Brain Renin-Angiotensin System: Fetal Epigenetic Programming by Maternal Protein Restriction During Pregnancy

Goyal, Ravi; Goyal, Dipali; Leitzke, Arthur; Gheorghe, Ciprian P.; Longo, Lawrence D.

doi:10.1177/1933719109351935

Cited by 156 publications

(111 citation statements)

References 58 publications

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“…High ACE2 protein levels and activity observed in the fetal brain suggest a role for ACE2 in brain development and regulation of local RAS activity. This possibility is supported by the finding that the fetal brain expresses all the components of the classic RAS that are subject to epigenetic programming by maternal protein restriction during gestation (28). The enrichment of ACE2 in pulmonary bronchioles supports a novel function for ACE2 in the regulation of epithelial branching morphogenesis.…”

Section: Ontogeny Of Ace2supporting

confidence: 63%

Ontogeny of angiotensin-converting enzyme 2

2011

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INTRODUCTION:This study examined the temporal expression of angiotensin (ang)-converting enzyme 2 (ace2) during renal, heart, lung, and brain organogenesis in the mouse. RESULTS: We demonstrate that kidney ace2 mRNa levels are low on embryonic day (e) 12.5, increase fourfold during development, and decline in adulthood. In extrarenal tissues, ace2 mRNa levels are also low during early gestation, increase in perinatal period, and peak in adulthood. The lung shows the highest age-related increase in ace2 mRNa levels followed by the brain, kidney, and heart. ace2 protein levels and enzymatic activity are high in all organs studied during gestation and decline postnatally. ang II decreases ace2 mRNa levels and enzymatic activity in kidneys grown ex vivo. These effects of ang II are blocked by the specific ang II aT 1 receptor (aT 1 R) antagonist candesartan, but not by the aT 2 receptor (aT 2 R) antagonist PD123319. DISCUSSION: We conclude that ACE2 gene and protein expression and enzymatic activity are developmentally regulated in a tissue-specific manner. ang II, acting through aT 1 R, exerts a negative feedback on ace2 during kidney development. We postulate that relatively high ace2 protein levels and enzymatic activity observed during gestation may play a role in kidney, lung, brain, and heart organogenesis.

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Section: Ontogeny Of Ace2supporting

confidence: 63%

Ontogeny of angiotensin-converting enzyme 2

2011

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“…Изменяя гломерулярное гидростатическое давление и влияя на сосудистое сопротивление приводящих артериол нефрона, РАС меняет скорость гломерулярной фильтра-ции [49]. Также показано, что активность ангиотензин-превращающего фермента 1, участвующего в превраще-нии ангиотензина I в ангиотензин II, увеличена у крыс, антенатально развивавшихся в условиях дефицита белка [50]. Свидетельством участия РАС в программировании АГ была способность блокатора ангиотензинпревраща-ющего фермента каптоприла нормализовывать артери-альное давление у крыс с подобной гипертензией [50].…”

Section: ренин-ангиотензиновая система и программирование гипертензииunclassified

“…Также показано, что активность ангиотензин-превращающего фермента 1, участвующего в превраще-нии ангиотензина I в ангиотензин II, увеличена у крыс, антенатально развивавшихся в условиях дефицита белка [50]. Свидетельством участия РАС в программировании АГ была способность блокатора ангиотензинпревраща-ющего фермента каптоприла нормализовывать артери-альное давление у крыс с подобной гипертензией [50]. В другой серии экспериментов с ограничением белка в питании матери было показано снижение активности ренина в плазме крови потомства с одновременным повышением уровня альдостерона [51].…”

Section: ренин-ангиотензиновая система и программирование гипертензииunclassified

“…В другой серии экспериментов с ограничением белка в питании матери было показано снижение активности ренина в плазме крови потомства с одновременным повышением уровня альдостерона [51]. В этой моде-ли было также продемонстрировано увеличение экс-прессии рецепторов к ангиотензину II [50]. Экспрессия микроРНК ангиотензинпревращающего фермента увели-чена в почках и жировой ткани взрослых животных, анте-натально подвергнутых действию дексаметазона [52].…”

Section: ренин-ангиотензиновая система и программирование гипертензииunclassified

See 1 more Smart Citation

Kidney Disease and Perinatal Programming of Arterial Hypertension: the Results of Experimental Researches

Ковтун¹,

Цывьян²

2017

Vopr. sovr. pediatr.

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“…There is emerging evidence that the environmental changes, triggered at different stages of development, lead to the self-propagation of epigenetic marks associated with changes in gene expression and an adult-onset phenotype [43][44][45][46][47][48][49][50][51][52][53][54][55] (for review see [56] ). Most studies have dealt with DNA methylation, histone modifications or chromatin occupancy by components of the epigenetic machinery, rarely with combinations of these factors.…”

Section: A�� mentioning

confidence: 99%

Epigenetic mechanisms involved in developmental nutritional programming

Gabory

Attig²,

Junien

2011

WJG

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The ways in which epigenetic modifications fix the ef�ects o� early environmental events, ensuring sustained responses to transient stimuli, which result in modi�ied gene expression patterns and phenotypes later in li�e, is a topic o� considerable interest. This review �ocuses on recently discovered mechanisms and calls into question prevailing views about the dynamics, position and �unctions o� epigenetic marks. Most epigenetic studies have addressed the long-term e��ects on a small number o� epigenetic marks, at the global or individual gene level, o� environmental stressors in humans and animal models. In parallel, increasing numbers o� studies based on high-throughput technologies and �ocusing on humans and mice have revealed additional complexity in epigenetic processes, by highlighting the importance o� crosstalk between the di�-�erent epigenetic marks. A number o� studies �ocusing on the developmental origin o� health and disease and metabolic programming have identified links between early nutrition, epigenetic processes and long-term illness. The existence o� a sel�-propagating epigenetic cycle has been demonstrated. Moreover, recent studies demonstrate an obvious sexual dimorphism both �or programming trajectories and in response to the same environmental insult. Despite recent progress, we are still �ar �rom understanding how, when and where environmental stressors disturb key epigenetic mechanisms. Thus, identi�ying the original key marks and their changes throughout development during an individual's li�etime or over several generations remains a challenging issue.

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Brain Renin-Angiotensin System: Fetal Epigenetic Programming by Maternal Protein Restriction During Pregnancy

Abstract: For the developing fetal brain RAS, MLPD leads to significant alterations in the mRNA and protein expression, with changes in DNA methylation and miRNA, key regulators of hypertension in adults.

Cited by 156 publications

References 58 publications

Ontogeny of angiotensin-converting enzyme 2

Ontogeny of angiotensin-converting enzyme 2

Kidney Disease and Perinatal Programming of Arterial Hypertension: the Results of Experimental Researches

Epigenetic mechanisms involved in developmental nutritional programming

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