Abstract 15771: Cardiosphere-Derived Cell Extracellular Vesicles (CDC-EVs) Alter C-C Chemokine Receptor Type 2 (CCR2) Mediated Monocyte Pro-Inflammatory Signaling Following Cardiac Injury

Abstract

Background: Following cardiac damage, CCL2 (a cytokine released by the injured cardiac tissue) recruits CCR2+ monocytes to the site of injury. Heightened CCL2 levels, however, can over activate the CCR2+ mediated pro-inflammatory response leading to poor cardiac healing. Cardiosphere-derived cell extracellular vesicles (CDC-EVs) have been shown to suppress the inflammatory response by decreasing CCR2 monocyte expression. We hypothesized that treatment with CDC-EVs would suppress CCR2 expression of peripheral monocyte in patients with acute MI. Methods: A prospective single arm observational study was performed. Inpatients at Buffalo General Medical Center were recruited following these criteria: 1) >18 years of age AND 2) a type I MI. Subjects were excluded for the following: 1) fever in last 2 days/infection, 2) is or may be pregnant, or 3) currently undergoing cancer treatment. Monocytes were isolated from peripheral blood samples using Ficoll/centrifugation followed by magnetic activated cell sorting. Isolated monocytes were incubated with either PBS, normal human dermal fibroblast EVs (NHDF-EVs) or CDC-EVs. Monocytes then were analyzed for CCR2 expression by flow cytometry. Multi-variate analysis was performed. Results: CDC-EVs significantly reduced classical monocyte expression of CCR2 by 23% as quantified by flow cytometry compared with PBS (p<0.05, one way ANOVA, n=23) and by 13% compared with NHDF-EVs (p<0.05, one way ANOVA, n=23) in patients with recent MI. This reduction was seen regardless of patients’ pre-existing co-morbidities, medications, LVEF, or history of PCI. Smoking was associated with decreased response to CDC-EV mediated CCR2 suppression (Linear regression model R -0.93, p<0.05, n=23). Conclusions: CDC-EVs effectively downregulate CCR2 expression in patients with recent MI, representing a potential adjunct to current clinical therapies in patients with a heightened pro-inflammatory response post-MI.