Characterization of βARKct engineered extracellular vesicles and model specific cardioprotection.

In this study we tested whether βARKct-CDC EVs would be efficacious when applied to stressed myocytes in vitro and in vivo. When isolated EVs from βARKct-CDC and control GFP-CDC were added to cardiomyocytes in culture, they both protected against hypoxia-induced apoptosis. We tested whether these EVs could protect the mouse heart in vivo following exposure either to myocardial infarction (MI) or acute catecholamine toxicity. Both types of EVs significantly protected against ischemic injury and improved cardiac function after MI compared to mice treated with EVs from mouse embryonic fibroblasts, however βARKct EVs treated mice did display some unique beneficial properties including significantly altered pro- and anti-inflammatory cytokines. Importantly, in a catecholamine toxicity model of heart failure (HF), myocardial injections of βARKct-containing EVs were superior at preventing HF compared to control EVs and this catecholamine toxicity protection was recapitulated in vitro. Therefore, introduction of the βARKct into cellular EVs can have improved reparative properties in the heart especially against catecholamine damage, which is significant since sympathetic nervous system activity is increased in HF. PMID: 33513081 [PubMed - as supplied by publisher]
Source: American Journal of Physiology. Heart and Circulatory Physiology - Category: Physiology Authors: Tags: Am J Physiol Heart Circ Physiol Source Type: research