Chronic anemia-induced hypoxia triggers regulatory pathways that mediate long-term adaptive cardiac and cerebral changes, particularly at the transcriptional level. These adaptative mechanisms include a regulated cerebral blood flow and cardiac output, angiogenesis and cytoprotection triggered by hypoxia-inducible factor 1 alpha (HIF-1α), vascular endothelial growth factor (VEGF), neuronal nitric oxide synthase (nNOS) and Epo pathways. All these compensatory mechanisms aim to optimize oxygen delivery and to protect the brain and heart from hypoxic injury. We reviewed the effects of chronic hypobaric hypoxia as well as chronic anemia in the heart and brain, and we compared for the first time the effects of chronic hypobaric hypoxia combined with a severe lack of Epo (chronic anemia) in these vital organs. Functional cardiac adaptations such as cardiac hypertrophy, increased cardiac output as well as angiogenesis occurred along with the activation of HIF1α/VEGF and Epo/EpoR pathways under chronic anemia or hypoxia. Similarly, cerebrovascular adaptations take place through the same molecular mechanisms under chronic hypoxia or anemia. However, when both arterial pressure and content of oxygen are decreased, the cerebral and cardiac adaptative mechanisms showed their limitations. In addition, cerebral and cardiac cell injuries may have occurred following the combined effect of chronic anemia and hypoxia. By emphasizing the anemia and hypoxia-induced cerebral and myocardial adaptations, this review highlighted the crucial role of Epo in its non-erythropoietic functions such as angiogenesis and neuroprotection. Indeed, a better understanding of these protective mechanisms is of great clinical importance to the development of new therapeutic strategies for the management of ischemic heart and brain.
Part of the book: Hypoxia and Human Diseases