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超细碳颗粒介导的老年自发性高血压大鼠心血管损伤

Ultrafine carbon particle mediated cardiovascular impairment of aged spontaneously hypertensive rats.

作者信息

Upadhyay Swapna, Stoeger Tobias, George Leema, Schladweiler Mette C, Kodavanti Urmila, Ganguly Koustav, Schulz Holger

机构信息

Institute of Lung Biology and Disease, Comprehensive Pneumology Center Helmholtz Zentrum München, German Research Center for Environmental Health, Munich, Germany.

Department of Biotechnology, Indian Institute of Technology, Madras, Chennai, 600036, India.

出版信息

Part Fibre Toxicol. 2014 Sep 17;11:36. doi: 10.1186/s12989-014-0036-6.

Abstract

BACKGROUND

Studies provide compelling evidences for particulate matter (PM) associated cardiovascular health effects. Elderly individuals, particularly those with preexisting conditions like hypertension are regarded to be vulnerable. Experimental data are warranted to reveal the molecular pathomechanism of PM related cardiovascular impairments among aged/predisposed individuals. Thus we investigated the cardiovascular effects of ultrafine carbon particles (UfCP) on aged (12-13 months) spontaneously hypertensive rats (SHRs) and compared the findings with our pervious study on adult SHRs (6-7 months) to identify age related predisposition events in cardiovascular compromised elderly individuals.

METHODS

Aged SHRs were inhalation exposed to UfCP for 24 h (~180 μg/m³) followed by radio-telemetric assessment for blood pressure (BP) and heart rate (HR). Bronchoalveolar lavage (BAL) fluid cell differentials, interleukin 6 (IL-6) and other proinflammatory cytokines; serum C-reactive protein (CRP) and haptoglobin (HPT); and plasma fibrinogen were measured. Transcript levels of hemeoxygenase 1 (HO-1), endothelin 1 (ET1), endothelin receptors A, B (ETA, ETB), tissue factor (TF), and plasminogen activator inhibitor-1 (PAI-1) were measured in the lung and heart to assess oxidative stress, endothelial dysfunction and coagulation cascade.

RESULT

UfCP exposed aged SHRs exhibited increased BP (4.4%) and HR (6.3%) on 1(st) recovery day paralleled by a 58% increase of neutrophils and 25% increase of IL-6 in the BAL fluid. Simultaneously higher CRP, HPT and fibrinogen levels in exposed SHRs indicate systemic inflammation. HO-1, ET1, ET-A, ET-B, TF and PAI-1 were induced by 1.5-2.0 folds in lungs of aged SHRs on 1(st) recovery day. However, in UfCP exposed adult SHRs these markers were up-regulated (2.5-6 fold) on 3(rd) recovery day in lung without detectable pulmonary/systemic inflammation.

CONCLUSIONS

The UfCP induced pulmonary and systemic inflammation in aged SHRs is associated with oxidative stress, endothelial dysfunction and disturbed coagulatory hemostasis. UfCP exposure increased BP and HR in aged SHRs rats which was associated with lung inflammation, and increased expression of inflammatory, vasoconstriction and coagulation markers as well as systemic changes in biomarkers of thrombosis in aged SHRs. Our study provides further evidence for potential molecular mechanisms explaining the increased risk of particle mediated cardiac health effects in cardiovascular compromised elderly individuals.

摘要

背景

研究为颗粒物(PM)对心血管健康的影响提供了有力证据。老年人,尤其是那些患有高血压等既往疾病的人被认为较为脆弱。需要实验数据来揭示老年/易感个体中PM相关心血管损伤的分子发病机制。因此,我们研究了超细碳颗粒(UfCP)对老年(12 - 13个月)自发性高血压大鼠(SHR)的心血管影响,并将结果与我们之前对成年SHR(6 - 7个月)的研究进行比较,以确定心血管功能受损的老年个体中与年龄相关的易感事件。

方法

将老年SHR吸入UfCP 24小时(~180μg/m³),然后通过无线电遥测评估血压(BP)和心率(HR)。检测支气管肺泡灌洗(BAL)液细胞分类、白细胞介素6(IL - 6)和其他促炎细胞因子;血清C反应蛋白(CRP)和触珠蛋白(HPT);以及血浆纤维蛋白原。测量肺和心脏中血红素加氧酶1(HO - 1)、内皮素1(ET1)、内皮素受体A、B(ETA、ETB)、组织因子(TF)和纤溶酶原激活物抑制剂 - 1(PAI - 1)的转录水平,以评估氧化应激、内皮功能障碍和凝血级联反应。

结果

暴露于UfCP的老年SHR在第1天恢复时血压(BP)升高4.4%,心率(HR)升高6.3%,同时BAL液中中性粒细胞增加58%,IL - 6增加25%。同时,暴露的SHR中较高的CRP、HPT和纤维蛋白原水平表明全身炎症。在第1天恢复时,老年SHR肺中HO - 1、ET1、ET - A、ET - B、TF和PAI - 1诱导增加1.5 - 2.0倍。然而,在暴露于UfCP的成年SHR中,这些标志物在第3天恢复时在肺中上调(2.5 - 6倍),且未检测到肺部/全身炎症。

结论

UfCP在老年SHR中诱导的肺部和全身炎症与氧化应激、内皮功能障碍和凝血止血紊乱有关。UfCP暴露使老年SHR大鼠的血压和心率升高,这与肺部炎症有关,并且老年SHR中炎症、血管收缩和凝血标志物的表达增加以及血栓形成生物标志物的全身变化有关。我们的研究为解释心血管功能受损的老年个体中颗粒介导的心脏健康影响风险增加的潜在分子机制提供了进一步证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41ed/4410795/8ab37f73c904/12989_2014_36_Fig1_HTML.jpg

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