Homocysteine accelerates atherosclerosis via inhibiting LXRα–mediated ABCA1/ABCG1–dependent cholesterol efflux from macrophages

Publication date: Available online 28 October 2018Source: Life SciencesAuthor(s): Ping Jin, Yitong Bian, Kai Wang, Guangzhi Cong, Ru Yan, Yong Sha, Xueping Ma, Juan Zhou, Zuyi Yuan, Shaobin JiaAbstractAimsMacrophage-derived foam-cell formation plays a crucial role in the development of atherosclerosis, and liver X receptor alpha (LXRα) is a key regulator of lipid metabolism in macrophages. Homocysteine (Hcy) is an independent risk factor of atherosclerosis; however, the regulation of lipid metabolism and role of LXRα induced by Hcy in macrophages is still unknown. The present study aimed to investigate the potential role of Hcy in disordered lipid metabolism and atherosclerotic lesions, especially the effects of Hcy on cholesterol efflux in macrophages and the possible mechanisms.Main methodsIn vitro, lipid accumulation and cholesterol efflux were evaluated in THP-1 macrophages with Hcy intervention. Real-time quantitative PCR and western blot analyses were used to assess mRNA and protein levels. In vivo, atherosclerotic lesions and lipid profiles were evaluated by methionine diet-induced hyperhomocysteinemia (HHcy) in ApoE−/− mice. The LXRα agonist T0901317 was used to verify the role of LXRα in HHcy-accelerated atherosclerosis.Key findingsHcy promoted lipid accumulation and inhibited cholesterol efflux in THP-1 macrophages. HHcy mice showed increased lesion area and lipid accumulation in plaque. Both studies in vitro and in vivo showed decreased expression of ATP bi...
Source: Life Sciences - Category: Biology Source Type: research