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内脏脂肪组织源性丝氨酸蛋白酶抑制剂通过 NF-κB/miR-33a 通路上调 ABCA1 表达促进 THP-1 巨噬细胞源性泡沫细胞胆固醇外流。

Visceral adipose tissue-derived serine protease inhibitor accelerates cholesterol efflux by up-regulating ABCA1 expression via the NF-κB/miR-33a pathway in THP-1 macropahge-derived foam cells.

机构信息

Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, Hunan 421001, China.

Department of Cardiovascular Medicine, Second Affiliated Hospital of University of South China, Hengyang 421001, Hunan, China; Department of Cardiovascular Medicine, Chenzhou NO.1 People's Hospital, Chenzhou, Hunan 423000, China.

出版信息

Biochem Biophys Res Commun. 2018 Jun 2;500(2):318-324. doi: 10.1016/j.bbrc.2018.04.066. Epub 2018 Apr 17.

DOI:10.1016/j.bbrc.2018.04.066
PMID:29653102
Abstract

Atherosclerosis is a dyslipidemia disease characterized by foam cell formation driven by the accumulation of lipids. Visceral adipose tissue-derived serine protease inhibitor (vaspin) is known to suppress the development of atherosclerosis via its anti-inflammatory properties, but it is not yet known whether vaspin affects cholesterol efflux in THP-1 macrophage-derived foam cells. Here, we investigated the effects of vaspin on ABCA1 expression and cholesterol efflux, and further explored the underlying mechanism. We found that vaspin decreased miR-33a levels, which in turn increased ABCA1 expression and cholesteorl efflux. We also found that inhibition of NF-κB reduced miR-33a expression and vaspin suppressed LPS-mediated NF-κB phosphorylation. Our findings suggest that vaspin is not only a regular of inflammasion but also a promoter of cholesterol efflux.

摘要

动脉粥样硬化是一种血脂异常疾病,其特征是脂质积累导致泡沫细胞形成。已知内脏脂肪组织衍生的丝氨酸蛋白酶抑制剂(vaspin)通过其抗炎特性抑制动脉粥样硬化的发展,但尚不清楚 vaspin 是否影响 THP-1 巨噬细胞源性泡沫细胞中的胆固醇流出。在这里,我们研究了 vaspin 对 ABCA1 表达和胆固醇流出的影响,并进一步探讨了潜在的机制。我们发现 vaspin 降低了 miR-33a 的水平,从而增加了 ABCA1 的表达和胆固醇的流出。我们还发现,抑制 NF-κB 减少了 miR-33a 的表达,而 vaspin 抑制了 LPS 介导的 NF-κB 磷酸化。我们的研究结果表明,vaspin 不仅是炎症的调节剂,也是胆固醇流出的促进剂。

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