Heat shock protein 27 (HSP27) as a marker of atherosclerosis

热休克蛋白 27 (HSP27) 作为动脉粥样硬化的标志物

• 批准号: 8609507
• 负责人: William T Gerthoffer
• 金额: $ 13.54万
• 依托单位: UNIVERSITY OF SOUTH ALABAMA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-02-01 至 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8609507
• 关键词: Acute; Acute Coronary Event; Address; African American; Age; Aging; Anti-Inflammatory Agents; Anti-inflammatory; Antiatherogenic; Apoptotic; Arterial Fatty Streak; Atherosclerosis; Biochemical; Biochemical Markers; Biological Assay; Biological Markers; Blood; Blood Proteins; Blood Vessels; Blood specimen; Cardiac Catheterization Procedures; Cardiac Death; Cardiology; Cardiovascular Diseases; Cardiovascular system; Carotid Atherosclerotic Disease; Caucasians; Caucasoid Race; Cells; Clinical; Clinical Data; Clinical Research; Cohort Studies; Comorbidity; Complex; Coronary artery; Drops; Endothelial Cells; Event; Future; Goals; HSPB1 gene; Health; Health Services Accessibility; Health system; Heat Shock Protein 27; Hospitalization; Immunoassay; Individual; Instruction; Kinetics; Knowledge; Lead; Measures; Medical Staff; Methods; Modeling; Molecular Chaperones; Molecular Sieve Chromatography; Monitor; Myocardial Infarction; Outcome; Outpatients; Patients; Phosphorylation; Pilot Projects; Plasma; Population; Predictive Value of Tests; Pregnancy; Pregnancy-Associated Plasma Protein-A; Production; Prognostic Marker; Proteins; Recovery; Research; Risk; Risk Assessment; Role; Sampling; Smooth Muscle Myocytes; Stress Tests; Study Subject; Testing; Time; Tissues; Underserved Population; acute coronary syndrome; artery occlusion; base; cardiovascular risk factor; case control; effective therapy; high risk; medically underserved; medically underserved population; minority health; molecular size; patient population; protective effect; protein complex; volunteer

PROJECT SUMMARY (See instructions): African-Americans die from atherosclerotic cardiovascular disease at a higher rate than Caucasians. African-Americans present late and suffer from multiple co-morbidities. These factors all support the need for inexpensive, non-invasive outpatient methods to identify patients at risk for an acute coronary event. There are no established biochemical markers of acute coronary syndrome (ACS) that could be routinely employed to address the disparate risk in medically underserved populations. This issue will be addressed by a 5 yr cohort study with a nested case-control component, involving 200 subjects who are patients in the USA Health System. The patient demographic will be >40% medically underserved. Plasma levels of two candidate biomarkers of ACS, Hsp27 and pregnancy associated protein A (PAPPA), will be assayed biannually in volunteers 45-80 years old who are being monitored for cardiovascular disease by medical staff of the Division of Cardiology. Both Hsp27 and PAPP-A are biochemical components of atherosclerotic plaque that have been proposed as prognostic biomarkers of cardiovascular risk. Hsp27 in vascular smooth muscle and endothelial cells is considered an "antiatherogenic" protein because it has anti-proliferative and anti-inflammatory effects. Hsp27 is secreted into the blood in all individuals. Levels diminish during aging and appear to be further reduced as plaque burden increases. The major goal of the study is test the predictive value of Hsp27 compared to the better established PAPP-A as a biomarker of acute coronary syndrome and overall cardiovascular risk. The project has three specific aims: 1. Make repeated measures of plasma biomarker levels over a 5 yr time span that establishes the baseline variability in the biomarkers with age, 2. Make repeated measures of the biomarkers after an acute coronary event to determine the utility of the biomarkers in predicting cardiovascular risk, and 3. Conduct assays of the biochemical state of Hsp27 to test for predictive value of phosphorylation or oligomer size in assessing cardiovascular risk. Successful completion of the study would enhance the validity of plasma Hsp27 levels and Hsp27 phosphorylation as simple noninvasive outpatient tests for cardiovascular risk assessment in medically underserved populations.

项目摘要（请参阅说明）： 非裔美国人以比高加索人高的动脉粥样硬化心血管疾病死亡。 非裔美国人迟到，并患有多种合并症。这些因素都支持需要廉价，非侵入性门诊方法来识别有急性冠状动脉事件风险的患者。急性冠状动脉综合征（AC）没有建立的生化标志物，可以通常使用来解决医疗服务不足的人群中不同的风险。这一问题将通过一项为期5年的队列研究与嵌套的病例对照组件解决，其中涉及200名是美国卫生系统患者的受试者。患者人群在医学上> 40％。 两种ACS，HSP27和妊娠相关蛋白A（PAPPA）的血浆水平将在45-80岁的志愿者中每两年通过双志愿者进行测定，这些志愿者正在由心脏病学系的医疗人员监测患心血管疾病的志愿者。 HSP27和PAPP-A都是动脉粥样硬化斑块的生化成分，已被认为是心血管风险的预后生物标志物。血管平滑肌和内皮细胞中的HSP27被认为是一种“抗动脉粥样硬化”蛋白，因为它具有抗增殖和抗炎作用。 HSP27在所有个体中被分泌到血液中。随着斑块负担的增加，衰老过程中的水平会降低，并且似乎进一步降低。该研究的主要目的是测试HSP27的预测值与成为更好的PAPP-A作为急性冠状动脉综合征和整体心血管风险的生物标志物相比。该项目具有三个具体的目的：1。在5年的时间范围内重复测量血浆生物标志物水平，以建立生物标志物的基线变异性，随着年龄的增长，2。对急性冠状动脉事件后的生物标志物进行重复测量，以确定生物标志物在预测心血管风险中的测试和3的测试。评估心血管风险时，磷酸化或低聚物大小。这项研究的成功完成将提高血浆HSP27水平和HSP27磷酸化的有效性，作为简单的非侵入性门诊检验，用于在医疗服务不足的人群中进行心血管风险评估。