Extracellular matrix proteomics identifies molecular signature of symptomatic carotid plaques

Another paper from Manuel Mayr, this time combining tissue/cell culture-based MS proteomics and transcriptomics to look for a protein signature to identify symptomatic carotid plaques prior to cardiac events occurring. In the experimental phase they used MS on extracellular matrix (ECM) samples extracted from human carotid endarterectomy specimens to look for differences in protein expression between symptomatic and non-symptomatic patients. This was combined with gene expression profiling of carotid endarterectomies and analysis of proteins secreted from lipid-loaded vascular smooth muscle cells (the lipid loading induces an atherosclerotic-like phenotype in these cells). Proteins that scored in the ECM proteomics study along with at least one of the other two methods were considered as candidates for a symptomatic plaque signature. This identified 7 candidate markers that were then taken for epidemiological validation in two independent cohorts. Two of these proteins were measured using OlinkOlink panels, and five using ELISA (see comments). Using 685 subjects from the Brunbeck cohort, 4/7 candidate proteins were found to be associated with progression to advanced atherosclerosis and incidence of cardiac disease over the 10 year follow-up period. This 4-marker “panel” (MMP9, S100A8/A9, Cathepsin-D and Galectin 3 binding protein) significantly improved the risk prediction when combined with standard CVD risk factors. The 4-protein panel was also successfully replicated in the independent SAPHIR cohort. The authors concluded that this 4-biomarker signature could improve risk prediction and diagnosis for the management of CVD, and also point to the potential strengths of using tissue-based proteomics in such studies.