Abstract 12620: Myeloid Cell-Specific Arginase-1 is Essential for Cardiosphere-Derived Cell Extracellular Vesicle Mediated Angiogenesis Following Acute MI

• Published in: Circulation (New York, N.Y.) N.Y.), 2021-11, Vol.144 (Suppl_1), p.A12620-A12620
• Main Authors: Mentkowski, Kyle I, Manzanero, Cody A, Eagler, Lisa A, Lang, Jennifer K
• Format: Article
• Language: English
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/circ.144.suppl_1.12620

IntroductionFollowing a myocardial infarction (MI), macrophages play a pivotal role in initiating and resolving inflammation. Extracellular vesicles (EVs) released by cardiosphere-derived cells (CDCs) have been shown to improve cardiac function in animal models of ischemia in part via effects on immunomodulation. We have recently shown that CDC-EVs polarize macrophages toward a unique pro-angiogenic phenotype, characterized by increased expression of Arginase-1 (Arg1) and enhanced release of pro-angiogenic factors. We hypothesized that CDC-EV dependent activation of Arg1 could underlie their therapeutic benefit in vivo. MethodsLysMCre mice were crossed with Arg1 fl/fl mice to generate a myeloid cell-specific Arg1 knockout model (Arg1-KO) according to institutional approved protocols. To assess the importance of myeloid-specific Arg1 in the therapeutic efficacy of CDC-EVs in vivo, Arg1-KO mice and their fl/fl littermates (wt) were subjected to permanent LAD ligation and randomized to receive 1) CDC-EVs or 2) vehicle control. Prior to euthanasia, mice were injected with BSL-1 Lectin to measure capillary density. Ejection fraction was measured by echocardiography at 5 days post-MI and tissue samples processed for western blot, PCR, flow cytometry, and histological analyses. ResultsArg1 protein expression was significantly repressed in splenic monocytes isolated from Arg1-KO mice compared with WT mice (fold change0.3 ± 0.1, p