Maternal High‐Sucrose Diet Accelerates Vascular Stiffness in Aged Offspring via Suppressing Ca<sub>v</sub>1.2 and Contractile Phenotype of Vascular Smooth Muscle Cells

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ScopePerinatal high‐fat diets (PHF) can influence fetal/neonate development, resulting in cardiovascular pathogenesis, but precise mechanisms remain unclear. This study tests aldosterone receptor‐mediated Ca2+ influx and the underlying mechanisms influenced by PHF.Methods and resultsMaternal S.D. rats receive PHF during pregnancy and lactation periods. Their male offspring are fed normal diets after weaning for four months. Mesenteric arteries (MA) are for electrophysiological testing, Ca2+ imaging, target gene expression, and promotor methylation. PHF increases aldosterone receptor gene Nr3c2‐mediated Ca2+ currents in the smooth muscle cells (SMCs) of the MA via L‐type Ca2+ channels (LTCC) in the offspring. The increased expression of aldosterone‐receptors and LTCC are responsible for an activated Nr3c2‐LTCC pathway in the vasculature, eventually predisposes an increase of Ca2+ influx in the myocytes of resistance arteries. The inhibitor of aldosterone‐receptors suppresses the increased Ca2+ currents in the SMCs. Nr3c2 and LTCC are upregulated through the transcriptional mechanism in methylation, which can be reversed in the functional changes by methylation inhibitor 5AZA.ConclusionThe results firstly demonstrate that aldosterone‐receptor activation can stimulate Ca2+ currents via LTCC in vascular myocytes, which can be altered by perinatal foods via epigenetic changes of DNA methylation in the promoters of Nr3c2 and LTCC.

Section: Discussionmentioning

confidence: 99%

Fat‐Diets in Perinatal Stages Altered Nr3c2‐Mediated Ca²⁺ Currents in Mesenteric Arteries of Offspring Rats

Zheng

Zhang

et al. 2023

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“…Consistent with a population‐based cohort study with 40 years of follow‐up investigated that prenatal hyperglycemia increased rates of early onset cardiovascular diseases from childhood to early adulthood, [ 34 ] our previous data confirmed that prenatal high sucrose impaired the micro‐vascular function of adult and aged offspring. [ 7,8 ] But whether it will affect fetal vessels development is still unknown. Fetal thoracic aorta is a good model in study of fetal vascular structures and functions in rodents.…”

Section: Discussionmentioning

confidence: 99%

“…[ 4–6 ] Our previous study demonstrated that maternal high‐sucrose diet during pregnancy could induce microvascular dysfunction in both adult and aged offspring. [ 7,8 ] However, information on whether and how vascular changes have been initiated in the fetal life exposed to prenatal high‐sucrose diet is limited. Addressing such question is certainly important for further understanding development of chronic vascular diseases in fetal origins.…”

Section: Introductionmentioning

confidence: 99%

Prenatal High‐Sucrose Diet Induced Vascular Dysfunction in Thoracic Artery of Fetal Offspring

Feng

Zhang

et al. 2021

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Scope Maternal nutrition during pregnancy is related to intrauterine fetal development. The authors’ previous work reports that prenatal high sucrose (HS) diet impaired micro‐vascular functions in postnatal offspring. It is unclear whether/how prenatal HS causes vascular injury during fetal life. Methods and results Pregnant rats are fed with normal drinking water or 20% high‐sucrose solution during the whole gestational period. Pregnant HS increases maternal weight before delivery. Fetal thoracic aorta is separated for experiments. Angiotensin II (AII)‐stimulated vascular contraction of fetal thoracic arteries in HS group is greater, which mainly results from the enhanced AT1 receptor (AT1R) function and the downstream signaling. Nifedipine significantly increases vascular tension in HS group, indicating that the L‐type calcium channels (LTCCs) function is strengthened. 2‐Aminoethyl diphenylborinate (2‐APB), inositol 1,4,5‐trisphosphate receptors (IP3Rs) inhibitor, increases vascular tension induced by AII in HS group and ryanodine receptors‐sensitive vascular tone shows no difference in the two groups, which suggested that the activity of IP3Rs‐operated calcium channels is increased. Conclusion These findings suggest that prenatal HS induces vascular dysfunction of thoracic arteries in fetal offspring by enhancing AT1R, LTCCs function and IP3Rs‐associated calcium channels, providing new information regarding the impact of prenatal HS on the functional development of fetal vascular systems.

“…Pregnant rats in CON were provided with standard food and tap water, and the HS group was fed with the same food and 20% sucrose solution from gestational day 1-21. [10,[13][14][15][16] Caesarean delivery was conducted on pregnant rats at gestational day 21, and the fetal kidneys were obtained immediately. Other pregnant rats were vaginal delivery naturally.…”

Section: Animalsmentioning

confidence: 99%

“…[13,14] Our previous study revealed that maternal high-sucrose diet altered vascular contraction in the offspring. [10,15,16] However, there has limited information on underlying mechanisms to interpret the association of prenatal high-sucrose diet with vascular diseases in renal interlobar arteries from the offspring.…”

Section: Introductionmentioning

confidence: 99%

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

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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.