Hemodialysis exacerbates proteolytic imbalance and pro-fibrotic platelet dysfunction

Abstract Multi-organ fibrosis among end stage renal disease (ESRD) patients cannot be explained by uremia alone. Despite mitigation of thrombosis during hemodialysis (HD), subsequent platelet dysfunction and tissue dysregulation are less understood. We comprehensively profiled plasma and platelets f...

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Autores principales:	Aaron J. Velasquez-Mao, Mark A. Velasquez, Zhengxiong Hui, Denise Armas-Ayon, Jingshen Wang, Moriel H. Vandsburger
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4b0723b32a1342b4a390eadbc03000a0
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spelling	oai:doaj.org-article:4b0723b32a1342b4a390eadbc03000a02021-12-02T18:25:03ZHemodialysis exacerbates proteolytic imbalance and pro-fibrotic platelet dysfunction10.1038/s41598-021-91416-82045-2322https://doaj.org/article/4b0723b32a1342b4a390eadbc03000a02021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91416-8https://doaj.org/toc/2045-2322Abstract Multi-organ fibrosis among end stage renal disease (ESRD) patients cannot be explained by uremia alone. Despite mitigation of thrombosis during hemodialysis (HD), subsequent platelet dysfunction and tissue dysregulation are less understood. We comprehensively profiled plasma and platelets from ESRD patients before and after HD to examine HD-modulation of platelets beyond thrombotic activation. Basal plasma levels of proteolytic regulators and fibrotic factors were elevated in ESRD patients compared to healthy controls, with isoform-specific changes during HD. Platelet lysate (PL) RNA transcripts for growth and coagulative factors were elevated post-HD, with upregulation correlated to HD vintage. Platelet secretome correlations to plasma factors reveal acutely induced pro-fibrotic platelet phenotypes in ESRD patients during HD characterized by preferentially enhanced proteolytic enzyme translation and secretion, platelet contribution to inflammatory response, and increasing platelet dysfunction with blood flow rate (BFR) and Vintage. Compensatory mechanisms of increased platelet growth factor synthesis with acute plasma matrix metalloproteinase (MMP) and tissue inhibitor of MMPs (TIMP) increases show short-term mode-switching between dialysis sessions leading to long-term pro-fibrotic bias. Chronic pro-fibrotic adaptation of platelet synthesis were observed through changes in differential secretory kinetics of heterogenous granule subtypes. We conclude that chronic and acute platelet responses to HD contribute to a pro-fibrotic milieu in ESRD.Aaron J. Velasquez-MaoMark A. VelasquezZhengxiong HuiDenise Armas-AyonJingshen WangMoriel H. VandsburgerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Aaron J. Velasquez-Mao Mark A. Velasquez Zhengxiong Hui Denise Armas-Ayon Jingshen Wang Moriel H. Vandsburger Hemodialysis exacerbates proteolytic imbalance and pro-fibrotic platelet dysfunction
description	Abstract Multi-organ fibrosis among end stage renal disease (ESRD) patients cannot be explained by uremia alone. Despite mitigation of thrombosis during hemodialysis (HD), subsequent platelet dysfunction and tissue dysregulation are less understood. We comprehensively profiled plasma and platelets from ESRD patients before and after HD to examine HD-modulation of platelets beyond thrombotic activation. Basal plasma levels of proteolytic regulators and fibrotic factors were elevated in ESRD patients compared to healthy controls, with isoform-specific changes during HD. Platelet lysate (PL) RNA transcripts for growth and coagulative factors were elevated post-HD, with upregulation correlated to HD vintage. Platelet secretome correlations to plasma factors reveal acutely induced pro-fibrotic platelet phenotypes in ESRD patients during HD characterized by preferentially enhanced proteolytic enzyme translation and secretion, platelet contribution to inflammatory response, and increasing platelet dysfunction with blood flow rate (BFR) and Vintage. Compensatory mechanisms of increased platelet growth factor synthesis with acute plasma matrix metalloproteinase (MMP) and tissue inhibitor of MMPs (TIMP) increases show short-term mode-switching between dialysis sessions leading to long-term pro-fibrotic bias. Chronic pro-fibrotic adaptation of platelet synthesis were observed through changes in differential secretory kinetics of heterogenous granule subtypes. We conclude that chronic and acute platelet responses to HD contribute to a pro-fibrotic milieu in ESRD.
format	article
author	Aaron J. Velasquez-Mao Mark A. Velasquez Zhengxiong Hui Denise Armas-Ayon Jingshen Wang Moriel H. Vandsburger
author_facet	Aaron J. Velasquez-Mao Mark A. Velasquez Zhengxiong Hui Denise Armas-Ayon Jingshen Wang Moriel H. Vandsburger
author_sort	Aaron J. Velasquez-Mao
title	Hemodialysis exacerbates proteolytic imbalance and pro-fibrotic platelet dysfunction
title_short	Hemodialysis exacerbates proteolytic imbalance and pro-fibrotic platelet dysfunction
title_full	Hemodialysis exacerbates proteolytic imbalance and pro-fibrotic platelet dysfunction
title_fullStr	Hemodialysis exacerbates proteolytic imbalance and pro-fibrotic platelet dysfunction
title_full_unstemmed	Hemodialysis exacerbates proteolytic imbalance and pro-fibrotic platelet dysfunction
title_sort	hemodialysis exacerbates proteolytic imbalance and pro-fibrotic platelet dysfunction
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/4b0723b32a1342b4a390eadbc03000a0
work_keys_str_mv	AT aaronjvelasquezmao hemodialysisexacerbatesproteolyticimbalanceandprofibroticplateletdysfunction AT markavelasquez hemodialysisexacerbatesproteolyticimbalanceandprofibroticplateletdysfunction AT zhengxionghui hemodialysisexacerbatesproteolyticimbalanceandprofibroticplateletdysfunction AT denisearmasayon hemodialysisexacerbatesproteolyticimbalanceandprofibroticplateletdysfunction AT jingshenwang hemodialysisexacerbatesproteolyticimbalanceandprofibroticplateletdysfunction AT morielhvandsburger hemodialysisexacerbatesproteolyticimbalanceandprofibroticplateletdysfunction
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Hemodialysis exacerbates proteolytic imbalance and pro-fibrotic platelet dysfunction

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