Abstract P136: First Steps In Uncovering Mechanisms In Late Onset Preeclampsia

Abstract

Preeclampsia is a leading cause of maternal morbidity and mortality worldwide, complicating 2-8% of pregnancies. The etiology of PE is poorly understood, the role of placental extracellular matrix (pECM) in PE is understudied. Extravillous trophoblasts (HTR8/svneo) and pECM are crucial in placental blood vessel formation, including spiral arteries. The objective is to identify changes in signaling mechanisms in late onset PE and how HTR8/svneo respond. Additionally, we explored a novel therapeutic to restore HTR8/svneo phenotype by phototherapy using a 670nm LED light. Western blot analysis shows eNOS, phospho-eNOS and Hsp90 expressions are unchanged in late onset PE placental samples despite previous reports in early onset of PE. The association of Hsp90 to eNOS and eNOS to phospho-eNOS is reduced in the PE sample. Soluble Flt, a diagnostic marker for PE, levels are increased in media from HTR8/svneo trophoblasts cultured on PE pECM. Endothelial function is significantly reduced in an isolated vessel as determined by acetylcholine stimulation. 670nm light reverses this impairment. Migration of HTR8/SVneo on PE pECM is reduced (control 86.29±18.58, PE 30.16±15.49) but proliferation of HTR8/SVneo on PE pECM is unaffected in patients (control: 59.125±6262.9, PE:67.125±7706.5). Proliferation and migration are improved by 670nm light (proliferation control 101.375±2075.4; PE 106.875±4870.7, migration control 125±11.97, PE 144.84±16.01). An increase of apoptotic HTR8/SVneo cultured on PE pECM is observed compared to healthy pECM in patients control 2.4±0.24, PE 3±0.4 samples. 670nm light treatment decreases the number of apoptotic cells, control 1.2 ±0.58, PE 1.4±0.5. Conclusion: In late onset preeclampsia, endothelial function is decreased, sFlt release is increased, the eNOS/Hsp90/p-eNOS axis is slightly reduced pointing to O 2 - synthesis. Migration is decreased likely due to impaired trophoblast invasion, but proliferation is unaffected. 670nm light treatment can reverse some of the effects of the preeclamptic microenvironment. Extracellular matrix is altered in late onset PE leading to an abnormal HTR8/SVneo phenotype. 670nm light restores the phenotype of HTR8/SVneo on PE pECM suggesting 670nm light as a therapeutic treatment.