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.

中文翻译：

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心力衰竭患者血浆中消化酶活性和蛋白质降解

介绍

心力衰竭与细胞功能和细胞外基质蛋白的退化有关，但触发机制尚不确定。我们最近的证据表明，活性消化酶可以从小肠泄漏到全身循环中，导致细胞功能障碍和器官衰竭。

方法

因此，我们在心力衰竭 (HF) 患者的早晨空腹血浆中研究了胰腺胰蛋白酶的存在，这是一种负责消化的主要酶。

结果

西方分析表明，与匹配的对照相比，HF 患者血浆中的胰蛋白酶显着升高，并且它们的浓度与心功能障碍生物标志物 BNP 和炎症生物标志物 CRP 和 TNF-α 相关。HF 中的血浆胰蛋白酶水平伴随着升高的胰脂肪酶浓度。如底物切割所确定的，胰蛋白酶具有显着提高的活性。质谱显示，HF 患者的血浆蛋白数量与对照组相似，而 HF 患者的肽数量增加了约 20%。这些肽来源于细胞外和细胞内蛋白质来源，并表现出胰蛋白酶和其他降解蛋白酶的切割位点（数据可通过ProteomeXchange 获得，标识符为 PXD026332）。

结论

这些结果提供了第一个证据表明活性消化酶泄漏到体循环中并可能参与心衰患者的心肌细胞功能障碍和组织破坏。

结论

这些结果提供了第一个证据表明活性消化酶泄漏到体循环中并可能参与心衰患者的心肌细胞功能障碍和组织破坏。