MOLECULAR MECHANISMS ASSOCIATED WITH CARDIOVASCULAR AGING

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 随着年龄的增长，心血管系统（心脏和血管）会发生一些不利的变化。 例如，血管应该响应于不同的刺激（例如血压升高）而扩张或收缩，以防止血压的剧烈变化。 年龄的增长通常与血管扩张能力的受损有关。 这种损害部分是由于体内氧化应激水平的增加。 氧化应激是身体细胞暴露于分子（即。活性氧类），其作为正常代谢的功能在体内连续产生。 活性氧会对细胞产生损伤，干扰人体的正常功能，如血管扩张的能力。 此外，血管功能受各种蛋白质（由血管壁细胞（称为内皮细胞）产生的分子）的影响，这些蛋白质与活性氧的破坏以及血管的扩张和收缩有关。 重要的是，我们知道定期有氧运动与改善血管功能以及减少氧化应激有关。 因此，拟议的研究将检验这一假设，即随着年龄的增长，血管功能的不利变化可归因于血管壁中蛋白质表达的变化。 此外，定期有氧训练可以通过有益地改变内皮细胞蛋白质表达来预防血管功能中与年龄相关的损伤。 为了检验这一假设，将从健康成年人的血管中收集内皮细胞，并使用免疫荧光染色以确定各种感兴趣的蛋白质的表达。 将在一个广泛的年龄范围内比较久坐和接受过耐力训练的成年人中感兴趣的蛋白质的表达，并将其与血管功能的测量进行比较。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A number of adverse changes occur to the cardiovascular system (heart and blood vessels) with advancing age. For example, blood vessels should dilate or contract in response to different stimuli, such as increased blood pressure, to prevent drastic changes in blood pressure. Advancing age is generally associated with an impairment in the blood vessel's ability to dilate. This impairment is due in part to an increase in oxidative stress levels in the body. Oxidative stress is the exposure of the body's cells to molecules (ie. reactive oxygen species) that are generated continuously in the body as a function of normal metabolism. Reactive oxygen species can produce damage to cells and interfere with the body's normal function, such as the ability of blood vessels to dilate. Additionally, blood vessel function is affected by various proteins (molecules produced from cells that line your blood vessel wall called endothelial cells) that are associated with the destruction of reactive oxygen species as well as the dilation and constriction of a vessel. Importantly, we know that regular aerobic exercise is associated with improved vascular function as well as reduced oxidative stress. Accordingly, the proposed research will test the hypothesis that the adverse changes in vascular function with aging can be attributed to changes in the expression of proteins in the vessel wall. Furthermore, regular aerobic training may prevent the age-related impairments in vascular function by beneficially altering endothelial cell protein expression. To test this hypothesis, endothelial cells will be collected from the blood vessels of healthy adult humans and stained using immunofluroescence to determine the expression of various proteins of interest. The expression of the proteins of interest will be compared in sedentary and endurance-trained adults across a wide age range and will be compared to measures of vascular function.