Macrophage-derived FGFR1 drives atherosclerosis through PLCγ-mediated activation of NF-κB inflammatory signaling pathway.

BACKGROUND: Atherosclerosis is a leading cause of cardiovascular morbidity and mortality. Atherosclerotic lesions show increased levels of proteins associated with the fibroblast growth factor receptor (FGFR) pathway. However, the functional significance and mechanisms governed by FGFR signaling in atherosclerosis are not known. In the present study, we investigated FGFR1 signaling in atherosclerosis development and progression. METHODS AND RESULTS: Examination of human atherosclerotic lesions and aortas of Apoe-/- mice fed a high-fat diet (HFD) showed increased levels of FGFR1 in macrophages. We deleted myeloid-expressed Fgfr1 in Apoe-/- mice and showed that Fgfr1 deficiency reduces atherosclerotic lesions and lipid accumulations in both male and female mice upon HFD feeding. These protective effects of myeloid Fgfr1 deficiency were also observed when mice with intact FGFR1 were treated with FGFR inhibitor AZD4547. To understand the mechanistic basis of this protection, we harvested macrophages from mice and show that FGFR1 is required for macrophage inflammatory responses and uptake of oxidized LDL. RNA sequencing showed that FGFR1 activity is mediated through phospholipase-C-gamma (PLCγ) and the activation of nuclear factor-κB (NF-κB) but is independent of FGFR substrate 2. CONCLUSION: Our study provides evidence of a new FGFR1-PLCγ- NF-κB axis in macrophages in inflammatory atherosclerosis, supporting FGFR1 as a potentially therapeutic target for atherosclerosis-related diseases.

Application of Marine Microbial Natural Products in Cosmetics.

As the market size of the cosmetics industry increases, the safety and effectiveness of new products face higher requirements. The marine environment selects for species of micro-organisms with metabolic pathways and adaptation mechanisms different from those of terrestrial organisms, resulting in their natural products exhibiting unique structures, high diversity, and significant biological activities. Natural products are usually safe and non-polluting. Therefore, considerable effort has been devoted to searching for cosmetic ingredients that are effective, safe, and natural for marine micro-organisms. However, marine micro-organisms can be difficult, or impossible, to culture because of their special environmental requirements. Metagenomics technology can help to solve this problem. Moreover, using marine species to produce more green and environmentally friendly products through biotransformation has become a new choice for cosmetic manufacturers. In this study, the natural products of marine micro-organisms are reviewed and evaluated with respect to various cosmetic applications.