Multianalyte Assays for Cardiovascular Disease

描述（由申请人提供）： RAAS在降低死亡率的治疗中是靶向的。 然而，越来越多的证据表明，改善是独立的血压降低或血管紧张素II的变化。 事实上，激活的RAAS与细胞因子和其他炎症标志物之间的密切联系作为早期高血压、动脉粥样硬化和糖尿病的起始因素变得越来越明显。 因此，更好地了解整个RAAS以及更广泛的补充其他激素系统相互作用，以控制血压和影响靶器官损伤是必要的。 目前，全面评估所涉及的激素系统是困难和昂贵的，在样品的体积和所需的多次测定的费用方面。 因此，我们希望了解RAAS和心血管（CV）病理学相关系统之间的复杂相互作用，这促使我们考虑新技术。 该提案的目标是开发新的工具，用于统一评估这些重要的激素系统，其前提是我们将传统的ELISA和放射免疫测定法与新技术Luminex LabMAP系统结合使用。 这将减少多个单独测定所需的样品体积，并最终降低评估多个系统的复杂性和成本。 除了定量分析，我们还将使用相同的基于颗粒的技术开发半定量蛋白质悬浮微阵列，以加快基因阵列和其他分子技术的验证，这些技术记录了CV疾病相关机制的激活或抑制模式。 我们预计，新技术的应用将简化RAAS和其他相关激素系统同步或反向激活的评估。 此外，减少样本量和成本还应允许扩大临床和基础科学研究，以包括对CV疾病所涉及的主要激素系统的更现实的评估。 最后，一个优点是，它需要相对便宜的仪器，并提供更大的灵活性，定量，和灵敏度相比，目前可用的固定平台蛋白质阵列。 因此，本提案中开发的肽和蛋白质应用将是广泛使用的理想选择。

DESCRIPTION (provided by applicant): The RAAS is targeted in therapies that reduce mortality. However, increasing evidence suggests that improvement is independent of reductions in blood pressure or changes in angiotensin II. In fact, a strong link between an activated RAAS and cytokine and other inflammation markers is becoming more apparent as an initiating factor in early hypertension, atherosclerosis and diabetes. Thus, better understanding of the entire RAAS as well as a more extensive complement of other hormonal systems interacting to control blood pressure and influence target organ damage is needed. At present, full assessment of the hormonal systems involved is difficult and costly, in terms of volume of sample and expense of the multiple assays required. Thus, our desire to understand complex interactions among RAAS and associated systems in cardiovascular (CV) pathology has driven us to consider new technologies. The goal of this proposal is to develop new tools for unified assessment of these important hormonal systems, based on the premise that we adapt conventional ELISAs and radioimmunoassays for use with a new technology, the Luminex LabMAP system. This will reduce sample volumes required for multiple individual assays and ultimately reduce complexity and cost of assessing multiple systems. In addition to quantitative assays, we will develop semi-quantitative protein suspension microarrays using the same particle based technology to expedite verification of gene arrays and other molecular techniques that document patterns of activation or inhibition of mechanisms involved in CV disease. We anticipate that application of the new technology will simplify assessment of RAAS and other associated hormonal systems activated synchronously or in opposition. In addition, reduced sample volumes and costs should also allow expansion of both clinical and basic science studies to include more realistic assessment of major hormonal systems involved in CV disease. Finally, an advantage is that it requires relatively inexpensive instrumentation, and provides greater flexibility, quantification, and sensitivity compared with fixed platform protein arrays currently available. As such the peptide and protein applications developed in this proposal will be ideal for widespread use.