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Abstract: TH-PO745

Mechanisms of Vascular Dysfunction in the Interleukin-10-Deficient Murine Model of Preeclampsia

Session Information

Category: Women’s Health and Kidney Diseases

  • 2000 Women’s Health and Kidney Diseases

Authors

  • Cubro, Hajrunisa, Mayo Clinic, Rochester, Minnesota, United States
  • Nath, Karl A., Mayo Clinic, Rochester, Minnesota, United States
  • Suvakov, Sonja, Mayo Clinic, Rochester, Minnesota, United States
  • Garcia Valencia, Oscar Alejandro, Mayo Clinic, Rochester, Minnesota, United States
  • Parashuram, Santosh, Mayo Clinic, Rochester, Minnesota, United States
  • White, Wendy, Mayo Clinic, Rochester, Minnesota, United States
  • Weissgerber, Tracey L., Mayo Clinic, Rochester, Minnesota, United States
  • Nath, Meryl C., University of Alabama at Birmingham, Rochester, Minnesota, United States
  • Milic, Natasa, Medical Faculty University of Belgrade, Belgrade, Serbia, Serbia
  • Sontag, Fernando, Mayo Clinic, Rochester, Minnesota, United States
  • d'Uscio, Livius V., Mayo Clinic, Rochester, Minnesota, United States
  • Kirkland, James L., Mayo Clinic, Rochester, Minnesota, United States
  • Tchkonia, Tamara, Mayo Clinic, Rochester, Minnesota, United States
  • Katusic, Zvonimir S., Mayo Clinic, Rochester, Minnesota, United States
  • Grande, Joseph P., Mayo Foundation for Medical Research, Rochester, Minnesota, United States
  • Garovic, Vesna D., Mayo Clinic, Rochester, Minnesota, United States
Background

Preeclampsia (PE) is characterized by new-onset hypertension, proteinuria, endothelial dysfunction, and both macrovascular and microvascular injury in the second half of pregnancy. Based on observations that PE is associated with derangements in IL-10 signaling, we sought to test the hypothesis that endothelium-dependent vascular dysfunction is exacerbated in a murine model of PE based on the administration of human PE sera to interleukin (IL)-10-/- mice.

Methods

Pregnant wild type (WT) and IL-10-/- mice were injected with either normotensive (NT) or severe preeclamptic (sPE) patient sera on the 10th day of gestation. Blood pressure was measured at the beginning of pregnancy and before sacrifice on the 17th day of gestation. Vasomotor function of isolated aortas, albuminuria, and aortic gene expression were assessed.

Results

Pregnant IL-10-/- mice injected with sPE sera exhibited higher blood pressure (P = 0.002) and albuminuria (P = 0.0066) compared to controls. Contractions of the isolated aortas to phenylephrine were significantly augmented in the IL-10-/- mice injected with sPE sera compared to the pregnant controls (P < 0.001). This group also demonstrated impaired endothelium-dependent relaxation to acetylcholine compared to controls (P = 0.002). Treatment of isolated aortas with indomethacin normalized vascular reactivity of aortas derived from pregnant IL-10-/- mice injected with sPE sera (contraction: P = 0.009; relaxation to acetylcholine: P < 0.001).

Conclusion

In aggregate, this murine IL-10-/- PE model exhibits significant pregnancy-specific macrovascular dysfunction caused by enhanced contraction to phenylephrine and impaired endothelium-dependent relaxation. Observed alterations in vasomotor function are predominantly caused by enhanced activation of the cyclooxygenase pathway.

Funding

  • NIDDK Support