Recently, a so far unknown disease mechanism leading to short-term organ failure was identified. According to new findings, the release of the cardiac depressant factor Dipeptidyl Peptidase 3 (DPP3) into the bloodstream plays a major role in sudden loss of heart function.1,2 DPP3 is an endogenous enzyme that plays a vital role in the recycling of cellular peptides. When massive, uncontrolled cell death occurs, for example, in major surgeries5, cardiogenic shock1,4, sepsis, or burns3, DPP3 is released into the bloodstream, having a toxic-like effect in the human body. This is because in the bloodstream, DPP3 inactivates peptide hormones such as angiotensin II, that is important for the heart function. This inactivation is leading to cardiac depression and consequently hemodynamic instability, which paves the way for organ dysfunction.
High or rising DPP3 blood levels (1) indicate worsening of the patient’s status that can lead to short-term organ failure and death. On the other hand, decreasing DPP3 levels (2) indicate a substantially reduced mortality risk.1
In healthy state, DPP3 is located intracellularly (1a) and active angiotensin II (1b) contributes to maintaining a normal heart function (1c).
In disease state, uncontrolled cell death results in the release of DPP3 (2a). Angiotensin II is inactivated by DPP3 (2b), which leads to hemodynamic instability and cardiac depression (2c).
Discover the science behind the newly identified disease mechanism leading to cardiac depression: release of DPP3 into the bloodstream. To learn more on how to diagnose and monitor dysregulated cell death leading to pathological DPP3 blood levels, watch the video.
1. Deniau et al. (2019), Circulating dipeptidyl peptidase 3 is a myocardial depressant factor - dipeptidyl peptidase 3 inhibition rapidly and sustainably improves haemodynamics, Eur J Heart Fail, DOI: 10.1002/ejhf.1601.
2. Magliocca et al. (2019), Dipeptidyl peptidase 3, a biomarker in cardiogenic shock and hopefully much more, Eur J Heart Fail, DOI: 10.1002/ejhf.1649
3. Dépret et al. (2020), Circulating dipeptidyl peptidase-3 at admission is associated with circulatory failure, acute kidney injury and death in severely ill burn patients, Crit. Care,. DOI: 10.1186/s13054-020-02888-5.
4. Takagi et al. (2019), Circulating dipeptidyl-peptidase 3 and alteration in hemodynamics in cardiogenic shock: Results from the OptimaCC Trial, Eur J Heart Fail., DOI: 10.1002/ejhf.1600
5. Gombert et al (2020), In-hospital mortality and organ failure after open and endovascular thoraco-abdominal aortic surgery can be predicted by increased levels of circulating dipeptidyl peptidase 3, Eur J Cardiothorac Surg, DOI: 10.1093/ejcts/ezaa413