Ramoni D, Liberale L, Carbone F, Montecucco F. Reimagining risk stratification: Dipeptidyl peptidase 3 in the new era of cardiovascular biomarkers. World J Cardiol 2025; 17(12): 113443 [DOI: 10.4330/wjc.v17.i12.113443]
Corresponding Author of This Article
Fabrizio Montecucco, MD, PhD, Professor, Department of Internal Medicine, University of Genoa, Viale Benedetto XV 6, Genoa 16132, Italy. fabrizio.montecucco@unige.it
Research Domain of This Article
Cardiac & Cardiovascular Systems
Article-Type of This Article
Editorial
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Dec 26, 2025 (publication date) through Dec 24, 2025
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Journal Information of This Article
Publication Name
World Journal of Cardiology
ISSN
1949-8462
Publisher of This Article
Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
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Ramoni D, Liberale L, Carbone F, Montecucco F. Reimagining risk stratification: Dipeptidyl peptidase 3 in the new era of cardiovascular biomarkers. World J Cardiol 2025; 17(12): 113443 [DOI: 10.4330/wjc.v17.i12.113443]
Davide Ramoni, Luca Liberale, Federico Carbone, Fabrizio Montecucco, Department of Internal Medicine, University of Genoa, Genoa 16132, Italy
Luca Liberale, Federico Carbone, Fabrizio Montecucco, First Clinic of Internal Medicine, Department of Internal Medicine, Italian Cardiovascular Network, IRCCS Ospedale Policlinico San Martino, Genoa 16132, Italy
Author contributions: Montecucco F designed the manuscript; Ramoni D wrote the full paper; Carbone F and Liberale L critically revised the entire work; and all authors have read and approved the final version of the manuscript.
Conflict-of-interest statement: There are no conflicts of interest or financial activities for any aspect of the submitted manuscript. Outside the submitted work, declaration of competing interest LL is coinventor on the International Patent (WO/2020/226993) filed in April 2020 and relating to the use of antibodies which specifically bind IL-1α to reduce various sequelae of ischemia–reperfusion injury to the central nervous system. LL has received speaker fees outside of this work from Daichi-Sankyo. MF and CF have received funding from the Italian Ministry of Health. The other authors have no conflict to disclose.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Fabrizio Montecucco, MD, PhD, Professor, Department of Internal Medicine, University of Genoa, Viale Benedetto XV 6, Genoa 16132, Italy. fabrizio.montecucco@unige.it
Received: August 26, 2025 Revised: September 18, 2025 Accepted: November 25, 2025 Published online: December 26, 2025 Processing time: 120 Days and 23.5 Hours
Abstract
The rapid evolution of cardiovascular (CV) research demands innovative strategies to enhance risk stratification, diagnosis, and management. While traditional biomarkers, such as natriuretic peptides and troponins, remain essential, they often fall short due to suboptimal sensitivity and specificity, particularly in complex or early-stage cases. Emerging biomarkers are central to advancing personalized medicine by enabling earlier, more accurate detection of CV diseases and enhancing predictive algorithms, including those powered by artificial intelligence and machine learning. Among these novel biomarkers, dipeptidyl peptidase 3 (DPP3) has recently garnered attention as a highly specific indicator of cardiogenic shock, offering both prognostic value and therapeutic target potential. Released during cellular stress, circulating DPP3 (cDPP3) plays a mechanistic role in myocardial depression and blood pressure regulation, positioning it as a compelling candidate for inclusion in multi-marker panels. Its integration into predictive models could further refine therapeutic decision-making and patient stratification in acute cardiac care. This editorial discusses the clinical value of incorporating cDPP3 into CV biomarker research and advocates its inclusion in next-generation predictive algorithms and real-time decision-support tools. Continued exploration of such biomarkers may enable tailored interventions and improve outcomes in complex CV cases.
Core Tip: Dipeptidyl peptidase 3 (DPP3) is a novel biomarker and active mediator in cardiovascular disease. Unlike traditional markers that simply reflect tissue injury, circulating DPP3 (cDPP3) directly influences hemodynamics by degrading angiotensin II and other vasoactive peptides, contributing to vasodilation, myocardial depression, and shock progression. Elevated cDPP3 predicts cardiogenic shock and mortality in acute coronary syndromes and heart failure, while its dynamic trajectory provides unique prognostic value. Beyond risk stratification, therapeutic neutralization of cDPP3 shows promise in reversing circulatory failure, positioning it at the interface of biomarker discovery and targeted intervention.
