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

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. 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.

Epigenetic Contributions to Clinical Risk Prediction of Cardiovascular Disease

“…However, recent studies provide evidence that trypsin can leak from the small intestine into the bloodstream and digest myocardial tissue during heart failure. 31 Trypsin-mediated degradation of heart tissue was also observed in cases of dilated cardiomyopathy following influenza A infection. 32 CNTN4, in turn, encodes a cell adhesion molecule implicated in the development of autism spectrum disorders.…”

Plasma enzymatic activity, proteomics and peptidomics in COVID-19-induced sepsis: A novel approach for the analysis of hemostasis

“…To quantify peptides in plasma, high molecular weight proteins were removed following addition of methanol (without any tryptic digestion step in order to avoid ex vivo protein hydrolysis); the remaining peptides (exclusively generated by in vivo proteolysis) were quantified by tandem mass spectrometry (LC-MS/MS) using nano-spray ionization with a Orbitrap fusion Lumos hybrid mass spectrometer (Thermo Fisher Scientific). The sample preparation procedure both for proteomics and peptidomics and the setting of the mass spectrometry parameters followed established and previously described protocols ( Courelli et al, 2021 ). PEAKS Studio 8.5 (Bioinformatics Solutions, Inc.) proteomics software was used for protein identification and quantification.…”