Hypoxia-inducible factor (HIF): The link between obesity and COVID-19
| العنوان: | Hypoxia-inducible factor (HIF): The link between obesity and COVID-19 |
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| المؤلفون: | Sherouk Mokhtar, Mahenar Gadalla, Meryam El Shershaby, Aya Kamel, Nourhan Ibrahim, Mirna Albehairy, Nour Aboushadi, Farid Hanna, Reem J. Husseiny, Nihal Zahra, Engy Hussein, Jianping Ye, Hadeel Mustafa, Tasneem Elahmady, Nadine Emad, Shenoda Yacoub, Elaria Yacoub, Maryam Elahmady, Alaa A. Hassan, Laila Moris, Aya S. Abou-Zeid, Mahinour Hussein, A. Hassan, Maryam A. Eid, Maram Rajab, Antoine Fakhry AbdelMassih, Nancy Anis, Mohamed E. Khallaf, Nadine El Nahhas, Rafeef Hozaien |
| المصدر: | Obesity Medicine |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Endocrinology, Diabetes and Metabolism, Fulminant, Adipose tissue, 030209 endocrinology & metabolism, Review, Lung injury, Resveratrol, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Immune system, Internal Medicine, Medicine, HIF, 030109 nutrition & dietetics, business.industry, Public Health, Environmental and Occupational Health, COVID-19, Adipose tissue hypoxia, Hypoxia (medical), Hypoxia-inducible factors, chemistry, Obesity related obstructive sleep apnea, Cancer research, HIF1alpha switch to HIF2alpha, medicine.symptom, business, Viral load |
| الوصف: | The COVID-19 death toll has involved to date more than 1 million confirmed deaths. The death rate is even higher in the obese COVID-19 patients, as a result of hypoxia, due to the interplay between adipose tissue hypoxia and obstructive sleep apnea. The discrepancy of manifestations seen in COVID-19 seems to be mediated by a differential immune response rather than a differential viral load. One of the key players of the immune response is HIF. HIF-1β is a stable constitutively expressed protein in the nucleus; and under hypoxic changes, its activity is unaffected, whereas the HIF-α subunit has a short half-life and because of its degradation by an enzyme known as propyl hydroxylase; under hypoxic conditions, propyl hydroxylase gets deactivated thus leading to the stabilization of HIF-1α. As mentioned before, HIF-1α expression is triggered by hypoxic states, this crippling condition will aggravate the pro-inflammatory characteristics of HIF-1α. The vast majority of decompensated COVID19 cases manifest with drastic lung injury and severe viral pneumonia, the infection-induced hypoxia will the existing hypoxia in obesity. This will additionally augment HIF-1α levels that will provoke the already existing cytokines' storm to fulminant. Consequently, this will directly correlate the effect of a hypoxic environment with the increase of HIF-1α level. HIFɑ exists in two main isoforms HIF-1α and HIF-2α. HIF-1α and HIF-2α act in distinct ways in how they work on different target genes. For example, HIF-2α may act on hemopoietin genes (heme-regulating genes); while HIF-1α acts on EPO. HIF-1α release seems to be markedly augmented in obesity due to adipose tissue hypoxia and obstructive sleep apnea resulting in cyclic hypoxia. HIF-1α can also be secreted by direct viral proteolytic effects. Whereas, HIF-2α is stimulated by chronic hypoxia. HIF-1α exerts detrimental effects on the immune system, characterized by unopposed pro-inflammation at the macrophages, dendritic cells, T cells, and complement levels resulting in cytokines’ storm, which is linked to the poor outcomes of COVID-19. On the other hand, HIF-2α role is regulatory and largely opposes the actions mediated by HIF-1α. In view of this, inhibiting HIF-1α release or switching its production to HIF-2α by natural products such as resveratrol or by synthetic drugs, offer a good therapeutic strategy that can prevent COVID-19 worst outcome in infected patients. The approach of breaking the vicious circle between lung damage-induced hypoxia and HIF-1α pro-inflammatory stimulant through drugs is considered to be extremely promising as a therapeutic manner to combat further deterioration of COVID19 cases. Highlights • HIFɑ exists in two isoforms HIF-1α (pro-inflammatory) and HIF-2α (regulatory); HIF-1α is increased in obesity, due to the presence of ATH and OSA. • Despite being a transcription factor, HIFɑ circulates to nearby cells through the so called extracellular vesicles. • COVID-19 associated lung damage induces an acute hypoxic state, which activates HIF-1α. • HIF-1α, in turn, exacerbates the production of pro-inflammatory cytokines, thus increasing the likelihood of cytokine storm in COVID-19. • In view of the above, HIF-1α inhibitors or alternatively switchers to HIF-2α can prevent COVID-19-induced cytokine storm. |
| تدمد: | 2451-8476 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::eb147e0095678b293c5769f94c66e130 https://pubmed.ncbi.nlm.nih.gov/33521378 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....eb147e0095678b293c5769f94c66e130 |
| قاعدة البيانات: | OpenAIRE |
Full Text via ClinicalKey | تدمد: | 24518476 |
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