Project 5 - Cardiovascular Systems Area

微血管稀疏，由微血管的解剖学损失定义，是 高血压。因为血管的丧失伴随着高血压治疗，目的是 逆转稀疏化是治疗这种疾病的候选方法。然而，这样的发展 治疗需要了解网络模式和 衰老过程中的微血管阻力与分子成员的识别 对受损的网络增长负责。PI的最新数据表明，在 成年自发性高血压大鼠动脉/静脉吻合增加，表明 稀疏化比血管损失要复杂得多。我们还观察到血管周围细胞减少 神经胶质抗原2(NG2)的表达与硫酸软骨素蛋白多糖的功能关系 血管生成。NG2是内皮细胞增殖和迁移的正向调节因子，并直接 会影响当前的船只数量。我们的观察表明了一种新的分子机制 高血压时微血管疏松。我们假设NG2的表达减少在 高血压微血管网络导致结构模式改变，导致抬高 微血管阻力。为了验证这一假设，我们将使用以下具体目标 自发性高血压大鼠模型： 目的1：确定微血管网络结构和NG2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NG2抑制足以改变微血管网络结构。 目的3：使用计算模型来定量确定高血压改变的影响 微血管网络结构对微血管网络阻力的影响。 这项工作的结果将为研究微血管之间的关系提供新的方向 高血压时血管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.