Počet záznamů: 1
Reprogramming of the developing heart by Hif1a-deficient sympathetic system and maternal diabetes exposure
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SYSNO ASEP 0585336 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Reprogramming of the developing heart by Hif1a-deficient sympathetic system and maternal diabetes exposure Tvůrce(i) Kolesová, Hana (FGU-C) RID, ORCID, SAI
Hrabalová, Petra (BTO-N) RID
Bohuslavová, Romana (BTO-N) RID
Abaffy, Pavel (BTO-N)
Fabriciová, Valeria (BTO-N)
Sedmera, David (FGU-C) RID, ORCID, SAI
Pavlínková, Gabriela (BTO-N) RID, ORCIDČíslo článku 1344074 Zdroj.dok. Frontiers in Endocrinology. - : Frontiers Media - ISSN 1664-2392
Roč. 15, Mar 5 (2024)Poč.str. 18 s. Jazyk dok. eng - angličtina Země vyd. CH - Švýcarsko Klíč. slova mouse model ; maternal diabetes ; coronary arteries ; sympathetic neurons ; cardiac sympathetic system Obor OECD Cardiac and Cardiovascular systems CEP GA21-03847S GA ČR - Grantová agentura ČR LX22NPO5104 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy EF18_046/0016045 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Výzkumná infrastruktura Czech-BioImaging II - 90129 - Ústav molekulární genetiky AV ČR, v. v. i.
CCP II - 90126 - Ústav molekulární genetiky AV ČR, v. v. i.Způsob publikování Open access Institucionální podpora FGU-C - RVO:67985823 ; BTO-N - RVO:86652036 UT WOS 001186659800001 EID SCOPUS 85188125317 DOI 10.3389/fendo.2024.1344074 Anotace 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. Pracoviště Fyziologický ústav Kontakt Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Rok sběru 2025 Elektronická adresa https://doi.org/10.3389/fendo.2024.1344074
Počet záznamů: 1