Antiatherosclerotic effects of a novel aspirin-anthraquinone derivative through the induction of macrophage apoptosis

Atherosclerosis is the main cause of cardiovascular diseases. These diseases can lead to mortality and morbidity worldwide. Macrophage apoptosis plays an important role in the progression of atherosclerosis. ASA-X 3 has anticancer effects by inducing significant apoptosis in gastric cancer cells. We conducted a preliminary experiment and reported that ASA-X 3 promotes macrophage apoptosis. Therefore, we hypothesize that ASA-X 3 might play a role in anti-atherosclerosis by inducing macrophage apoptosis. The effects of ASA-X 3 and ASA on RAW264.7 cells (in vitro) and mice (in vivo) were investigated. In vitro, RAW264.7 cell viability and apoptosis rates were assessed, and the levels of PARP, caspase-9, p-JNK, and p53 in cells treated with the two substances were compared. In vivo, Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling (TUNEL) assays revealed macrophage apoptosis in mice treated with medium- or high-dose ASA-X 3 or ASA. Aortic plaques in mice treated with either drug were examined using oil red O and H&E staining. Masson and collagen staining was performed on the aortic rings of mice treated with high-dose ASA-X 3 or ASA. In vitro, unlike ASA, which had no effect, ASA-X 3 markedly reduced RAW264.7 cell viability. ASA-X 3 induced apoptosis at a rate about four times higher than ASA, with increased levels of PARP, caspase-9, phosphorylated JNK, and p53. In vivo, medium- and high-dose ASA-X 3 significantly increased macrophage apoptosis in mice compared with ASA. In addition, ASA-X 3 (at medium and high doses) reduced the number of aortic plaques, as shown by oil red O and H&E staining. Masson and collagen staining of aortic rings revealed similar results for the high-dose ASA-X 3 and ASA treatments. ASA-X 3 appeared to exhibit anti-atherosclerosis effects via a mechanism that involves the induction of macrophage apoptosis and the lowering of blood plasma lipid levels, eventually resulting in reduced aortic plaque. ASA-X 3 could, therefore, be considered a promising candidate for the treatment of this cardiovascular disease. Graphical