Submitted November 20, 2006
Returned for revision December 18, 2006
Accepted January 29, 2007
Pregnancy
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 D.V. Hankins ,
and
Chandra Yallampalli
* To whom correspondence should be addressed. E-mail: chyallam{at}utmb.edu.
Abstract
Recent studies have shown that homozygous knockout of gene
for 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. 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 and assess whether CALCA
regulates in vitro angiogenesis of human endothelial
cells, and if CALCA can improve angiogenic imbalance in
preeclamptic placental explants. Our studies demonstrated
that both protein and mRNA for CALCA are expressed
by the villous and extravillous trophoblasts and decidual
cells in the first-trimester villous tissues. CALCA
receptor components, CALCRL and RAMP1, are expressed by
both villous and extravillous trophoblast cells, as well
as vascular endothelial cells. CALCA induces both
endothelial proliferation and migration in a dose- and
time-dependent manner, and promotes capillary-like tube
formation of HUVECs on Matrigel. CALCA-induced
angiogenesis of human endothelial cells are completely
blocked by CALCA antagonist, CALCA8-37.
Further, conditioned medium from preeclamptic placental
explants significantly inhibits HUVECs capillary-like tube
formation compared to gestation age-matched control, and
conditioned medium from preeclamptic placental explants
incubated with CALCA significantly improves capillary-like
tube formation. Conclusion: CALCA induces in vitro
angiogenesis by stimulating endothelial cell
proliferation, migration, and capillary-like tube
formation; thus, CALCA at the human implantation site may
constitute a potential autocrine or paracrine mechanism
that could modify placental angiogenesis and
neovascularization.
Key words:
Decidua •
Placenta •
Trophoblast
