A host lipase prevents lipopolysaccharide-induced foam cell formation

• Published in: iScience Vol. 24; no. 9; p. 103004
• Main Authors: Feng, Jintao, Jiang, Wei, Cheng, Xiaofang, Zou, Benkun, Varley, Alan W., Liu, Ting, Qian, Guojun, Zeng, Wenjiao, Tang, Jianguo, Zhao, Qiang, Chu, Yiwei, Wei, Yuanyuan, Li, Xiaobo, Munford, Robert S., Lu, Mingfang
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 24.09.2021; Elsevier
• Subjects: cell biology; lipid; molecular biology; molecular biology; lipid; cell biology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2021.103004

Although microbe-associated molecular pattern (MAMP) molecules can promote cholesterol accumulation in macrophages, the existence of a host-derived MAMP inactivation mechanism that prevents foam cell formation has not been described. Here, we tested the ability of acyloxyacyl hydrolase (AOAH), the host lipase that inactivates gram-negative bacterial lipopolysaccharides (LPSs), to prevent foam cell formation in mice. Following exposure to small intraperitoneal dose(s) of LPSs, Aoah−/− macrophages produced more low-density lipoprotein receptor and less apolipoprotein E and accumulated more cholesterol than did Aoah+/+ macrophages. The Aoah−/− macrophages also maintained several pro-inflammatory features. Using a perivascular collar placement model, we found that Aoah−/− mice developed more carotid artery foam cells than did Aoah+/+ mice after they had been fed a high fat, high cholesterol diet, and received small doses of LPSs. This is the first demonstration that an enzyme that inactivates a stimulatory MAMP in vivo can reduce cholesterol accumulation and inflammation in arterial macrophages. [Display omitted] •Acyloxyacyl hydrolase prevents LPS-induced cholesterol accumulation in macrophages•AOAH also prevents prolonged inflammation after LPS exposure•AOAH enhances mitochondrial function in LPS-exposed macrophages•AOAH ameliorates LPS-induced foam cell accumulation in carotid arterial lesions Lipid; Molecular biology; Cell biology