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ADENOSINE KINASE AND CARDIOVASCULAR FETAL PROGRAMMING IN GESTATIONAL DIABETES MELLITUS

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2020
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BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
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GESTATIONAL DIABETES MELLITUS (GDM) IS A DETRIMENTAL CONDITION FOR HUMAN PREGNANCY ASSOCIATED WITH ENDOTHELIAL DYSFUNCTION AND ENDOTHELIAL INFLAMMATION IN THE FETOPLACENTAL VASCULATURE AND LEADS TO INCREASED CARDIO-METABOLIC RISK IN THE OFFSPRING. IN THE FETOPLACENTAL VASCULATURE, GDM IS ASSOCIATED WITH ALTERED ADENOSINE METABOLISM. ADENOSINE IS AN IMPORTANT VASOACTIVE MOLECULE AND IS AN INTERMEDIARY AND FINAL PRODUCT OF TRANSMETHYLATION REACTIONS IN THE CELL. ADENOSINE KINASE IS THE MAJOR REGULATOR OF ADENOSINE LEVELS. DISRUPTION OF THIS ENZYME IS ASSOCIATED WITH ALTERATIONS IN METHYLATION-DEPENDENT GENE EXPRESSION REGULATION MECHANISMS, WHICH ARE ASSOCIATED WITH THE FETAL PROGRAMMING PHENOMENON. HERE WE PROPOSE THAT CELLULAR AND MOLECULAR ALTERATIONS ASSOCIATED WITH GDM CAN DYSREGULATE ADENOSINE KINASE LEADING TO FETAL PROGRAMMING IN THE FETOPLACENTAL VASCULATURE. THIS CAN CONTRIBUTE TO THE CARDIO-METABOLIC LONG-TERM CONSEQUENCES OBSERVED IN OFFSPRING AFTER EXPOSURE TO GDM.
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