A mechanistic study of mitochondria-targeted PCSK9 liposomes attenuate oxidative damage in carotid artery plaques

mouse model, TPP-LIP@PCSK9 treatment significantly inhibited carotid artery plaque progression and reduced oxidative damage within the plaques. It markedly enhanced the activity of antioxidant enzymes (T-SOD, CAT) and decreased the level of lipid peroxidation products (MDA) in plaque tissue. Further analysis by Western blot and transcriptomics revealed that TPP-LIP@PCSK9 downregulated the mitochondrial damage marker proteins PINK1/Parkin, activated the Nrf2/UCP2-mediated antioxidant pathway, and modulated signaling pathways closely associated with oxidative stress and metabolism. This study is the first to report the direct role of PCSK9 in mitochondrial oxidative damage within plaque endothelial cells and to achieve effective intervention via nanotechnology, providing a new perspective for the treatment of atherosclerosis.