Enhanced functional response of CD133+ circulating progenitor cells in patients early after acute myocardial infarction.

ABSTRACT

AIMS: Circulating progenitor cells (PC) may contribute to myocardial recovery following infarction. Growth factors including VEGF are produced during ischaemia and stimulate PC release and activation. In this study, we focused on the functional chemotactic response of PC to VEGF in subjects early after myocardial ischaemia. METHODS AND RESULTS: Number and phenotype of PC were characterized using flow-cytometry. CD133(+)PC were isolated from peripheral blood using positive MACS isolation. The chemotactic response towards members of the VEGF family (VEGF-A, PlGF-1, and VEGF-E) was analysed in three groups (i) early period following acute myocardial infarction (days 2-4) treated with primary PCI (AMI) (n = 35), (ii) stable coronary artery disease (CAD) (n = 35), and (iii) controls (CTR) (n = 20). CD133(+)PC number was 2-fold higher in AMI when compared with CAD and CTR (P = 0.0001), whereas CAD was not different from CTR. The chemotactic response of CD133(+)PC to VEGF-A, PlGF-1, and VEGF-E was significantly enhanced (2-fold) in AMI when compared with CAD (P = 0.0001). While the increase of the VEGFR-1-mediated/PlGF-triggered response was rapid (2 days following infarction), the VEGFR-2-mediated/VEGF-E-triggered response was maximally increased on day 4 post-AMI, thus correlating with the kinetics of maximal inflammatory activation reflected by increased CRP levels (P = 0.019). CONCLUSION: The enhanced chemotactic response of CD133(+)PC following myocardial infarction represents a novel principle potentially involved in cardiovascular repair early after myocardial infarction. Acute inflammatory processes are closely associated with this increased cellular function.