Calcitonin gene-related peptide (CALCA) is a proangiogenic growth factor in the human placental development

Yuan Lin Dong, Deepti M. Reddy, Kortney E. Green, Madhu S. Chauhan, Hui Qun Wang, Manubai Nagamani, Gary Hankins, Chandra Yallampalli

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Recent studies have shown that homozygous knockout of gene for calcitonin gene-related peptide (CALCA) receptor component, calcitonin receptor-like receptor (CALCRL), led to extreme hydrops fetalis and embryonic death, underlining the critical role of CALCA in embryonic development and fetal growth. The present study was designed to determine the cellular localization of CALCA and its receptor components, CALCRL and receptor activity modifying protein 1 (RAMP1), at the human implantation site during early pregnancy; to assess whether CALCA regulates in vitro angiogenesis of human endothelial cells; and to examine whether CALCA can improve angiogenic imbalance in preeclamptic placental explants. Our studies demonstrated that both protein and mRNA for CALCA were expressed by the villous and extravillous trophoblasts and decidual cells in the first-trimester villous tissues. CALCA receptor components, CALCRL and RAMP1, were expressed by both villous and extravillous trophoblast cells, as well as vascular endothelial cells. CALCA induced both endothelial proliferation and migration in a dose- and time-dependent manner, and it promoted capillarylike tube formation of human umbilical vein endothelial cells (HUVECs) on Matrigel. CALCA-induced angiogenesis of human endothelial cells was completely blocked by CALCA antagonist CALCA8-37. Further, conditioned medium from preeclamptic placental explants significantly inhibited HUVEC capillarylike tube formation compared with gestational age-matched controls, and conditioned medium from preeclamptic placental explants incubated with CALCA significantly improved capillarylike tube formation. We conclude that CALCA induces in vitro angiogenesis by stimulating endothelial cell proliferation, migration, and capillarylike tube formation; thus, CALCA at the human implantation site may constitute a potential autocrine or paracrine mechanism that could modify placental angiogenesis and neovascularization.

Original languageEnglish (US)
Pages (from-to)892-899
Number of pages8
JournalBiology of Reproduction
Volume76
Issue number5
DOIs
StatePublished - May 2007

Fingerprint

Placentation
Calcitonin Receptor-Like Protein
Calcitonin Gene-Related Peptide
Human Development
Receptor Activity-Modifying Protein 1
Intercellular Signaling Peptides and Proteins
Endothelial Cells
Human Umbilical Vein Endothelial Cells
Trophoblasts
Conditioned Culture Medium
Calcitonin Gene-Related Peptide Receptors
Hydrops Fetalis
Gene Knockout Techniques
First Pregnancy Trimester
Fetal Development
Gestational Age
Embryonic Development
Cell Movement
Cell Proliferation
Pregnancy

Keywords

  • Angiogenesis
  • CALCA
  • Decidua
  • Placenta
  • Trophoblast

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Embryology

Cite this

Dong, Y. L., Reddy, D. M., Green, K. E., Chauhan, M. S., Wang, H. Q., Nagamani, M., ... Yallampalli, C. (2007). Calcitonin gene-related peptide (CALCA) is a proangiogenic growth factor in the human placental development. Biology of Reproduction, 76(5), 892-899. https://doi.org/10.1095/biolreprod.106.059089

Calcitonin gene-related peptide (CALCA) is a proangiogenic growth factor in the human placental development. / Dong, Yuan Lin; Reddy, Deepti M.; Green, Kortney E.; Chauhan, Madhu S.; Wang, Hui Qun; Nagamani, Manubai; Hankins, Gary; Yallampalli, Chandra.

In: Biology of Reproduction, Vol. 76, No. 5, 05.2007, p. 892-899.

Research output: Contribution to journalArticle

Dong, YL, Reddy, DM, Green, KE, Chauhan, MS, Wang, HQ, Nagamani, M, Hankins, G & Yallampalli, C 2007, 'Calcitonin gene-related peptide (CALCA) is a proangiogenic growth factor in the human placental development', Biology of Reproduction, vol. 76, no. 5, pp. 892-899. https://doi.org/10.1095/biolreprod.106.059089
Dong, Yuan Lin ; Reddy, Deepti M. ; Green, Kortney E. ; Chauhan, Madhu S. ; Wang, Hui Qun ; Nagamani, Manubai ; Hankins, Gary ; Yallampalli, Chandra. / Calcitonin gene-related peptide (CALCA) is a proangiogenic growth factor in the human placental development. In: Biology of Reproduction. 2007 ; Vol. 76, No. 5. pp. 892-899.
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abstract = "Recent studies have shown that homozygous knockout of gene for calcitonin gene-related peptide (CALCA) receptor component, calcitonin receptor-like receptor (CALCRL), led to extreme hydrops fetalis and embryonic death, underlining the critical role of CALCA in embryonic development and fetal growth. The present study was designed to determine the cellular localization of CALCA and its receptor components, CALCRL and receptor activity modifying protein 1 (RAMP1), at the human implantation site during early pregnancy; to assess whether CALCA regulates in vitro angiogenesis of human endothelial cells; and to examine whether CALCA can improve angiogenic imbalance in preeclamptic placental explants. Our studies demonstrated that both protein and mRNA for CALCA were expressed by the villous and extravillous trophoblasts and decidual cells in the first-trimester villous tissues. CALCA receptor components, CALCRL and RAMP1, were expressed by both villous and extravillous trophoblast cells, as well as vascular endothelial cells. CALCA induced both endothelial proliferation and migration in a dose- and time-dependent manner, and it promoted capillarylike tube formation of human umbilical vein endothelial cells (HUVECs) on Matrigel. CALCA-induced angiogenesis of human endothelial cells was completely blocked by CALCA antagonist CALCA8-37. Further, conditioned medium from preeclamptic placental explants significantly inhibited HUVEC capillarylike tube formation compared with gestational age-matched controls, and conditioned medium from preeclamptic placental explants incubated with CALCA significantly improved capillarylike tube formation. We conclude that CALCA induces in vitro angiogenesis by stimulating endothelial cell proliferation, migration, and capillarylike tube formation; thus, CALCA at the human implantation site may constitute a potential autocrine or paracrine mechanism that could modify placental angiogenesis and neovascularization.",
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