Serum Protemic Patterns Associated With Atherosclerosis

描述(申请人提供)：在血清中发现的蛋白质的复杂混合物(“血清蛋白质组”)可能提供有关正在进行的病理生理过程和亚临床疾病的存在的有价值的信息。特别是通过质谱仪测量的血清蛋白质组模式的分析，在检测卵巢癌和前列腺癌等病理生理障碍方面显示出了希望。由于动脉粥样硬化主要是一个血管内过程，我们假设它也可能服从于血清蛋白质组模式分析。因此，这一建议的主要目的是检验血清蛋白质组学模式将反映亚临床动脉粥样硬化的存在或不存在的假设。为了确定与动脉粥样硬化相关的血清蛋白质组模式，我们计划对200名动脉粥样硬化患者和200名无动脉粥样硬化血管造影证据的患者进行病例对照研究，这些患者的血清之前是为加州大学旧金山分校的动脉硬化基因组资源收集的。盲标血清将用新的超灵敏电喷雾电离质谱仪进行分析。由此产生的光谱将被处理，然后使用各种分类和识别技术进行分析，以找到识别患有和不患有动脉粥样硬化的患者的模式。我们将使用前100个案例和100个对照来开发决策规则，然后使用第二个100个案例和100个对照来验证规则。这一规则区分动脉粥样硬化患者和非动脉粥样硬化患者的能力将根据使用标准的冠心病危险因素数据的规则进行测试。光谱中的峰是特别强的鉴别器，将被用来识别表征动脉粥样硬化的特定血清蛋白。这项研究旨在深入了解冠状动脉疾病的发病机制，这是一种动脉粥样硬化的血清测试，并开始揭示基因、蛋白质和表型冠心病之间的相互作用，冠心病是美国的主要死亡原因。

DESCRIPTION (provided by applicant): The complex mix of proteins found in serum ("the serum proteome") may provide valuable information about ongoing pathophysiologic processes and the presence of subclinical disease. Analysis of serum proteomic patterns measured by mass spectrometry, in particular, has shown promise in detecting such pathophysiologic disturbances as ovarian and prostate cancer. Since atherosclerosis is primarily an intravascular process, we hypothesize that it too may be amenable to serum proteomic pattern analysis. The primary aim of this proposal, therefore, is to test the hypothesis that serum proteomic patterns will reflect the presence or absence of subclinical atherosclerosis. In order to identify serum proteomic patterns associated with atherosclerosis, we plan to conduct a case-control study of 200 patients with, and 200 without angiographic evidence of atherosclerosis whose serum was previously collected for the UCSF Genomic Resource in Arteriosclerosis. Blindly labeled sera will be analyzed with new ultra-sensitive electrospray ionization mass spectrometry. The resulting spectra will be processed and then analyzed using a variety of classification and discrimination techniques to find patterns that identify patients with and without atherosclerosis. We will use the first 100 cases and 100 controls to develop a decision rule, then use the second 100 cases and 100 controls to validate the rule. The ability of this rule to discriminate between patients with and without atherosclerosis will be tested against rules utilizing standard coronary heart disease risk factor data. Peaks in the spectrum that are particularly strong discriminators will be used to identify the specific serum proteins that characterize atherosclerosis. This research is designed to yield insight into the pathogenesis of coronary artery disease, a serum test for atherosclerosis, and a start towards unraveling the interplay between genes, proteins and phenotypic coronary heart disease, the leading cause of death in the US.