Reduced CD26 expression is associated with improved cardiac function after acute myocardial infarction: Insights from the REPERATOR study

Abstract

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, 1week and 3months after MI. Soluble CD26 (sCD26) and membrane bound CD26 expression on MNCs (mncCD26) were determined. Left ventricular function and infarct size were measured within 1day, 1week and 3months follow up by magnetic resonance imaging.One week post MI, sCD26 was down regulated compared to baseline, while mncCD26 was higher at baseline and 1week compared to 3months. Increased mncCD26 expression at 1week 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 1week 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 capacities 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.