Abstract TAC264: Perivascular Adipose Tissue Modulates Uterine Artery Reactivity in The Late-Gestation Preeclamptic-Like BPH/5 Mouse

Perivascular adipose tissue (PVAT) surrounds most blood vessels and plays a key role in vascular homeostasis. Likewise, PVAT surrounding the uterine arteries seems to modulate vascular adaptations to increased blood flow demands in healthy pregnancies. Preeclampsia (PE), a leading hypertensive disorder of pregnancy, is marked by poor uteroplacental perfusion, fetal compromise, and maternal endothelial dysfunction. Although poor vascular remodeling and increased uterine artery resistance are common PE features, the role of uterine artery PVAT in this condition remains unknown. The BPH/5 mouse model spontaneously exhibits PE-like features, including gestational hypertension, poor placental perfusion, proteinuria, and fetal demise. We aimed to elucidate the role of uterine artery PVAT in PE-like BPH/5 pregnancies. We hypothesized that PVAT modulation of uterine artery responses was impaired in late-gestation BPH/5 females. Adult (8–12 weeks old) BPN/3 and BPH/5 females underwent strain-matched timed mating and the day of copulation was designated embryonic day (e) 0.5. At e18.5, BPH/5 and BPN/3 uterine arteries were dissected, cut into 2 mm rings with either PVAT intact (PVAT+) or removed (PVAT-), and mounted on a DMT 620M myograph for ex vivo vascular reactivity assays (n=4-7/group). Concentration-response curves were generated for the following agonists: KCl (1–80 mM), angiotensin II (10 pM– 30 nM), phenylephrine (1 nM–30 µM), and acetylcholine (1 nM–3 µM). Response area under the curves (AUC) and agonist half maximal effective concentrations (EC50) were compared using Two-way ANOVA and Tukey’s multiple comparisons tests (GraphPad Prism 10.3.1). PVAT- BPH/5 uterine arteries showed increased contractile responses and sensitivity to angiotensin II and KCl compared to PVAT- uterine arteries from normotensive BPN/3 mice (p<0.05, Fig. 1 - 2). PVAT did not have a significant effect on BPN/3 uterine artery reactivity (p>0.05). Conversely, in BPH/5 mice, PVAT attenuated vasoconstrictor responses to angiotensin II, reflected by a significant PVAT × strain interaction: AUC (p = 0.0104); –logEC50 (p=0.0127). Acetylcholine-induced relaxation was diminished in PVAT+ BPH/5 arteries relative to controls (p<0.001, Fig. 3), consistent with endothelial dysfunction observed in PE. In summary, uterine artery PVAT seems to exert an important compensatory role during late gestation in PE-like pregnancies, reducing vascular tone under conditions of increased vasoconstriction.