Angiotensin II and angiotensin-(1-7) decrease sFlt1 release in normal but not preeclamptic chorionic villi: an in vitro study

<p>Abstract</p> <p>Background</p> <p>During preeclampsia, placental angiogenesis is impaired. Factors released from the placenta including vascular endothelial growth factor (VEGF), placental growth factor (PLGF), soluble VEGF receptor 1 (sFlt1), and soluble endoglin (sEng) are regulatory molecules of placental development and function. While the renin angiotensin system has been shown to regulate angiogenic factors in other research fields, these mechanisms have not been extensively studied during pregnancy.</p> <p>Methods</p> <p>We evaluated the effects of angiotensin II (Ang II) and angiotensin-(1-7) [Ang-(1-7)] on the release of VEGF, PLGF, sFlt1, and sEng from placental chorionic villi (CV). CV were collected from nulliparous third-trimester normotensive and preeclamptic subjects. CV were incubated for 0, 2, 4, and 16 hours with or without Ang II (1 nM and 1 microM) or Ang-(1-7) (1 nM and 1 microM). The release of VEGF, PLGF, sFlt1, sEng, lactate dehydrogenase (LDH), and human placenta lactogen (HPL) was measured by ELISA.</p> <p>Results</p> <p>The release of sFlt1, PLGF, sEng from normal and preeclamptic CV increased over time. Release of sFlt1 and sEng was significantly higher from preeclamptic CV. VEGF was below the detectable level of the assay in normal and preeclamptic CV. After 2 hours, sFlt1 release from normal CV was significantly inhibited with Ang II (1 nM and 1 microM) and Ang-(1-7) (1 nM and 1 microM). There was a time-dependent increase in HPL indicating that the CV were functioning normally.</p> <p>Conclusions</p> <p>Our study demonstrates a critical inhibitory role of angiotensin peptides on sFlt1 in normal pregnancy. Loss of this regulation in preeclampsia may allow sFlt1 to increase resulting in anti-angiogenesis and end organ damage in the mother.</p

Perceptions of Wildfire and Landscape Change in the Kenai Peninsula, Alaska

Despite a broad literature addressing the human dimensions of wildfire, current approaches often compartmentalize results according to disciplinary boundaries. Further, relatively few studies have focused on the public’s evolving perceptions of wildfire as communities change over time. This paper responds to these gaps by exploring perceptions of landscape dynamics and wildfire between 2003 and 2007 using a typological framework of intersecting ecological, social, and cultural processes. Designed as a restudy, and using key informant interviews, this research allowed us to observe risk perception as they are related to community challenges and opportunities in the Kenai Peninsula, Alaska. Risk perceptions were examined as an integral part of community and landscape change. Wildfire was a concern among informants in 2003 and remained a concern in 2007, although informants were less likely to discuss it as a major threat compared to the original study. Informants in the western part of the peninsula tended to express more concern about wildfire than their eastern counterparts largely due to their experiences with recent fires. Other important factors residents considered included changing forest fuels, the expanding wildland urban interface, and contrasting values of new residents. Underscoring the localized nature of risk perceptions, informants had difficulty describing the probability of a wildfire event in a geographical context broader than the community scale. This paper demonstrates how a holistic approach can help wildfire and natural resource professionals, community members, and other stakeholders understand the social and physical complexities influencing collective actions or inactions to address the threat of wildfire

The Uterine Placental Bed Renin-Angiotensin System in Normal and Preeclamptic Pregnancy

Previously, we demonstrated activation of the renin-angiotensin system in the fetal placental chorionic villi, but it is unknown whether the immediately adjacent area of the maternal uterine placental bed is regulated similarly. This study measured angiotensin peptides, renin-angiotensin system component mRNAs, and receptor binding in the fundus from nonpregnant subjects (n = 19) and in the uterine placental bed from normal (n = 20) and preeclamptic (n = 14) subjects. In the uterine placental bed from normal pregnant women, angiotensin II peptide levels and angiotensinogen, angiotensin-converting enzyme, angiotensin receptor type 1 (AT1), AT2, and Mas mRNA expression were lower as compared with the nonpregnant subjects. In preeclamptic uterine placental bed, angiotensin II peptide levels and renin and angiotensin-converting enzyme mRNA expression were significantly higher than normal pregnant subjects. The AT2 receptor was the predominant receptor subtype in the nonpregnant fundus, whereas all angiotensin receptor binding was undetectable in normal and preeclamptic pregnant uterine placental bed compared with nonpregnant fundus. These findings suggest that the maternal uterine placental bed may play an endocrine role by producing angiotensin II, which acts in the adjacent placenta to vasoconstrict fetal chorionic villi vessels where we have shown previously that AT1 receptors predominate. This would lead to decreased maternal-fetal oxygen exchange and fetal nutrition, a known characteristic of preeclampsia