Serum Protemic Patterns Associated With Atherosclerosis

与动脉粥样硬化相关的血清蛋白质模式

• 批准号: 7000315
• 负责人: Mark J Pletcher
• 金额: $ 14.79万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-01-01 至 2008-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7000315
• 关键词: atherosclerosis; biomarker; blood chemistry; blood proteins; cardiovascular disorder diagnosis; clinical research; diagnosis design /evaluation; electrospray ionization mass spectrometry; human data; human tissue; proteomics

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.

描述（由申请人提供）：血清中发现的蛋白质的复杂混合物（“血清蛋白质组”）可能会提供有关正在进行的病理生理过程和存在亚临床疾病的有价值的信息。尤其是通过质谱法测量的血清蛋白质组学模式的分析，已经显示出在检测诸如卵巢癌和前列腺癌等病理生理障碍方面的希望。由于动脉粥样硬化主要是一种血管内过程，因此我们假设它也可能适合血清蛋白质组学模式分析。因此，该提案的主要目的是检验血清蛋白质组学模式将反映出存在或不存在亚临床动脉粥样硬化的假设。为了鉴定与动脉粥样硬化相关的血清蛋白质组学模式，我们计划对200例患者进行病例对照研究，而200例没有动脉粥样硬化的动脉粥样硬化证据，其血清先前是在动脉粥样硬化中为UCSF基因组资源收集的。盲目标记的血清将通过新的超敏感电离电离质谱法分析。将处理所得的光谱，然后使用各种分类和歧视技术进行处理，以找到鉴定有和没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个控件来制定决策规则，然后使用第二个100个案例和100个控件来验证该规则。该规则区分和没有动脉粥样硬化患者区分患者的能力将通过使用标准冠心病危险因素数据的规则进行测试。光谱中特别强大的歧视剂的峰将用于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理，用于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，这是美国的主要死亡原因。