Adverse effects of Hif1a mutation and maternal diabetes on the offspring heart

Cardiovascular Diabetology
Radka CerychovaGabriela Pavlinkova

Abstract

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. 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 Hif1a and exposure to maternal diabetes resulted in impaired macrophage infiltration, increased levels...Continue Reading

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Citations

Jun 15, 2019·Proceedings of the National Academy of Sciences of the United States of America·Romana BohuslavovaGabriela Pavlinkova
Aug 31, 2018·Frontiers in Endocrinology·Radka Cerychova, Gabriela Pavlinkova
Feb 13, 2021·Developmental Biology·Haruko NakanoAtsushi Nakano
Apr 7, 2021·Pharmacology & Therapeutics·Amir AjoolabadyJun Ren
Jul 3, 2021·International Journal of Molecular Sciences·Romana BohuslavovaGabriela Pavlinkova
Jul 24, 2021·Immunologic Research·N B ThummadiP Manimaran
Sep 10, 2021·Genesis : the Journal of Genetics and Development·Talita Z ChoudhuryVidu Garg
Nov 23, 2021·Frontiers in Endocrinology·Eva ZateckaGabriela Pavlinkova

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Datasets Mentioned

BETA
GSE109633

Methods Mentioned

BETA
PCR
RNAseq
Profiler

Software Mentioned

htseq
GraphPad Prism
TrimmomaticPE
Image J
Sortmerna
GOST Gene Group Functional
count
MouseMine Analysis Tools
: Profiler
Harmonizome

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