Clinical Project

Glycocalyx pathways linking pregnancy profile with microvascular dysfunction postpartum

CarlHubelPI: Carl A. Hubel, PhD
Center Director
Associate Professor
Magee-Womens Research Institute and Foundation
Department of Medicine


Epidemiologic evidence indicates that women with adverse pregnancy outcomesincluding preeclampsia (PE), preterm birth (PTB) and fetal growth restriction (FGR) are at increased risk of later-life cardiovascular disease (CVD). Our Center program studies cardio-metabolic responses to the stress of pregnancy provides insight on later CVD risk, and also on pathophysiological mechanisms, risk stratification, and early therapeutic targets. In this clinical project we focus on the glycocalyx (GC), a glycoprotein-polysaccharide matrix on the luminal surface of endothelial cells. The GC is critical for vascular homeostasis. GC damage/dysfunction contributes to CVD, and our data suggests it also contributes to the adverse maternal systemic vascular, renal and cardiac changes of PE.

We hypothesize that GC damage during pregnancy will more generally (both within and independent of adverse pregnancy outcomes) identify women prone to GC damage post pregnancy, and that GC derangements will be mechanistically linked to lasting microvascular dysfunction and related indicators of later-life CVD risk. We are evaluating four groups of women according to pregnancy outcome, 1) PE, 2) PTB, 3) FGR and 4) uncomplicated pregnancy controls, both during pregnancy (after diagnosis) and at 1 year postpartum. Aim 1 tests whether between-group differences in microvascular GC red blood cell exclusion capacity and related measures of GC damage are greater (more distinguishing; amplified) during pregnancy compared to post pregnancy. Further, we test if the abnormal outcome groups that did not manifest a pregnancy hypertensive syndrome (PTB, FGR) evidence adverse GC profiles intermediate between PE and controls, both during and after pregnancy.

Aim 1 also asks whether the GC abnormalities correlate with placental vascular lesions, the latter proposed in Project 1 to be more sensitive and inclusive indicators of later-life CVD than abnormal pregnancy outcomes. In Aim 2 we determine whether GC abnormalities are linked to microvascular endothelium-dependent vasodilatory dysfunction, increased vascular stiffness, and cardiac dysfunction post pregnancy. Aim 3 explores the role of candidate circulating lipid and inflammatory factors as mediators of GC and microvascular dysfunction. Given evidence that GC damage/dysfunctiona cause and early warning signal of CVDis treatable, this longitudinal study could lead to early, targeted therapies for CVD risk reduction.

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