Abstract 15438: Cardiac Myosin-Binding Protein C (cMyBPC) as a Potential New Serum Biomarker of Myocardial Infarction
cMyBPC is a sarcomeric thick filament protein involved in modulating contractility. Previous work in our laboratory identified cMyBPC as a potential marker for MI by LC-MS/MS of coronary effluent from buffer perfused isolated mouse hearts. As cMyBPC dissociates from the sarcomere under acidic conditions it is possibly released earlier following ischaemic injury than other cardiac specific sarcomeric proteins. This preliminary study examined the temporal serum concentration profile of a novel biomarker of myocardial infarction (MI) in a mouse model of ischaemia/reperfusion and patients with STEMI. Left anterior descending coronary artery ligation was performed for thirty minutes and mice sacrificed at 30 seconds and 30, 45, 60 or 120 minutes of reperfusion and serum collected. Sham operated mice served as negative controls. In humans with STEMI undergoing primary PCI, 2 hourly serial serum samples were collected up to 18 hours from symptom onset and then daily to day 3. Healthy volunteers acted as negative controls. Serum cMyBPC was compared to traditional biomarkers of MI, Myoglobin, Troponin I and CK-MB. For detection serum samples were depleted of high abundant proteins and Western blotting performed using affinity-purified rabbit polyclonal anti-cMyBPC antibodies against the N-terminus. In murine serum, cMyBPC was detected in full length and fragmented forms from 30 seconds of reperfusion. Their concentration increased to the final sample at 2 hours. In STEMI patients, full length cMyBPC was detected 3 hours after chest pain onset peaking at 9.6 hours (SD±5.8). The dominant breakdown fragment was detected at 3 hours and peaked at 12 hours (SD±3.4). cMyBPC protein was no longer detectable at 72 hours. Myoglobin, CK-MB and Troponin I followed time courses typical for MI. In Conclusions we describe for the first time detection of cMyBPC within the serum and demonstrate its temporal profile of release in a murine model and in STEMI patients. Despite the limited sensitivity of our assay, early peak concentration, rapid clearance and cardiac specificity make cMyBPC an interesting and novel potential biomarker for MI. Further studies are warranted comparing cMyBPC to established biomarkers of MI in different settings including NSTEMI.
- © 2010 by American Heart Association, Inc.