At the heart of programming: the role of micro-RNAs

Siddeek, Bénazir; Mauduit, Claire; Yzydorczyk, Catherine; Benahmed, Mohamed; Simeoni, Umberto

doi:10.1017/s2040174418000387

Cited by 6 publications

(6 citation statements)

References 345 publications

(237 reference statements)

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“…In the early origins of heart diseases, epigenetic mechanisms are likely key players. In particular, micro-RNAs, which belong to small non-coding RNAs (around 22 nucleotides in length) involved in each step of heart development, seem to play a crucial role in the unfavorable programming of heart diseases 8 . By controlling about 60% of all protein-coding genes in mammals, micro-RNAs are considered as significant post-transcriptional regulators of gene expression 9 , and regulate almost all biological processes including development, differentiation, proliferation, apoptosis, metabolism and tissue remodeling.…”

Section: Introductionmentioning

confidence: 99%

Long-term impact of maternal high-fat diet on offspring cardiac health: role of micro-RNA biogenesis

et al. 2019

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Heart failure is a worldwide leading cause of death. Diet and obesity are particularly of high concern in heart disease etiology. Gravely, altered nutrition during developmental windows of vulnerability can have long-term impact on heart health; however, the underlying mechanisms are poorly understood. In the understanding of the initiation of chronic diseases related to developmental exposure to environmental challenges, deregulations in epigenetic mechanisms including micro-RNAs have been proposed as key events. In this context, we aimed at delineating the role of micro-RNAs in the programming of cardiac alterations induced by early developmental exposure to nutritional imbalance. To reach our aim, we developed a human relevant model of developmental exposure to nutritional imbalance by maternally exposing rat to high-fat diet during gestation and lactation. In this model, offspring exposed to maternal high-fat diet developed cardiac hypertrophy and increased extracellular matrix depot compared to those exposed to chow diet. Microarray approach performed on cardiac tissue allowed the identification of a micro-RNA subset which was down-regulated in high-fat diet-exposed animals and which were predicted to regulate transforming growth factor-beta (TGFβ)-mediated remodeling. As indicated by in vitro approaches and gene expression measurement in the heart of our animals, decrease in DiGeorge critical region 8 (DGCR8) expression, involved in micro-RNA biogenesis, seems to be a critical point in the alterations of the micro-RNA profile and the TGFβ-mediated remodeling induced by maternal exposure to high-fat diet. Finally, increasing DGCR8 activity and/or expression through hemin treatment in vitro revealed its potential in the rescue of the pro-fibrotic phenotype in cardiomyocytes driven by DGCR8 decrease. These findings suggest that cardiac alterations induced by maternal exposure to high-fat diet is related to abnormalities in TGFβ pathway and associated with down-regulated micro-RNA processing. Our study highlighted DGCR8 as a potential therapeutic target for heart diseases related to early exposure to dietary challenge.

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Section: Introductionmentioning

confidence: 99%

Long-term impact of maternal high-fat diet on offspring cardiac health: role of micro-RNA biogenesis

et al. 2019

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“…Other mechanisms that should be further explored are the epigenetic regulations of SERCA2 expression. Indeed, in the developmental origins of health and disease, epigenetics is described as a key player [ 29 ]. Interestingly, studies reported DNA methylation [ 30 ] and microRNAs [ 31 , 32 ] as regulators of SERCA2.…”

Section: Discussionmentioning

confidence: 99%

Transient Post-Natal Exposure to Xenoestrogens Induces Long-Term Alterations in Cardiac Calcium Signaling

Tabasso

Frossard

Ducret

et al. 2022

Toxics

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Today, non-communicable disorders are widespread worldwide. Among them, cardiovascular diseases represent the main cause of death. At the origin of these diseases, exposure to challenges during developmental windows of vulnerability (peri-conception, in utero, and early infancy periods) have been incriminated. Among the challenges that have been described, endocrine disruptors are of high concern because of their omnipresence in the environment. Worrisomely, since birth, children are exposed to a significant number of endocrine disruptors. However, the role of such early exposure on long-term cardiac health is poorly described. In this context, based on a model of rats exposed postnatally and transiently to an estrogenic compound prototype (estradiol benzoate, EB), we aimed to delineate the effects on the adult heart of such transient early exposure to endocrine disruptors and identify the underlying mechanisms involved in the potential pathogenesis. We found that this transient post-natal exposure to EB induced cardiac hypertrophy in adulthood, with increased cardiomyocyte size. The evaluation of cardiac calcium signaling, through immunoblot approaches, highlighted decreased expression of the sarcoplasmic reticulum calcium ATPase 2 (SERCA2) and decreased Nuclear Factor of Activated T Cells (NFAT3) phosphorylation as a potential underlying mechanism of cardiac hypertrophy. Furthermore, the treatment of cardiomyocytes with EB in vitro induced a decrease in SERCA2 protein levels. Overall, our study demonstrates that early transient exposure to EB induces permanent cardiac alterations. Together, our data highlight SERCA2 down-regulation as a potential mechanism involved in the cardiac pathogenesis induced by EB. These results suggest programming of adult heart dysfunctions such as arrhythmia and heart failures by early exposure to endocrine disruptors and could open new perspectives for treatment and prevention.

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“…These exposures alter one's cardiac metabolism and the microRNAs involved in each development stage of the heart and seem to play a crucial role in the unfavorable programming of CVDs. 22 Thus, diets that are restrictive in macronutrients and/or obesogenic diets, characterized by the excess of calories, sugars, and lipids, can lead to malnutrition and, if consumed by the mother during gestation and/ or lactation, can be equally capable of programming the offspring for cardiometabolic diseases. 23 Maternal malnutrition (F0 generation) programs its direct descendants (F1 generation), and it is capable of programming its subsequent generations (F2, F3, for example).…”

Section: Maternal Malnutrition: Lack or Excess Of Macronutrientsmentioning

confidence: 99%

Nutrition and Cardiovascular Diseases: Programming and Reprogramming

Marques¹,

Souza²,

Alvim-Silva³

et al. 2021

International Journal of Cardiovascular Sciences

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The Developmental Origin of Health and Disease (DOHaD) is an area of science dedicated to studying the processes by which insults during critical periods of mammals development leading to physiological changes resultig in diseases throughout life. Studies point to a complex interaction between nutritional status in early life and cardiovascular system homeostasis in which maternal malnutrition during gestation and/or lactation, as well as early weaning, are associated with development of cardiovascular diseases in adulthood. In this context, epigenetic c h a n g e s , s u c h a s D N A m e t h yl a t i o n , h i s t o n e acetylation, and change in microRNA expression have been considered molecular bases of cellular plasticity, which can also be gender-dependent. Experimental studies have demonstrated that interventions encompassing the consumption of functional food/bioactive compounds, as well as energetic and nutrients adjustments on the diet, may attenuate or even prevent consequences associated with plasticity of development, improving cardiovascular health. This review aimed to gather and discuss the findings within this context, published over the last ten years.

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At the heart of programming: the role of micro-RNAs

Cited by 6 publications

References 345 publications

Long-term impact of maternal high-fat diet on offspring cardiac health: role of micro-RNA biogenesis

Long-term impact of maternal high-fat diet on offspring cardiac health: role of micro-RNA biogenesis

Transient Post-Natal Exposure to Xenoestrogens Induces Long-Term Alterations in Cardiac Calcium Signaling

Nutrition and Cardiovascular Diseases: Programming and Reprogramming

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