TY - JOUR
T1 - The L-NAME mouse model of preeclampsia and impact to long-term maternal cardiovascular health
AU - de Alwis, Natasha
AU - Binder, Natalie K.
AU - Beard, Sally
AU - Mangwiro, Yeukai T.M.
AU - Kadife, Elif
AU - Cuffe, James S.M.
AU - Keenan, Emerson
AU - Fato, Bianca R.
AU - Kaitu'u-Lino, Tu'uhevaha J.
AU - Brownfoot, Fiona C.
AU - Marshall, Sarah A.
AU - Hannan, Natalie J.
N1 - Funding Information:
We would like to acknowledge the staff at the Austin Health BioResources Facility (Heidelberg) for assisting with the care of the animals. Support for this work was provided by the Trevor B Kilvington Bequest. Salary support was provided by the National Health and Medical Research Council Fellowships to NJ Hannan (#1146128). The funder played no role in study design or analysis.
Publisher Copyright:
© 2022 de Alwis et al.
PY - 2022/12
Y1 - 2022/12
N2 - Preeclampsia affects ∼2-8% of pregnancies worldwide. It is associated with increased long-term maternal cardiovascular disease risk. This study assesses the effect of the vasoconstrictor N(ω)-nitro-L-arginine methyl ester (L-NAME) in modelling preeclampsia in mice, and its long-term effects on maternal cardiovascular health. In this study, we found that L-NAME administration mimicked key characteristics of preeclampsia, including elevated blood pressure, impaired fetal and placental growth, and increased circulating endothelin-1 (vasoconstrictor), soluble fms-like tyrosine kinase-1 (anti-angiogenic factor), and C-reactive protein (inflammatory marker). Post-delivery, mice that received L-NAME in pregnancy recovered, with no discernible changes in measured cardiovascular indices at 1-, 2-, and 4-wk post-delivery, compared with matched controls. At 10-wk post-delivery, arteries collected from the L-NAME mice constricted significantly more to phenylephrine than controls. In addition, thesemice had increased kidney Mmp9:Timp1 and heart Tnf mRNA expression, indicating increased inflammation. These findings suggest that though administration of L-NAME in mice certainly models key characteristics of preeclampsia during pregnancy, it does not appear to model the adverse increase in cardiovascular disease risk seen in individuals after preeclampsia.
AB - Preeclampsia affects ∼2-8% of pregnancies worldwide. It is associated with increased long-term maternal cardiovascular disease risk. This study assesses the effect of the vasoconstrictor N(ω)-nitro-L-arginine methyl ester (L-NAME) in modelling preeclampsia in mice, and its long-term effects on maternal cardiovascular health. In this study, we found that L-NAME administration mimicked key characteristics of preeclampsia, including elevated blood pressure, impaired fetal and placental growth, and increased circulating endothelin-1 (vasoconstrictor), soluble fms-like tyrosine kinase-1 (anti-angiogenic factor), and C-reactive protein (inflammatory marker). Post-delivery, mice that received L-NAME in pregnancy recovered, with no discernible changes in measured cardiovascular indices at 1-, 2-, and 4-wk post-delivery, compared with matched controls. At 10-wk post-delivery, arteries collected from the L-NAME mice constricted significantly more to phenylephrine than controls. In addition, thesemice had increased kidney Mmp9:Timp1 and heart Tnf mRNA expression, indicating increased inflammation. These findings suggest that though administration of L-NAME in mice certainly models key characteristics of preeclampsia during pregnancy, it does not appear to model the adverse increase in cardiovascular disease risk seen in individuals after preeclampsia.
UR - http://www.scopus.com/inward/record.url?scp=85136651541&partnerID=8YFLogxK
U2 - 10.26508/lsa.202201517
DO - 10.26508/lsa.202201517
M3 - Article
C2 - 36260752
AN - SCOPUS:85136651541
SN - 2575-1077
VL - 5
JO - Life Science Alliance
JF - Life Science Alliance
IS - 12
M1 - e202201517
ER -
