Proteomics associated with coronary high-risk plaque features on optical coherence tomography

Abstract

Abstract Introduction Cardiovascular disease is the major cause of death worldwide. The physiological status of the cardiovascular system is reflected in plasma proteins and a newly developed technique based on proximity extension assays has enabled the analysis of a broad range of protein biomarkers associated with cardiovascular disease. However, biomarkers for coronary high-risk plaques, including lipid-rich plaques, macrophages, cholesterol crystals, and microvessels, have not yet been found. Purpose This study aimed to identify proteins specific for coronary high-risk plaques. Methods We analyzed 57 patients (71.1 ± 10.6 years, male: 68.4%) who underwent intracoronary optical coherence tomography and provided blood samples for proteomic analysis. Forty-seven patients (86.0%) had lipid-rich plaques, 46 patients (80.7%) had macrophages, 16 patients (28.1%) had cholesterol crystals, and 27 patients (47.4%) had microvessels. A total of 1,470 plasma proteins were analyzed using the Olink® Explore 1,536 Reagent Kit and P2 100 cycle reagent kit on a NextSeq 2000 sequencer. Results In patients with lipid-rich plaques, the protein expressions of Interstitial collagenase (MMP1), Wiskott-Aldrich syndrome protein family member 1 (WASF1), and Protein phosphatase 1 regulatory subunit 12A (PPP1R12RA) were significantly increased, while the expressions of Fc receptor-like protein 3 (FCRL3), Folate receptor gamma (FOLR3), Cobalamin binding intrinsic factor (CBLIF), Glutathione S-transferase A1 (GSTA1), and Keratin, type I cytoskeletal 18 (KRT18) were significantly decreased (Figure A). In patients with macrophages, the protein expressions of MMP1, WASF1, PPP1R12RA, and Scavenger receptor cysteine-rich domain-containing group B protein (SSC4D) were significantly increased, while the expressions of Fatty acid-binding protein, intestinal (FABP2), FOLR3, CBLIF, GSTA1, and Fibroblast growth factor 21 (FGF21) were significantly decreased (Figure B). In patients with cholesterol crystals, the protein expressions of FOLR3, Secreted frizzled-related protein 1 (SFRP1), and Anterior gradient protein 2 homolog (AGR2) were significantly decreased (Figure C). In patients with microvessels, the expression of FOLR3 was significantly decreased (Figure D). Conclusion These proteins might be new biomarkers in patients with coronary high-risk plaques.