In:
Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 121, No. suppl_1 ( 2017-07-21)
Abstract:
The heart switches its energy substrate from glucose to fatty acids at birth, and maternal hyperglycemia is known to be associated with congenital heart disease. However, little is known about the mechanism how blood glucose impacts heart formation. Using a chemically-defined human pluripotent stem cell-derived cardiomyocyte differentiation system, we found that high glucose inhibits the maturation of cardiomyocytes at genetic, structural, metabolic and electrophysiological levels via nucleotide biosynthesis through the pentose phosphate pathway. Even though blood glucose level stays stable in utero during normal pregnancy, glucose uptake by fetal cardiac tissue was found drastically reduced at late gestational stages in the mouse. Interestingly, perturbation of glucose dynamics during gestation in a murine model of diabetic pregnancy promoted mitosis and inhibited maturation of fetal cardiomyocytes. Therefore, this observation suggests that the metabolic switch is not only to meet the energy demand but also to induce a genetic program to facilitate cardiac maturation, providing a possible mechanistic basis for the congenital heart disease in diabetic pregnancy.
Type of Medium:
Online Resource
ISSN:
0009-7330
,
1524-4571
DOI:
10.1161/res.121.suppl_1.346
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2017
detail.hit.zdb_id:
1467838-X
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