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

项目总结(见说明)： 非洲裔美国人死于动脉粥样硬化性心血管疾病的比率高于高加索人。 非洲裔美国人迟到，并患有多种并存疾病。这些因素都支持需要廉价、非侵入性的门诊方法来识别有急性冠状动脉事件风险的患者。没有已建立的急性冠脉综合征(ACS)生化标志物可以常规用于解决医疗服务不足人群中不同的风险。这一问题将通过一项为期5年的包含嵌套病例对照成分的队列研究来解决，该研究涉及美国卫生系统的200名患者。患者群体中将有40%的人得不到医疗服务。 心脏病科医务人员将每两年检测一次45-80岁的志愿者的血浆中两种候选的ACS生物标志物Hsp27和妊娠相关蛋白A(Pappa)的水平。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的蛋白质，因为它具有抗增殖和抗炎的作用。HSP27在所有个体中都会分泌到血液中。随着年龄的增长，水平会降低，随着斑块负担的增加，水平似乎会进一步降低。这项研究的主要目的是测试Hsp27与公认的更好的PAPP-A作为急性冠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记物的水平，以建立生物标记物随年龄变化的基线；2.在急性冠状动脉事件后重复测量生物标记物，以确定生物标记物在预测心血管风险方面的作用；3.对Hsp27的生化状态进行分析，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Hsp27水平和Hsp27磷酸化作为简单的非侵入性门诊测试在医疗服务不足的人群中评估心血管风险的有效性。

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.