Acrolein-induced dyslipidemia and acute-phase response are independent of HMG-CoA reductase.
Acrolein-induced dyslipidemia and acute-phase response are independent of HMG-CoA reductase.
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DOI：
10.1002/mnfr.201100225
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发表时间：
2011-09
影响因子：
5.2
通讯作者：
Bhatnagar, Aruni
中科院分区：
文献类型：
--
作者：
Conklin, Daniel J.;Prough, Russell A.;Juvan, Peter;Rezen, Tadeja;Rozman, Damjana;Haberzettl, Petra;Srivastava, Sanjay;Bhatnagar, Aruni
醛是食品、水和饮料中普遍存在的天然成分。膳食摄入是丙烯醛和相关醛类暴露的最大来源。口服丙烯醛可引起小鼠急性血脂异常，并长期增加动脉粥样硬化，但其机制尚不清楚。由于脂质合成和运输很大程度上受肝脏控制，因此我们在急性和慢性口服丙烯醛暴露的小鼠模型中检查了肝脏基因。使用 Steroltalk 微阵列检查肝基因表达的变化。急性丙烯醛喂养会在 15 分钟内改变血浆和肝蛋白并增加血浆甘油三酯。到 6 小时，丙烯醛改变了肝脏基因表达，包括 Insig1、Insig2 和 Hmgcr 基因，并刺激急性期反应 (APR)，导致血清淀粉样蛋白 A 基因 (Saa) 上调和全身性低白蛋白血症。为了测试降低的 HMG-CoA 还原酶活性是否可以改变丙烯醛诱导的血脂异常或 APR，用辛伐他汀对小鼠进行预处理。然而，他汀类药物治疗并没有改变丙烯醛诱导的血脂异常或与 APR 相关的低蛋白血症。在 apoE 缺失小鼠中，长期喂食丙烯醛，很少有肝基因失调。这些研究证实，急性丙烯醛暴露改变了与脂质合成和运输以及 APR 相关的肝脏基因的表达，因此表明丙烯醛诱导的血脂异常和 APR 的肝脏位点不依赖于 HMG CoA 还原酶。膳食中摄入丙烯醛可能会干扰肝功能，从而增加心血管疾病的风险。
Aldehydes are ubiquitous natural constituents of foods, water and beverages. Dietary intake represents the greatest source of exposure to acrolein and related aldehydes. Oral acrolein induces dyslipidemia acutely and chronically increases atherosclerosis in mice, yet the mechanisms are unknown. Because lipid synthesis and trafficking are largely under hepatic control, we examined hepatic genes in murine models of acute and chronic oral acrolein exposure. Changes in hepatic gene expression were examined using a Steroltalk microarray. Acute acrolein feeding modified plasma and hepatic proteins and increased plasma triglycerides within 15 min. By 6h, acrolein altered hepatic gene expression including Insig1, Insig2 and Hmgcr genes and stimulated an acute phase response (APR) with up-regulation of serum amyloid A genes (Saa) and systemic hypoalbuminemia. To test if decreased HMG-CoA reductase activity could modify acrolein-induced dyslipidemia or the APR, mice were pretreated with simvastatin. Statin treatment, however, did not alter acrolein-induced dyslipidemia or hypoalbuminemia associated with an APR. Few hepatic genes were dysregulated by chronic acrolein feeding in apoE-null mice. These studies confirmed that acute acrolein exposure altered expression of hepatic genes involved with lipid synthesis and trafficking and APR, and thus, indicated a hepatic locus of acrolein-induced dyslipidemia and APR that was independent of HMG CoA-reductase. Dietary intake of acrolein could contribute to cardiovascular disease risk by disturbing hepatic function.
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DOI：
10.1080/15287390490276539
发表时间：
2004-03-26
影响因子：
2.6
作者：
Li, H;Wang, JL;Khan, MF
通讯作者：
Khan, MF
影响因子：
3.7
作者：
Roe, AL;Warren, G;Blouin, RA
通讯作者：
Blouin, RA
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
4.8
作者：
Memon, RA;Moser, AH;Feingold, KR
通讯作者：
Feingold, KR
影响因子：
3.7
作者：
CLEVELAND, WS;DEVLIN, SJ
通讯作者：
DEVLIN, SJ