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Adverse effects of Hif1a mutation and maternal diabetes on the offspring heart
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SYSNO ASEP 0491883 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Adverse effects of Hif1a mutation and maternal diabetes on the offspring heart Tvůrce(i) Čerychová, Radka (BTO-N)
Bohuslavová, Romana (BTO-N) RID
Papoušek, František (FGU-C)
Sedmera, David (FGU-C) RID, ORCID, SAI
Abaffy, Pavel (BTO-N)
Benes, V. (DE)
Kolář, František (FGU-C) RID, ORCID, SAI
Pavlínková, Gabriela (BTO-N) RID, ORCIDCelkový počet autorů 8 Číslo článku 68 Zdroj.dok. Cardiovascular Diabetology. - : BioMed Central
Roč. 17, MAY 12 2018 (2018)Poč.str. 16 s. Jazyk dok. eng - angličtina Země vyd. GB - Velká Británie Klíč. slova Fetal programming ; Maternal diabetes ; Hif1a haploinsufficiency Vědní obor RIV FB - Endokrinologie, diabetologie, metabolizmus, výživa Obor OECD Endocrinology and metabolism (including diabetes, hormones) Vědní obor RIV – spolupráce Fyziologický ústav - Fyziologie CEP GA16-06825S GA ČR - Grantová agentura ČR ED1.1.00/02.0109 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy LM2015062 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Institucionální podpora BTO-N - RVO:86652036 ; FGU-C - RVO:67985823 UT WOS 000432264400001 EID SCOPUS 85046801833 DOI 10.1186/s12933-018-0713-0 Anotace Background: Epidemiological studies show that maternal diabetes predisposes offspring to cardiovascular and metabolic disorders. However, the precise mechanisms for the underlying penetrance and disease predisposition remain poorly understood. We examined whether hypoxia-inducible factor 1 alpha, in combination with exposure to a diabetic intrauterine environment, influences the function and molecular structure of the adult offspring heart.
Methods and results: In a mouse model, we demonstrated that haploinsufficient (Hif1a(+/-)) offspring from a diabetic pregnancy developed left ventricle dysfunction at 12 weeks of age, as manifested by decreased fractional shortening and structural remodeling of the myocardium. Transcriptional profiling by RNA-seq revealed significant transcriptome changes in the left ventricle of diabetes-exposed Hif1a(+/-) offspring associated with development, metabolism, apoptosis, and blood vessel physiology. In contrast, both wild type and Hif1a(+/-) offspring from diabetic pregnancies showed changes in immune system processes and inflammatory responses. Immunohistochemical analyses demonstrated that the combination of haploinsufficiency of Hifia and exposure to maternal diabetes resulted in impaired macrophage infiltration, increased levels of advanced glycation end products, and changes in vascular homeostasis in the adult offspring heart.
Conclusions: Together our findings provide evidence that a global reduction in Hifia gene dosage increases predisposition of the offspring exposed to maternal diabetes to cardiac dysfunction, and also underscore Hif1a as a critical factor in the fetal programming of adult cardiovascular disease.Pracoviště Biotechnologický ústav Kontakt Monika Kopřivová, Monika.Koprivova@ibt.cas.cz, Tel.: 325 873 700 Rok sběru 2019
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