Total RNA expression in mouse heart tissues after injections of VEGFA-containing extracellular vessicle, lipidnanoparticles and naked-VEGFA mRNA

The study used the next-generation sequencing to compare mRNA content of mouse heart tissue after direct injection of different VEGFA-containining extracellular vesicles (EVs), lipidnanoparticles (LNPs) or naked VEGFA-mRNA to untreated control. The EVs used were originated from human lung epithelial (HTB), umbilical vein endothelial (HUVEC), or cardiac progenitor cells (CPCs) in which the cells were treated with LNPs containing VEGFA prior to the collection of EVs, fractions of the VEGFA-mRNA ended up in the EVs. Our goal is to carry out functional and pathway analysis of the differentially expressed genes. The RNA profiles of EV content from heart tissues were generated by RNA-Seq using Illumina NovaSeq6000. Differentially expressed genes were identified using the DESeq2 package. We found that the VEGFA mRNA was among the most upregulated genes in the injected hearts. We also identified multiple genes and pathways that are significantly associated with angiogenesis and cardiac conditions. Inflamatory response genes and pathways were upregulated by the LNPs and naked-mRNA injection to a greater extend compared to EV injection. The result suggested that the injection of EVs caused less transcriptional changes in the heart tissue.