Heart failure (HF) is the most widespread chronic complication of acute myocardial infarction (MI). This study aimed to understand the plasma proteins associated with post-MI HF and their gene expression, in order to detect new candidates for drug target and biomarker discovery.
Aptamer-based affinity-capture plasma proteomics were utilized to measure 1305 plasma proteins at one-month post-MI in a New Zealand cohort (CDCS) including 181 patients post-MI who were subsequently hospitalized for HF. 223 patients of a Singapore based cohort post-MI, of which 33 were hospitalized for HF, was used for further candidate enrichment of plasma proteins by using machine learning, resampling-based statistical testing, and Fisher meta-analysis. In the CDCS cohort, 212 distinctively expressed plasma proteins were associated with subsequent HF events. Of these, 96 correlated with left ventricular ejection fraction measured at four months post-MI.
The large-scale plasma proteomics of two independent post-MI cohorts, cross-referenced to unbiased transcriptomics of murine TAC HF and MI model systems at single-cell resolution, identified 83 proteins as potential biomarkers and drug discovery targets of post-MI HF. Many of these proteins were secretable matricellular proteins, highlighting the extracellular matrix’s prominence in post-MI HF. Four out of the six most highly enriched proteins namely: FSTL3, LTBP4, THBS2, and ANGPT2, were found to be nascent candidates requiring further validation.
Ref: https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.119.045158
