VENOARTERIAL SIGNALING IN THE UTERINE CIRCULATION

描述(来自应用程序的逐字)：静脉动脉转移提供 血管活性和促生长因子在胎盘中的作用途径 污水可能会潜在地影响邻近地区的行为和结构 子宫动脉。该项目旨在探索这一概念，并 围绕将建立生物物理(AIM)的四个特定目标构建 1)和生理(AIM 2)性质的静脉-动脉转移，决定如何 这一过程在怀孕期间被改变(目标3)，并评估 ITS中的三个特异性分子信号(雌激素、孕激素、血管内皮生长因子) 监管。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相邻节段被插管 并使用荧光示踪剂分子(以确定渗透性)和 通过直接观察静脉注射血管活性物质对血管紧张素转换酶的影响 动脉直径在物理和化学条件下 环境控制得很好(信号传输)。工作假说是 在每个目标下提出，包括以下内容：目标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 毗邻的子宫动脉。(2)特定化合物的生物利用度 主要取决于其浓度、相对分子质量和静脉 跨壁压力。(3)跨壁压力的影响是成比例的。 并与周向壁张力有关。目标2：(4)钙和 磷脂酶C-蛋白激酶C系统是重要的静脉调节因子 通过它们对内皮肌动蛋白作用的通透性：肌球蛋白相互作用。 目的3：(5)怀孕改变大脑皮质的结构和功能 静脉内皮细胞促进血管活性物质的静脉-动脉传递 以及有丝分裂刺激。目的4：(6)雌激素、孕激素和血管内皮生长因子 静脉-动脉转移的分子决定因素。(7)通透性增强 血管内皮生长因子的作用部分是通过其刺激一氧化氮来实现的 静脉内皮细胞分泌。初步数据支持每一项 本申请的正文中提供了假设。这些研究将 提供新的、定量的关于分子 信号和怀孕调节体内静脉通透性和信号传递 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.