Myocardial fibrosis induced by exposure to subclinical lipopolysaccharide is associated with decreased miR-29c and enhanced NOX2 expression in mice.
Myocardial fibrosis induced by exposure to subclinical lipopolysaccharide is associated with decreased miR-29c and enhanced NOX2 expression in mice.
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DOI：
10.1371/journal.pone.0107556
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Tang T
中科院分区：
文献类型：
--
作者：
Lew WY;Bayna E;Dalle Molle E;Contu R;Condorelli G;Tang T
暴露于亚临床水平的脂多糖（LPS）通常发生，似乎耐受良好。然而，在小鼠模型中，反复的LPS暴露在2至3个月内诱导心脏纤维化，而不是由肾素-血管紧张素系统介导的。亚临床LPS通过独特的机制诱导心脏纤维化。在C57/B16小鼠中，每周一次腹膜内注射LPS（10 mg/kg）或盐水（对照），持续1-4周。小鼠没有表现出痛苦的迹象，活动，食欲或体重减轻的变化。在3天、1周、2周或4周后对小鼠实施安乐死，以测量纤维化相关基因和潜在介质（通过QRT-PCR测量）的心脏表达，包括微RNA（miR）和NADPH氧化酶（NOX）。天狼猩红染色法测定左心室胶原分数面积。将从成年小鼠心脏分离的心脏成纤维细胞与0、0.1、1.0或10 ng/ml LPS孵育48小时。心脏miR表达谱显示LPS后3天和7天miR-29 c减少，这通过QRT-PCR证实。LPS后3天发生的纤维化相关基因和介质的最早变化是TIMP-1和NOX-2（但不是NOX-4）的心脏表达增加。这种情况在第1周和第2周持续存在，胶原蛋白Iα1、胶原蛋白IIIα1、MMP 2、MMP 9、TIMP 1、TIMP 2和骨膜蛋白额外增加。TGF-β或结缔组织生长因子无变化。左心室胶原分数面积在LPS后2周和4周增加。在分离的心脏成纤维细胞中，LPS降低miR-29 c并增加NOX-2。反复暴露于亚临床LPS在2-4周后诱导心脏纤维化。LPS后3天的早期变化是miR-29 c减少，NOX 2和TIMP 1增加，这些变化沿着纤维化相关基因的广泛激活，在1周和2周持续存在。在其他条件下诱导心脏纤维化的miR-29 c减少和NOX 2增加可能独特地介导LPS诱导的心脏纤维化。
Exposure to subclinical levels of lipopolysaccharide (LPS) occurs commonly and is seemingly well tolerated. However, recurrent LPS exposure induces cardiac fibrosis over 2 to 3 months in a murine model, not mediated by the renin-angiotensin system. Subclinical LPS induces cardiac fibrosis by unique mechanisms. In C57/Bl6 mice, LPS (10 mg/kg) or saline (control) were injected intraperitoneally once a week for 1–4 weeks. Mice showed no signs of distress, change in activity, appetite, or weight loss. Mice were euthanized after 3 days, 1, 2, or 4 weeks to measure cardiac expression of fibrosis-related genes and potential mediators (measured by QRT-PCR), including micro-RNA (miR) and NADPH oxidase (NOX). Collagen fraction area of the left ventricle was measured with picrosirius red staining. Cardiac fibroblasts isolated from adult mouse hearts were incubated with 0, 0.1, 1.0 or 10 ng/ml LPS for 48 hours. Cardiac miR expression profiling demonstrated decreased miR-29c after 3 and 7 days following LPS, which were confirmed by QRT-PCR. The earliest changes in fibrosis-related genes and mediators that occurred 3 days after LPS were increased cardiac expression of TIMP-1 and NOX-2 (but not of NOX-4). This persisted at 1 and 2 weeks, with additional increases in collagen Iα1, collagen IIIα1, MMP2, MMP9, TIMP1, TIMP2, and periostin. There was no change in TGF-β or connective tissue growth factor. Collagen fraction area of the left ventricle increased after 2 and 4 weeks of LPS. LPS decreased miR-29c and increased NOX-2 in isolated cardiac fibroblasts. Recurrent exposure to subclinical LPS induces cardiac fibrosis after 2–4 weeks. Early changes 3 days after LPS were decreased miR-29c and increased NOX2 and TIMP1, which persisted at 1 and 2 weeks, along with widespread activation of fibrosis-related genes. Decreased miR-29c and increased NOX2, which induce cardiac fibrosis in other conditions, may uniquely mediate LPS-induced cardiac fibrosis.
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影响因子：
20.1
作者：
Dobaczewski M;Bujak M;Li N;Gonzalez-Quesada C;Mendoza LH;Wang XF;Frangogiannis NG
通讯作者：
Frangogiannis NG
影响因子：
16.2
作者：
Ghanim H;Abuaysheh S;Sia CL;Korzeniewski K;Chaudhuri A;Fernandez-Real JM;Dandona P
通讯作者：
Dandona P
DOI：
10.1161/hypertensionaha.109.148635
发表时间：
2010-08
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
Meléndez GC;McLarty JL;Levick SP;Du Y;Janicki JS;Brower GL
通讯作者：
Brower GL
影响因子：
15.9
作者：
Parker, Matthew W.;Rossi, Daniel;Bitterman, Peter B.
通讯作者：
Bitterman, Peter B.
影响因子：
120.1
作者：
Drummond, Grant R.;Selemidis, Stavros;Griendling, Kathy K.;Sobey, Christopher G.
通讯作者：
Sobey, Christopher G.