Pravastatin therapy during preeclampsia prevents long-term adverse health effects in mice

Garrett, Nicola; Pombo, Joaquim; Umpierrez, Michelle; Clark, James E.; Simmons, Mark A.; Girardi, Guillermina

doi:10.1172/jci.insight.120147

Cited by 38 publications

(34 citation statements)

References 61 publications

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“…In addition, complement split product C5a might induce microglial inflammatory polarization in the fetal and neonatal brain. Activation of microglia has been associated with neurogenic hypertension and behavioral abnormalities in the offspring ( 72 , 119 ).…”

Section: Complement In Fetal Developmentmentioning

confidence: 99%

“…However, the mechanism behind the maternal and offspring health complications after a preeclamptic pregnancy remain unknown. It is possible that abnormal placentation during preeclampsia results in placental insufficiency leading to the release of vasoactive and proinflammatory molecules that compromise the maternal and fetal health after pregnancy ( 72 ).…”

Section: Complement Activation During Pregnancy and Preeclampsia: Lonmentioning

confidence: 99%

“…In the mouse, a paternal deficiency of C1q results in impaired trophoblast migration and abnormal placentation leading to onset of preeclampsia-like symptoms including endothelial dysfunction and hypertension in the mother, along with high levels of C5a ( 72 , 141 , 142 ). Offspring of these pregnancies also experienced health complications ( Figure 5 ).…”

Section: Complement Activation During Pregnancy and Preeclampsia: Lonmentioning

confidence: 99%

“…Glomerular injury persisted after the preeclampsia-like pregnancy, leading to fibrosis. In addition, left ventricular remodeling with increased collagen deposition and MMP-9 expression and enlarged cardiomyocytes developed after the preeclampsia-like pregnancy ( 72 ). Hearts were characterized by increased left ventricular internal wall thickness and mass, increased end diastolic and end systolic volumes, and increased stroke volume.…”

Section: Complement Activation During Pregnancy and Preeclampsia: Lonmentioning

confidence: 99%

“…Placenta-derived bioactive and proinflammatory factors (endothelin-1, IL-6, and C5a) increased in maternal sera during and after a preeclamptic pregnancy. Offspring of preeclamptic mice developed endothelial dysfunction, hypertension, and indicators of metabolic disease ( 72 ). Pravastatin treatment normalized C5a values in preeclamptic-mice and normalized cardiovascular and metabolic function in both mothers and offspring.…”

Section: Complement Activation During Pregnancy and Preeclampsia: Lonmentioning

confidence: 99%

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Essential Role of Complement in Pregnancy: From Implantation to Parturition and Beyond

et al. 2020

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The complement cascade was identified over 100 years ago, yet investigation of its role in pregnancy remains an area of intense research. Complement inhibitors at the maternal-fetal interface prevent inappropriate complement activation to protect the fetus. However, this versatile proteolytic cascade also favorably influences numerous stages of pregnancy, including implantation, fetal development, and labor. Inappropriate complement activation in pregnancy can have adverse lifelong sequelae for both mother and child. This review summarizes the current understanding of complement activation during all stages of pregnancy. In addition, consequences of complement dysregulation during adverse pregnancy outcomes from miscarriage, preeclampsia, and pre-term birth are examined. Finally, future research directions into complement activation during pregnancy are considered.

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Section: Complement In Fetal Developmentmentioning

confidence: 99%

Section: Complement Activation During Pregnancy and Preeclampsia: Lonmentioning

confidence: 99%

Section: Complement Activation During Pregnancy and Preeclampsia: Lonmentioning

confidence: 99%

Section: Complement Activation During Pregnancy and Preeclampsia: Lonmentioning

confidence: 99%

Section: Complement Activation During Pregnancy and Preeclampsia: Lonmentioning

confidence: 99%

See 3 more Smart Citations

Essential Role of Complement in Pregnancy: From Implantation to Parturition and Beyond

et al. 2020

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Preeclampsia: Linking Placental Ischemia with Maternal Endothelial and Vascular Dysfunction

Bakrania

Spradley

Drummond

et al. 2020

Comprehensive Physiology

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Maternal Microvascular Dysfunction During and After Preeclamptic Pregnancy

Schwartz,

Stanhewicz

2024

Comprehensive Physiology

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Preeclampsia, a pregnancy disorder characterized by de novo hypertension and maternal multisystem organ dysfunction, is the leading cause of maternal mortality worldwide and is associated with a fourfold greater risk of cardiovascular disease throughout the lifespan. Current understanding of the etiology of preeclampsia remains unclear, due in part to the varying phenotypical presentations of the disease, which has hindered the development of effective and mechanism‐specific treatment or prevention strategies both during and after the affected pregnancy. These maternal sequelae of preeclampsia are symptoms of systemic vascular dysfunction in the maternal nonreproductive microvascular beds that drives the development and progression of adverse cardiovascular outcomes during preeclampsia. Despite normalization of vascular disturbances after delivery, subclinical dysfunction persists in the nonreproductive microvascular beds, contributing to an increased lifetime risk of cardiovascular and metabolic diseases and all‐cause mortality. Given that women with a history of preeclampsia demonstrate vascular dysfunction despite an absence of traditional CVD risk factors, an understanding of the underlying mechanisms of microvascular dysfunction during and after preeclampsia is essential to identify potential therapeutic avenues to mitigate or reverse the development of overt disease. This article aims to provide a summary of the existing literature on the pathophysiology of maternal microvascular dysfunction during preeclampsia, the mechanisms underlying the residual dysfunction that remains after delivery, and current and potential treatments both during and after the affected pregnancy that may reduce microvascular dysfunction in these high‐risk women. © 2024 American Physiological Society. Compr Physiol 14:5703‐5727, 2024.

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Pravastatin therapy during preeclampsia prevents long-term adverse health effects in mice

Cited by 38 publications

References 61 publications

Essential Role of Complement in Pregnancy: From Implantation to Parturition and Beyond

Essential Role of Complement in Pregnancy: From Implantation to Parturition and Beyond

Preeclampsia: Linking Placental Ischemia with Maternal Endothelial and Vascular Dysfunction

Maternal Microvascular Dysfunction During and After Preeclamptic Pregnancy

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