Reprogramming of the developing heart by Hif1a-deficient sympathetic system and maternal diabetes exposure

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F24%3A00585336" target="_blank" >RIV/67985823:_____/24:00585336 - isvavai.cz</a>

Alternative codes found

RIV/86652036:_____/24:00585336 RIV/00216208:11110/24:10478264 RIV/00216208:11310/24:10478264

Result on the web

<a href="https://doi.org/10.3389/fendo.2024.1344074" target="_blank" >https://doi.org/10.3389/fendo.2024.1344074</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/fendo.2024.1344074" target="_blank" >10.3389/fendo.2024.1344074</a>

Result language

angličtina

Original language name

Reprogramming of the developing heart by Hif1a-deficient sympathetic system and maternal diabetes exposure

Original language description

Introduction: Maternal diabetes is a recognized risk factor for both short-term and long-term complications in offspring. Beyond the direct teratogenicity of maternal diabetes, the intrauterine environment can influence the offspring's cardiovascular health. Abnormalities in the cardiac sympathetic system are implicated in conditions such as sudden infant death syndrome, cardiac arrhythmic death, heart failure, and certain congenital heart defects in children from diabetic pregnancies. However, the mechanisms by which maternal diabetes affects the development of the cardiac sympathetic system and, consequently, heightens health risks and predisposes to cardiovascular disease remain poorly understood.Methods and results: In the mouse model, we performed a comprehensive analysis of the combined impact of a Hif1a-deficient sympathetic system and the maternal diabetes environment on both heart development and the formation of the cardiac sympathetic system. The synergic negative effect of exposure to maternal diabetes and Hif1a deficiency resulted in the most pronounced deficit in cardiac sympathetic innervation and the development of the adrenal medulla. Abnormalities in the cardiac sympathetic system were accompanied by a smaller heart, reduced ventricular wall thickness, and dilated subepicardial veins and coronary arteries in the myocardium, along with anomalies in the branching and connections of the main coronary arteries. Transcriptional profiling by RNA sequencing (RNA-seq) revealed significant transcriptome changes in Hif1a-deficient sympathetic neurons, primarily associated with cell cycle regulation, proliferation, and mitosis, explaining the shrinkage of the sympathetic neuron population.Discussion: Our data demonstrate that a failure to adequately activate the HIF-1 alpha regulatory pathway, particularly in the context of maternal diabetes, may contribute to abnormalities in the cardiac sympathetic system. In conclusion, our findings indicate that the interplay between deficiencies in the cardiac sympathetic system and subtle structural alternations in the vasculature, microvasculature, and myocardium during heart development not only increases the risk of cardiovascular disease but also diminishes the adaptability to the stress associated with the transition to extrauterine life, thus increasing the risk of neonatal death.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30201 - Cardiac and Cardiovascular systems

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2024

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Frontiers in Endocrinology

ISSN

1664-2392

e-ISSN

1664-2392

Volume of the periodical

15

Issue of the periodical within the volume

Mar 5

Country of publishing house

CH - SWITZERLAND

Number of pages

18

Pages from-to

1344074

UT code for WoS article

001186659800001

EID of the result in the Scopus database

2-s2.0-85188125317