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Purpose <p>Myocardial injury is a prevalent complication of sepsis, significantly contributing to its high morbidity and mortality rates. Dipeptidyl peptidase 3 (DPP3), a zinc-dependent hydrolase, has been found to be elevated in patients experiencing cardiogenic shock. Numerous recent studies have suggested that DPP3 may play a role in cardiovascular diseases such as hypertension and heart failure. Nevertheless, its specific function in sepsis-induced myocardial injury remains poorly understood. Additionally, inducible nitric oxide synthase (iNOS) is recognized as a critical myocardial depressant factor involved in the pathogenesis of sepsis-associated myocardial injury. Therefore, the present study aims to investigate the role of DPP3 in sepsis-induced myocardial injury and to elucidate the underlying mechanisms, with a particular emphasis on its interaction with the renin-angiotensin system and the iNOS/nitric oxide (NO) pathway.</p> Methods <p>Sepsis models were induced by intraperitoneal injection of lipopolysaccharide in wild type mice and <i>DPP3</i> knockout mice. And the effects on myocardial function, angiotensin-(1–7) (Ang-(1–7)) levels, and the iNOS/NO pathway were assessed.</p> Results <p>The level of DPP3 was increased in both plasma and myocardial tissues in sepsis models. Intravenous injection of DPP3 induced cardiac function impairment and increased the iNOS/NO pathway. Conversely, <i>DPP3</i> knockout inhibited the iNOS/NO pathway and attenuated impaired myocardial function by increasing the content of Ang-(1–7), but these effects were weakened by the Mas receptor blocker A779.</p> Conclusions <p>DPP3-mediated iNOS activation plays a critical role in sepsis-induced myocardial injury at least partially by reducing Ang-(1–7). Genetic ablation of DPP3 may represent a novel potential therapeutic strategy for treating the sepsis-associated myocardial injury.</p>

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Dipeptidyl peptidase 3-mediated iNOS activation participates in myocardial injury in sepsis partially through reduction of angiotensin-(1-7)

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月27日

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  • Chang Liu,
  • Xue-jiao Zhou,
  • Deng-Hui Liu,
  • Qi Shen,
  • Wei-Zhong Wang,
  • Xing Tan

摘要

Purpose

Myocardial injury is a prevalent complication of sepsis, significantly contributing to its high morbidity and mortality rates. Dipeptidyl peptidase 3 (DPP3), a zinc-dependent hydrolase, has been found to be elevated in patients experiencing cardiogenic shock. Numerous recent studies have suggested that DPP3 may play a role in cardiovascular diseases such as hypertension and heart failure. Nevertheless, its specific function in sepsis-induced myocardial injury remains poorly understood. Additionally, inducible nitric oxide synthase (iNOS) is recognized as a critical myocardial depressant factor involved in the pathogenesis of sepsis-associated myocardial injury. Therefore, the present study aims to investigate the role of DPP3 in sepsis-induced myocardial injury and to elucidate the underlying mechanisms, with a particular emphasis on its interaction with the renin-angiotensin system and the iNOS/nitric oxide (NO) pathway.

Methods

Sepsis models were induced by intraperitoneal injection of lipopolysaccharide in wild type mice and DPP3 knockout mice. And the effects on myocardial function, angiotensin-(1–7) (Ang-(1–7)) levels, and the iNOS/NO pathway were assessed.

Results

The level of DPP3 was increased in both plasma and myocardial tissues in sepsis models. Intravenous injection of DPP3 induced cardiac function impairment and increased the iNOS/NO pathway. Conversely, DPP3 knockout inhibited the iNOS/NO pathway and attenuated impaired myocardial function by increasing the content of Ang-(1–7), but these effects were weakened by the Mas receptor blocker A779.

Conclusions

DPP3-mediated iNOS activation plays a critical role in sepsis-induced myocardial injury at least partially by reducing Ang-(1–7). Genetic ablation of DPP3 may represent a novel potential therapeutic strategy for treating the sepsis-associated myocardial injury.