Objective
To validate and to compare the circulating microRNA (miR) expression profiles between pre‐eclampsia and healthy pregnant women, to perform correlation analysis of the differently expressed ...miRs with clinical and biochemical parameters, and to verify the extracellular localisation of miRs in apoptotic bodies, microvesicles, and exosomes.
Design
A case–control study with a replication study.
Setting
Pregnant women attending maternity hospitals in Southeastern Brazil.
Population
Two obstetric white populations: a case–control study (19 pre‐eclampsia and 14 healthy pregnant) and a replication study (eight pre‐eclampsia and eight healthy pregnant).
Methods
PCR‐array with 84 different miRs was performed in plasma from five pre‐eclampsia and four healthy pregnant women. In the case–control study, differently expressed miRs were validated using quantitative real‐time reverse transcription polymerase chain reaction (qRT‐PCR), and correlated with clinical and biochemical parameters. The plasma was then fractioned to study the extracellular localisation of miRs.
Main outcome measures
Gene expression profiles of miRs.
Results
From PCR‐array, three miRs (miR‐376c‐3p, miR‐19a‐3p, and miR‐19b‐3p) were found to be down‐regulated and the miR‐885‐5p was found to be up‐regulated in pre‐eclampsia compared with healthy pregnant women. In the validation step, miR‐885‐5p was the only significantly different miR (fold‐change = 5.0, P < 0.05), which was confirmed in the replication study (fold‐change = 4.5, P < 0.05). Moreover, miR‐885‐5p was significantly correlated with the hepatic enzyme aspartate transaminase (r = 0.66; P = 0.0034) and it was mostly associated with the exosomes (32‐fold higher than apoptotic bodies).
Conclusions
miR‐885‐5p is increased in plasma from pre‐eclampsia compared with healthy pregnant women, and it is released into circulation mainly inside exosomes.
Tweetable
miR‐885‐5p is increased in pre‐eclampsia and is released into circulation mainly inside exosomes.
Tweetable
miR‐885‐5p is increased in pre‐eclampsia and is released into circulation mainly inside exosomes.
Background and purpose: Increased oxidative stress and up‐regulation of matrix metalloproteinases (MMPs) may cause structural and functional vascular changes in renovascular hypertension. We ...examined whether treatment with spironolactone (SPRL), hydrochlorothiazide (HCTZ) or both drugs together modified hypertension‐induced changes in arterial blood pressure, aortic remodelling, vascular reactivity, oxidative stress and MMP levels and activity, in a model of renovascular hypertension.
Experimental approach: We used the two‐kidney,one‐clip (2K1C) model of hypertension in Wistar rats. Sham‐operated or hypertensive rats were treated with vehicle, SPRL (25 mg·kg−1·day−1), HCTZ (20 mg·kg−1·day−1) or a combination for 8 weeks. Systolic blood pressure was monitored weekly. Aortic rings were isolated to assess endothelium‐dependent and ‐independent relaxations. Morphometry of the vascular wall was carried out in sections of aorta. Aortic NADPH oxidase activity and superoxide production were evaluated. Formation of reactive oxygen species was measured in plasma as thiobarbituric acid‐reactive substances. Aortic MMP‐2 levels and activity were determined by gelatin and in situ zymography, fluorimetry and immunohistochemistry.
Key results: Treatment with SPRL, HCTZ or the combination attenuated 2K1C‐induced hypertension, and reversed the endothelial dysfunction in 2K1C rats. Both drugs or the combination reversed vascular aortic remodelling induced by hypertension, attenuated hypertension‐induced increases in oxidative stress and reduced MMP‐2 levels and activity.
Conclusions and implications: SPRL or HCTZ, alone or combined, exerted antioxidant effects, and decreased renovascular hypertension‐induced MMP‐2 up‐regulation, thus improving the vascular dysfunction and remodelling found in this model of hypertension.
BACKGROUND AND PURPOSE Mounting evidence implicates matrix metalloproteinase (MMP) in the vascular dysfunction and remodelling associated with hypertension. We tested the hypothesis that treatment ...with pyrrolidine dithiocarbamate (PDTC), which interferes with NF‐κB‐induced MMPs gene transcription, could exert antihypertensive effects, prevent MMP‐2 and MMP‐9 up‐regulation, and protect against the functional alterations and vascular remodelling of two‐kidney, one clip (2K1C) hypertension.
EXPERIMENTAL APPROACH Sham‐operated or hypertensive rats were treated with vehicle or PDTC (100 mg·Kg−1·day−1) by gavage for 8 weeks. Systolic blood pressure (SBP) was monitored weekly. Aortic rings were isolated to assess endothelium‐dependent relaxations. Quantitative morphometry of structural alterations of the aortic wall was carried out in haematoxylin/eosin sections. Formation of vascular reactive oxygen species (ROS), and inducible (i) NOS and phosphorylated‐p65 NF‐κB subunit expression were measured in the aortas. MMP‐2 and MMP‐9 aortic levels and gelatinolytic activity were determined by gelatin and in situ zymography and by immunofluorescence.
KEY RESULTS Treatment with PDTC attenuated the increases in SBP and prevented the endothelial dysfunction associated with 2K1C hypertension. Moreover, PDTC reversed the vascular aortic remodelling, the increases in aortic ROS levels and in iNOS and phosphorylated‐p65 NF‐κB expression found in 2K1C rats. These effects were associated with attenuation of 2K1C up‐regulation of aortic MMP‐2 and MMP‐9 levels and gelatinolytic activity.
CONCLUSION AND IMPLICATIONS These findings suggest that PDTC down‐regulates vascular MMPs and ameliorates vascular dysfunction and remodelling in renovascular hypertension, thus providing evidence supporting the suggestion that PDTC is probably a good candidate to be used to treat hypertension.
Lead concentration in whole blood (BPb) is the primary biomarker used to monitor exposure to this metallic element. The U.S. Centers for Disease Control and Prevention and the World Health ...Organization define a BPb of 10 μg/dL (0.48 μmol/L) as the threshold of concern in young children. However, recent studies have reported the possibility of adverse health effects, including intellectual impairment in young children, at BPb levels < 10 μg/dL, suggesting that there is no safe level of exposure. It appears impossible to differentiate between low-level chronic Pb exposure and a high-level short Pb exposure based on a single BPb measurement; therefore, serial BPb measurements offer a better estimation of possible health outcomes. The difficulty in assessing the exact nature of Pb exposure is dependent not so much on problems with current analytical methodologies, but rather on the complex toxicokinetics of Pb within various body compartments (i.e., cycling of Pb between bone, blood, and soft tissues). If we are to differentiate more effectively between Pb stored in the body for years and Pb from recent exposure, information on other biomarkers of exposure may be needed. None of the current biomarkers of internal Pb dose have yet been accepted by the scientific community as a reliable substitute for a BPb measurement. This review focuses on the limitations of biomarkers of Pb exposure and the need to improve the accuracy of their measurement. We present here only the traditional analytical protocols in current use, and we attempt to assess the influence of confounding variables on BPb levels. Finally, we discuss the interpretation of BPb data with respect to both external and endogenous Pb exposure, past or recent exposure, as well as the significance of Pb determinations in human specimens including hair, nails, saliva, bone, blood (plasma, whole blood), urine, feces, and exfoliated teeth.
Hypertension is associated with cardiovascular remodeling. Given that impaired redox state activates matrix metalloproteinase (MMP)− 2 and promotes vascular remodeling, we hypothesized that nitrite ...treatment at a non-antihypertensive dose exerts antioxidant effects and attenuates both MMP-2 activation and vascular remodeling of hypertension. We examined the effects of oral sodium nitrite at antihypertensive (15 mg/kg) or non-antihypertensive (1 mg/kg) daily dose in hypertensive rats (two kidney, one clip; 2K1C model). Sham-operated and 2K1C hypertensive rats received vehicle or nitrite by gavage for four weeks. Systolic blood pressure decreased only in hypertensive rats treated with nitrite 15 mg/Kg/day. Both low and high nitrite doses decreased 2K1C-induced vascular remodeling assessed by measuring aortic cross-sectional area, media/lumen ratio, and number of vascular smooth muscle cells/aortic length. Both low and high nitrite doses decreased 2K1C-induced vascular oxidative stress assessed in situ with the fluorescent dye DHE and with the lucigenin chemiluminescence assay. Vascular MMP-2 expression and activity were assessed by gel zymography, Western blot, and in situ zymography increased with hypertension. While MMP-2 levels did not change in response to both doses of nitrite, both doses completely prevented hypertension-induced increases in vascular MMP activity. Moreover, incubation of aortas from hypertensive rats with nitrite at 1–20 μmol/L reduced gelatinolytic activity by 20–30%. This effect was fully inhibited by the xanthine oxidase (XOR) inhibitor febuxostat, suggesting XOR-mediated generation of nitric oxide (NO) from nitrite as a mechanism explaining the responses to nitrite. In vitro incubation of aortic extracts with nitrite 20 μmol/L did not affect MMP-2 activity. These results show that nitrite reverses the vascular structural alterations of hypertension, independently of anti-hypertensive effects. This response is mediated, at least in part, by XOR and is attributable to antioxidant effects of nitrite blunting vascular MMP-2 activation. Our findings suggest nitrite therapy to reverse structural alterations of hypertension.
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•Hypertension promotes vascular remodeling.•We investigated the effects of nitrite on vascular remodeling of hypertension.•Nitrite exerted antioxidant effects and inhibited vascular MMP-2 activity.•Antioxidant effects of nitrite inhibit MMP-2 and vascular remodeling of hypertension.
Summary
Fractures are common in the Earth's crust due to different factors, for instance, tectonic stresses and natural or artificial hydraulic fracturing caused by a pressurized fluid. A dense set ...of fractures behaves as an effective long-wavelength anisotropic medium, leading to azimuthally varying velocity and attenuation of seismic waves. Effective in this case means that the predominant wavelength is much longer than the fracture spacing. Here, fractures are represented by surface discontinuities in the displacement u and particle velocity v as , where the brackets denote the discontinuity across the surface, is a fracture stiffness and is a fracture viscosity.
We consider an isotropic background medium, where a set of fractures are embedded. There exists an analytical solution-with five stiffness components-for equispaced plane fractures and an homogeneous background medium. The theory predicts that the equivalent medium is transversely isotropic and viscoelastic. We then perform harmonic numerical experiments to compute the stiffness components as a function of frequency, by using a Galerkin finite-element procedure, and obtain the complex velocities of the medium as a function of frequency and propagation direction, which provide the phase velocities, energy velocities (wavefronts) and quality factors. The algorithm is tested with the analytical solution and then used to obtain the stiffness components for general heterogeneous cases, where fractal variations of the fracture compliances and background stiffnesses are considered.
SUMMARY
A dominant P‐wave attenuation mechanism in reservoir rocks at seismic frequencies is due to wave‐induced fluid flow (mesoscopic loss). The P‐wave induces a fluid‐pressure difference at ...mesoscopic‐scale inhomogeneities (larger than the pore size but smaller than the wavelength), generating fluid flow and slow (diffusion) Biot waves. The theory has been developed in the 1970s for the symmetry axis of the equivalent transversely isotropic (TI) medium corresponding to a finely layered medium, and has recently been generalized to all propagation angles. The new theory states that the fluid‐flow direction is perpendicular to the layering plane and it is independent of the loading direction. As a consequence, the relaxation behaviour can be described by a single relaxation function, since the medium consists of plane homogeneous layers. Besides P‐wave losses, the coupling between the qP and qSV waves generates shear‐wave anisotropic velocity dispersion and attenuation.
In this work, we introduce a set of quasi‐static numerical experiments to determine the equivalent viscoelastic TI medium to a finely layered poroelastic medium, which is validated using a recently developed analytical solution. The modelling technique is the finite‐element (FE) method, where the equations of motion are solved in the space‐frequency domain. Numerical rock physics may, in many circumstances, offer an alternative to laboratory measurements. Numerical experiments are inexpensive and informative since the physical process of wave propagation can be inspected during the experiment. Moreover, they are repeatable, essentially free from experimental errors, and may easily be run using alternative models of the rock and fluid properties.
We apply the methodology to the Utsira aquifer of the North Sea, where carbon dioxide (CO2) has been injected during the last 15 years. The tests consider alternating layers of the same rock saturated with gas and brine and a sequence of gas‐saturated sandstone and mudstone layers, which represent possible models of the reservoir and cap rock of the aquifer system. The numerical examples confirm the new theory and illustrate the implementation of the harmonic tests to determine the complex and frequency‐dependent effective stiffnesses and the associated wave velocities and quality factors.
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