Prenatal dexamethasone exposure impaired vascular reactivity in adult male offspring cerebral arteries

Lei, Jiahui; Zhao, Meng; Deng, Fengying; Xu, Tao; Ji, Bingyu; Wang, Xietong; Zhang, Meihua; Sun, Miao; Gao, Qinqin

doi:10.1016/j.yjmcc.2023.05.008

Cited by 3 publications

(2 citation statements)

References 30 publications

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“…Confocal NO and Ca 2+ imaging of VECs was performed as previously described. 11 , 30 Briefly, isolated VECs were incubated with 3‐amino,4‐aminomethyl‐2′,7′‐difluorescein, diacetate (10 −6 mol/L; #S0019, Beyotime, China) or Fluo‐3 AM (10 −6 mol/L; Invitrogen) in Tyrode's solution (containing mmol/L: NaCl, 135.0; KCl, 4.7; MgCl 2 , 1.0; CaCl 2 , 2.0; HEPES, 10.0; NaH 2 PO 4 ·2H 2 O, 1.2; and glucose, 10.0; pH 7.4) for 20 minutes at room temperature. After loading, VECs were washed 3 times with Tyrode's solution and transferred to a recording chamber.…”

Section: Methodsmentioning

confidence: 99%

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Gestational Hypoxia Impaired Endothelial Nitric Oxide Synthesis Via miR‐155‐5p/NADPH Oxidase/Reactive Oxygen Species Axis in Male Offspring Vessels

Zhao,

Lei,

Deng

et al. 2024

JAHA

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Background Nitric oxide (NO) is the most important vasodilator secreted by vascular endothelial cells, and its abnormal synthesis is involved in the development of cardiovascular disease. The prenatal period is a critical time for development and largely determines lifelong vascular health in offspring. Given the high incidence and severity of gestational hypoxia in mid‐late pregnancy, it is urgent to further explore whether it affects the long‐term synthesis of NO in offspring vascular endothelial cells. Methods and Results Pregnant Sprague–Dawley rats were housed in a normoxic or hypoxic (10.5% O 2 ) chamber from gestation days 10 to 20. The thoracic aortas of fetal and adult male offspring were isolated for experiments. Gestational hypoxia significantly reduces the NO‐dependent vasodilation mediated by acetylcholine in both the fetal and adult offspring thoracic aorta rings. Meanwhile, acetylcholine‐induced NO synthesis is impaired in vascular endothelial cells from hypoxic offspring thoracic aortas. We demonstrate that gestational hypoxic offspring exhibit a reduced endothelial NO synthesis capacity, primarily due to increased expression of NADPH oxidase 2 and enhanced reactive oxygen species. Additionally, gestational hypoxic offspring show elevated levels of miR‐155‐5p in vascular endothelial cells, which is associated with increased expression of NADPH oxidase 2 and reactive oxygen species generation, as well as impaired NO synthesis. Conclusions The present study is the first to demonstrate that gestational hypoxia impairs endothelial NO synthesis via the miR‐155‐5p/NADPH oxidase 2/reactive oxygen species axis in offspring vessels. These novel findings indicate that the detrimental effects of gestational hypoxia on fetal vascular function can persist into adulthood, providing new insights into the development of vascular diseases.

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Section: Methodsmentioning

confidence: 99%

“…All experiments were repeated 3 times using independently prepared cells and were performed as previously described. 30 , 31 …”

Section: Methodsmentioning

confidence: 99%

Gestational Hypoxia Impaired Endothelial Nitric Oxide Synthesis Via miR‐155‐5p/NADPH Oxidase/Reactive Oxygen Species Axis in Male Offspring Vessels

Zhao,

Lei,

Deng

et al. 2024

JAHA

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Prenatal High‐Sucrose Diet Induced Vascular Dysfunction of Renal Interlobar Arteries in the Offspring via PPARγ‐RXRg‐ROS/Akt Signaling

Feng,

Liu,

Wang

et al. 2024

Molecular Nutrition Food Res

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ScopePrenatal nutrition imbalance correlates with developmental origin of cardiovascular diseases; however whether maternal high‐sucrose diet (HS) during pregnancy causes vascular damage in renal interlobar arteries (RIA) from offspring still keeps unclear.Methods and resultsPregnant rats are fed with normal drinking water or 20% high‐sucrose solution during the whole gestational period. Swollen mitochondria and distributed myofilaments are observed in vascular smooth muscle cells of RIA exposed to prenatal HS. Maternal HS increases phenylephrine (PE)‐induced vasoconstriction in the RIA from adult offspring. NG‐Nitro‐l‐arginine (L‐Name) causes obvious vascular tension in response to PE in offspring from control group, not in HS. RNA‐Seq of RIA is performed to reveal that the gene retinoid X receptor g (RXRg) is significantly decreased in the HS group, which could affect vascular function via interacting with PPARγ pathway. By preincubation of RIA with apocynin (NADPH inhibitor) or capivasertib (Akt inhibitor), the results indicate that ROS and Akt are the vital important factors to affect the vascular function of RIA exposure to prenatal HS.ConclusionMaternal HS during the pregnancy increases PE‐mediated vasoconstriction of RIA from adult offspring, which is mainly related to the enhanced Akt and ROS regulated by the weakened PPARγ‐RXRg.

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Prenatal glucocorticoids exposure and adverse cardiovascular effects in offspring

Zhao,

He,

et al. 2024

Front. Endocrinol.

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Glucocorticoids (GCs) are steroid hormones fundamental to the body’s normal physiological functions and are pivotal in fetal growth and development. During gestation, the mother’s cortisol concentration (active GCs) escalates to accommodate the requirements of fetal organ development and maturation. A natural placental GCs barrier, primarily facilitated by 11β hydroxysteroid dehydrogenase 2, exists between the mother and fetus. This enzyme transforms biologically active cortisol into biologically inactive corticosterone, thereby mitigating fetal GCs exposure. However, during pregnancy, the mother may be vulnerable to adverse factor exposures such as stress, hypoxia, caffeine, and synthetic GCs use. In these instances, maternal serum GCs levels may surge beyond the protective capacity of the placental GCs barrier. Moreover, these adverse factors could directly compromise the placental GCs barrier, resulting in excessive fetal exposure to GCs. It is well-documented that prenatal GCs exposure can detrimentally impact the offspring’s cardiovascular system, particularly in relation to blood pressure, vascular function, and heart function. In this review, we succinctly delineate the alterations in GCs levels during pregnancy and the potential mechanisms driving these changes, and also analyze the possible causes of prenatal GCs exposure. Furthermore, we summarize the current advancements in understanding the adverse effects and mechanisms of prenatal GCs exposure on the offspring’s cardiovascular system.

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Prenatal dexamethasone exposure impaired vascular reactivity in adult male offspring cerebral arteries

Cited by 3 publications

References 30 publications

Gestational Hypoxia Impaired Endothelial Nitric Oxide Synthesis Via miR‐155‐5p/NADPH Oxidase/Reactive Oxygen Species Axis in Male Offspring Vessels

Gestational Hypoxia Impaired Endothelial Nitric Oxide Synthesis Via miR‐155‐5p/NADPH Oxidase/Reactive Oxygen Species Axis in Male Offspring Vessels

Prenatal High‐Sucrose Diet Induced Vascular Dysfunction of Renal Interlobar Arteries in the Offspring via PPARγ‐RXRg‐ROS/Akt Signaling

Prenatal glucocorticoids exposure and adverse cardiovascular effects in offspring

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