| First Author | Maitra U | Year | 2013 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 33 |
| Issue | 1 | Pages | 24-33 |
| PubMed ID | 23117655 | Mgi Jnum | J:216920 |
| Mgi Id | MGI:5609937 | Doi | 10.1161/ATVBAHA.112.300049 |
| Citation | Maitra U, et al. (2013) Molecular mechanisms responsible for the reduced expression of cholesterol transporters from macrophages by low-dose endotoxin. Arterioscler Thromb Vasc Biol 33(1):24-33 |
| abstractText | OBJECTIVE: Atherosclerosis is characterized as a chronic inflammatory condition that involves cholesterol deposition in arteries. Together with scavenger receptor B1 (SR-B1), the ATP-binding cassette transporters ABCA1 and ABCG1 are the major components of macrophage cholesterol efflux. Recent studies have shown that low-grade inflammation plays a distinct regulatory role in the expression of SR-B1 and ABCA1/ABCG1. However, the mechanisms linking low-grade inflammation and cholesterol accumulation are poorly understood. METHODS AND RESULTS: Using primary bone-marrow-derived macrophages, we demonstrate that subclinical low-dose lipopolysaccharide potently reduces the expression of SR-B1 and ABCA1/ABCG1, as well as cholesterol efflux from macrophages through interleukin-1 receptor-associated kinase 1 and Toll-interacting-protein. Low-dose lipopolysaccharide downregulates the nuclear levels of retinoic acid receptor-alpha, leading to their reduced binding to the promoters of SR-B1 and ABCA1/ABCG1. We observe that glycogen synthase kinase 3beta activation by low-dose lipopolysaccharide through interleukin-1 receptor-associated kinase 1 and Toll-interacting-protein is responsible for reduced levels of retinoic acid receptor-alpha, and reduced expression of SR-B1 and ABCA1/ABCG1. Interleukin-1 receptor-associated kinase M, however, counteracts the function of interleukin-1 receptor associated kinase 1. CONCLUSIONS: Collectively, our data reveal a novel intracellular network regulated by low-dose endotoxemia that disrupts cholesterol efflux from macrophages and leads to the pathogenesis of atherosclerosis. |
