Endothelial response to hypoxia: physiologic adaptation and pathologic dysfunction.
When subjected to a period of oxygen deprivation, endothelial cells exhibit a characteristic pattern of responses that can be considered either adaptive or pathologic, depending on the circumstances. In this review, the molecular basis for these responses is detailed. Hypoxia shifts the endothelial phenotype towards one in which anticoagulant properties are diminished, permeability and leukoadhesivity are increased, and proinflammatory features dominate the endovascular milieu. Of all the different points of intersection between the coagulation and inflammatory axes in the vasculature, perhaps most fundamentally, hypoxia alters several key transcriptional factors, including early growth response gene 1 (Egr1) and hypoxia-inducible factor (HIF) 1, which coordinate separate programs of gene activation. The preponderance of forces in the hypoxic endovascular environment, perhaps designed as an evolutionary adaptation to oxygen deprivation, can trigger severe, pathologic, clinical consequences in the setting of tissue ischemia.
Ten
Vadim S
VS
Department of Pediatrics, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
Pinsky
David J
DJ
D000222:Adaptation, Physiological; D002450:Cell Communication; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D016228:Endothelial Growth Factors / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005260:Female; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D010101:Oxygen Consumption / Q000502:physiology; D012680:Sensitivity and Specificity
D016207:Cytokines; D016228:Endothelial Growth Factors