Oral or Poster Presentation
Concurrent Session 2B - Maternal Fetal Medicine
Introduction: Preeclampsia is a pregnancy-specific syndrome characterized by vascular dysfunction and increased circulating levels of oxidized LDL cholesterol (oxLDL). In vitro studies have shown that oxLDL-induced lectin-like oxLDL receptor-1 (LOX-1) activation leads to activation of the angiotensin II (AngII) type 1 receptor (AT1). Whether this LOX-1 and AT1 interaction associates with vascular dysfunction in preeclampsia is unknown. We hypothesized that oxLDL-mediated LOX-1 and AT1 activation contributes to vascular dysfunction in pregnancy.
Methods: Pregnant LOX-1 overexpressing (LOX-1OE) and wild type (WT) mice were fed a high-cholesterol (HC) diet or control diet between gestational day (GD) 13.5 and GD18 (term=GD19). Mice were euthanized at GD18 and pregnancy outcomes were recorded (n=5-8 each group). Ex vivo vascular function was assessed in aortas by wire myography. Vasoconstriction to AngII was evaluated in the presence or absence of oxLDL (50 µg/mL), LOX-1 blocking antibody (10 µg/mL) and/or candesartan (AT1 antagonist, 10 µM).
Results: HC diet during pregnancy decreased fetal weight in WT mice (0.97±0.09 vs 1.12±0.05 grams) but not in LOX-1OE mice, and did not change placental and maternal weight or food intake. Contrary to our hypothesis, the HC diet did not alter AngII responses (p>0.05). However, aligned with our hypothesis, the exposure to oxLDL enhanced AngII vasoconstriction in aortas from WT and LOX-1OE mice on control diet (Emax: 0.95±0.33 vs 2.17±0.5mN/mm and 0.33±0.11 vs 1.15±0.16mN/mm, respectively). This oxLDL-mediated AngII vasoconstriction was prevented by LOX-1 blocking antibody in aortas from WT mice on control diet (p<0.05). Finally, the exposure to candesartan completely inhibited AngII-induced vasoconstriction (p<0.05), but remarkably, the responsiveness to AngII was partially restored in the presence of oxLDL.
Conclusion: HC diet during pregnancy impaired fetal outcomes but did not contribute to vascular LOX-1 and AT1 interaction in this study. However, oxLDL-induced LOX-1 activation could increase AT1 activity during pregnancy, thereby contributing to vascular dysfunction.