Significance: Endothelial cells (ECs) are specialized cells lining the interior surface
of blood vessels, playing a crucial role in vascular biology. They exhibit remarkable
versatility, adapting to various tissue requirements. Their ability to respond to
physiological and pathological stimuli ensures proper tissue function and homeostasis.
Recent Advances: Hypoxia is when the oxygen level in a given organ, tissue, or cell
type drops below the physiological level and is insufficient to maintain adequate
homeostasis. ECs respond to hypoxia by activating various mechanisms. Hypoxia-induced
changes in ECs can promote survival in low-oxygen environments by altering cellular
metabolism and inducing neoangiogenesis. However, hypoxia-induced EC responses can
also be detrimental, leading to increased production of reactive oxygen species, heightened
inflammation, changes in vascular tone, increased permeability of the endothelial
barrier, and a higher risk of coagulation. Critical Issues: Hypoxia-induced EC responses
contribute to the pathogenesis of various diseases, including metabolic diseases (e.g.,
diabetes, chronic kidney disease), infectious diseases, chronic inflammation, neoplastic
diseases, cardiovascular diseases (e.g., atherosclerosis, myocardial infarction, and
stroke) lung diseases (e.g., chronic obstructive pulmonary disease and pulmonary hypertension),
eye diseases (age-related macular degeneration and retinopathy), and neurodegenerative
diseases (e.g., Alzheimer’s disease and Parkinson’s disease). Future Directions: Detailed,
disease-specific investigations are essential to delineate how endothelial hypoxia
responses contribute to various pathologies. Understanding these mechanisms could
reveal whether targeting endothelial hypoxia holds therapeutic potential. Antioxid.
Redox Signal. 00, 000-000. Copyright 2025, Mary Ann Liebert, Inc., publishers.
