Oral nicotine aggravates endothelial dysfunction and vascular inflammation in diet-induced obese rats: Role of macrophage TNFα.
Oral nicotine aggravates endothelial dysfunction and vascular inflammation in diet-induced obese rats: Role of macrophage TNFα.
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口服尼古丁加重饮食诱导的肥胖大鼠的内皮功能障碍和血管炎症：巨噬细胞TNFα的作用。
DOI：
10.1371/journal.pone.0188439
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Raij L
中科院分区：
文献类型：
--
作者：
Liu C;Zhou MS;Li Y;Wang A;Chadipiralla K;Tian R;Raij L
肥胖和吸烟是主要的心血管（CV）风险因素，当在同一个体中共存时，对CVD具有累加/协同效应。我们研究了尼古丁增强饮食诱导肥胖的Sprague道利大鼠CVD的机制。给大鼠喂食高脂肪（HFD）或正常大鼠饲料（含或不含尼古丁）（100 mg/L饮用水）20周。HFD大鼠出现向心性肥胖、收缩压（SBP）升高、主动脉超氧化物（O2-）生成增加、内皮型一氧化氮合酶（eNOS）受损和乙酰胆碱（EDR）内皮依赖性舒张功能受损。尼古丁进一步增加SBP，O2-和受损eNOS和EDR在肥胖大鼠。在肥胖大鼠腹腔巨噬细胞中，肿瘤坏死因子（TNF）α、白细胞介素1β和CD 36均升高，在尼古丁治疗的肥胖大鼠中进一步升高。通过PCR芯片检测发现，肥胖大鼠主动脉中84个靶促炎基因中有3个增加了2-4倍，其中11个在尼古丁治疗后进一步增加。用尼古丁处理的肥胖大鼠腹腔巨噬细胞的条件培养基孵育的HUVECs显示eNOS减少，NADPH氧化酶亚基gp 91 phox和p22 phox表达增加。在条件培养基中加入抗TNF α抗体可部分阻止这些作用。我们的研究结果表明，尼古丁减轻了饮食诱导的肥胖的CV效应，包括氧化应激，血管炎症和内皮功能障碍。其机制可能与增强巨噬细胞源性TNFα的内皮靶向性有关。
Obesity and cigarette smoke are major cardiovascular (CV) risk factors and, when coexisting in the same individuals, have additive/synergistic effects upon CVD. We studied the mechanisms involved in nicotine enhancement of CVD in Sprague Dawley rats with diet–induced obesity. The rats were fed either a high fat (HFD) or normal rat chow diet with or without nicotine (100 mg/L in drinking water) for 20 weeks. HFD rats developed central obesity, increased systolic blood pressure (SBP), aortic superoxide (O2-) production, and impaired endothelial nitric oxide synthase (eNOS) and endothelium-dependent relaxation to acetylcholine (EDR). Nicotine further increased SBP, O2- and impaired eNOS and EDR in obese rats. In the peritoneal macrophages from obese rats, tumor necrosis factor (TNF) α, interleukin 1β and CD36 were increased, and were further increased in nicotine-treated obese rats. Using PCR array we found that 3 of 84 target proinflammatory genes were increased by 2–4 fold in the aorta of obese rats, 11 of the target genes were further increased in nicotine-treated obese rats. HUVECs, incubated with conditioned medium from the peritoneal macrophages of nicotine treated-obese rats, exhibited reduced eNOS and increased NADPH oxidase subunits gp91phox and p22phox expression. Those effects were partially prevented by adding anti-TNFα antibody to the conditioned medium. Our results suggest that nicotine aggravates the CV effects of diet–induced obesity including the oxidative stress, vascular inflammation and endothelial dysfunction. The underlying mechanisms may involve in targeting endothelium by enhancement of macrophage-derived TNFα.
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影响因子：
20.1
作者：
Harwani SC;Ratcliff J;Sutterwala FS;Ballas ZK;Meyerholz DK;Chapleau MW;Abboud FM
通讯作者：
Abboud FM
影响因子：
37.8
作者：
Chen Z;Wen L;Martin M;Hsu CY;Fang L;Lin FM;Lin TY;Geary MJ;Geary GG;Zhao Y;Johnson DA;Chen JW;Lin SJ;Chien S;Huang HD;Miller YI;Huang PH;Shyy JY
通讯作者：
Shyy JY
影响因子：
15.9
作者：
Besler, Christian;Heinrich, Kathrin;Landmesser, Ulf
通讯作者：
Landmesser, Ulf
DOI：
10.1007/s11481-015-9601-5
发表时间：
2015-09
期刊：
Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology
影响因子：
--
作者：
Báez-Pagán CA;Delgado-Vélez M;Lasalde-Dominicci JA
通讯作者：
Lasalde-Dominicci JA
影响因子：
2.2
作者：
Marsot, A;Simon, N
通讯作者：
Simon, N