Recent Progress Toward the Understanding of the Pathophysiology of Hypertension During Preeclampsia

Alterations in maternal and fetal heart functions accompany failed spiral arterial remodeling in pregnant mice

“…15 Thus, identifying links between uterine vascular remodeling and systemic cardiovascular abnormalities is critical for appropriate management of human gestational complications. 16 Early in normal human and mouse pregnancies, mean arterial blood pressure decreases slightly or is stable. 17,18 This indicates that gains in uterine flow are more attributable to morphological remodeling of uterine arteries than to alterations in their smooth muscle tone.…”

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Abstract OBJECTIVE-Our goal was to define mechanisms that protect murine pregnancies deficient in spiral arterial (SA) remodeling from hypertension, hypoxia and intra-uterine growth restriction.STUDY DESIGN-Micro-ultrasound analyses were conducted on virgin, gestation day (gd) 2,4,7,9,10,12,14,16,18 and postpartum BALB/c (WT) mice and BALB/c-Rag2 −/− /Il2rg −/− mice, an immunodeficient strain lacking SA remodeling.

RESULTS-Rag2−/− /Il2rg −/− dams had normal SA flow velocities, greatly elevated uterine artery flow velocities between gd10-16 and smaller areas of placental flow from gd14 to term than controls. Maternal heart weight and output increased transiently.

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“…STUDY DESIGN-Micro-ultrasound analyses were conducted on virgin, gestation day (gd) 2,4,7,9,10,12,14,16,18 and postpartum BALB/c (WT) mice and BALB/c-Rag2 −/− /Il2rg −/− mice, an immunodeficient strain lacking SA remodeling.…”

Approaching the Threshold for Predicting Preeclampsia

“…In the following years, additional progress has been made with respect to our understanding of the mechanisms underlying the role of antiangiogenic factors in the pathophysiology of preeclampsia. [2][3][4][5][6] Viewed in concert, these studies have clearly established the importance of angiogenic balance in the maintenance of cardiovascular function in normal pregnancy.Despite marked progress toward these ends, the translation of these findings into clinically useful paradigms has moved at a much slower pace. In lieu of the development of novel treatments for preeclampsia, much current attention has been paid to determining the usefulness of these biomarkers for identification of patients who will go on to develop preeclampsia.…”

“…[1][2][3][4] Elegant translational studies reported by Maynard et al 3 and Venkatesha et al 4 from the Karumanchi laboratory clearly demonstrated that the antiangiogenic factors soluble Fms-like tyrosine kinase 1 (sFlt-1; a vascular endothelial growth factor antagonist) and soluble endoglin (a transforming growth factor-␤ antagonist) play important roles in the pathophysiology of preeclampsia. In the following years, additional progress has been made with respect to our understanding of the mechanisms underlying the role of antiangiogenic factors in the pathophysiology of preeclampsia.…”