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Changes in Ca2+ Signaling and Nitric Oxide Output by Human Umbilical Vein Endothelium in Diabetic and Gestational Diabetic Pregnancies1
- Source :
- Biology of Reproduction. 93
- Publication Year :
- 2015
- Publisher :
- Oxford University Press (OUP), 2015.
-
Abstract
- Diabetes (DM) complicates 3%-10% of pregnancies, resulting in significant maternal and neonatal morbidity and mortality. DM pregnancies are also associated with vascular dysfunction, including blunted nitric oxide (NO) output, but it remains unclear why. Herein we examine changes in endothelial NO production and its relationship to Ca(2+) signaling in endothelial cells of intact umbilical veins from control versus gestational diabetic (GDM) or preexisting diabetic subjects. We have previously reported that endothelial cells of intact vessels show sustained Ca(2+) bursting in response to ATP, and these bursts drive prolonged NO production. Herein we show that in both GDM and DM pregnancies, the incidence of Ca(2+) bursts remains similar, but there is a reduction in overall sustained phase Ca(2+) mobilization and a reduction in NO output. Further studies show damage has occurred at the level of NOS3 protein itself. Since exposure to DM serum is known to impair normal human umbilical vein endothelial cell (HUVEC) function, we further studied the ability of HUVEC to signal through Ca(2+) after they were isolated from DM and GDM subjects and maintained in culture for several days. These HUVEC showed differences in the rate of Ca(2+) bursting, with DM > GDM = control HUVEC. Both GDM- and DM-derived HUVEC showed smaller Ca(2+) bursts that were less capable of NOS3 activation compared to control HUVEC. We conclude that HUVEC from DM and GDM subjects are reprogrammed such that the Ca(2+) bursting peak shape and duration are permanently impaired. This may explain why ROS therapy alone is not effective in DM and GDM subjects.
- Subjects :
- medicine.medical_specialty
Endothelium
Nitric Oxide Synthase Type III
Cell Biology
General Medicine
Biology
medicine.disease
Umbilical vein
Nitric oxide
chemistry.chemical_compound
Endocrinology
medicine.anatomical_structure
Reproductive Medicine
chemistry
Diabetes mellitus
Internal medicine
Ionomycin
cardiovascular system
medicine
Gestation
Human umbilical vein endothelial cell
Subjects
Details
- ISSN :
- 15297268 and 00063363
- Volume :
- 93
- Database :
- OpenAIRE
- Journal :
- Biology of Reproduction
- Accession number :
- edsair.doi...........1df850fe07db59af567323bea15e3a39