Abstract
Simple SummaryThe regulation of hypoxia has recently emerged as having a central impact in mitochondrial function and dysfunction in various diseases, including the major disorders threatening worldwide: cardiovascular diseases and cancer. Despite the studies in this matter, its effective role in protection and disease progression even though its direct molecular mechanism in both disorders is still to be elucidated. This review aims to cover the current knowledge about the effect of hypoxia on mitochondrial function and dysfunction, and inflammation, in cardiovascular diseases and cancer, and reports further therapeutic strategies based on the modulation of hypoxic pathways.Cardiovascular diseases (CVDs) and cancer continue to be the primary cause of mortality worldwide and their pathomechanisms are a complex and multifactorial process. Insufficient oxygen availability (hypoxia) plays critical roles in the pathogenesis of both CVDs and cancer diseases, and hypoxia-inducible factor 1 (HIF-1), the main sensor of hypoxia, acts as a central regulator of multiple target genes in the human body. Accumulating evidence demonstrates that mitochondria are the major target of hypoxic injury, the most common source of reactive oxygen species during hypoxia and key elements for inflammation regulation during the development of both CVDs and cancer. Taken together, observations propose that hypoxia, mitochondrial abnormality, oxidative stress, inflammation in CVDs, and cancer are closely linked. Based upon these facts, this review aims to deeply discuss these intimate relationships and to summarize current significant findings corroborating the molecular mechanisms and potential therapies involved in hypoxia and mitochondrial dysfunction in CVDs and cancer.
Highlights
Cardiovascular disease (CVD) and cancer are the major issues threatening public health globally and relatively widespread with enhanced morbidity and mortality
This review aims to cover the actual comprehensions about the effect of hypoxiamediating signaling pathways on mitochondrial function, and inflammation in key human diseases such as CVDs and cancer
Biological studies of HIF-1α have improved the understanding of O2 homeostasis and notably gained much attention recently in many research fields
Summary
Cardiovascular disease (CVD) and cancer are the major issues threatening public health globally and relatively widespread with enhanced morbidity and mortality. HIF-1α has drawn much attention in many research fields, as it is outlined as the master O2 regulator within the cells, a hallmark transcriptional factor in the cellular response to a hypoxic environment, and a primary element for the regulation of several genes during hypoxic condition [17]. This review aims to cover the actual comprehensions about the effect of hypoxiamediating signaling pathways on mitochondrial function, and inflammation in key human diseases such as CVDs and cancer. The complexity of these impacts will be examined in Biology 2022, 11, 300 the light of recent studies that shall help us to better dissecting the molecular mechanism and designing potential therapeutic approaches against both disorders
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