The Interplay of Hypoxia Signaling on Mitochondrial Dysfunction and Inflammation in Cardiovascular Diseases and Cancer: From Molecular Mechanisms to Therapeutic Approaches

Abstract

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.

[Retracted] Identifying the Effect of Nuanxin Capsules on Myocardial Injury Induced by Chronic Hypoxia via Network Pharmacology Analysis and Experimental Validation

“…It was further verified that the NX substantially decreased the early and late apoptosis rates induced by chronic hypoxia, suggesting that NX protected cardiomyocytes from apoptosis. Mitochondrial dysfunction has been implicated in the development of HF due to myocardial hypoxia [28]. The inability of oxidative metabolism to generate and transfer energy is considered the primary mechanism linking to mitochondrial dysfunction and contractile failure [29].…”

“…Mitochondrial dysfunction has been implicated in the development of HF due to myocardial hypoxia [ 28 ]. The inability of oxidative metabolism to generate and transfer energy is considered the primary mechanism linking to mitochondrial dysfunction and contractile failure [ 29 ].…”

Perspectives on mitochondrial relevance in cardiac ischemia/reperfusion injury

“…During hypoxia, HIF-1α is a central regulator mediating the cellular response and plays a key role in multiple CVDs, such as IHD ( Bouhamida et al, 2022 ). Interestingly, the expression of the mitochondrial-targeted HIF-1α significantly decreases Drp1 mitochondrial association and Opa1 levels, as well as attenuates apoptosis mediated by hypoxia ( Li H. S. et al, 2019 ).…”

“…It has been reported that upon hypoxia, mitophagy is upregulated through activation of the HIF-1α/BNIP3 axis, promoting cardioprotection by removing damaged mitochondria and promoting myocardial remodeling after IRI ( Zhang et al, 2008 ; Bouhamida et al, 2022 ; Hamacher-Brady et al, 2007 ; Zhang et al, 2019b ). However, other studies suggested that after cardiac stress, overexpression of BNIP3 induces cardiomyocytes death and a decreased myocardial function ( Regula et al, 2002 ; Diwan et al, 2007 ).…”

Mitochondria inter-organelle relationships in cancer protein aggregation

“…Increasing evidence supports the involvement of mitochondrial inter-organelle interactions in several essential cellular responses such as mitophagy, intracellular Ca 2+ handling, cell proliferation, cell death, and proteostasis ( Gelmetti et al, 2017 ; Marchi et al, 2018 ; Ali et al, 2021 ; Fontana and Limonta, 2021 ; Suárez-Rivero et al, 2022 ; Zheng et al, 2022 ). Furthermore, the deregulation of the mentioned processes is oftentimes related to several pathological conditions, from neurodegeneration to inflammation and from cancer to diabetes and cardiac defects ( Giorgi et al, 2018 ; Missiroli et al, 2020a ; Liu et al, 2020 ; Simoes et al, 2020 ; Morciano et al, 2021 ; Bouhamida et al, 2022 ; Patergnani et al, 2022 ; Tang et al, 2022 ).…”