruitment, translocation, and clearance—functions critical for maintaining homeostasis in the heart
and lungs. In cardiopulmonary diseases, ECs undergo substantial transcriptional reprogramming,
leading to a shift from homeostasis to an activated state marked by heightened immunomodulatory
activity. This transformation has highlighted the critical role for ECs in disease pathogenesis and their
potential as future therapy targets. This review emphasizes the diverse functions of ECs in the heart
and lungs, particularly adaptive and maladaptive immuno-regulatory roles in cardiopulmonary health
and disease.