Work

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

Year: 2026

Type: article

Abstract: 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. 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. 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. 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.

Source: European journal of medical research

DOI: 10.1186/s40001-026-04939-z

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

Institutions: Second Military Medical University, Southwest Medical University, Shanxi Medical University

Language: English

Topic: Renin-Angiotensin System Studies

Subfield: Cardiology and Cardiovascular Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,190