Mutual Regulation between Redox and Hypoxia-Inducible Factors in Cardiovascular and Renal Complications of Diabetes
Oxidative stress and hypoxia-inducible factors (HIFs) have been implicated in the pathogenesis of diabetic cardiovascular and renal diseases. Reactive oxygen species (ROS) mediate physiological and pathophysiological processes, being involved in the modulation of cell signaling, differentiation, and...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-11-01
|
| Series: | Antioxidants |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3921/11/11/2183 |
| _version_ | 1797469275633483776 |
|---|---|
| author | Carla Iacobini Martina Vitale Jonida Haxhi Carlo Pesce Giuseppe Pugliese Stefano Menini |
| author_facet | Carla Iacobini Martina Vitale Jonida Haxhi Carlo Pesce Giuseppe Pugliese Stefano Menini |
| author_sort | Carla Iacobini |
| collection | DOAJ |
| description | Oxidative stress and hypoxia-inducible factors (HIFs) have been implicated in the pathogenesis of diabetic cardiovascular and renal diseases. Reactive oxygen species (ROS) mediate physiological and pathophysiological processes, being involved in the modulation of cell signaling, differentiation, and survival, but also in cyto- and genotoxic damage. As master regulators of glycolytic metabolism and oxygen homeostasis, HIFs have been largely studied for their role in cell survival in hypoxic conditions. However, in addition to hypoxia, other stimuli can regulate HIFs stability and transcriptional activity, even in normoxic conditions. Among these, a regulatory role of ROS and their byproducts on HIFs, particularly the HIF-1α isoform, has received growing attention in recent years. On the other hand, HIF-1α and HIF-2α exert mutually antagonistic effects on oxidative damage. In diabetes, redox-mediated HIF-1α deregulation contributes to the onset and progression of cardiovascular and renal complications, and recent findings suggest that deranged HIF signaling induced by hyperglycemia and other cellular stressors associated with metabolic disorders may cause mitochondrial dysfunction, oxidative stress, and inflammation. Understanding the mechanisms of mutual regulation between HIFs and redox factors and the specific contribution of the two main isoforms of HIF-α is fundamental to identify new therapeutic targets for vascular complications of diabetes. |
| first_indexed | 2024-03-09T19:19:04Z |
| format | Article |
| id | doaj.art-67887eccef284c5091aa342bc65303a0 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T19:19:04Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-67887eccef284c5091aa342bc65303a02023-11-24T03:30:35ZengMDPI AGAntioxidants2076-39212022-11-011111218310.3390/antiox11112183Mutual Regulation between Redox and Hypoxia-Inducible Factors in Cardiovascular and Renal Complications of DiabetesCarla Iacobini0Martina Vitale1Jonida Haxhi2Carlo Pesce3Giuseppe Pugliese4Stefano Menini5Department of Clinical and Molecular Medicine, “La Sapienza” University, 00189 Rome, ItalyDepartment of Clinical and Molecular Medicine, “La Sapienza” University, 00189 Rome, ItalyDepartment of Clinical and Molecular Medicine, “La Sapienza” University, 00189 Rome, ItalyDepartment of Neurosciences, Rehabilitation, Ophthalmology, Genetic and Maternal Infantile Sciences (DINOGMI), Department of Excellence of MIUR, University of Genoa Medical School, 16132 Genoa, ItalyDepartment of Clinical and Molecular Medicine, “La Sapienza” University, 00189 Rome, ItalyDepartment of Clinical and Molecular Medicine, “La Sapienza” University, 00189 Rome, ItalyOxidative stress and hypoxia-inducible factors (HIFs) have been implicated in the pathogenesis of diabetic cardiovascular and renal diseases. Reactive oxygen species (ROS) mediate physiological and pathophysiological processes, being involved in the modulation of cell signaling, differentiation, and survival, but also in cyto- and genotoxic damage. As master regulators of glycolytic metabolism and oxygen homeostasis, HIFs have been largely studied for their role in cell survival in hypoxic conditions. However, in addition to hypoxia, other stimuli can regulate HIFs stability and transcriptional activity, even in normoxic conditions. Among these, a regulatory role of ROS and their byproducts on HIFs, particularly the HIF-1α isoform, has received growing attention in recent years. On the other hand, HIF-1α and HIF-2α exert mutually antagonistic effects on oxidative damage. In diabetes, redox-mediated HIF-1α deregulation contributes to the onset and progression of cardiovascular and renal complications, and recent findings suggest that deranged HIF signaling induced by hyperglycemia and other cellular stressors associated with metabolic disorders may cause mitochondrial dysfunction, oxidative stress, and inflammation. Understanding the mechanisms of mutual regulation between HIFs and redox factors and the specific contribution of the two main isoforms of HIF-α is fundamental to identify new therapeutic targets for vascular complications of diabetes.https://www.mdpi.com/2076-3921/11/11/2183advanced glycation end productsatherosclerosisdiabetic kidney diseaseinflammationmethylglyoxalprolyl hydroxylase domain proteins |
| spellingShingle | Carla Iacobini Martina Vitale Jonida Haxhi Carlo Pesce Giuseppe Pugliese Stefano Menini Mutual Regulation between Redox and Hypoxia-Inducible Factors in Cardiovascular and Renal Complications of Diabetes Antioxidants advanced glycation end products atherosclerosis diabetic kidney disease inflammation methylglyoxal prolyl hydroxylase domain proteins |
| title | Mutual Regulation between Redox and Hypoxia-Inducible Factors in Cardiovascular and Renal Complications of Diabetes |
| title_full | Mutual Regulation between Redox and Hypoxia-Inducible Factors in Cardiovascular and Renal Complications of Diabetes |
| title_fullStr | Mutual Regulation between Redox and Hypoxia-Inducible Factors in Cardiovascular and Renal Complications of Diabetes |
| title_full_unstemmed | Mutual Regulation between Redox and Hypoxia-Inducible Factors in Cardiovascular and Renal Complications of Diabetes |
| title_short | Mutual Regulation between Redox and Hypoxia-Inducible Factors in Cardiovascular and Renal Complications of Diabetes |
| title_sort | mutual regulation between redox and hypoxia inducible factors in cardiovascular and renal complications of diabetes |
| topic | advanced glycation end products atherosclerosis diabetic kidney disease inflammation methylglyoxal prolyl hydroxylase domain proteins |
| url | https://www.mdpi.com/2076-3921/11/11/2183 |
| work_keys_str_mv | AT carlaiacobini mutualregulationbetweenredoxandhypoxiainduciblefactorsincardiovascularandrenalcomplicationsofdiabetes AT martinavitale mutualregulationbetweenredoxandhypoxiainduciblefactorsincardiovascularandrenalcomplicationsofdiabetes AT jonidahaxhi mutualregulationbetweenredoxandhypoxiainduciblefactorsincardiovascularandrenalcomplicationsofdiabetes AT carlopesce mutualregulationbetweenredoxandhypoxiainduciblefactorsincardiovascularandrenalcomplicationsofdiabetes AT giuseppepugliese mutualregulationbetweenredoxandhypoxiainduciblefactorsincardiovascularandrenalcomplicationsofdiabetes AT stefanomenini mutualregulationbetweenredoxandhypoxiainduciblefactorsincardiovascularandrenalcomplicationsofdiabetes |