Glycocalyx in Pregnancy and the Preeclampsia Syndrome

妊娠期糖萼和先兆子痫综合征

• 批准号: 9034793
• 负责人: ROBIN E GANDLEY
• 金额: $ 22.62万
• 依托单位: MAGEE-WOMEN'S RES INST AND FOUNDATION
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-12-11 至 2017-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9034793
• 关键词: Adhesions; Affect; Age; Apical; Archives; Atherosclerosis; Attenuated; Bacteria; Binding Proteins; Biological Availability; Blood; Blood Circulation; Blood Platelets; Blood Pressure; Blood Vessels; Cell surface; Cells; Charge; Chorionic villi; Coagulation Process; Complex; Computer software; Diabetes Mellitus; Diagnosis; Dimensions; Disease; Endothelial Cells; Enzymes; Epithelial Cells; Erythrocytes; Exposure to; Fatty acid glycerol esters; Free Radicals; Functional disorder; Glycocalyx; Glycolipids; Glycoproteins; Goals; Health; Heparin; Human; Hypertension; Image; Inflammation; Inflammatory; Injury; Inorganic Sulfates; Ischemia; Leukocytes; Life; Lipids; Lipoproteins; Liver; Measures; Microcirculation; Mothers; Nitric Oxide; Nitrogen; Operative Surgical Procedures; Organ; Osmotic Pressure; Oxidative Stress; Oxygen; Pathway interactions; Patients; Phenotype; Placenta; Polysaccharides; Postpartum Period; Pre-Eclampsia; Pregnancy; Pregnant Women; Prevention; Process; Production; Proteins; Proteinuria; Proteoglycan; Recruitment Activity; Reperfusion Injury; Research; Risk; Role; Sampling; Sepsis; Severities; Side; Site; Stream; Surface; Syncytiotrophoblast; Syndrome; System; Technology; Therapeutic; Thick; Tissues; Transducers; Trauma; Umbilical cord structure; Umbilical vein; Unspecified or Sulfate Ion Sulfates; Urine; Vascular Endothelial Cell; Vascular Endothelium; Woman; cell type; fetal; heparanase; in vivo; lipid transport; novel; oxidative damage; pathophysiology of preeclampsia; pregnancy disorder; pregnancy hypertension; prevent; public health relevance; repository; response; stressor; subcutaneous; therapeutic target

 DESCRIPTION (provided by applicant): The glycocalyx is a negatively charged, complex meshwork of glycoproteins, glycolipids produced by cells, along with associated proteins bound primarily to heparin sulfate side-chains of proteoglycans. Endothelial and epithelial cells produce distinct apical cell surface glycocalyx, which have significant functional roles for both cell type. The endothelial glycocalyx acts as a mechano-shear transducer for nitric oxide release, attenuates inflammatory cell and platelet adhesion, and regulates vascular osmotic pressure gradients, and lipid transport. The pregnancy disorder preeclampsia (PE) has been shown to encompass dysfunction within these inter-related systems that can be influenced by gycocalyx integrity. We propose that glycocalyx disruption and shedding, within the syncytiotrophoblasts (epithelial cells of the placental villi), and maternal vascular endothelium is present and contributory to in a "final common pathway" to preeclampsia. In the current proposal we hypothesize that disruption and loss glycocalyx components accompanies preeclampsia. We will utilize newly developed noninvasive technologies of side-stream darkfield (SDF) imaging couple with Glycocheck software to quantify glycocalyx dimensions in the sublingual microcirculation of pregnant women and post-partum (Aim 1). We will determine if this imaging measure of glycocalyx is representative of ex vivo assessments of glycocalyx in the maternal vasculature (subcutaneous fat), placental syncytiotrophoblasts, vessels in the placental villi and umbilical vein (Aim 2) and if components of shed glycocalyx in the circulation or urine of pregnant women change with preeclampsia (Aim 2). Lastly, we will determine if reduced glycocalyx depth or other measures of shed or disrupted glycocalyx correlate with increased severity of preeclampsia or specific criteria of severity (Aim 3). If disruption of the maternal endothelial glycocalyx is demonstrated both in vivo using non-invasive side-stream darkfield imaging and ex vivo and a relationship to severity of PE is established, in subsequent studies we would plan to examine: the longitudinal progression of glycocalyx disruption, the implications of glycocalyx disruption to placental and vascular function, and potential therapeutic strategies targeting the glycocalyx. The ultimate goal of this research is to develop therapeutic strategies to prevent PE.

 描述（由申请人提供）：糖萼是一种带负电荷的复杂网络，由细胞产生的糖蛋白、糖脂以及主要与内皮细胞和上皮细胞产生的硫酸肝素侧链结合的相关蛋白质组成。 不同的顶端细胞表面糖萼，对两种细胞类型都有重要的功能作用内皮糖萼充当​​一氧化氮释放的机械剪切传感器，减弱炎症细胞和血小板粘附，并调节血管渗透压梯度和脂质运输。子痫前期 (PE) 已被证明涵盖这些相互关联的系统内的功能障碍，这些系统可能受到 gycocalyx 的影响我们认为，合体滋养层（胎盘绒毛上皮细胞）和母体血管内皮细胞中的糖萼破坏和脱落是导致先兆子痫的“最终共同途径”的原因。我们将利用新开发的侧流暗场 (SDF) 成像非侵入性技术。 Glycocheck 软件可量化孕妇和产后舌下微循环中的糖萼尺寸（目标 1），我们将确定糖萼的成像测量是否代表母体脉管系统（皮下脂肪）、胎盘合体滋养层中糖萼的离体评估。 ，胎盘绒毛和脐静脉中的血管（目标 2）以及如果脱落的糖萼成分孕妇的循环或尿液随着先兆子痫而改变（目标 2），最后，我们将确定糖萼深度的减少或糖萼脱落或破坏的其他测量是否与先兆子痫的严重程度增加或严重程度的破坏相关（目标 3）。使用非侵入性侧流暗视野成像在体内和体外均证明了母体内皮糖萼，并建立了与 PE 严重程度的关系，在后续研究中，我们计划研究：糖萼破坏的纵向进展、糖萼破坏对胎盘和血管功能的影响以及针对糖萼的潜在治疗策略本研究的最终目标是开发预防PE的治疗策略。