TY - JOUR
T1 - Profiling of the plasma proteome across different stages of human heart failure
AU - Egerstedt, Anna
AU - Berntsson, John
AU - Smith, Maya Landenhed
AU - Gidlöf, Olof
AU - Nilsson, Roland
AU - Benson, Mark
AU - Wells, Quinn S.
AU - Celik, Selvi
AU - Lejonberg, Carl
AU - Farrell, Laurie
AU - Sinha, Sumita
AU - Shen, Dongxiao
AU - Lundgren, Jakob
AU - Rådegran, Göran
AU - Ngo, Debby
AU - Engström, Gunnar
AU - Yang, Qiong
AU - Wang, Thomas J.
AU - Gerszten, Robert E.
AU - Smith, J. Gustav
N1 - Funding Information:
We acknowledge the contributions of the Region Skåne Biobank (Lund, Sweden) for storage and retrieval of the LCPR and MDCS samples, and of Science for Life Laboratory (Stockholm, Sweden) for RNA-sequencing of heart samples. This work was supported by grants (to J.G.S.) from the European Research Council (ERC-STG-2015-679242), the Swedish Research Council (2017-02554), the Swedish Heart-Lung Foundation (2016-0134 and 2016-0315), the Crafoord Foundation, Skåne University Hospital, the Scania county, governmental funding of clinical research within the Swedish National Health Service, a generous donation from the Knut and Alice Wallenberg foundation to the Wallenberg Center for Molecular Medicine in Lund, and funding from the Swedish Research Council (Linnaeus grant Dnr 349-2006-237, Strategic Research Area Exodiab Dnr 2009-1039) and Swedish Foundation for Strategic Research (Dnr IRC15-0067) to the Lund University Diabetes Center. This work was also supported by grants from NIH (R01HL132320 and R01HL133870 to T.J.W. and R.E.G., and K award 5K01GM103817 to D.N.), and the LaDue Foundation (to M.B.). Open access funding provided by Lund University.
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-019-13306-y
DO - 10.1038/s41467-019-13306-y
M3 - Article
C2 - 31862877
AN - SCOPUS:85076787755
SN - 2041-1723
VL - 10
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 5830
ER -