Recurrent exposure to subclinical lipopolysaccharide increases mortality and induces cardiac fibrosis in mice.
Recurrent exposure to subclinical lipopolysaccharide increases mortality and induces cardiac fibrosis in mice.
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DOI：
10.1371/journal.pone.0061057
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发表时间：
2013
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;Molle ED;Dalton ND;Lai NC;Bhargava V;Mendiola V;Clopton P;Tang T
循环亚临床脂多糖（LPS）发生在健康和疾病。摄入高脂肪食物会增加LPS，导致代谢性内毒素血症。牙周病中的亚临床LPS可能损害内皮功能。心脏可以作为靶向，因为心脏细胞表达TLR 4，LPS受体。假设反复暴露于亚临床LPS会增加死亡率并导致心脏纤维化。用腹膜内盐水（对照）、低剂量LPS（0.1或1 mg/kg）或中等剂量LPS（10或20 mg/kg）注射C57 B1/6小鼠，每周一次，持续3个月。测量左心室（LV）功能（超声心动图）、血流动力学（尾袖压）和心电图（遥测）。通过天狼星红染色和纤维化相关基因的LV表达（QRT-PCR）评估心脏纤维化。分离成年心脏成纤维细胞并暴露于LPS。LPS注射短暂增加心率和血压（<6小时），轻度降低LV功能，24小时完全恢复。小鼠每周耐受LPS 2-3个月，活动、外观、食欲、体重、血压、LV功能、血氧测定或血液化学没有变化。60-90天后，死亡率增加，但不是低剂量的LPS。心律失常是在死亡前几小时发生的。LV胶原分数面积从生理盐水对照组的3.0±0.5%（SEM）剂量依赖性地增加到低剂量LPS的5.6±0.5%和中等剂量LPS的9.7±0.9%（P<0.05中等剂量vs低剂量LPS，以及每个LPS剂量vs对照）。LPS使Iα1、IIIα1、MMP 2、MMP 9、TIMP 1、periostin和IL 6的表达增加（P<0.05）。LPS使肌成纤维细胞α-SMA免疫染色增强。LPS剂量依赖性地增加分离的成人心脏成纤维细胞中的IL-6。反复暴露于亚临床LPS会增加死亡率并诱导心脏纤维化。
Circulating subclinical lipopolysaccharide (LPS) occurs in health and disease. Ingesting high fatty meals increases LPS that cause metabolic endotoxemia. Subclinical LPS in periodontal disease may impair endothelial function. The heart may be targeted as cardiac cells express TLR4, the LPS receptor. It was hypothesized that recurrent exposure to subclinical LPS increases mortality and causes cardiac fibrosis. C57Bl/6 mice were injected with intraperitoneal saline (control), low dose LPS (0.1 or 1 mg/kg), or moderate dose LPS (10 or 20 mg/kg), once a week for 3 months. Left ventricular (LV) function (echocardiography), hemodynamics (tail cuff pressure) and electrocardiograms (telemetry) were measured. Cardiac fibrosis was assessed by picrosirius red staining and LV expression of fibrosis related genes (QRT-PCR). Adult cardiac fibroblasts were isolated and exposed to LPS. LPS injections transiently increased heart rate and blood pressure (<6 hours) and mildly decreased LV function with full recovery by 24 hours. Mice tolerated weekly LPS for 2–3 months with no change in activity, appearance, appetite, weight, blood pressure, LV function, oximetry, or blood chemistries. Mortality increased after 60–90 days with moderate, but not low dose LPS. Arrhythmias occurred a few hours before death. LV collagen fraction area increased dose-dependently from 3.0±0.5% (SEM) in the saline control group, to 5.6±0.5% with low dose LPS and 9.7±0.9% with moderate dose LPS (P<0.05 moderate vs low dose LPS, and each LPS dose vs control). LPS increased LV expression of collagen Iα1, collagen IIIα1, MMP2, MMP9, TIMP1, periostin and IL-6 (P<0.05 moderate vs low dose LPS and vs control). LPS increased α-SMA immunostaining of myofibroblasts. LPS dose-dependently increased IL-6 in isolated adult cardiac fibroblasts. Recurrent exposure to subclinical LPS increases mortality and induces cardiac fibrosis.
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影响因子：
7.7
作者：
Cani, Patrice D.;Amar, Jacques;Burcelin, Remy
通讯作者：
Burcelin, Remy
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：
37.8
作者：
Desvarieux, M;Demmer, RT;Papapanou, PN
通讯作者：
Papapanou, PN