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

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34900012", "kind": "science-record", "revision": 3, "content_hash": "sha256:d014eb5c8c72bf96f2b0fa88a7cc499fa96e4caf9a9bdccff40f8959d9875f7e", "created_at": "2026-11-01T17:36:37Z", "updated_at": "2026-11-01T21:26:47Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Digestive Enzyme Activity and Protein Degradation in Plasma of Heart Failure Patients.", "doi": "10.1007/s12195-021-00693-w", "pmid": "34900012", "authors": ["Vasiliki Courelli", "Alla Ahmad", "Majid Ghassemian", "Chris Pruitt", "Paul J Mills", "Geert W Schmid-Schönbein"], "journal": "Cellular and molecular bioengineering", "year": 2021, "abstract": "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.\nMETHODS: Accordingly, we investigated in morning fasting plasma of heart failure (HF) patients the presence of pancreatic trypsin, a major enzyme responsible for digestion.\nRESULTS: 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).ConnclusionsThese 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.\nCONCLUSIONS: 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.\nSUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12195-021-00693-w.", "claims": [{"id": "claim-method", "statement": "Difference in means between the Control and HF group were evaluated by Hotelling T2-test. 2-D Scatterplots were used to examine trends in plasma, to show comparison of means in 2-D scatterplots using the Hotelling T2 test for independent, heteroscedastic sample distributions. Means between groups were compared using p-values and CIs of the means from two-tailed, unpaired, heteroscedastic t-tests. The D’Agostino-Pearson omnibus normality test was used to determine if the data distributions were normal and to calculate the 95% CIs. Any data that was not normally distributed were log normalized prior to analysis. Group differences were determined with the Kolmogorov-Smirnoff (KS) test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34900012", "locator": "sections[15] \"Statistical Analysis\" paragraph 2", "quote": "Difference in means between the Control and HF group were evaluated by Hotelling T2-test. 2-D Scatterplots were used to examine trends in plasma, to show comparison of means in 2-D scatterplots using the Hotelling T2 test for independent, heteroscedastic sample distributions. Means between groups were compared using p-values and CIs of the means from two-tailed, unpaired, heteroscedastic t-tests. The D’Agostino-Pearson omnibus normality test was used to determine if the data distributions were normal and to calculate the 95% CIs. Any data that was not normally distributed were log normalized prior to analysis. Group differences were determined with the Kolmogorov-Smirnoff (KS) test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD026332.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34900012", "locator": "sections[31] \"Data Availability\" paragraph 2", "quote": "The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD026332."}], "state": "complete"}, {"id": "claim-target-result", "statement": "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.", "kind": "quantitative", "target": {"value": 20.0, "unit": "per cent", "tolerance": null, "source": "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."}, "evidence": [{"asset": "source:pmid:34900012", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "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."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "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.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:34900012"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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Mass spectrometry shows that the number of plasma proteins in", "trypsin activity in plasma of HF patients, a mass spectrometric analysis of the endogenous free peptides in", "dentity of unique peptides (b) identified by mass spectrometry in the combined datasets of all 40 HF patien", "ease in the number of peptides identified by mass spectrometry. The bar graph (d) comparisons of the protea"], "order_basis": "paper_text_order:956", "id": "assay:1"}, {"role": "data_generation", "definition_id": "elisa", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["nd Cohort 2 Western (trypsin and lipase) and ELISA analysis (BNP, CRP, TNF-a) showed significan", "compared to Control (p < 0.0001) (Fig. 1c). 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