Exacerbation of Thrombotic Responses to Silver Nanoparticles in Hypertensive Mouse Model

Abstract

With advent of nanotechnology, silver nanoparticles, AgNPs owing majorly to their antibacterial properties, are used widely in food industry and biomedical applications implying human exposure by various routes including inhalation. Several reports have suggested AgNPs induced pathophysiological effects in a cardiovascular system. However, cardiovascular diseases such as hypertension may interfere with AgNPs-induced response, yet majority of them are understudied. The aim of this work was to evaluate the thrombotic complications in response to polyethylene glycol- (PEG-) coated AgNPs using an experimental hypertensive (HT) mouse model. Saline (control) or PEG-AgNPs (0.5 mg/kg) were intratracheally (i.t.) instilled four times, i.e., on days 7, 14, 21, and 28 post-angiotensin II-induced HT, or vehicle (saline) infusion. On day 29, various parameters were assessed including thrombosis in pial arterioles and venules, platelet aggregation in whole blood in vitro, plasma markers of coagulation, and fibrinolysis and systemic oxidative stress. Pulmonary exposure to PEG-AgNPs in HT mice induced an aggravation of in vivo thrombosis in pial arterioles and venules compared to normotensive (NT) mice exposed to PEG-AgNPs or HT mice given saline. The prothrombin time, activated partial thromboplastin time, and platelet aggregation in vitro were exacerbated after exposure to PEG-AgNPs in HT mice compared with either NT mice exposed to nanoparticles or HT mice exposed to saline. Elevated concentrations of fibrinogen, plasminogen activator inhibitor-1, and von Willebrand factor were seen after the exposure to PEG-AgNPs in HT mice compared with either PEG-AgNPs exposed NT mice or HT mice given with saline. Likewise, the plasma levels of superoxide dismutase and nitric oxide were augmented by PEG-AgNPs in HT mice compared with either NT mice exposed to nanoparticles or HT mice exposed to saline. Collectively, these results demonstrate that PEG-AgNPs can potentially exacerbate the in vivo and in vitro procoagulatory and oxidative stress effect in HT mice and suggest that population with hypertension are at higher risk of the toxicity of PEG-AgNPs.

Mapping research performance and hotspots on nanoparticles in cardiovascular diseases

“…In the second decade, the number of publications increased sharply, and the increasing numbers of researchers began to focus on the effects of nanoparticles in cardiovascular field, denoting that the research of nanoparticles is becoming even more mature. [33][34][35][36] China and the US contribute the most to this sphere, generating nearly all the most influential authors and institutions of the top 10 list. Not only do they possess their own cooperation networks, but there is also plenty of cooperation between these 2 countries.…”

“…In the second decade, the number of publications increased sharply, and the increasing numbers of researchers began to focus on the effects of nanoparticles in cardiovascular field, denoting that the research of nanoparticles is becoming even more mature. [33–36]…”

Palliative effects of carnosol on lung‐deposited pollutant particles‐induced thrombogenicity and vascular injury in mice

“…In vitro evaluation of aPTT and PT in blood was carried out as previously described. 19 , 20 After pulmonary administration of DEP or saline, with or without carnosol treatment, animals were anesthetized as indicated earlier, and blood was collected from the inferior vena cava and mixed with 3.8% citrate solution (blood to anticoagulant ratio: 9:1). PT was assessed on freshly obtained platelet‐poor plasma using recombiplastin (human relipidated recombinant thromboplastin) from Instrumentation Laboratory (Orangeburg, NY, USA) with a coagulometer (MC 1 VET, Merlin, Lemgo, Germany).…”

“…In vitro evaluation of aPTT and PT in blood was carried out as previously described 19,20 . After pulmonary administration of DEP or saline, with or without carnosol treatment, animals were anesthetized as indicated earlier, and blood was collected from the inferior vena cava and mixed with 3.8% citrate solution (blood to anticoagulant ratio: 9:1).…”

Metal-Based Nanoparticles for Cardiovascular Diseases

“…AgNPs have been shown to harm the skin, sperm cells, liver, bone marrow, lungs, spleen, kidneys, and vasculature. Evidence indicates that these NPs cause defective ubiquitination autophagosome-lysosome fusion at the subcellular level [82]. Future, in-depth studies on the genotoxicity of AgNPs and their potential role in cancer are now of interest, as evidenced by multiple studies [83].…”