Project 5 - Cardiovascular Systems Area

微血管稀疏，定义为微血管的解剖损失，是一个共同的特点， 高血压因为血管的损失伴随着血压升高， 逆转稀疏化代表疾病的候选治疗。然而，这种发展 治疗需要理解网络模式之间的功能关系， 微血管阻力随时间的老化和分子球员的鉴定 导致网络增长受阻。PI最近的数据表明， 成年自发性高血压大鼠动脉/静脉血栓增加，表明 稀疏化比仅仅损失血管更复杂。我们还观察到血管周围细胞减少 神经胶质细胞抗原2（NG 2）的表达，NG 2是一种硫酸软骨素蛋白聚糖，在功能上参与 血管生成NG 2是内皮细胞增殖和迁移的正性调节因子， 影响了现有船只的数量。我们的观察表明， 微血管稀疏。我们假设NG 2表达的减少与肿瘤的发生有关。 高血压微血管网络导致结构模式改变， 微血管阻力为了验证这个假设，我们将使用以下方法完成以下具体目标： 自发性高血压大鼠模型： 目的1：确定微血管网络结构和NG 2表达随时间的变化 自发性高血压大鼠的衰老过程。 目的2：确定NG 2抑制足以改变微血管网络结构。 目的3：使用计算模型定量确定改变的高血压 微血管网络结构对微血管网络阻力的影响。 本研究的结果将为微血管与肿瘤的关系研究提供新的方向。 结构和微血管阻力升高。

Microvascular rarefaction, defined by the anatomical loss of microvessels, is a common characteristic of hypertension. Because the loss of vessels accompanies elevated blood pressure therapies aimed at reversing rarefaction represent candidate treatments for the disease. However, the development of such therapies requires an understanding of the functional relationship between network patterns and microvascular resistance over the time course of aging and the identification of the molecular players responsible for the impaired network growth. Recent data by the PI suggests that microvascular networks in the adult spontaneously hypertensive rat have increased arterial/venous anastomoses indicating that rarefaction is more complex that just a loss of vessels. We also have observed reduced perivascular cell expression of Neuron-Glia Antigen 2 (NG2), a chondroitin sulfate proteoglycan functionally involved in angiogenesis. NG2 is a positive regulator of endothelial cell proliferation and migration and directly influences the number of vessels present. Our observations suggest a novel molecular meachanism for microvascular rarefaction during hypertension. We hypothesize that reduced NG2 expression in hypertensive microvascular networks results in altered architectural patterns leading to elevated microvascular resistance. In order to test this hypothesis, we will complete the following specific aims using the spontaneously hypertensive rat model: AIM 1: Determine the microvascular network architecture and NG2 expression alterations over the time course of aging in spontaneously hypertensive rats. AIM 2: Establish that NG2 inhibition is sufficient to alter microvascular network architectures. AIM 3: Use a computational model to quantitatively determine the effect of altered hypertensive microvascular network architectures on microvascular network resistance. The results from this work will set new directions for investigating the relationships between microvascular structure and elevated microvasuclar resistance in hypertension.