Hypoxia: molecular pathophysiological mechanisms in human diseases

Abstract

Hypoxia, a low O2 tension, is a fundamental feature that occurs in physiological events as well as pathophysiological conditions, especially mentioned for its role in the mechanism of angiogenesis, glucose metabolism, and cell proliferation/survival. The hypoxic state through the activation of specific mechanisms is an aggravating circumstance commonly noticed in multiple sclerosis, cancer, heart disease, kidney disease, liver disease, lung disease, and in inflammatory bowel disease. On the other hand, hypoxia could play a key role in tissue regeneration and repair of damaged tissues, especially by acting on specific tissue stem cells, but their features may result as a disadvantage when it is concerned for neoplastic stem cells. Furthermore, hypoxia could also have a potential role in tissue engineering and regenerative medicine due to its capacity to improve the performance of biomaterials. The current review aims to highlight the hypoxic molecular mechanisms reported in different pathological conditions to provide an overview of hypoxia as a therapeutic agent in regenerative and molecular therapy. Graphical abstract

Differential Effects of Oligosaccharides, Antioxidants, Amino Acids and PUFAs on Heat/Hypoxia-Induced Epithelial Injury in a Caco-2/HT-29 Co-Culture Model

“…Although the association between exercise-induced heat and enhanced intestinal permeability is clear [ 10 ], the exact mechanism behind the pathology of hypoxia- and heat-induced epithelial breakdown still needs to be elucidated. The TJ protein claudin-1 can act as a target protein for hypoxia-inducible factors (HIFs) suggesting a direct relationship between hypoxia and intestinal barrier damage [ 11 ]. Additionally, hypoxia and heat can lead to increased ROS activity and thus cause peroxidative damage to epithelial cells and is one of the hypotheses proposed so far [ 11 ].…”

“…The TJ protein claudin-1 can act as a target protein for hypoxia-inducible factors (HIFs) suggesting a direct relationship between hypoxia and intestinal barrier damage [ 11 ]. Additionally, hypoxia and heat can lead to increased ROS activity and thus cause peroxidative damage to epithelial cells and is one of the hypotheses proposed so far [ 11 ]. A suitable intervention strategy for this intestinal barrier injury is of great importance.…”

Polymeric Micellar Systems—A Special Emphasis on “Smart” Drug Delivery

“…Cancer, cardiomyopathy, ischemia, rheumatoid arthritis, and vascular illnesses have all been linked to hypoxia (low oxygen levels) [ 145 ]. Lowered oxygen partial pressure enables tumor-specific medication delivery because hypoxic and normoxic cells are characterize by dissimilar microenvironments [ 145 ]. The tumoral microenvironments have significantly less oxygen than normal tissues, as seen by the oxygen-sensitive sensors [ 145 ].…”

“…Lowered oxygen partial pressure enables tumor-specific medication delivery because hypoxic and normoxic cells are characterize by dissimilar microenvironments [ 145 ]. The tumoral microenvironments have significantly less oxygen than normal tissues, as seen by the oxygen-sensitive sensors [ 145 ]. There is proof that persistent hypoxia changes the biology of tumors and long-term hypoxia changes their pathophysiology.…”

“…There is proof that persistent hypoxia changes the biology of tumors and long-term hypoxia changes their pathophysiology. This includes choosing genotypes that promote survival under hypoxic rearrangement damage and altering genes expression to promote survival by reducing apoptosis, enhancing tumor angiogenesis, and encouraging autophagy [ 145 ].…”