Placental angiogenesis markers sFlt-1 and PlGF: response to cigarette smoke.
OBJECTIVE
Excess soluble vascular endothelial growth factor receptor, fms-like tyrosine kinase-1 (sFlt-1), and reduced placental growth factor (PlGF) mediate the genesis of preeclampsia. Cigarette smoking reduces the risk of preeclampsia. We hypothesized that placental secretion of sFlt-1 and PlGF was affected by exposure to cigarette smoke extract.


METHODS
Term placental villous explants were cultured with cigarette smoke extract. Media were analyzed for sFlt-1 and PlGF. Apoptosis was measured by TUNEL staining. Results are reported as sFlt-1 or PlGF picogram/milliliter/milligram wet weight of explant.


RESULTS
Exposure to cigarette smoke extract reduced secretion of sFlt-1 in a dose-dependent manner. There was no difference in apoptosis. In contrast with sFlt-1, PlGF did not decline when incubated with cigarette smoke extract.


CONCLUSIONS
Exposure of placental villous explants to cigarette smoke extract results in a proangiogenic state with reduced sFlt-1 and relative abundance of PlGF. This is the reverse of changes that are seen in preeclampsia and may explain the reduction of preeclampsia in smokers.
Mehendale
Ramkrishna
R
Department of Obstetrics and Gynecology, University of Illinois at Chicago, Chicago, IL 60612, USA. rmehenda@uic.edu
Hibbard
Judith
J
Fazleabas
Asgerally
A
Leach
Richard
R
D017209:Apoptosis / Q000187:drug effects*; D005260:Female; D006801:Humans; D020287:In Situ Nick-End Labeling; D066298:In Vitro Techniques; D018919:Neovascularization, Physiologic; D009538:Nicotine / Q000097:blood; D010100:Oxygen / Q000378:metabolism; D010920:Placenta / Q000098:blood supply* / Q000378:metabolism; D000072483:Placenta Growth Factor; D011225:Pre-Eclampsia / Q000503:physiopathology; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000378:metabolism*; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism*
C000608036:PGF protein, human; D011257:Pregnancy Proteins; D014028:Tobacco Smoke Pollution; D000072483:Placenta Growth Factor; D009538:Nicotine; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1; D010100:Oxygen