Inhibition of HIF-prolyl 4-hydroxylases as a promising approach to the therapy of cardiometabolic diseases
Аитбаев К. А., Муркамилов И. Т., Фомин В. В.
Терапевтический архив
Т. 90, Вып. 8, С. 86-94
Опубликовано: 2018
Тип ресурса: Статья
DOI:10.26442/terarkh201890886-94
Аннотация:
Prolyl-4-hydroxylases of hypoxia-inducible factor (HIF-P4Hs) are enzymes that, under the conditions of normoxia, cause degradation of the HIF-transcriptional protein, which regulates a number of metabolic processes, including erythropoiesis, glucose level and lipid metabolism. In hypoxic conditions, on the contrary, their activity is suppressed and HIF stabilization takes place. This mechanism, i.e. stabilization of HIF by inhibition of HIF-P4Hs was the basis for the development of drugs designed for treatment of renal anemia, which are currently in stages 2 and 3 of clinical trials and are showing encouraging results. Recently, it has also been reported that inhibition of HIF-P4Hs can be effective in treatment of cardiometabolic diseases - coronary heart disease, hypertension, obesity, metabolic syndrome, diabetic cardiomyopathy and atherosclerosis. The review, based on the most recent data, discusses in detail molecular mechanisms of therapeutic effect of HIF-P4Hs inhibition in these
Ключевые слова:
Atherosclerosis; Cardiometabolic diseases; HIF-prolyl-4-hydroxylases (HIF-P4Hs); Hypoxia; Hypoxia-inducible factor (HIF); Ischemic heart disease; Metabolic syndrome; Obesity
enzyme inhibitor; hypoxia inducible factor proline dioxygenase; animal; antagonists and inhibitors; drug effect; enzymology; gene therapy; genetics; heart disease; human; metabolic disorder; metabolism; mutation; Animals; Enzyme Inhibitors; Genetic Therapy; Heart Diseases; Humans; Hypoxia-Inducible Factor-Proline Dioxygenases; Metabolic Diseases; Metabolic Networks and Pathways; Mutation
Язык текста: Русский
ISSN: 2309-5342
Аитбаев К. А.
Муркамилов И. Т.
Фомин В. В. Виктор Викторович 1978-
Aitbaev K. A.
Murkamilov I. T.
Fomin V. V. Viktor Viktorovich 1978-
Inhibition of HIF-prolyl 4-hydroxylases as a promising approach to the therapy of cardiometabolic diseases
Текст визуальный непосредственный
Терапевтический архив
Медицинское маркетинговое агентство "МедиаМедика"
Т. 90, Вып. 8 С. 86-94
2018
Статья
Atherosclerosis Cardiometabolic diseases HIF-prolyl-4-hydroxylases (HIF-P4Hs) Hypoxia Hypoxia-inducible factor (HIF) Ischemic heart disease Metabolic syndrome Obesity
enzyme inhibitor hypoxia inducible factor proline dioxygenase animal antagonists and inhibitors drug effect enzymology gene therapy genetics heart disease human metabolic disorder metabolism mutation Animals Enzyme Inhibitors Genetic Therapy Heart Diseases Humans Hypoxia-Inducible Factor-Proline Dioxygenases Metabolic Diseases Metabolic Networks and Pathways Mutation
Prolyl-4-hydroxylases of hypoxia-inducible factor (HIF-P4Hs) are enzymes that, under the conditions of normoxia, cause degradation of the HIF-transcriptional protein, which regulates a number of metabolic processes, including erythropoiesis, glucose level and lipid metabolism. In hypoxic conditions, on the contrary, their activity is suppressed and HIF stabilization takes place. This mechanism, i.e. stabilization of HIF by inhibition of HIF-P4Hs was the basis for the development of drugs designed for treatment of renal anemia, which are currently in stages 2 and 3 of clinical trials and are showing encouraging results. Recently, it has also been reported that inhibition of HIF-P4Hs can be effective in treatment of cardiometabolic diseases - coronary heart disease, hypertension, obesity, metabolic syndrome, diabetic cardiomyopathy and atherosclerosis. The review, based on the most recent data, discusses in detail molecular mechanisms of therapeutic effect of HIF-P4Hs inhibition in these