Intravenous administration of miRNA-21 nanoparticles targeted cardiac macrophages, elicited a reparative phenotype switch, promoted angiogenesis, and reduced hypertrophy, fibrosis, and apoptosis.
Does intravenous nanoparticle delivery of miRNA-21 mimic improve myocardial remodeling after myocardial infarction?
Nanoparticle-mediated delivery of miRNA-21 to cardiac macrophages promotes a reparative phenotype and attenuates adverse remodeling post-myocardial infarction, presenting a potential new therapeutic strategy for heart failure.
MicroRNA-based therapy that targets cardiac macrophages holds great potential for treatment of myocardial infarction (MI). Here, we explored whether boosting the miRNA-21 transcript level in macrophage-enriched areas of the infarcted heart could switch their phenotype from pro-inflammatory to reparative, thus promoting resolution of inflammation and improving cardiac healing. We employed laser capture microdissection (LCM) to spatially monitor the response to this treatment in the macrophage-enriched zones. MiRNA-21 mimic was delivered to cardiac macrophages post MI by nanoparticles (NPs), spontaneously assembled due to the complexation of hyaluronan-sulfate with the nucleic acid mediated by calcium ion bridges, yielding slightly anionic NPs with a mean diameter of 130 nm. Following intravenous administration, the miRNA-21 NPs were targeted to cardiac macrophages at the infarct zone, elicited their phenotype switch from pro-inflammatory to reparative, promoted angiogenesis, and reduced hypertrophy, fibrosis and cell apoptosis in the remote myocardium. Our work thus presents a new therapeutic strategy to manipulate macrophage phenotype using nanoparticle delivery of miRNA-21 with a potential for use to attenuate post-MI remodeling and heart failure.
Bejerano et al. (Fri,) conducted a other in Myocardial infarction. miRNA-21 mimic delivered by nanoparticles was evaluated on Macrophage phenotype switch, angiogenesis, hypertrophy, fibrosis, and cell apoptosis. Intravenous administration of miRNA-21 nanoparticles targeted cardiac macrophages, elicited a reparative phenotype switch, promoted angiogenesis, and reduced hypertrophy, fibrosis, and apoptosis.