Development of an MRM assay panel with application to biobank samples from patients with myocardial infarction

Abstract

As part of a Swedish national cardiological research initiative, the development of a quantitative MRM assay is reported for the quantification of eleven putative cardiovascular disease markers. Within the study, patient samples from the LUNDHEARTGENE biobank were processed and nanoLC-MS/MS analysis was performed together with a stable isotope dilution strategy for absolute quantification of the target proteins. Excellent linear regressions were achieved for 9 of the 11 peptides with LOQ ranged in the attomolar range. We have utilized the assay for the screening of plasma samples from patients with chest pain, and performed a comparative analysis of patients with ST-segment elevation myocardial infarction and chest pain due to other causes. The assay demonstrates high reproducibility and correlate with clinical findings. Strong correlations were found for several of the apolipoproteins and their respective lipid subfractions (LDL, HDL or triglycerides). APOC1, APOC2 and APOE were elevated in patients with STEMI.

Biological significance: An MRM assay were developed for putative cardiovascular disease markers as target proteins, and applied to biobanking sample material. The comparative analysis of patients with ST-segment elevation myocardial infarction and chest pain due to other causes showed elevated levels of APOC1, APOC2 and APOE in patients with STEMI. These observations raise interesting novel hypotheses about the role of apolipoproteins C1, C2 and E in the pathophysiology of acute myocardial infarction, which merits further studies.