Abstract 18859: Blockade of Exosome Generation With GW4869 Reduce Cardiac Dysfunction After Myocardial Infarction
Introduction: Myocardial infarction induces severe inflammatory responses that lead to progressive heart failure. It also has been reported that large amounts of circulating pro-inflammatory cytokines trigger myocardial dysfunction. Moreover, recent studies have shown that exosomes (Exo) released from activated macrophages are pro-inflammatory.
Hypothesis: Here, we examined whether blocking the generation of exosomes was protective against ventricular dysfunction after myocardial infarction (MI).
Methods: Wistar rats were injected IP with GW4869, a chemical inhibitor of exosome biogenesis, or saline, 1 h before left anterior coronary artery ligation. Cardiac function was assessed in vivo using trans-thoracic echocardiography. Left ventricular (LV) function was assessed before MI (baseline) at 24hrs, 7days, and 28 days after MI. Myeloperoxidase (MPO) activity, which is induced by neutrophil infiltration and pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) was measured in homogenized heart samples and plasma. The number and size profile of Exo particle in sera was assessed by Nanosight technique at baseline and 24hrs after MI.
Results: While the total number of circulating extracellular vesicles was significantly increased 24hrs after MI in both groups as compared with baseline conditions, circulating Exo was reduced in animals injected with GW4896 as compared with controls 24 hrs post-MI. Left ventricular ejection fraction (EF%) was comparably reduced in both groups at 24 hrs post-MI but recovered to a greater extent in the GW4869-treated group than in control rats at 7 and 28 days post-MI (Figure). Scar size was reduced in GW4869 treated group (18%± 9% PBS vs 4%±1% GW).
Conclusions: These results show that secreted exosomes contribute to ventricular dysfunction after MI.
Author Disclosures: V. Biemmi: None. G. Milano: None. E. Cervio: None. N. Pernigoni: None. T. Moccetti: None. G. Vassalli: None. L. Barile: None.
- © 2016 by American Heart Association, Inc.