Evaluation of phosphatidylserine HDL-nanoimmunotherapy anti-atherosclerotic effect


Torrescasana Dominguez, Elisa


Cardiovascular diseases (CVDs) represent the leading cause of mortality worldwide. Their main underlying cause is atherosclerosis, which is a chronic, inflammatory disease characterized by focal plaque lesion formation in the arterial intima. Atheromatous plaque development is initiated by mechanical lesions on the vessels’ endothelia, which triggers the innate immune response, promoting monocyte and macrophage recruitment resulting in a chronic inflammatory state in the plaques. Atherosclerosis treatment currently relies on lipid-lowering drugs, but their limited success in reducing CVD prevalence has spurred the search for new therapeutic options. In this study, we developed a myeloid cell-targeted phosphatidylserine HDL-based nanoimmunotherapy (PS-HDL). Phosphatidylserine is recognized by macrophages as an apoptotic signal and was chosen as the nanoparticles’ cargo to promote efferocytosis and induce inflammation resolution in the plaques. Comprehensive in vivo studies were carried out using the Apoe -/- mouse model of the disease to investigate the anti-atherosclerosis effects of the nanotherapy. Noticeably, PS-HDL administration led to a decreased aortic weight and myeloid cell burden in aorta of Apoe -/- mice fed high fat diet for 36 weeks. These mice showed decreased Ly6Chigh monocyte levels and increased Ly6Clow monocyte levels. However, myeloid cell burden reduction was not observed in aortas of mice who were fed high fat diet for 14 weeks. These results suggest a shift from a pro-inflammatory to a pro-resolutive plaque environment in this atherosclerosis model after being fed a high fat diet for 36 weeks, which would indicate the suitability of our nanoimmunotherapy in advanced stages of the disease. Therefore, PS-HDL might be a useful nanotherapeutic to induce resolution of atherosclerosis-related inflammation and to stabilize plaques in at-risk patients.



Guerra Rebollo, Marta
Bernal Mera, Aurora; Pérez Medina, Carlos


IQS SE - Undergraduate Program in Biotechnology