| First Author | Lai Z | Year | 2011 |
| Journal | Hypertension | Volume | 57 |
| Issue | 3 | Pages | 505-14 |
| PubMed ID | 21263114 | Mgi Jnum | J:280634 |
| Mgi Id | MGI:6368946 | Doi | 10.1161/HYPERTENSIONAHA.110.163329 |
| Citation | Lai Z, et al. (2011) A critical role of interleukin-10 in modulating hypoxia-induced preeclampsia-like disease in mice. Hypertension 57(3):505-14 |
| abstractText | Hypoxia has been implicated in the pathogenesis of preeclampsia, a hypertensive disorder of pregnancy. However, in vivo evidence and mechanistic understanding remain elusive. Preeclampsia is associated with impaired placental angiogenesis. We have recently shown that interleukin (IL)-10 can support trophoblast-driven endovascular crosstalk. Accordingly, we hypothesize that pathological levels of oxygen coupled with IL-10 deficiency induce severe preeclampsia-like features coupled with elevated production of antiangiogenic factors, apoptotic pathways, and placental injury. Exposure of pregnant wild-type and IL-10(-/-) mice to 9.5% oxygen resulted in graded placental injury and systemic symptoms of renal pathology, proteinuria (wild-type 645.15 +/- 115.73 versus 198.09 +/- 93.45; IL-10(-/-) 819.31 +/- 127.85 versus 221.45 +/- 82.73 mug/mg/24 hours) and hypertension (wild-type 118.37 +/- 14.45 versus 78.67 +/- 14.07; IL-10(-/-) 136.03 +/- 22.59 versus 83.97 +/- 18.25 mm Hg). Recombinant IL-10 reversed hypoxia-induced features in pregnant IL-10(-/-) mice confirming the protective role of IL-10 in preeclampsia. Hypoxic exposure caused marked elevation of soluble fms-like tyrosine kinase 1 (110.8 +/- 20.1 versus 44.7 +/- 11.9 ng/mL) in IL-10(-/-) mice compared with their wild-type counterparts (81.6 +/- 13.1 versus 41.2 +/- 8.9 ng/mL), whereas soluble endoglin was induced to similar levels in both strains (approximately 380 +/- 50 versus 180 +/- 31 ng/mL). Hypoxia-induced elevation of p53 was associated with marked induction of proapoptotic protein Bax, downregulation of Bcl-2, and trophoblast-specific apoptosis in utero-placental tissue. Collectively, we conclude that severe preeclampsia pathology could be triggered under certain threshold oxygen levels coupled with intrinsic IL-10 deficiency, which lead to excessive activation of antiangiogenic and apoptotic pathways. |
