beta Common Receptor Mediates Erythropoietin-Conferred Protection on OxLDL-Induced Lipid Accumulation and Inflammation in Macrophages

摘要

Erythropoietin (EPO), the key factor for erythropoiesis, also protects macrophage foam cells from lipid accumulation, yet the definitive mechanisms are not fully understood. beta common receptor (beta CR) plays a crucial role in the nonhematopoietic effects of EPO. In the current study, we investigated the role of beta CR in EPO-mediated protection in macrophages against oxidized low-density lipoprotein-(oxLDL-) induced deregulation of lipid metabolism and inflammation. Here, we show that beta CR expression was mainly in foamy macrophages of atherosclerotic aortas from apolipoprotein E-deficient mice. Results of confocal microscopy and immunoprecipitation analyses revealed that beta CR was colocalized and interacted with EPO receptor (EPOR) in macrophages. Inhibition of beta CR activation by neutralizing antibody or small interfering RNA (siRNA) abolished the EPO-conferred protection in oxLDL-induced lipid accumulation. Furthermore, EPO-promoted cholesterol efflux and upregulation of ATP-binding cassette (ABC) transporters ABCA1 and ABCG1 were prevented by pretreatment with beta CR neutralizing antibody or beta CR siRNA. Additionally, blockage of beta CR abrogated the EPO-conferred anti-inflammatory action on oxLDL-induced production of macrophage inflammatory protein-2. Collectively, our findings suggest that beta CR may play an important role in the beneficial effects of EPO against oxLDL-elicited dysfunction of macrophage foam cells.