Impact of pulmonary exposure to gold core silver nanoparticles of different size and capping agents on cardiovascular injury.
Impact of pulmonary exposure to gold core silver nanoparticles of different size and capping agents on cardiovascular injury.
复制标题
DOI：
10.1186/s12989-016-0159-z
复制
发表时间：
2016-08-24
影响因子：
10
通讯作者：
Wingard CJ
中科院分区：
文献类型：
--
作者：
Holland NA;Thompson LC;Vidanapathirana AK;Urankar RN;Lust RM;Fennell TR;Wingard CJ
工程纳米材料在生物医学技术和消费制造业中的应用已经扩大。此外，肺部暴露于各种工程纳米材料也同样被证明有能力加剧心脏缺血再灌注（I/R）损伤。然而，颗粒大小或封盖剂的影响尚不清楚。为了解决这些影响，我们在2个不同的时间点研究了两种不同封盖剂对2种不同尺寸的金芯纳米银颗粒（AgNP）的反应。我们假设肺部暴露于AgNP可诱导受炎症和血管功能障碍影响的心血管毒性，导致对颗粒大小和封盖剂敏感的心脏I/R损伤扩大。雄性Sprague-Dawley大鼠分别暴露于200 μg的20或110 nm聚乙烯丙烯酮（PVP）或柠檬酸盐覆盖AgNP。在气管内灌注1天和7天后分析血清中选定细胞因子的浓度；评估心脏I/R损伤和离体冠状动脉和主动脉段收缩反应、内皮依赖性松弛和内皮非依赖性一氧化氮依赖性松弛。AgNP灌注导致选定的血清细胞因子适度增加，IL-2、IL-18和IL-6升高。注射导致血管对收缩剂5 -羟色胺或苯肾上腺素的反应紊乱，以及乙酰胆碱的内皮依赖性松弛或硝普钠的内皮依赖性松弛以一种覆盖和大小依赖的方式。暴露于20 nm和110 nm AgNP下，在IT灌注1天后，心脏I/R损伤加重，而20 nm AgNP不依赖于封堵剂，其损伤程度略大。IT灌注7天后，I/R损伤持续扩大，但最大的损伤与暴露于110 nm PVP覆盖的AgNP相关，导致梗死面积比naïve大近两倍。暴露于AgNP可能导致血管功能障碍，免疫系统对继发性损伤（如心脏I/R）的潜在适应性不良敏化，这可能在IT注入后1天和7天导致I/R损伤扩大，其中损伤程度可能与封盖剂和AgNP大小相关。本文的在线版本（doi:10.1186/s12989-016-0159-z）包含补充材料，可供授权用户使用。
The uses of engineered nanomaterials have expanded in biomedical technology and consumer manufacturing. Furthermore, pulmonary exposure to various engineered nanomaterials has, likewise, demonstrated the ability to exacerbate cardiac ischemia reperfusion (I/R) injury. However, the influence of particle size or capping agent remains unclear. In an effort to address these influences we explored response to 2 different size gold core nanosilver particles (AgNP) with two different capping agents at 2 different time points. We hypothesized that a pulmonary exposure to AgNP induces cardiovascular toxicity influenced by inflammation and vascular dysfunction resulting in expansion of cardiac I/R Injury that is sensitive to particle size and the capping agent. Male Sprague–Dawley rats were exposed to 200 μg of 20 or 110 nm polyvinylprryolidone (PVP) or citrate capped AgNP. One and 7 days following intratracheal instillation serum was analyzed for concentrations of selected cytokines; cardiac I/R injury and isolated coronary artery and aorta segment were assessed for constrictor responses and endothelial dependent relaxation and endothelial independent nitric oxide dependent relaxation. AgNP instillation resulted in modest increase in selected serum cytokines with elevations in IL-2, IL-18, and IL-6. Instillation resulted in a derangement of vascular responses to constrictors serotonin or phenylephrine, as well as endothelial dependent relaxations with acetylcholine or endothelial independent relaxations by sodium nitroprusside in a capping and size dependent manner. Exposure to both 20 and 110 nm AgNP resulted in exacerbation cardiac I/R injury 1 day following IT instillation independent of capping agent with 20 nm AgNP inducing marginally greater injury. Seven days following IT instillation the expansion of I/R injury persisted but the greatest injury was associated with exposure to 110 nm PVP capped AgNP resulted in nearly a two-fold larger infarct size compared to naïve. Exposure to AgNP may result in vascular dysfunction, a potentially maladaptive sensitization of the immune system to respond to a secondary insult (e.g., cardiac I/R) which may drive expansion of I/R injury at 1 and 7 days following IT instillation where the extent of injury could be correlated with capping agents and AgNP size. The online version of this article (doi:10.1186/s12989-016-0159-z) contains supplementary material, which is available to authorized users.