VENOARTERIAL SIGNALING IN THE UTERINE CIRCULATION

描述（来自应用程序的逐字描述）：静脉动脉转移提供了 胎盘中的血管活性和生长促进因子 污水可能会影响附近的行为和结构， 子宫动脉本项目旨在探索这一概念， 围绕四个具体目标构建，将建立生物物理学（AIM 1)和生理（AIM 2）特性的静脉动脉转移，确定如何 这一过程在怀孕期间改变（AIM 3），并评估 三个特定的分子信号（雌激素，孕激素，VEGF）在其 调控实验将使用一种新的体外系统进行， 子宫动脉和静脉的成对的相邻节段被插管 并使用荧光示踪分子进行研究（以确定渗透性）， 通过直接观察静脉内血管活性化合物对 动脉直径的条件下，其中的物理和化学 环境被精细地控制（信号传递）。工作假设是 在每个目标下列出，包括以下内容：AIM 1：（1）血管活性 静脉腔内的物质能够施加显著的， 对管腔直径的双向（收缩、扩张）调节作用 子宫动脉破裂(2)特定化合物的生物利用度 主要取决于其浓度、分子量和静脉 透壁压(3)跨壁压的影响是成比例的 并且与周向壁张力有关。目的2：（4）钙和 磷脂酶C-蛋白激酶C系统是静脉血中重要调节剂， 通过其对内皮肌动蛋白：肌球蛋白相互作用的作用来渗透。 目的3：（5）妊娠改变了细胞的结构和功能特性， 静脉内皮以增强血管活性物质的静脉动脉转移的方式 和促有丝分裂刺激。目的4：（6）雌激素、孕激素和VEGF在乳腺癌发病中起重要作用 静脉动脉转移的分子决定因素。(7)渗透性增强 VEGF的作用部分是通过刺激一氧化氮而实现的 静脉内皮分泌物。初步数据，以支持每个 假设在本申请的文本中提供。这些研究将 提供了新的，定量的信息机制， 信号和妊娠调节静脉渗透性和内信号传递 子宫循环

DESCRIPTION (Verbatim from the application): Venoarterial transfer offers a pathway through which vasoactive and growth-promoting factors in the placental effluent can potentially influence the behavior and structure of adjacent uterine arteries. This project is designed to explore this concept, and is structured around four Specific Aims that will establish the biophysical (AIM 1) and physiological (AIM 2) properties of venoarterial transfer, determine how this process is altered during pregnancy (AIM 3), and evaluate the role of three specific molecular signals (estrogen, progesterone, VEGF) in its regulation. Experiments will be carried out using a novel in vitro system in which paired, adjacent segments of uterine arteries and veins are cannulated and studied using fluorescent tracer molecules (to determine permeability) and by directly observing the effects of intravenous vasoactive compounds on arterial diameter under conditions in which the physical and chemical environment is finely controlled (signal transfer). Working hypotheses are presented under each aim and include the following: AIM 1: (1) Vasoactive substances within the venous lumen are capable of exerting a significant, bi-directional (contraction, dilation) modulatory effect on the lumen diameter of an adjacent uterine artery. (2) The bioavailability of a particular compound is primarily dependent on its concentration, molecular weight and venous transmural pressure. (3) The effects of transmural pressure are proportional and related to circumferential wall tension. AIM 2: (4) Calcium and the phospholipase C-protein kinase C system are important modulators of venous permeability through their actions on endothelial actin:myosin interactions. AIM 3: (5) Pregnancy alters the structure and functional properties of the venous endothelium in a way that augments venoarterial transfer of vasoactive and mitogenic stimuli. AIM 4: (6) Estrogen, progesterone and VEGF are important molecular determinants of venoarterial transfer. (7) The permeability-enhancing effects of VEGF are partly effected through its stimulation of nitric oxide secretion from the venous endothelium. Preliminary data to support each hypothesis are provided in the text of this application. These studies will provide new, quantitative information on the mechanisms by which molecular signals and pregnancy modulate venous permeability and signal transfer within the uterine circulation.