Pathophysiological implications of hypoxia in human diseases

Abstract

Oxygen is essentially required by most eukaryotic organisms as a scavenger to remove harmful electron and hydrogen ions or as a critical substrate to ensure the proper execution of enzymatic reactions. All nucleated cells can sense oxygen concentration and respond to reduced oxygen availability (hypoxia). When oxygen delivery is disrupted or reduced, the organisms will develop numerous adaptive mechanisms to facilitate cells survived in the hypoxic condition. Normally, such hypoxic response will cease when oxygen level is restored. However, the situation becomes complicated if hypoxic stress persists (chronic hypoxia) or cyclic normoxia-hypoxia phenomenon occurs (intermittent hypoxia). A series of chain reaction-like gene expression cascade, termed hypoxia-mediated gene regulatory network, will be initiated under such prolonged or intermittent hypoxic conditions and subsequently leads to alteration of cellular function and/or behaviors. As a result, irreversible processes occur that may cause physiological disorder or even pathological consequences. A growing body of evidence implicates that hypoxia plays critical roles in the pathogenesis of major causes of mortality including cancer, myocardial ischemia, metabolic diseases, and chronic heart and kidney diseases, and in reproductive diseases such as preeclampsia and endometriosis. This review article will summarize current understandings regarding the molecular mechanism of hypoxia in these common and important diseases.

Hypoxia-Associated Prognostic Markers and Competing Endogenous RNA Co-Expression Networks in Breast Cancer

“…During the growth of malignant tumors, tumor cells grow faster than their blood vessels grow. The effective oxygen diffusion range of the capillaries around the tumor cells cannot meet the needs of rapid tumor growth, resulting in uneven supply of oxygen and nutrients in tumor tissue, thereby forming the hypoxic microenvironment ( 3 , 4 ). Hypoxia is one of the leading characteristics of solid tumors including breast cancer, and plays an important role in the occurrence and development of cancers ( 5 ).…”

Integrative Analysis of Hypoxia-Associated Signature in Pan-Cancer

“…It is worth noting that the cellular fitness here was performed in cancer cells, which were cultured under normoxia. Multiple hypoxia-mediated gene regulatory networks will be initiated and produced under lasting or temporary hypoxic situations and finally lead to significant change of cellular functions and behaviors ( Chen et al., 2020 ). Subsequently, irreversible processes develop, which could result in pathophysiological disorder consequences.…”

HYPOXIA AND REPRODUCTIVE HEALTH: The role of hypoxia in the development and progression of endometriosis

“…Both endometriotic lesions and the members in the microenvironment are found to release pro-survival factors to promote lesion growth. Hypoxia is known as a strong factor for promoting angiogenesis, cell proliferation, and even metastasis in cancer cells (Chen et al 2020). Similarly, the growth of endometriotic lesions is also largely affected by the hypoxic force.…”