Mice overexpressing both human angiotensinogen and human renin as a model of superimposed preeclampsia on chronic hypertension.
Preeclampsia is the major cause of maternal and fetal mortality/morbidity. Because hypertension is an important risk factor for preeclampsia, we investigated whether hypertensive mice that overexpress human renin and angiotensinogen develop superimposed preeclampsia. Given that the mechanisms underlying this disease are still poorly understood, animal models are of great use for elucidation. Blood pressure and proteinuria were measured by telemetry and ELISA, respectively. Heart function was evaluated by echocardiography, whereas pathological cardiac hypertrophy-related genes were assessed by real-time PCR. Soluble fms-like tyrosine kinase 1 plasma concentrations were quantitated by ELISA and placental expression by real-time PCR. Transgenic mice develop de novo proteinuria during gestation and marked blood pressure elevation, which are hallmarks of superimposed preeclampsia on chronic hypertension. Abnormal placentation present in these mothers produced a significant decrease in pup and placental weight and was associated with an increased placental expression of soluble fms-like tyrosine kinase 1. We also found heightened circulating levels of this receptor, when adjusted for placental mass, as has been observed in women who suffer from preeclampsia. Cardiac hypertrophy could be observed in the transgenic mice and was exacerbated by gestation. As a result, heart function was significantly decreased, and markers of pathological hypertrophy were increased. Our data, thus, confirm the characterization of a new model of superimposed preeclampsia on chronic hypertension. Because chronically hypertensive women are at risk of developing the pathology, our model reflects a clinical reality and is, thus, an excellent tool to elucidate the molecular mechanisms triggering this disease.
Falcao
Stéphanie
S
Centre de Recherche, CHUM-Technopôle Angus, 2901 Rachel St East, Suite 310, Montréal, Québec H1W 4A4, Canada.
Stoyanova
Ekatherina
E
Cloutier
Guy
G
Maurice
Roch L
RL
Gutkowska
Jolanta
J
Lavoie
Julie L
JL
D000808:Angiotensinogen / Q000235:genetics*; D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure / Q000502:physiology; D006332:Cardiomegaly / Q000503:physiopathology; D002908:Chronic Disease; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010920:Placenta / Q000473:pathology; D011225:Pre-Eclampsia / Q000473:pathology / Q000503:physiopathology*; D011247:Pregnancy; D011507:Proteinuria / Q000503:physiopathology; D012083:Renin / Q000235:genetics*; D012084:Renin-Angiotensin System / Q000502:physiology
D000808:Angiotensinogen; D012083:Renin