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

项目总结（见说明）： 非裔美国人死于动脉粥样硬化性心血管疾病的比率高于白人。 非裔美国人出现较晚，并患有多种合并症。这些因素都支持需要廉价的，非侵入性的门诊方法来识别急性冠状动脉事件的风险患者。目前还没有确定的急性冠状动脉综合征（ACS）生化标志物可以常规用于解决医疗服务不足人群的不同风险。这个问题将通过一项5年队列研究解决，该研究包括一个嵌套病例对照组，涉及200名美国卫生系统的患者。患者人口统计将>40%的医疗服务不足。 ACS的两种候选生物标志物Hsp 27和妊娠相关蛋白A（PAPPA）的血浆水平将每半年在45-80岁的志愿者中进行测定，这些志愿者正在接受心脏病科医务人员的心血管疾病监测。Hsp 27和PAPP-A都是动脉粥样硬化斑块的生化成分，已被提议作为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热休克蛋白27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。Hsp 27在所有个体中分泌到血液中。水平在衰老过程中减少，并随着斑块负担的增加而进一步减少。该研究的主要目的是测试Hsp 27与更好地建立的PAPP-A相比作为急性冠状动脉综合征和总体心血管风险的生物标志物的预测价值。该项目有三个具体目标：1。在5年的时间跨度内重复测量血浆生物标志物水平，建立生物标志物随年龄的基线变异性，2.在急性冠状动脉事件后重复测量生物标志物，以确定生物标志物在预测心血管风险中的效用，以及3.进行热休克蛋白27的生化状态的测定，以测试磷酸化或寡聚体大小在评估心血管风险中的预测价值。这项研究的成功完成将提高血浆Hsp 27水平和Hsp 27磷酸化的有效性，作为医疗服务不足人群心血管风险评估的简单无创门诊测试。

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.