Original article Reduced CD26 expression is associated with improved cardiac function after acute myocardial infarction Insights from the REPERATOR study Simone Post a, b, c, ⁎, Alexandra J. van den Broek a , Benno J. Rensing b , Gerard Pasterkamp a, c , Marie-José Goumans a, d , Pieter A. Doevendans a, c a University Medical Center, Division Heart & Lungs, Laboratory Experimental Cardiology, G02-523, Postbus 85500, 3508 GA Utrecht, The Netherlands b Department of Cardiology, St. Antonius Hospital, Postbus 2500, 3430 EM Nieuwegein, The Netherlands c Interuniversity Cardiology Institute of the Netherlands (ICIN), Postbus 19258, 3501 DG Utrecht, The Netherlands d Leiden University Medical Center, Department of Molecular Cell Biology, Postbus 9600, 2300 RC Leiden, The Netherlands abstract article info Article history: Received 7 August 2012 Accepted 31 August 2012 Available online 9 September 2012 Keywords: Myocardial infarction Homing Blood cells Magnetic resonance imaging Remodeling CD26 Peripheral blood mononuclear cells (MNC) enhance cardiac recovery and repair after myocardial infarction (MI). The SDF-1α/CXCR4 axis plays a major role in cell homing to infarcted myocardium and is negatively regulated by CD26. Therefore, we studied the expression of CD26 during MI and its effects on cardiac function. Blood samples from forty-two patients who underwent a primary percutaneous coronary intervention (PCI) for a first ST-elevated MI were collected during primary PCI, 1 week and 3 months after MI. Soluble CD26 (sCD26) and membrane bound CD26 expression on MNCs (mncCD26) were determined. Left ventricular function and infarct size were measured within 1 day, 1 week and 3 months follow up by magnetic resonance imaging. One week post MI, sCD26 was down regulated compared to baseline, while mncCD26 was higher at baseline and 1 week compared to 3 months. Increased mncCD26 expression at 1 week after MI was associated with decreased overall recovery of left ventricular function as measured by left ventricular end systolic volume index. Furthermore, the in vitro migration capacity of MNCs to SDF-1α was decreased 1 week post MI and the migration capacity to SDF-1α was negatively correlated with mncCD26 expression. CD26 inhibition with sitagliptin – a drug currently used in diabetic patients – resulted in improved in vitro migration capac- ities of MNCs. In conclusion, our preliminary results suggest that high cellular CD26 expression decreases the migration of MNCs towards SDF-1α and high cellular CD26 expression negatively influences cardiac function post MI. Treating patients shortly post MI with sitagliptin to inhibit CD26 may therefore increase MNC homing to the infarct area and could improve cardiac recovery and repair. © 2012 Elsevier Ltd. All rights reserved. 1. Introduction Myocardial infarction (MI) is the leading cause of death world- wide [1]. Despite the modern management of MI with for example beta-blockers, statins and percutaneous coronary intervention (PCI), MI still has a high morbidity due to heart failure and/or arrhythmia: the 1-month mortality is 4–9% [2,3]. New treatment modalities are needed to prevent post-MI adverse remodeling. Both bone marrow and peripheral blood mononuclear cells (MNCs) are currently tested in clinical studies where they are infused intracoronary following suc- cessful reperfusion in MI patients. These MNCs were shown to mod- estly improve cardiac recovery and repair [4–7]. The mechanism by which MNCs improve cardiac function is not fully understood, but homing of MNCs is an important feature to be able to integrate in the damaged myocardial wall. A key chemokine regulating directed cellular migration is stromal cell-derived factor-1α (SDF-1α or CXCL12) [8]. SDF-1α is upregulated in the ischemic myocardium shortly after MI, resulting in recruitment of cells expressing the SDF-1α receptor CXCR4 on their surface from the circulation into the ischemic area of the heart [9]. The SDF-1α/CXCR4 homing axis is negatively regulated by the peptidase CD26 (dipeptidylpeptidase IV (DPPIV)) which cleaves the amino-terminal dipeptide from SDF-1α, generating an inactive protein [10,11]. Recently we showed Journal of Molecular and Cellular Cardiology 53 (2012) 899–905 Abbreviations: DPPV, dipeptidylpeptidase IV; LV, left ventricle; LVESVI, left ventricle end-systolic volume index; MI, myocardial infarction; MNC, mononuclear cell; mncCD26, membrane bound CD26 expression on MNCs; PEA, percentage enhanced area; PCI, percutaneous coronary intervention; SDF-1α, stromal cell-derived factor-1α; sCD26, soluble CD26. ⁎ Corresponding author at: University Medical Center, Division Heart & Lungs, Lab- oratory Experimental Cardiology, G02-523, Postbus 85500, 3508 GA Utrecht, The Netherlands. Tel.: +31 88 755 7155; fax: +31 252 2693. E-mail addresses: s.post@umcutrecht.nl (S. Post), alexandra.vd.broek@gmail.com (A.J. van den Broek), b.rensing@antoniusziekenhuis.nl (B.J. Rensing), gpasterk@umcutrecht.nl (G. Pasterkamp), M.J.Goumans@lumc.nl (M.-J. Goumans), p.doevendans@umcutrecht.nl (P.A. Doevendans). 0022-2828/$ – see front matter © 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.yjmcc.2012.08.026 Contents lists available at SciVerse ScienceDirect Journal of Molecular and Cellular Cardiology journal homepage: www.elsevier.com/locate/yjmcc