The contribution of foam cells to angiogenesis and inflammation after spinal cord injury

After spinal cord injury (SCI), macrophages engage in the phagocytosis of myelin debris and dead cells, transforming into foam cells. Nevertheless, the ultimate fate and functional role of these foam cells remain unclear, while their inflammatory phenotype elicits ongoing controversy. We discovered that macrophages transform into foam cells through 3 stages, which were phagocytosis, digestion, and lipid overload. Macrophages possess a certain degree of antioxidant capacity. When confronted with excessive lipid pressure, they undergo lipid droplets formation and metabolic reprogramming to alleviate lipotoxicity, also promoting angiogenesis. The anti-inflammatory phenotype of macrophages gradually diminished after SCI, phagocytosing debris could assist in maintaining this phenotype. Moreover, most genes expression patterns were conserved both in the SCI mice and rats. Our study provides a detailed description of the changes in gene expression and function during foam cell formation and long-term fate after SCI, which provides a theoretical basis for further research. Overall design: To investigate whether the genetic profile of bone marrow-derived macrophages (BMDM) changes when they engulf myelin debris (MD) under different conditions, we conducted RNA-seq sequencing, including genetic profiling of BMDM in different polarized states (M1, M2), MD ingested at different concentrations (50ug/ml, 1mg/ml) and at different times (6h, 24h, 72h), as well as genetic profiling of BMDM after they have been treated with two possible drugs that may reduce lipid content within BMDM: badoxifene and bafometrin.