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Urinary peptides in heart failure: a link to molecular pathophysiology

Tianlin He 1, 2 Michaela Mischak 1 Andrew Clark 3 Ross Campbell 4 Christian Delles 4 Javier Díez 5, 6 Gerasimos Filippatos 7, 8 Alexandre Mebazaa 9, 10 John Mcmurray 4 Arantxa González 5, 6 Julia Raad 1 Rafael Stroggilos 11 Helle Bosselmann 12 Archie Campbell 13, 14 Shona Kerr 13, 14 Colette Jackson 15 Jane Cannon 16 Morten Schou 17 Nicolas Girerd 18, 19, 20, 21 Patrick Rossignol 18, 19, 20, 21 Alex Mcconnachie 22 Kasper Rossing 12 Joost Schanstra 23 Faiez Zannad 18, 19, 20, 21 Antonia Vlahou 11 William Mullen 4 Vera Jankowski 2 Harald Mischak 1, 4 Zhenyu Zhang 24 Jan Staessen 25, 24 Agnieszka Latosinska 1
Abstract : Aims: Heart failure (HF) is a major public health concern worldwide. The diversity of HF makes it challenging to decipher the underlying complex pathological processes using single biomarkers. We examined the association between urinary peptides and HF with reduced (HFrEF), mid-range (HFmrEF) and preserved (HFpEF) ejection fraction, defined based on the European Society of Cardiology guidelines, and the links between these peptide biomarkers and molecular pathophysiology. Methods and results: Analysable data from 5608 participants were available in the Human Urinary Proteome database. The urinary peptide profiles from participants diagnosed with HFrEF, HFmrEF, HFpEF and controls matched for sex, age, estimated glomerular filtration rate, systolic and diastolic blood pressure, diabetes and hypertension were compared applying the Mann-Whitney test, followed by correction for multiple testing. Unsupervised learning algorithms were applied to investigate groups of similar urinary profiles. A total of 577 urinary peptides significantly associated with HF were sequenced, 447 of which (77%) were collagen fragments. In silico analysis suggested that urinary biomarker abnormalities in HF principally reflect changes in collagen turnover and immune response, both associated with fibrosis. Unsupervised clustering separated study participants into two clusters, with 83% of non-HF controls allocated to cluster 1, while 65% of patients with HF were allocated to cluster 2 (P < 0.0001). No separation based on HF subtype was detectable. Conclusions: Heart failure, irrespective of ejection fraction subtype, was associated with differences in abundance of urinary peptides reflecting collagen turnover and inflammation. These peptides should be studied as tools in early detection, prognostication, and prediction of therapeutic response.
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https://hal.univ-lorraine.fr/hal-03236035
Contributor : Erwan Bozec <>
Submitted on : Wednesday, May 26, 2021 - 10:06:02 AM
Last modification on : Wednesday, June 9, 2021 - 4:02:06 PM

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Tianlin He, Michaela Mischak, Andrew Clark, Ross Campbell, Christian Delles, et al.. Urinary peptides in heart failure: a link to molecular pathophysiology. European Journal of Heart Failure, Oxford University Press (OUP), 2021, ⟨10.1002/ejhf.2195⟩. ⟨hal-03236035⟩

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