RPS5 modulates inflammatory response and angiogenesis in coronary heart disease through NF-κB signaling activation

Oxidized low-density lipoprotein (ox-LDL) and inflammation cause endothelial dysfunction in coronary heart disease (CHD). Although ribosomal protein S5 (RPS5) has been linked to cardiovascular disease, the mechanism by which it functions in the endothelium and its relationship to NF-κB signaling remain unknown. RPS5 was chosen as the hub gene for CHD after differential expression analysis was done on the GSE68506 dataset. The human coronary artery endothelial cells (HCAECs) injury model was established by ox-LDL. In vitro experiments were performed to evaluate the changes in RPS5 expression, apoptosis, inflammatory markers, vascular protective factors, cell proliferation, and Endothelial-to-Mesenchymal Transition (EndMT). Combining the dual luciferase reporter gene assay and the NF-κB nuclear translocation immunofluorescence assay, the effect of RPS5 on the NF-κB pathway was evaluated. Seven ribosomal genes (RPL11, RPL8, RPS13, RPS20, RPS3, RPS5, RPS8) were downregulated in coronary artery disease (CAD) samples in the GSE68506 dataset. In vitro, ox-LDL injury similarly reduced RPS5 expression in HCAECs. Functionally, RPS5 knockdown inhibits cell proliferation and enhances apoptosis and EndMT, while RPS5 overexpression has the opposite effect. Mechanistically, RPS5 overexpression diminished NF-κB nuclear accumulation, lowered κB-WT reporter activity, and reduced the phosphorylation levels of IKKα/β, IκBα, and p65. It also reduced pro-inflammatory mediators and decreased VEGF and HSP70. The pathway dependency was confirmed when LPS-induced NF-κB activation reversed these effects. Through the NF-κB signaling pathway, RPS5 plays a crucial role in controlling inflammation, apoptosis, EndMT, and vascular protection factors in injured HCAECs. Endothelial damage in CHD may be treatable by focusing on the RPS5-NF-κB axis.