K-80003 Inhibition of Macrophage Apoptosis and Necrotic Core Development in Atherosclerotic Vulnerable Plaques

• DOI: 10.1007/s10557-021-07237-4
• Publication Date: 2021-08-19T07:03:20Z
• Authors: Xiaolei Wang; Zhe Sun; Ruosen Yuan; Weifeng Zhang; Yejiao Shen; Anwen Yin; Yanjie Li; Qingqi Ji; Xia Wang; Yi Li; Min Zhang; Xin Pan; Linghong Shen; Ben He
• Keywords: Fibrous cap

Macrophage apoptosis coupled with a defective phagocytic clearance of the apoptotic cells promotes plaque necrosis in advanced atherosclerosis, which causes acute atherothrombotic vascular disease. Nonsteroidal anti-inflammatory drug sulindac derivative K-80003 treatment was previously reported to dramatically attenuate atherosclerotic progression and destabilization. However, underlying mechanisms are not fully understood. This study aimed determine role on macrophage elucidate mechanism.The mouse model vulnerable carotid ApoE-/- mice developed vivo. Consequently, were randomly grouped into two groups: control group (30 mg/kg/day). Samples arteries collected necrotic core area, cellular apoptosis, oxidative stress. The effects RAW264.7 stress, autophagic flux also examined vitro.K-80003 significantly suppressed formation inhibited plaques. can inhibit 7-ketocholesterol-induced vitro. Furthermore, intraplaque mainly through suppression is key cause lesional apoptosis. Mechanistically, prevented impairment macrophages, evidenced by decreased LC3II SQSTM1/p62 expression, GFP-RFP-LC3 cancellation upon treatment.Inhibition autophagy-mediated reduction stress one mechanism destabilization K-80003.