title: Carbon monoxide prevents hypertension and proteinuria in an adenovirus sFlt-1 preeclampsia-like mouse model.
abstract: Preeclampsia (PE) remains a leading cause of maternal and neonatal morbidity and mortality worldwide. Smoking cigarettes is associated with a decreased incidence of PE. Based on this observation and previous work, we hypothesize that women who smoke have a lower risk of developing PE because of elevated levels of carbon monoxide (CO) in their blood. The objective of this study was to determine if low-dose CO in ambient air could attenuate the late pregnancy hypertension (HTN) and proteinuria in the Adenovirus (Ad) sFlt-1 PE-like mouse model. Continuous low-dose CO treatment (250 ppm) was started on E10.5 and maintained until E17.5. Compared to control and Ad empty vector, AdsFlt-1 mice displayed late- gestation HTN (E14.5-17.5) (P<0.05), proteinuria (P<0.05) and reduced Bowman's space which were all prevented with CO treatment. Use of the Ad (with/without sFlt-1) or CO had no effect (p>0.05) on litter size, fetal resorption numbers and fetal or placental weights. This study shows that treatment with CO can prevent HTN and proteinuria in a mouse model of PE. It provides a possible mechanism for the reduced incidence of PE in smoking women, and supports the possibility of using CO as a future treatment for PE.
authors.affiliation: Department of Biomedical and Molecular Science, Queen's University, Kingston, Canada.
authors.forename: Carolina C
authors.initials: CC
authors.lastname: Venditti
authors.affiliation: Department of Biomedical and Molecular Science, Queen's University, Kingston, Canada.
authors.forename: Richard
authors.initials: R
authors.lastname: Casselman
authors.affiliation: Department of Health Sciences, Queen's University, Kingston, Canada.
authors.forename: Iain
authors.initials: I
authors.lastname: Young
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America.
authors.forename: S Ananth
authors.initials: SA
authors.lastname: Karumanchi
authors.affiliation: Department of Biomedical and Molecular Science, Queen's University, Kingston, Canada; Department of Obstetrics and Gynecology, Kingston General Hospital, Kingston, Canada.
authors.forename: Graeme N
authors.initials: GN
authors.lastname: Smith
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D002248:Carbon Monoxide / Q000097:blood / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D006973:Hypertension / Q000150:complications / Q000517:prevention & control*; D051379:Mice; D009035:Mothers; D011225:Pre-Eclampsia / Q000097:blood / Q000821:virology*; D011247:Pregnancy; D011507:Proteinuria / Q000150:complications / Q000517:prevention & control*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics*
chemical_list: D002248:Carbon Monoxide; D040281:Vascular Endothelial Growth Factor Receptor-1