Profiling of the plasma proteome across different stages of human heart failure

• Published in: Nature communications Vol. 10; no. 1; pp. 5830 - 13
• Main Authors: Egerstedt, Anna, Berntsson, John, Smith, Maya Landenhed, Gidlöf, Olof, Nilsson, Roland, Benson, Mark, Wells, Quinn S, Celik, Selvi, Lejonberg, Carl, Farrell, Laurie, Sinha, Sumita, Shen, Dongxiao, Lundgren, Jakob, Rådegran, Göran, Ngo, Debby, Engström, Gunnar, Yang, Qiong, Wang, Thomas J, Gerszten, Robert E, Smith, J Gustav
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 20.12.2019; Nature Publishing Group UK; Nature Portfolio
• Subjects: Adult; Aged; Aptamers; Aptamers, Peptide - metabolism; Biomarkers - blood; Biomarkers - metabolism; Blood circulation; Cardiac and Cardiovascular Systems; Clinical Medicine; Coagulation; Congestive heart failure; Coronary Sinus - metabolism; Coronary Sinus - pathology; Divergence; Female; Gelsolin; Gene Expression Profiling; Heart failure; Heart Failure - blood; Heart Failure - epidemiology; Heart Failure - pathology; Heart Failure - surgery; Heart Transplantation; Humans; Immunology; Incidence; Interleukin 18; Kardiologi; Klinisk medicin; Male; Medical and Health Sciences; Medicin och hälsovetenskap; Middle Aged; Prospective Studies; Proteins; Proteome - analysis; Proteome - metabolism; Proteomics; Proteomics - methods; Public health; Risk Factors; Target recognition; Therapeutic applications; Thrombospondin; Transplantation
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-13306-y

Heart failure (HF) is a major public health problem characterized by inability of the heart to maintain sufficient output of blood. The systematic characterization of circulating proteins across different stages of HF may provide pathophysiological insights and identify therapeutic targets. Here we report application of aptamer-based proteomics to identify proteins associated with prospective HF incidence in a population-based cohort, implicating modulation of immunological, complement, coagulation, natriuretic and matrix remodeling pathways up to two decades prior to overt disease onset. We observe further divergence of these proteins from the general population in advanced HF, and regression after heart transplantation. By leveraging coronary sinus samples and transcriptomic tools, we describe likely cardiac and specific cellular origins for several of the proteins, including Nt-proBNP, thrombospondin-2, interleukin-18 receptor, gelsolin, and activated C5. Our findings provide a broad perspective on both cardiac and systemic factors associated with HF development.