Mechanisms Of Endothelial And Embryonic Stem Cell Regulation In Pregnancy

12/01/2006 - 11/30/2012

Sponsor: NIH P01 HD038843 (Bird Project 1 PI, Core C CoPI)

Status: Completed

Studies under this proposal sought to further our understanding of the basic control of placental and uterine perfusion and mechanisms contributing to fetal pathophysiology in conditions such as pre-eclampsia and IUGR.

Publications:

Bird IM. Endothelial nitric oxide synthase activation and nitric oxide function: new light through old windows. J Endocrinol. 2011 Sep;210(3):239-41. doi: 10.1530/JOE-11-0216. PubMed PMID: 21824899.

Boeldt DS, Yi FX, Bird IM. eNOS activation and NO function: pregnancy adaptive programming of capacitative entry responses alters nitric oxide (NO) output in vascular endothelium--new insights into eNOS regulation through adaptive cell signaling. J Endocrinol. 2011 Sep;210(3):243-58. doi: 10.1530/JOE-11-0053. Epub 2011 May 9. Review. PubMed PMID: 21555345; PubMed Central PMCID: PMC4059042.

Yi FX, Boeldt DS, Magness RR, Bird IM. [Ca2+]i signaling vs. eNOS expression as determinants of NO output in uterine artery endothelium: relative roles in pregnancy adaptation and reversal by VEGF165. Am J Physiol Heart Circ Physiol. 2011 Apr;300(4):H1182-93. doi: 10.1152/ajpheart.01108.2010. Epub 2011 Jan 14. PubMed PMID: 21239633; PubMed Central PMCID: PMC3075018.

Yi FX, Boeldt DS, Gifford SM, Sullivan JA, Grummer MA, Magness RR, Bird IM. Pregnancy enhances sustained Ca2+ bursts and endothelial nitric oxide synthase activation in ovine uterine artery endothelial cells through increased connexin 43 function. Biol Reprod. 2010 Jan;82(1):66-75. doi: 10.1095/biolreprod.109.078253. Epub 2009 Sep 9. PubMed PMID: 19741206; PubMed Central PMCID: PMC2802114.

Grummer MA, Sullivan JA, Magness RR, Bird IM. Vascular endothelial growth factor acts through novel, pregnancy-enhanced receptor signalling pathways to stimulate endothelial nitric oxide synthase activity in uterine artery endothelial cells. Biochem J. 2009 Jan 15;417(2):501-11. doi: 10.1042/BJ20081013. PubMed PMID: 18816248; PubMed Central PMCID: PMC2680709.

Gifford SM, Yi FX, Bird IM. Pregnancy-enhanced store-operated Ca2+ channel function in uterine artery endothelial cells is associated with enhanced agonist-specific transient receptor potential channel 3-inositol 1,4,5-trisphosphate receptor 2 interaction. J Endocrinol. 2006 Aug;190(2):385-95. PubMed PMID: 16899571.

Gifford SM, Yi FX, Bird IM. Pregnancy-enhanced Ca2+ responses to ATP in uterine artery endothelial cells is due to greater capacitative Ca2+ entry rather than altered receptor coupling. J Endocrinol. 2006 Aug;190(2):373-84. PubMed PMID: 16899570.

Cale JM, Bird IM. Inhibition of MEK/ERK1/2 signalling alters endothelial nitric oxide synthase activity in an agonist-dependent manner. Biochem J. 2006 Sep 1;398(2):279-88. PubMed PMID: 16716148; PubMed Central PMCID: PMC1550315.

Sullivan JA, Grummer MA, Yi FX, Bird IM. Pregnancy-enhanced endothelial nitric oxide synthase (eNOS) activation in uterine artery endothelial cells shows altered sensitivity to Ca2+, U0126, and wortmannin but not LY294002—evidence that pregnancy adaptation of eNOS activation occurs at multiple levels of cell signaling. Endocrinology. 2006 May;147(5):2442-57. Epub 2006 Feb 2. PubMed PMID: 16455784.

Cale JM, Bird IM. Dissociation of endothelial nitric oxide synthase phosphorylation and activity in uterine artery endothelial cells. Am J Physiol Heart Circ Physiol. 2006 Apr;290(4):H1433-45. Epub 2005 Nov 4. PubMed PMID: 16272197.