Oxidative Stress-Induced Hypertension of Developmental Origins: Preventive Aspects of Antioxidant Therapy

Antioxidants, Год журнала: 2022, Номер 11(3), С. 511 - 511

Опубликована: Март 7, 2022

Hypertension remains the leading cause of disease burden worldwide. can originate in early stages life. A growing body evidence suggests that oxidative stress, which is characterized as a reactive oxygen species (ROS)/nitric oxide (NO) disequilibrium, has pivotal role hypertension developmental origins. Results from animal studies support idea early-life stress causes programming prime blood pressure (BP)-controlled organs such brain, kidneys, heart, and vessels, to adult offspring. Conversely, perinatal use antioxidants counteract therefore lower BP. This review discusses interaction between hypertension. It will also discuss models, how connects with other core mechanisms, potential antioxidant therapy novel preventive strategy prevent

Язык: Английский

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Chronic fetal hypoxia and antenatal Vitamin C exposure differentially regulate molecular signalling in the lung of female lambs in early adulthood

Frontiers in Physiology, Год журнала: 2025, Номер 15

Опубликована: Янв. 15, 2025

Chronic fetal hypoxia is commonly associated with growth restriction and can predispose to respiratory disease at birth in later life. Antenatal antioxidant treatment has been investigated overcome the effects of oxidative stress utero improve outcomes. We aimed determine if chronic antenatal administration persist lung early adulthood. Chronically catheterised pregnant sheep were exposed normoxia (N; n = 20) or (H; 18; 10% O2) ± maternal daily i. v. saline (N 11; H 8) Vitamin C (VC; NVC 9; HVC 10) from 105 138 days (term, ∼145 days). Lungs collected female lambs 9 months after (early adulthood). Lung tissue expression genes proteins regulating stress, mitochondrial function, signalling, glucocorticoid surfactant maturation, inflammation airway remodelling measured. upregulated markers prooxidant, lipid transport pathways normalized prooxidant markers, increased endogenous antioxidant, vasodilator inflammatory altered regulation signalling availability. There are differential on molecular lungs normoxic hypoxic pregnancy

Язык: Английский

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Placental mitochondrial metabolic adaptation maintains cellular energy balance in pregnancy complicated by gestational hypoxia

The Journal of Physiology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 27, 2025

Abstract The mechanisms that drive placental dysfunction in pregnancies complicated by hypoxia and fetal growth restriction remain poorly understood. Changes to mitochondrial respiration contribute cellular conditions of have been implicated the pathoaetiology pregnancy complications, such as pre‐eclampsia. We used bespoke isobaric hypoxic chambers a combination functional, molecular imaging techniques study metabolism dynamics sheep undergoing pregnancy. show triggers shift capacity away from β‐oxidation complex I‐mediated respiration, while maintaining total oxidative phosphorylation capacity. There are also complex‐specific changes electron transport chain composition switch towards fission. Hypoxic placentas increased activation non‐canonical unfolded protein response pathway enhanced insulin like factor 2 signalling. Combined, therefore, data placenta undergoes significant metabolic morphological adaptations maintain energy balance. Chronic during activated stress pathways, leading alterations dynamics, seen women with image Key points Hypoxia shifts I. Complex‐specific occur composition. Activation is heightened placentas. Enhanced signalling observed undergo functional for

Язык: Английский

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Translatable mitochondria-targeted protection against programmed cardiovascular dysfunction

Science Advances, Год журнала: 2020, Номер 6(34)

Опубликована: Авг. 19, 2020

Mitochondrial therapy may cure hypertension in adult offspring of complicated pregnancies.

Язык: Английский

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Pregnancy in obese women and mechanisms of increased cardiovascular risk in offspring

European Heart Journal, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 7, 2024

Pregnancy complicated by maternal obesity contributes to an increased cardiovascular risk in offspring, which is increasingly concerning as the rates of and disease are higher than ever before still growing. There has been much research humans preclinical animal models understand impact on offspring health. This review summarizes what known about phenotype, describing a mechanistic role for oxidative stress, metabolic inflexibility, mitochondrial dysfunction mediating these impairments. It also discusses secondary postnatal insults, may reveal latent deficits that originated utero. Finally, current interventional efforts gaps knowledge limit developmental origins obese pregnancy highlighted.

Язык: Английский

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Animal Models for Studying Developmental Origins of Cardiovascular–Kidney–Metabolic Syndrome

Biomedicines, Год журнала: 2025, Номер 13(2), С. 452 - 452

Опубликована: Фев. 12, 2025

Cardiovascular-kidney-metabolic syndrome (CKMS) has become a significant global health challenge. Since CKMS often originates early in life, as outlined by the developmental origins of and disease (DOHaD) concept, prevention is more effective strategy than treatment. Various animal models, classified environmental exposures or mechanisms, are used to explore CKMS. However, no single model can fully replicate all aspects its clinical stages, limiting advancement preventive therapeutic strategies. This review aims assist researchers comparing strengths limitations common models programming studies highlighting key considerations for selecting suitable models.

Язык: Английский

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Gestational intermittent hypoxia induces endothelial dysfunction, reduces perivascular adiponectin and causes epigenetic changes in adult male offspring

The Journal of Physiology, Год журнала: 2019, Номер 597(22), С. 5349 - 5364

Опубликована: Авг. 22, 2019

Key points Obstructive sleep apnoea (OSA) is characterized by intermittent hypoxia, which causes oxidative stress and inflammation increases the risk of cardiovascular disease. OSA during pregnancy adverse maternal fetal outcomes. The effects pre‐existing in pregnant women on cardiometabolic outcomes offspring are unknown. We evaluated basic metabolic parameters, as well aortic vascular perivascular adipose tissue (PVAT) function response to adiponectin, examined DNA methylation adiponectin gene promoter PVAT 16‐week‐old adult exposed gestational hypoxia (GIH). GIH decreased body weights at week 1 both male female offspring, caused subsequent weight food consumption only. Adult had normal levels lipids, glucose insulin, with no endothelial dysfunction. exhibited dyslipidaemia, insulin resistance hyperleptinaemia. Decreased endothelial‐dependent vasodilatation, loss anti‐contractile activity low circulating levels, increased pro‐inflammatory expression promoter, occurred offspring. Our results suggest that could be developing disease adulthood. Abstract Perturbations can program develop diseases later life. a chronic condition frequently affects pregnancies leads assessed mice experiencing (GIH), hallmark OSA, for changes profiles, nitric oxide (NO)‐dependent relaxations, activities responses tissue. Pregnant mouse dams were hypoxic cycles ( 21–12%) 18 days. resulted lower pups 1, followed significant gain 16 age but not Plasma leptin higher Endothelium‐dependent relaxation ACh abdominal aorta was reduced Incubation arteries from restored PVAT. Both homogenate PVAT, along an inflammatory cytokines. Pyrosequencing showed indicate through dysfunction, associated epigenetic modifications promoter.

Язык: Английский

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Animal Models for DOHaD Research: Focus on Hypertension of Developmental Origins

Biomedicines, Год журнала: 2021, Номер 9(6), С. 623 - 623

Опубликована: Май 31, 2021

Increasing evidence suggests that fetal programming through environmental exposure during a critical window of early life leads to long-term detrimental outcomes, by so-called developmental origins health and disease (DOHaD). Hypertension can originate in life. Animal models are essential for providing convincing causal relationship between diverse early-life insults the hypertension later These include nutritional imbalances, maternal illnesses, chemicals, medication use. In addition reviewing various contribute origins, this review focuses on benefits animal addressing underlying mechanisms which interventions reprogram processes prevent development hypertension. Our understanding has been enhanced each these models, narrowing knowledge gap future clinical translation.

Язык: Английский

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Breath of Life: Heart Disease Link to Developmental Hypoxia

Circulation, Год журнала: 2021, Номер 144(17), С. 1429 - 1443

Опубликована: Окт. 25, 2021

Heart disease remains one of the greatest killers. In addition to genetics and traditional lifestyle risk factors, we now understand that adverse conditions during pregnancy can also increase susceptibility cardiovascular in offspring. Therefore, mechanisms by which this occurs possible preventative therapies are significant contemporary interest community. A common suboptimal condition is a sustained reduction fetal oxygenation. Chronic hypoxia results from any with increased placental vascular resistance, such as preeclampsia, infection, or maternal obesity. may arise at high altitude because respiratory disease. This article reviews short- long-term effects on system, importance chronic triggering developmental origin future heart adult progeny. The work summarizes evidence derived human studies well rodent, avian, ovine models. There focus discovery molecular link between prenatal hypoxia, oxidative stress, Discussion mitochondria-targeted antioxidant therapy offers potential targets for clinical intervention complicated hypoxia.

Язык: Английский

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Effect of Combined Endurance Training and MitoQ on Cardiac Function and Serum Level of Antioxidants, NO, miR-126, and miR-27a in Hypertensive Individuals

BioMed Research International, Год журнала: 2022, Номер 2022, С. 1 - 13

Опубликована: Янв. 13, 2022

Objectives. Hypertension (HTN) is one of the most important risk factors for cardiovascular diseases. Despite advances in treatment and control HTN, prevalence HTN still increasing. MitoQ a supplement that acts on mitochondria attenuates reactive oxygen species (ROS), which plays an role health. miRNAs play pathophysiology HTN. We evaluated effects supplementation endurance training (ET), alone combination, functional indices heart serum levels miR-126, miR-27a, antioxidants, NO, patients with Methods. In double-blind randomized clinical trial, 52 male participants (age 40-55 years) were randomly divided into four groups ( $n=13$ ) placebo, (20 mg/day, oral), ET (cycle ergometer, moderate intensity, 40-60% VO2 peak, rate 120-140 b/min, 45 min day, three days/week six weeks), MitoQ+ET. Cardiac function assessed by echocardiography before after interventions. Results. Systolic blood pressure (SBP) significantly decreased all intervention id="M2"> P < 0.001 while DBP id="M3"> 0.01 LV hypertrophy id="M4"> 0.05 only MitoQ+ET group. Serum SOD, GPx, NO level miR-126 increased groups, miR-27a reduced id="M5"> id="M6"> groups. Conclusions. Compared to alone, their combination has more prominent improving cardiac health amelioration BP These are through modulation ameliorating mitochondrial ROS production.

Язык: Английский

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