Proteomics early after heart transplantation and relation to coronary intimal changes and prognosis

Abstract

Background: Long-term survival after heart transplantation (HTx) is limited by cardiac allograft vasculopathy (CAV). The pathogenesis of CAV is poorly understood, and treatment has not yet been well-established. In this exploratory study, we aimed to identify novel immune and nonimmune biomarkers correlated to CAV development, and biomarkers predicting CAV-related events. Methods: Using a proteomic panel, 92 cardiovascular disease-related proteins were evaluated in 26 de novo HTx patients at 3 and 12 months post-transplantation. Intima-area changes were assessed using optical coherence tomography. Major adverse cardiac events (MACE) included significant CAV progression, heart failure, and cardiovascular death. Results: The median follow-up was 6.8 years. We found changes in 4 inflammatory biomarkers: matrix metalloproteinase 3 (MMP-3) and matrix metalloproteinase 2 (MMP-2) were significantly increased after 3 months in the group of patients with the highest intima proliferation, and after 12 months in patients experiencing MACE, respectively. Monocyte chemotactic protein 1 (MCP-1) was increased after 12 months in patients experiencing MACE. Platelet-derived growth factor subunit A (PDGF-A) was significantly increased after 3 months in the group of patients with highest intima proliferation. Conclusions: We identified 4 biomarkers that may be associated with CAV development which differed significantly between groups of intima proliferation and MACE; MMP-2, MMP-3, MCP-1, and PDGF-A. Further studies are needed to examine whether our findings offer the basis to seek new markers of graft vasculopathy or treatment options.

Keywords

• heart transplantation
• cardiac allograft vasculopathy
• optical coherence tomography
• proteomics
• intravascular imaging