Molecular and Biochemical Mechanisms of Cardiomyopathy Development Following Prenatal Hypoxia—Focus on the NO System

Prenatal hypoxia (PH) adversely affects the development of the fetal heart, contributing to persistent cardiovascular impairments in postnatal life. A key component in regulating cardiac physiology is the nitric oxide (NO) system, which influences vascular tone, myocardial contractility, and endothe...

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Main Authors: Olena Popazova, Igor Belenichev, Nina Bukhtiyarova, Victor Ryzhenko, Nadia Gorchakova, Valentyn Oksenych, Oleksandr Kamyshnyi
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Antioxidants
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Online Access:https://www.mdpi.com/2076-3921/14/6/743
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author Olena Popazova
Igor Belenichev
Nina Bukhtiyarova
Victor Ryzhenko
Nadia Gorchakova
Valentyn Oksenych
Oleksandr Kamyshnyi
author_facet Olena Popazova
Igor Belenichev
Nina Bukhtiyarova
Victor Ryzhenko
Nadia Gorchakova
Valentyn Oksenych
Oleksandr Kamyshnyi
author_sort Olena Popazova
collection DOAJ
description Prenatal hypoxia (PH) adversely affects the development of the fetal heart, contributing to persistent cardiovascular impairments in postnatal life. A key component in regulating cardiac physiology is the nitric oxide (NO) system, which influences vascular tone, myocardial contractility, and endothelial integrity during development. Exposure to PH disrupts NO-related signaling pathways, leading to endothelial dysfunction, mitochondrial damage, and an escalation of oxidative stress—all of which exacerbate cardiac injury and trigger cardiomyocyte apoptosis. The excessive generation of reactive nitrogen species drives nitrosative stress, thereby intensifying inflammatory processes and cellular injury. In addition, the interplay between NO and hypoxia-inducible factor (HIF) shapes adaptive responses to PH. NO also modulates the synthesis of heat shock protein 70 (HSP70), a critical factor in cellular defense against stress. This review emphasizes the involvement of NO in cardiovascular injury caused by PH and examines the cardioprotective potential of NO modulators—Angiolin, Thiotriazoline, Mildronate, and L-arginine—as prospective therapeutic agents. These agents reduce oxidative stress, enhance endothelial performance, and alleviate the detrimental effects of PH on the heart, offering potential new strategies to prevent cardiovascular disorders in offspring subjected to prenatal hypoxia.
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series Antioxidants
spelling doaj-art-166d449e32d14e868e23e3d274e4e10d2025-08-20T03:26:16ZengMDPI AGAntioxidants2076-39212025-06-0114674310.3390/antiox14060743Molecular and Biochemical Mechanisms of Cardiomyopathy Development Following Prenatal Hypoxia—Focus on the NO SystemOlena Popazova0Igor Belenichev1Nina Bukhtiyarova2Victor Ryzhenko3Nadia Gorchakova4Valentyn Oksenych5Oleksandr Kamyshnyi6Department of Histology, Cytology and Embryology, Zaporizhzhia State Medical and Pharmaceutical University, 69000 Zaporizhzhia, UkraineDepartment of Pharmacology and Medical Formulation with Course of Normal Physiology, Zaporizhzhia State Medical and Pharmaceutical University, 69000 Zaporizhzhia, UkraineDepartment of Clinical Laboratory Diagnostics, Zaporizhzhia State Medical and Pharmaceutical University, 69000 Zaporizhzhia, UkraineDepartment of Medical and Pharmaceutical Informatics and Advanced Technologies, Zaporizhzhia State Medical University, 69000 Zaporizhzhia, UkraineDepartment of Pharmacology, Bogomolets National Medical University, 01601 Kyiv, UkraineFaculty of Medicine, University of Bergen, 5020 Bergen, NorwayDepartment of Microbiology, Virology and Immunology, I. Horbachevsky Ternopil State Medical University, 46001 Ternopil, UkrainePrenatal hypoxia (PH) adversely affects the development of the fetal heart, contributing to persistent cardiovascular impairments in postnatal life. A key component in regulating cardiac physiology is the nitric oxide (NO) system, which influences vascular tone, myocardial contractility, and endothelial integrity during development. Exposure to PH disrupts NO-related signaling pathways, leading to endothelial dysfunction, mitochondrial damage, and an escalation of oxidative stress—all of which exacerbate cardiac injury and trigger cardiomyocyte apoptosis. The excessive generation of reactive nitrogen species drives nitrosative stress, thereby intensifying inflammatory processes and cellular injury. In addition, the interplay between NO and hypoxia-inducible factor (HIF) shapes adaptive responses to PH. NO also modulates the synthesis of heat shock protein 70 (HSP70), a critical factor in cellular defense against stress. This review emphasizes the involvement of NO in cardiovascular injury caused by PH and examines the cardioprotective potential of NO modulators—Angiolin, Thiotriazoline, Mildronate, and L-arginine—as prospective therapeutic agents. These agents reduce oxidative stress, enhance endothelial performance, and alleviate the detrimental effects of PH on the heart, offering potential new strategies to prevent cardiovascular disorders in offspring subjected to prenatal hypoxia.https://www.mdpi.com/2076-3921/14/6/743prenatal hypoxiacardiomyopathyendothelial dysfunctionmitochondrial dysfunctionoxidative stressnitrosative stress
spellingShingle Olena Popazova
Igor Belenichev
Nina Bukhtiyarova
Victor Ryzhenko
Nadia Gorchakova
Valentyn Oksenych
Oleksandr Kamyshnyi
Molecular and Biochemical Mechanisms of Cardiomyopathy Development Following Prenatal Hypoxia—Focus on the NO System
Antioxidants
prenatal hypoxia
cardiomyopathy
endothelial dysfunction
mitochondrial dysfunction
oxidative stress
nitrosative stress
title Molecular and Biochemical Mechanisms of Cardiomyopathy Development Following Prenatal Hypoxia—Focus on the NO System
title_full Molecular and Biochemical Mechanisms of Cardiomyopathy Development Following Prenatal Hypoxia—Focus on the NO System
title_fullStr Molecular and Biochemical Mechanisms of Cardiomyopathy Development Following Prenatal Hypoxia—Focus on the NO System
title_full_unstemmed Molecular and Biochemical Mechanisms of Cardiomyopathy Development Following Prenatal Hypoxia—Focus on the NO System
title_short Molecular and Biochemical Mechanisms of Cardiomyopathy Development Following Prenatal Hypoxia—Focus on the NO System
title_sort molecular and biochemical mechanisms of cardiomyopathy development following prenatal hypoxia focus on the no system
topic prenatal hypoxia
cardiomyopathy
endothelial dysfunction
mitochondrial dysfunction
oxidative stress
nitrosative stress
url https://www.mdpi.com/2076-3921/14/6/743
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