ABSTRACT
This study considers a fabrication of magnetoactive scaffolds based on a copolymer of vinylidene fluoride and trifluoroethylene (P(VDF-TrFE)) and 5, 10, and 15 wt.% of magnetite (Fe3O4) nanoparticles modified with citric (CA) and oleic (OA) acids by solution electrospinning. The synthesized Fe3O4-CA and Fe3O4-OA nanoparticles are similar in particle size and phase composition, but differ in zeta potential values and magnetic properties. Pure P(VDF-TrFE) scaffolds as well as composites with Fe3O4-CA and Fe3O4-OA nanoparticles demonstrate beads-free 1 µm fibers. According to scanning electron (SEM) and transmission electron (TEM) microscopy, fabricated P(VDF-TrFE) scaffolds filled with CA-modified Fe3O4 nanoparticles have a more homogeneous distribution of magnetic filler due to both the high stabilization ability of CA molecules and the affinity of Fe3O4-CA nanoparticles to the solvent used and P(VDF-TrFE) functional groups. The phase composition of pure and composite scaffolds includes a predominant piezoelectric ß-phase, and a γ-phase, to a lesser extent. When adding Fe3O4-CA and Fe3O4-OA nanoparticles, there was no significant decrease in the degree of crystallinity of the P(VDF-TrFE), which, on the contrary, increased up to 76% in the case of composite scaffolds loaded with 15 wt.% of the magnetic fillers. Magnetic properties, mainly saturation magnetization (Ms), are in a good agreement with the content of Fe3O4 nanoparticles and show, among the known magnetoactive PVDF or P(VDF-TrFE) scaffolds, the highest Ms value, equal to 10.0 emu/g in the case of P(VDF-TrFE) composite with 15 wt.% of Fe3O4-CA nanoparticles.
ABSTRACT
Background: Cardiovascular disease had a global prevalence of 523 million cases and 18.6 million deaths in 2019. The current standard for diagnosing coronary artery disease (CAD) is coronary angiography either by invasive catheterization (ICA) or computed tomography (CTA). Prior studies employed single-molecule, amplification-independent RNA sequencing of whole blood to identify an RNA signature in patients with angiographically confirmed CAD. The present studies employed Illumina RNAseq and network co-expression analysis to identify systematic changes underlying CAD. Methods: Whole blood RNA was depleted of ribosomal RNA (rRNA) and analyzed by Illumina total RNA sequencing (RNAseq) to identify transcripts associated with CAD in 177 patients presenting for elective invasive coronary catheterization. The resulting transcript counts were compared between groups to identify differentially expressed genes (DEGs) and to identify patterns of changes through whole genome co-expression network analysis (WGCNA). Results: The correlation between Illumina amplified RNAseq and the prior SeqLL unamplified RNAseq was quite strong (r = 0.87), but there was only 9 % overlap in the DEGs identified. Consistent with the prior RNAseq, the majority (93 %) of DEGs were down-regulated ~1.7-fold in patients with moderate to severe CAD (>20 % stenosis). DEGs were predominantly related to T cells, consistent with known reductions in Tregs in CAD. Network analysis did not identify pre-existing modules with a strong association with CAD, but patterns of T cell dysregulation were evident. DEGs were enriched for transcripts associated with ciliary and synaptic transcripts, consistent with changes in the immune synapse of developing T cells. Conclusions: These studies confirm and extend a novel mRNA signature of a Treg-like defect in CAD. The pattern of changes is consistent with stress-related changes in the maturation of T and Treg cells, possibly due to changes in the immune synapse.
