Creating the Phenotype of Preeclamptic Endothelial Dysfunction in Placental Vessels
Authors: De La Pena Rosinda , Kozak Kaleigh , Gutterman David , Sigmund Curt , McIntosh Jennifer 
Published: May 2023

Objective: To determine if placental vessel endothelial dysfunction can be produced in control vessels by exposure to preeclamptic plasma, establishing a model to further explore the mechanisms of dysfunction and therapeutics to restore function in preeclampsia. Hypothesis: Preeclamptic plasma administered to unaffected vessels induces endothelial dysfunction. Methods: Placental microvessels were dissected from the maternal side of placentas from patients consented to the Medical College of Wisconsin Maternal Research Placenta and Cord Blood Bank. Control vessels were treated with 10% healthy maternal plasma or 10% preeclamptic (PreE) maternal plasma within the vessel lumen for 12-16 hours[MJ1]. PreE vessels were not treated with plasma. Microvessels were then cannulated on glass micropipettes, pressurized to 60mmHg and constricted with 0.1-1.0 nM Endothelin-1 (ET-1). A 1-100cm H2O pressure gradient was applied and the inner diameter of the vessel was measured by video microscopy. The change in diameter was calculated as a % of maximum diameter as assessed by exposure to 100μM papaverine. Flow mediated dilation (FMD) was evaluated by a two-way ANOVA test with Dunnett’s multiple comparisons. The maximum dilation values were evaluated by a Kruskal-Wallis test with Dunn’s multiple comparative test or t-test as appropriate. FMD is evaluated as mean +/- SEM. Data: Control vessels at maximum flow dilated to 81.1 % ± 7.1 % (n=5), whereas vessel from PreE placentas dilated to 36.9 % ± 8.6% (n=3,). Incubation of control vessels with normal plasma resulted in maximal dilation of 80.6% ± 3.3%, n=3. Control vessels incubated with plasma from PreE patients dilated to 44.7% ± 4.7%. n=3). Summary of Results: Control vessels dilated significantly more than PreE vessels when evaluated by t-test (p=0.05). Incubation of control vessels with normal plasma did not change maximal dilation (p>0.99). Control vessels incubated with PreE plasma demonstrated a near significant drop in dilatory capacity (p=0.05). PreE plasma exposed vessels compared to untreated PreE vessels showed no significant difference (p=0.46[DDG2] ).When comparing overall flow mediated dilatory responses in these vessels there is a significant difference observed between control vessels, control vessels treated with PreE plasma, and PreE vessels at 50cm H2O (p<0.05). This difference is even more significant (p<0.01) at the maximum pressure gradient when analyzed by two-way ANOVA. There is no significant difference at any point between control vessels and control vessels treated with normal plasma as evaluated by two-way ANOVA (p>0.99). Conclusions: The addition of PreE plasma to control vessels demonstrates similar impairment in endothelium-dependent vasodilation as seen in untreated PreE vessels. Future directions will include evaluation of the mechanisms of vasodilation and therapeutic options that could restore endothelial function in PreE vessels.

NHLBI 1K08HL150340-01

This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.