Signaling Regulation of Fetoplacental Angiogenesis

Overview

Journal J Endocrinol

Specialty Endocrinology

Date 2011 Nov 23

PMID 22106098

Citations 23

Authors

Kai Wang

Jing Zheng

Affiliations

Soon will be listed here.

Abstract

During normal pregnancy, dramatically increased placental blood flow is critical for fetal growth and survival as well as neonatal birth weights and survivability. This increased blood flow results from angiogenesis, vasodilatation, and vascular remodeling. Locally produced growth factors including fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor A (VEGFA) are key regulators of placental endothelial functions including cell proliferation, migration, and vasodilatation. However, the precise signaling mechanisms underlying such regulation in fetoplacental endothelium are less well defined, specifically with regard to the interactions amongst protein kinases (PKs), protein phosphatase, and nitric oxide (NO). Recently, we and other researchers have obtained solid evidence showing that different signaling mechanisms participate in FGF2- and VEGFA-regulated fetoplacental endothelial cell proliferation and migration as well as NO production. This review will briefly summarize currently available data on signaling mediating fetoplacental angiogenesis with a specific emphasis on PKs, ERK1/2, AKT1, and p38 MAPK and protein phosphatases, PPP2 and PPP3.

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References

Dembinska-Kiec A, Dulak J, Partyka L, Huk I, Mailnski T . VEGF-nitric oxide reciprocal regulation. Nat Med. 1997; 3(11):1177. DOI: 10.1038/nm1197-1177a. View

DAngelo G, Struman I, Martial J, Weiner R . Activation of mitogen-activated protein kinases by vascular endothelial growth factor and basic fibroblast growth factor in capillary endothelial cells is inhibited by the antiangiogenic factor 16-kDa N-terminal fragment of prolactin. Proc Natl Acad Sci U S A. 1995; 92(14):6374-8. PMC: 41520. DOI: 10.1073/pnas.92.14.6374. View

Noiri E, Hu Y, Bahou W, Keese C, Giaever I, Goligorsky M . Permissive role of nitric oxide in endothelin-induced migration of endothelial cells. J Biol Chem. 1997; 272(3):1747-52. DOI: 10.1074/jbc.272.3.1747. View

Sa G, Murugesan G, Jaye M, Ivashchenko Y, Fox P . Activation of cytosolic phospholipase A2 by basic fibroblast growth factor via a p42 mitogen-activated protein kinase-dependent phosphorylation pathway in endothelial cells. J Biol Chem. 1995; 270(5):2360-6. DOI: 10.1074/jbc.270.5.2360. View

Michell B, Griffiths J, Mitchelhill K, Rodriguez-Crespo I, Tiganis T, Bozinovski S . The Akt kinase signals directly to endothelial nitric oxide synthase. Curr Biol. 1999; 9(15):845-8. DOI: 10.1016/s0960-9822(99)80371-6. View

Wang K, Jiang Y, Chen D, Zheng J . Hypoxia enhances FGF2- and VEGF-stimulated human placental artery endothelial cell proliferation: roles of MEK1/2/ERK1/2 and PI3K/AKT1 pathways. Placenta. 2009; 30(12):1045-51. PMC: 2788063. DOI: 10.1016/j.placenta.2009.10.007. View

Bussolati B, Dunk C, Grohman M, Kontos C, Mason J, Ahmed A . Vascular endothelial growth factor receptor-1 modulates vascular endothelial growth factor-mediated angiogenesis via nitric oxide. Am J Pathol. 2001; 159(3):993-1008. PMC: 1850457. DOI: 10.1016/S0002-9440(10)61775-0. View

Li Y, Zheng J, Bird I, Magness R . Effects of pulsatile shear stress on nitric oxide production and endothelial cell nitric oxide synthase expression by ovine fetoplacental artery endothelial cells. Biol Reprod. 2003; 69(3):1053-9. DOI: 10.1095/biolreprod.102.013474. View

Myatt L, Brockman D, Eis A, Pollock J . Immunohistochemical localization of nitric oxide synthase in the human placenta. Placenta. 1993; 14(5):487-95. DOI: 10.1016/s0143-4004(05)80202-4. View

10.

Dimmeler S, Fleming I, Fisslthaler B, Hermann C, Busse R, Zeiher A . Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation. Nature. 1999; 399(6736):601-5. DOI: 10.1038/21224. View

11.

Gotz J, Probst A, Ehler E, Hemmings B, Kues W . Delayed embryonic lethality in mice lacking protein phosphatase 2A catalytic subunit Calpha. Proc Natl Acad Sci U S A. 1998; 95(21):12370-5. PMC: 22838. DOI: 10.1073/pnas.95.21.12370. View

12.

Vonnahme K, Wilson M, Li Y, Rupnow H, Phernetton T, Ford S . Circulating levels of nitric oxide and vascular endothelial growth factor throughout ovine pregnancy. J Physiol. 2005; 565(Pt 1):101-9. PMC: 1464494. DOI: 10.1113/jphysiol.2004.082321. View

13.

Young M, Kolesiak K, Meisinger J . Protein phosphatase-2A regulates endothelial cell motility and both the phosphorylation and the stability of focal adhesion complexes. Int J Cancer. 2002; 100(3):276-82. DOI: 10.1002/ijc.10491. View

14.

Myatt L . Control of vascular resistance in the human placenta. Placenta. 1992; 13(4):329-41. DOI: 10.1016/0143-4004(92)90057-z. View

15.

Urbich C, Reissner A, Chavakis E, Dernbach E, Haendeler J, Fleming I . Dephosphorylation of endothelial nitric oxide synthase contributes to the anti-angiogenic effects of endostatin. FASEB J. 2002; 16(7):706-8. DOI: 10.1096/fj.01-0637fje. View

16.

Lechward K, Awotunde O, SWIATEK W, Muszynska G . Protein phosphatase 2A: variety of forms and diversity of functions. Acta Biochim Pol. 2002; 48(4):921-33. View

17.

Ziche M, Morbidelli L, Masini E, Amerini S, Granger H, Maggi C . Nitric oxide mediates angiogenesis in vivo and endothelial cell growth and migration in vitro promoted by substance P. J Clin Invest. 1994; 94(5):2036-44. PMC: 294636. DOI: 10.1172/JCI117557. View

18.

Michell B, Chen Zp , Tiganis T, Stapleton D, Katsis F, Power D . Coordinated control of endothelial nitric-oxide synthase phosphorylation by protein kinase C and the cAMP-dependent protein kinase. J Biol Chem. 2001; 276(21):17625-8. DOI: 10.1074/jbc.C100122200. View

19.

Gratton J, Morales-Ruiz M, Kureishi Y, Fulton D, Walsh K, Sessa W . Akt down-regulation of p38 signaling provides a novel mechanism of vascular endothelial growth factor-mediated cytoprotection in endothelial cells. J Biol Chem. 2001; 276(32):30359-65. DOI: 10.1074/jbc.M009698200. View

20.

Sladek S, Magness R, Conrad K . Nitric oxide and pregnancy. Am J Physiol. 1997; 272(2 Pt 2):R441-63. DOI: 10.1152/ajpregu.1997.272.2.R441. View