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

Egerstedt, Anna LU ; Berntsson, John LU ; Smith, Maya Landenhed LU ; Gidlöf, Olof LU ; Nilsson, Roland ; Benson, Mark ; Wells, Quinn S. ; Celik, Selvi LU ; Lejonberg, Carl LU and Farrell, Laurie , et al. (2019) In Nature Communications 10(1).
Abstract

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... (More)

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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@article{5939f427-03cb-4d11-8476-76b515273cd2,
  abstract     = {{<p>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.</p>}},
  author       = {{Egerstedt, Anna and Berntsson, John and Smith, Maya Landenhed and Gidlöf, Olof and Nilsson, Roland and Benson, Mark and Wells, Quinn S. and Celik, Selvi and Lejonberg, Carl and Farrell, Laurie and Sinha, Sumita and Shen, Dongxiao and Lundgren, Jakob and Rådegran, Göran and Ngo, Debby and Engström, Gunnar and Yang, Qiong and Wang, Thomas J. and Gerszten, Robert E. and Smith, J. Gustav}},
  issn         = {{2041-1723}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{Profiling of the plasma proteome across different stages of human heart failure}},
  url          = {{http://dx.doi.org/10.1038/s41467-019-13306-y}},
  doi          = {{10.1038/s41467-019-13306-y}},
  volume       = {{10}},
  year         = {{2019}},
}