RAGE deficiency does not affect non-alcoholic steatohepatitis and atherosclerosis in Western type diet-fed Ldlr(-/-) mice.
RAGE deficiency does not affect non-alcoholic steatohepatitis and atherosclerosis in Western type diet-fed Ldlr(-/-) mice.
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DOI：
10.1038/s41598-018-33661-y
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发表时间：
2018-10-15
影响因子：
4.6
通讯作者：
Wouters K
中科院分区：
文献类型：
--
作者：
Bijnen M;Beelen N;Wetzels S;Gaar JV;Vroomen M;Wijnands E;Scheijen JL;van de Waarenburg MPH;Gijbels MJ;Cleutjens JP;Biessen EAL;Stehouwer CDA;Schalkwijk CG;Wouters K
非酒精性脂肪性肝病是一系列肝脏疾病，范围从仅脂肪变性到非酒精性脂肪性肝炎（NASH）。后者的特征是肝脏炎症，这会增加心血管疾病的风险。目前尚不清楚哪些因素导致肝脏炎症的发生，其特征是从脂肪变性进展为NASH。以前，我们证明了NASH患者肝脏中晚期糖基化终产物（AGEs）的增加。我们假设AGEs通过激活其促炎受体β 1在NASH的发展中起关键作用。RAGE缺陷型小鼠和野生型同窝出生的小鼠（均为Ldlr−/−背景）喂食西式饮食（WTD）3周或12周。通过流式细胞术、组织学、基因表达和AGE测量来评估β-内酰胺酶缺乏的影响。与对照小鼠相比，RAGE缺陷小鼠显示体重增加和内脏脂肪扩张减少。两组间未观察到脂肪组织炎症差异。维生素D缺乏不影响WTD诱导的单核细胞增多症，循环脂质或肝脂肪变性。WTD诱导的肝脏中性粒细胞和巨噬细胞积聚和动脉粥样硬化斑块的发展在对照组和RAGE缺陷小鼠之间是相当的。未观察到AGE水平的差异。在高脂血症小鼠模型中，NASH或动脉粥样硬化的发展中，β-淀粉样蛋白似乎并不起主要作用。
Non-alcoholic fatty liver disease is a spectrum of liver diseases ranging from steatosis only to non-alcoholic steatohepatitis (NASH). The latter is characterized by hepatic inflammation, which increases the risk of cardiovascular disease. It is poorly understood which factors contribute to the onset of hepatic inflammation characterizing the progression from steatosis to NASH. Previously, we demonstrated increased advanced glycation endproducts (AGEs) in the livers of NASH patients. We hypothesise that AGEs play a key role in NASH development by activating their proinflammatory receptor, RAGE. RAGE-deficient mice and wildtype littermates, both on Ldlr−/− background, were fed a Western type diet (WTD) for 3 or 12 weeks. Flow cytometry, histology, gene expression and AGE measurements were performed to evaluate the effects of RAGE deficiency. RAGE-deficient mice displayed reduced weight gain and visceral fat expansion compared to control mice. No difference in adipose tissue inflammation was observed between groups. RAGE deficiency did not affect WTD-induced monocytosis, circulating lipids or hepatic steatosis. WTD-induced hepatic neutrophil and macrophage accumulation and atherosclerotic plaque development was comparable between control and RAGE-deficient mice. No difference in AGE levels was observed. RAGE does not seem to play a major role in the development of NASH or atherosclerosis in a hyperlipidemic mouse model.
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DOI：
10.1111/j.1440-1746.2007.04943.x
发表时间：
2007-07-01
影响因子：
4.1
作者：
Hyogo, Hideyuki;Yamagishi, Sho-ichi;Tazuma, Susumu
通讯作者：
Tazuma, Susumu
影响因子：
5.8
作者：
Hanssen, Nordin M. J.;Engelen, Lian;Schalkwijk, Casper G.
通讯作者：
Schalkwijk, Casper G.
影响因子：
39.3
作者：
Hanssen, Nordin M. J.;Wouters, Kristiaan;Schalkwijk, Casper G.
通讯作者：
Schalkwijk, Casper G.
影响因子：
29
作者：
Mari, Montserrat;Caballero, Francisco;Garcia-Ruiz, Carmen
通讯作者：
Garcia-Ruiz, Carmen
DOI：
10.1111/j.1440-1746.2006.04225.x
发表时间：
2006-04-01
影响因子：
4.1
作者：
Ekong, U;Zeng, S;Emond, JC
通讯作者：
Emond, JC