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

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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.