DPP3, a biomarker for cardiac depression

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.^1,2DPP3 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 shock^1,4, 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

Healthy state

In healthy state, DPP3 is located intracellularly (1a) and active angiotensin II (1b) contributes to maintaining a normal heart function (1c).

Disease state

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).

Mode of action of DPP3

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.

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Blood-based biomarker

DPP3 can simply be measured in plasma

New disease mechanism

Quantifying the DPP3 release into the blood stream unravels one cause of shock

Monitoring tool

Measuring circulating DPP3 allows the assessment of high-risk patient’s status and identifies treatment responders and non-responders

Prediction tool

Identifying increased DPP3 blood levels as the root cause for short-term multi-organ failure

Risk stratification

DPP3 aids in the stratification of patients at high risk to develop short-term organ dysfunction

Applicable in critical care

Aids in the guidance for induction or escalation of therapy for critically ill patients

Reference Literature

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