Abstract
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 immunoregulatory roles in cardiopulmonary health and disease.