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Digestive Enzyme Activity and Protein Degradation in Plasma of Heart Failure Patients

INTRODUCTION: Heart failure is associated with degradation of cell functions and extracellular matrix proteins, but the trigger mechanisms are uncertain. Our recent evidence shows that active digestive enzymes can leak out of the small intestine into the systemic circulation and cause cell dysfuncti...

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Autores principales: Courelli, Vasiliki, Ahmad, Alla, Ghassemian, Majid, Pruitt, Chris, Mills, Paul J., Schmid-Schönbein, Geert W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8630255/
https://www.ncbi.nlm.nih.gov/pubmed/34900012
http://dx.doi.org/10.1007/s12195-021-00693-w
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author Courelli, Vasiliki
Ahmad, Alla
Ghassemian, Majid
Pruitt, Chris
Mills, Paul J.
Schmid-Schönbein, Geert W.
author_facet Courelli, Vasiliki
Ahmad, Alla
Ghassemian, Majid
Pruitt, Chris
Mills, Paul J.
Schmid-Schönbein, Geert W.
author_sort Courelli, Vasiliki
collection PubMed
description INTRODUCTION: Heart failure is associated with degradation of cell functions and extracellular matrix proteins, but the trigger mechanisms are uncertain. Our recent evidence shows that active digestive enzymes can leak out of the small intestine into the systemic circulation and cause cell dysfunctions and organ failure. METHODS: Accordingly, we investigated in morning fasting plasma of heart failure (HF) patients the presence of pancreatic trypsin, a major enzyme responsible for digestion. RESULTS: Western analysis shows that trypsin in plasma is significantly elevated in HF compared to matched controls and their concentrations correlate with the cardiac dysfunction biomarker BNP and inflammatory biomarkers CRP and TNF-α. The plasma trypsin levels in HF are accompanied by elevated pancreatic lipase concentrations. The trypsin has a significantly elevated activity as determined by substrate cleavage. Mass spectrometry shows that the number of plasma proteins in the HF patients is similar to controls while the number of peptides was increased about 20% in HF patients. The peptides are derived from extracellular and intracellular protein sources and exhibit cleavage sites by trypsin as well as other degrading proteases (data are available via ProteomeXchange with identifier PXD026332). Connclusions These results provide the first evidence that active digestive enzymes leak into the systemic circulation and may participate in myocardial cell dysfunctions and tissue destruction in HF patients. CONCLUSIONS: These results provide the first evidence that active digestive enzymes leak into the systemic circulation and may participate in myocardial cell dysfunctions and tissue destruction in HF patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12195-021-00693-w.
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spelling pubmed-86302552021-12-10 Digestive Enzyme Activity and Protein Degradation in Plasma of Heart Failure Patients Courelli, Vasiliki Ahmad, Alla Ghassemian, Majid Pruitt, Chris Mills, Paul J. Schmid-Schönbein, Geert W. Cell Mol Bioeng Original Article INTRODUCTION: Heart failure is associated with degradation of cell functions and extracellular matrix proteins, but the trigger mechanisms are uncertain. Our recent evidence shows that active digestive enzymes can leak out of the small intestine into the systemic circulation and cause cell dysfunctions and organ failure. METHODS: Accordingly, we investigated in morning fasting plasma of heart failure (HF) patients the presence of pancreatic trypsin, a major enzyme responsible for digestion. RESULTS: Western analysis shows that trypsin in plasma is significantly elevated in HF compared to matched controls and their concentrations correlate with the cardiac dysfunction biomarker BNP and inflammatory biomarkers CRP and TNF-α. The plasma trypsin levels in HF are accompanied by elevated pancreatic lipase concentrations. The trypsin has a significantly elevated activity as determined by substrate cleavage. Mass spectrometry shows that the number of plasma proteins in the HF patients is similar to controls while the number of peptides was increased about 20% in HF patients. The peptides are derived from extracellular and intracellular protein sources and exhibit cleavage sites by trypsin as well as other degrading proteases (data are available via ProteomeXchange with identifier PXD026332). Connclusions These results provide the first evidence that active digestive enzymes leak into the systemic circulation and may participate in myocardial cell dysfunctions and tissue destruction in HF patients. CONCLUSIONS: These results provide the first evidence that active digestive enzymes leak into the systemic circulation and may participate in myocardial cell dysfunctions and tissue destruction in HF patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12195-021-00693-w. Springer International Publishing 2021-08-13 /pmc/articles/PMC8630255/ /pubmed/34900012 http://dx.doi.org/10.1007/s12195-021-00693-w Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Article
Courelli, Vasiliki
Ahmad, Alla
Ghassemian, Majid
Pruitt, Chris
Mills, Paul J.
Schmid-Schönbein, Geert W.
Digestive Enzyme Activity and Protein Degradation in Plasma of Heart Failure Patients
title Digestive Enzyme Activity and Protein Degradation in Plasma of Heart Failure Patients
title_full Digestive Enzyme Activity and Protein Degradation in Plasma of Heart Failure Patients
title_fullStr Digestive Enzyme Activity and Protein Degradation in Plasma of Heart Failure Patients
title_full_unstemmed Digestive Enzyme Activity and Protein Degradation in Plasma of Heart Failure Patients
title_short Digestive Enzyme Activity and Protein Degradation in Plasma of Heart Failure Patients
title_sort digestive enzyme activity and protein degradation in plasma of heart failure patients
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8630255/
https://www.ncbi.nlm.nih.gov/pubmed/34900012
http://dx.doi.org/10.1007/s12195-021-00693-w
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