Soluble Flt-1 in AMI Patients Serum Inhibits Angiogenesis of Endothelial Progenitor Cells by Suppressing Akt and Erk's Activity.

Abstract

Simple SummaryAcute myocardial infarction (AMI) is the leading cause of mortality in the world. Endothelial progenitor cells (EPCs) exert important roles in the recovery of collateral circulation via angiogenesis. In this study, we studied the characteristics of EPCs isolated from the peripheral blood of AMI patients and healthy subjects. We found that the number of EPCs increased in AMI patients and exhibited faster migration compared to healthy subjects. However, no difference in angiogenic activity was observed in EPCs between AMI patients and healthy subjects. Interestingly, the serum level of sFlt-1 was elevated in AMI patients. Further analysis demonstrated that sFlt-1 inhibited EPCs angiogenesis in vitro by inhibiting the Akt and Erk signaling pathways. In conclusion, our study uncovered that EPCs increased in quantity, but their angiogenesis activity was inhibited by serum sFlt-1 in AMI patients.In acute myocardial infarction (AMI), endothelial progenitor cells (EPCs) are essential for the recovery of collateral circulation via angiogenesis. Clinical research has shown that the poor prognosis of the patients with AMI is closely associated with the cell quantity and function of EPCs. Whether there are differences in the biological features of EPCs from AMI patients and healthy subjects is worth exploring. In this study, EPCs were isolated from human peripheral blood and identified as late-stage EPCs by flow cytometry, immunofluorescence, and blood vessel formation assay. Compared to healthy subjects, AMI patients had more EPCs in the peripheral blood compared to healthy subjects. In addition, EPCs from AMI patients exhibited higher migration ability in the transwell assay compared to EPCs from healthy subjects. However, no difference in the angiogenesis of EPCs was observed between AMI patients and healthy subjects. Further studies revealed that soluble vascular endothelial growth factor receptor 1 (sFlt-1) in the serum of AMI patients was involved in the inhibition of EPCs angiogenesis by suppressing the Akt and Erk pathways. In conclusion, this study demonstrated that elevated serum sFlt-1 inhibits angiogenesis of EPC in AMI patients. Our findings uncover a pathogenic role of sFlt-1 in AMI.