Abstract 3: Human CD34+ Cells Deficient in miR-377 Attenuates Cardiac Dysfunction and Repair After Ischemia-reperfusion Injury
microRNAs (miRNA/miR) dysregulation has been implicated in cardiac remodeling after injury or stress, however its effects on Human CD34+ cells (hCD34+) biology and function, particularly in the context of cell-based therapy for cardiomyopathy is not fully understood. miRNA array data analysis indicates that miR-377 is a potential interest. pre-miR-377 transfection in EPCs inhibits their migration and vascular tube formation ability in HUVECs. Furthermore, hCD34+ cells treated with miR-377 mimic showed decrease in expression of STK35 (a novel serine/threonine kinase). Moreover, STK35 is predicted as a potential target gene of miR-377 by computational analysis. Interestingly, in a relevant mouse model of ischemia reperfusion, intramyocardial transplantation of miR-377-silenced hCD34+ cells promotes neovascularization leading to improvement in myocardial function and repair. Echocardiography showed LV function was significantly improved in mice receiving miR-377-silenced hCD34+ cells compared to control-miR-transfected hCD34+ cells. Taken together, these data suggest that inhibiting miR-377 in hCD34+ cells promotes their angiogenic ability after transplantation into ischemic myocardial tissue, potentially through activation of STK35 signaling.
Author Disclosures: D. Joladarashi: None. R. Thandavarayan: None. S. Suresh Babu: None. P. Jeyabal: None. S. Krishnamurthy: None. V. Garikipati: None. S. Verma: None. A. Mackie: None. M. Khan: None. E. Vaughan: None. R. Kishore: None. P. Krishnamurthy: None.
This research has received full or partial funding support from the American Heart Association, National Center.
- © 2015 by American Heart Association, Inc.