Macrophage KLF15 prevents foam cell formation and atherosclerosis via transcriptional suppression of OLR-1.

BACKGROUND: Macrophage-derived foam cells are a hallmark of atherosclerosis. Scavenger receptors, including lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (OLR-1), are the principal receptors responsible for the uptake and modification of LDL, facilitating macrophage lipid load and the uptake of oxidized LDL by arterial wall cells. Krüppel-like factor 15 (KLF15) is a transcription factor that regulates the expression of genes by binding to the promoter during transcription. Therefore, this study aimed to investigate the precise role of macrophage KLF15 in atherogenesis. METHODS: We used two murine models of atherosclerosis: mice injected with an adeno-associated virus (AAV) encoding the Asp374-to-Tyr mutant version of human PCSK9, followed by 12 weeks on a high-fat diet (HFD), and ApoE-/-- mice on a HFD. We subsequently injected mice with AAV-KLF15 and AAV-LacZ to assess the role of KLF15 in the development of atherosclerosis in vivo. Oil Red O, H&E, and Masson's trichome staining were used to evaluate atherosclerotic lesions. Western blots and RT-qPCR were used to assess protein and mRNA levels, respectively. RESULTS: We determined that KLF15 expression was downregulated during atherosclerosis formation, and KLF15 overexpression prevented atherosclerosis progression. KLF15 expression levels did not affect body weight or serum lipid levels in mice. However, KLF15 overexpression in macrophages prevented foam cell formation by reducing OLR-1-meditated lipid uptake. KLF15 directly targeted and transcriptionally downregulated OLR-1 levels. Restoration of OLR-1 reversed the beneficial effects of KLF15 in atherosclerosis. CONCLUSION: Macrophage KLF15 transcriptionally downregulated OLR-1 expression to reduce lipid uptake, thereby preventing foam cell formation and atherosclerosis. Thus, our results suggest that KLF15 is a potential therapeutic target for atherosclerosis.

Characterization of the complete chloroplast genome of Quercus virginiana Mill. (Fagaceae).

The complete chloroplast genome of Quercus virginiana was sequenced with Illumina HiSeq 2000 platform. It was a typical quadruple structure as other plants of Quercus with 161,221 bp in length, including a large single-copy (LSC: 90,553 bp) region and a small single-copy (SSC: 19,016 bp) which were separated by a pair of inverted repeats (IRa, b: 25,826 bp) region. The overall GC content is 36.9%. A total of 131 genes was annotated which contained 86 protein-coding genes including the Trans splicing gene of rps12, 37 tRNA genes, and 8 rRNA genes. ML phylogenetic analysis compared with 17 expressed chloroplast genomes revealed that Q. virginiana was a sister to other species of Quercus, which were grouped together with five species of Section Quercus and another 12 species of Quercus were divided into another group.

[Comparison of Soil Bacterial Community Structure Between Paddy Fields and Dry Land in the Huixian Karst Wetland, China].

In order to explore the effect of land-use change on soil bacteria in wetland systems, the topsoil (0-20 cm) of a natural wetland (NW), paddy field (PF), and dry land (DL) were collected in the Huixian karst wetland. The α-diversity, species composition, and abundance of soil bacterial communities were analyzed using high-throughput sequencing. The effect of environmental factors on bacterial community structure was also examined. The results showed that the soil bacteria in the Huixian karst wetland can be divided into 49 phyla and 145 classes. The Shannon index of bacteria in the PF was significantly higher, and the Simpson index of bacteria in the NW is significantly lower, than in the other two land-use types. The dominant phyla (operational taxonomic units, OTUs>1%) in the NW were Proteobacteria (52.15%), Actinobacteria (15.16%), and Acidobacteria (8.80%); the dominant phyla in the PF were Proteobacteria (45.79%), Acidobacteria (17.20%), and Chloroflexi (11.75%); the dominant phyla in the DL were Proteus (51.42%), Acidobacteria (15.51%), and Chloroflexi (7.43%). The dominant classes (OTUs>1%) in the NW were α-Proteobacteria (17.98%), ß-Proteobacteria (13.72%), and Actinobacteria (13.13%); the dominant classes in the PF were Acidobacteria (14.35%), ß-Proteobacteria (13.37%), and δ-Proteobacteria (12.02%); the dominant classes in the DL were α-Proteobacteria (19.44%), Formobacteria (13.30%), and Acidobacteria (13.03%). Among the dominant OTUs (>0.3%), the dominant genera of in the NW were Sphingomonas (OTU2, 59), Micromonospora (OTU5, 24 and 50487), Gemmatimonas (OTU1), and Tenotrophomonas (OTU8); the dominant genera in the PF were Lysobacter (OTU4 and 115) and Aquabacterium (OTU33); the dominant genera in the DL were Sphingomonas (OTU85, 157 and 2916), Rhodanobacter (OTU19 and 52), and Penlobacterium (OTU60). A heatmap showed that there were significant differences in soil bacterial community structure among the three land-use types. Redundancy analysis showed that pH, soil organic carbon (SOC), total nitrogen (TN), alkali-hydrolyzable nitrogen (AN), exchangeable Mg2+, exchangeable Ca2+, soluble organic carbon (DOC), and available phosphorus (AP) were the main factors that affected the bacterial community structure in the Huixian karst wetland. These results indicate that changes in land-use types have significantly shaped the structure of soil bacterial communities in this area.