Adverse effects of Hif1a mutation and maternal diabetes on the offspring heart
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F18%3A00491883" target="_blank" >RIV/67985823:_____/18:00491883 - isvavai.cz</a>
Alternative codes found
RIV/86652036:_____/18:00491883 RIV/00216208:11110/18:10376797 RIV/00216208:11310/18:10376797
Result on the web
<a href="http://dx.doi.org/10.1186/s12933-018-0713-0" target="_blank" >http://dx.doi.org/10.1186/s12933-018-0713-0</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1186/s12933-018-0713-0" target="_blank" >10.1186/s12933-018-0713-0</a>
Alternative languages
Result language
angličtina
Original language name
Adverse effects of Hif1a mutation and maternal diabetes on the offspring heart
Original language description
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. nMethods 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. nConclusions: 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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30105 - Physiology (including cytology)
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2018
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Cardiovascular Diabetology
ISSN
1475-2840
e-ISSN
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Volume of the periodical
17
Issue of the periodical within the volume
MAY 12 2018
Country of publishing house
GB - UNITED KINGDOM
Number of pages
16
Pages from-to
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UT code for WoS article
000432264400001
EID of the result in the Scopus database
2-s2.0-85046801833