Sites Of Vascular Disease Research Articles

Nanoparticle translocation and multi-organ toxicity: A particularly small problem.

Environmental nanoparticles and manufactured nanoparticles (MNMs) can share many of the same physicochemical properties and, therefore, could have similar toxicological profiles. Inhalation of nanoparticles in air pollution has effects throughout the body; however, the potential for inhaled MNMs to affect multiple organs requires further investigation. The biological mechanisms that link nanoparticles deposition in the lung to their systemic actions remain to be established; however, the passage of nanoparticles into the blood ("translocation") represents a compelling explanation. This article highlights experimental work in animals and man showing that inhaled gold nanoparticles pass into the blood and accumulate at sites of vascular disease. The article discusses the properties of nanoparticles that could influence translocation and highlights some avenues for future research. The processes described have clear relevance, both for MNMs and sources of nanoparticles in air pollution. The authors emphasise the need for risk assessment of potential nanoparticle exposure routes that consider the multiple organ systems.

Correction to"Inhaled Nanoparticles Accumulate at Sites of Vascular Disease".

RETURN TO ISSUEPREVAdditions and Correc...Additions and CorrectionsNEXTORIGINAL ARTICLEThis notice is a correctionCorrection to“Inhaled Nanoparticles Accumulate at Sites of Vascular Disease”Mark R. Miller*, Jennifer B. Raftis, Jeremy P. Langrish, Steven G. McLean, Pawitrabhorn Samutrtai, Shea P. Connell, Simon Wilson, Alex T. Vesey, Paul H. B. Fokkens, A. John F. Boere, Petra Krystek, Colin J. Campbell, Patrick W. F. Hadoke, Ken Donaldson, Flemming R. Cassee, David E. Newby, Rodger Duffin, and Nicholas L. MillsCite this: ACS Nano 2017, 11, 10, 10623–10624Publication Date (Web):October 4, 2017Publication History Received5 September 2017Published online4 October 2017Published inissue 24 October 2017https://doi.org/10.1021/acsnano.7b06327Copyright © 2017 American Chemical SocietyRIGHTS & PERMISSIONSwith CC-BYlicenseArticle Views1490Altmetric-Citations15LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (243 KB) Get e-AlertsSUBJECTS:Anatomy,Gold,Nanoparticles,Chemical calculations Get e-Alerts

Inhaled Nanoparticles Accumulate at Sites of Vascular Disease.

The development of engineered nanomaterials is growing exponentially, despite concerns over their potential similarities to environmental nanoparticles that are associated with significant cardiorespiratory morbidity and mortality. The mechanisms through which inhalation of nanoparticles could trigger acute cardiovascular events are emerging, but a fundamental unanswered question remains: Do inhaled nanoparticles translocate from the lung in man and directly contribute to the pathogenesis of cardiovascular disease? In complementary clinical and experimental studies, we used gold nanoparticles to evaluate particle translocation, permitting detection by high-resolution inductively coupled mass spectrometry and Raman microscopy. Healthy volunteers were exposed to nanoparticles by acute inhalation, followed by repeated sampling of blood and urine. Gold was detected in the blood and urine within 15 min to 24 h after exposure, and was still present 3 months after exposure. Levels were greater following inhalation of 5 nm (primary diameter) particles compared to 30 nm particles. Studies in mice demonstrated the accumulation in the blood and liver following pulmonary exposure to a broader size range of gold nanoparticles (2–200 nm primary diameter), with translocation markedly greater for particles <10 nm diameter. Gold nanoparticles preferentially accumulated in inflammation-rich vascular lesions of fat-fed apolipoproteinE-deficient mice. Furthermore, following inhalation, gold particles could be detected in surgical specimens of carotid artery disease from patients at risk of stroke. Translocation of inhaled nanoparticles into the systemic circulation and accumulation at sites of vascular inflammation provides a direct mechanism that can explain the link between environmental nanoparticles and cardiovascular disease and has major implications for risk management in the use of engineered nanomaterials.

In vivo assessment of endothelial function in human lower extremity arteries

Endothelial function has been measured in preclinical studies in human brachial and coronary arteries but not in lower extremity arteries affected by atherosclerosis. We describe a novel, first-in-man evaluation of endothelial function of the superficial femoral arteries (SFAs) in patients with peripheral arterial disease (PAD). Enrolled were 25 patients with PAD requiring lower extremity angiography. Endothelial-dependent relaxation was measured using intravascular ultrasound (IVUS) imaging and a Doppler flow wire after the infusion of acetylcholine (Ach). IVUS-derived virtual histology of the same vessel was calculated. Endothelial-independent relaxation was measured with an infusion of nitroglycerin (200 μg). Levels of nitric oxide and serum nitric oxide metabolites were determined by laboratory analysis. Patients (48% male; mean age, 62 years) had a history of hypertension (80%), coronary disease (36%), and diabetes (40%). The mean SFA diameter was 5.2 ± 1 mm (range, 3.2-6.9 mm). Patients tolerated Ach infusion with no adverse events. Endothelial-dependent relaxation increased over baseline for all patients with Ach infusion of 10(-6) to 10(-4). At Ach 10(-4), diameter (0.5%) and area (1.8%) changes in the diseased SFAs were modest and insignificant; however, average peak velocity of blood flow significantly increased 26%, 46%, and 63% with an Ach 10(-6) to 10(-4) infusion. Calculations of limb volumetric flow (68% at Ach 10(-4)) were significantly increased after Ach infusion. Lower extremity nitric oxide levels were slightly lower than systemic venous levels (P = .04). Nitroglycerin infusion indicated normal smooth muscle responsiveness (3% diameter, 9% area, and 116% velocity change over baseline). IVUS-virtual histology plaque stratification indicated predominantly fibrous morphology (46%; necrotic core, 29%; calcium, 18%). Atheroma burden was 14.9 ± 5.5 mm(3)/cm and did not correlate with endothelial responsiveness. Endothelial function can be measured directly in human lower extremity arteries at the sites of vascular disease. Despite extensive atherosclerosis, endothelial function is still intact. These data support the application of regional endothelial-specific biologic therapies in patients with PAD.

The role of tenascin C in cardiovascular disease

The extracellular matrix protein tenascin C (TnC) is expressed in a variety of embryonic tissues, but its expression in adult arteries is co-incident with sites of vascular disease. TnC expression has been linked to the development and complications of intimal hyperplasia, pulmonary artery hypertension, atherosclerosis, myocardial infarction, and heart failure. This review identifies the growing collection of evidence linking TnC with cardiovascular disease development. The transient upregulation of this extracellular matrix protein at sites of vascular disease could provide a means to target TnC in the development of diagnostics and new therapies. Studies in TnC-deficient mice have implicated this protein in the development of intimal hyperplasia. Further animal and human studies are required to thoroughly assess the role of TnC in some of the other pathologies it has been linked with, such as atherosclerosis and pulmonary hypertension. Large population studies are also warranted to clarify the diagnostic value of this extracellular matrix protein in cardiovascular disease, for example by targeting its expression using radiolabelled antibodies or measuring circulating concentrations of TnC.

Overview: the current role of the vascular diagnostic laboratory.

T HE TESTING METHODS used in the noninvasive vascular diagnostic laboratory have evolved over the last 40 years to bridge the gap between the subjective clinical assessment of vascular disorders and invasive contrast studies of the arteries and veins. Many of the early noninvasive tests utilized continuous wave Doppler ultrasound to detect blood flow. These tests were referred to as indirect methods because they relied on detection of major changes in pressure or flow produced by arterial or venous disease. Therefore, only hemodynamically significant lesions could be identified reliably. The indirect tests included the periorbital Doppler examination for extracranial carotid artery disease, the continuous wave Doppler evaluation for deep vein thrombosis, and segmental arterial blood pressure measurement in the extremities. Some of these tests, such as measurement of ankle systolic blood pressure, still are useful in the clinical setting, but most have given way to the direct approach of duplex scanning. 1 The principal advantage of duplex scanning is that it obtains both anatomic and physiologic information directly from sites of vascular disease. Since duplex scanning emerged in the 1980s as the preferred noninvasive test for extracranial carotid artery disease, advances in ultrasound technology have extended its applications to the vessels of the abdomen and extremities. This combination of B-mode imaging and spectral analysis of pulsed Doppler signals provided the first opportunity to accurately characterize vascular disease without resorting to invasive procedures. The duplex approach is based on the concept that arterial lesions produce localized disturbances in blood flow patterns that can be characterized by analysis of Doppler flow signals. Accordingly, the B-mode image is used to place a pulsed Doppler sample volume within the vessel of interest, and the local flow pattern is assessed by spectral waveform analysis. Although the B-mode image may be valuable for identifying anatomic variants, arterial wall thickening or calcification, and thrombi in the venous system, it has not been possible to determine accurately the degree of arterial narrowing from the B-mode image alone. Therefore, the classification of arterial disease severity mainly is based on interpretation of pulsed Doppler spectral waveforms. Color-flow imaging is an alternative to spectral waveform analysis for displaying Doppler information. Within certain technical limitations, the color-flow image permits visualization of moving blood in the plane of the B-mode image; it can be helpful for identifying vessels, particularly when they are small, deeply located, or anatomically complex. However, it is difficult to assess disease severity based on the color-flow image alone, and spectral waveforms still are necessary for accurate disease classification. While the noninvasive vascular diagnostic laboratory initially was of interest only to vascular