Hypoxia-Induced Changes in Endothelial Cell Phenotype and Function

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.