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1.
ACS Nano ; 16(6): 9142-9149, 2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35604126

RESUMO

Biological ion pumps selectively transport target ions against the concentration gradient, a process that is crucial to maintaining the out-of-equilibrium states of cells. Building an ion pump with ion selectivity has been challenging. Here we show that a Ti3C2Tx MXene film suspended in air with a trapezoidal shape spontaneously pumps K+ ions from the base end to the tip end and exhibits a K+/Na+ selectivity of 4. Such a phenomenon is attributed to a range of properties of MXene. Thanks to the high stability of MXene in water and the dynamic equilibrium between evaporation and swelling, the film keeps a narrow interlayer spacing of ∼0.3 nm when its two ends are connected to reservoirs. Because of the polar electrical structure and hydrophilicity of the MXene nanosheet, K+ ions experience a low energy barrier of ∼4.6 kBT when entering these narrow interlayer spacings. Through quantitative simulations and consistent experimental results, we further show that the narrow spacings exhibit a higher energy barrier to Na+, resulting in K+/Na+ selectivity. Finally, we show that the spontaneous ion transport is driven by the asymmetric evaporation of the interlayer water across the film, a mechanism that is similar to pressure driven streaming current. This work shows how ion transport properties can be facilely manipulated by tuning the macroscopic shape of nanofluidic materials, which may attract interest in the interface of kirigami technologies and nanofluidics and show potential in energy and separation applications.

2.
Adv Mater ; 34(2): e2102026, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34668245

RESUMO

The ever-growing market of electric vehicles and the upcoming grid-scale storage systems have stimulated the fast growth of renewable energy storage technologies. Aluminum-based batteries are considered one of the most promising alternatives to complement or possibly replace the current lithium-ion batteries owing to their high specific capacity, good safety, low cost, light weight, and abundant reserves of Al. However, the anode problems in primary and secondary Al batteries, such as, self-corrosion, passive film, and volume expansion, severely limit the batteries' practical performance, thus hindering their commercialization. Herein, an overview of the currently emerged Al-based batteries is provided, that primarily focus on the recent research progress for Al anodes in both primary and rechargeable systems. The anode reaction mechanisms and problems in various Al-based batteries are discussed, and various strategies to overcome the challenges of Al anodes, including surface oxidation, self-corrosion, volume expansion, and dendrite growth, are systematically summarized. Finally, future research perspectives toward advanced Al batteries with higher performance and better safety are presented.

3.
Mater Sci Eng C Mater Biol Appl ; 113: 110959, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32487381

RESUMO

Developing new materials with high strength and ductility, low modulus and high biocompatibility is a continuing demand in the field of surgical implants. Inspired by the high-entropy design philosophy, two medium entropy alloys (MEAs), i.e. equiatomic TiZrHf and equi-weight Ti40Zr20Hf10Nb20Ta10 were designed and their mechanical properties and biocompatibility were assessed. Both the single-phase hexagonal close-packed (HCP) structured TiZrHf alloy and the single-phase body-centered cubic (BCC) structured Ti40Zr20Hf10Nb20Ta10 alloy show high strength-ductility combinations close to commercial Ti-6Al-4V wrought alloy and remarkably lower young's modulus than commercial pure titanium (CP-Ti) and Ti-6Al-4V. From the aspects of adhesion, proliferation, toxicity and related gene expression of human gingival fibroblasts (HGFs), the Ti40Zr20Hf10Nb20Ta10 alloy exhibits distinctively better biocompatibility than that of CP-Ti while the TiZrHf shows only slightly better biocompatibility as compared with CP-Ti. These results indicate that these two ductile MEAs are potential candidates for dental application.


Assuntos
Ligas/química , Materiais Biocompatíveis/química , Implantes Dentários , Materiais Biocompatíveis/farmacologia , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Corrosão , Planejamento de Prótese Dentária , Módulo de Elasticidade , Entropia , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Resistência à Tração , Titânio/química , Regulação para Cima/efeitos dos fármacos
4.
Materials (Basel) ; 13(11)2020 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-32521734

RESUMO

In this study, a new model involving energy is established to characterize the size effect on flow stress. The new model treats the experimental machine and the specimen as an isolated system, and this isolated system satisfies the Energy Conservation Law. The total work performed on the specimen by the experimental machine is nearly equal to the energy consumed by the specimen plastic deformation and the energy consumed by friction (which can be ignored when working without friction). The new model predicts the energy consumption of the specimen deformation by quantifying the total energy input to the specimen by the experimental machine and then obtaining the relevant parameters of the constitutive model. Through uniaxial tensile tests of pure nickel thin sheets with various thickness/average grain sizes (t/d), the new model was used to optimize the parameters of the existing constitutive model that predicts the flow stress of specimens with different t/d. The prediction accuracy of the optimized constitutive model is improved, especially for specimens with a t/d < 1. The new model is established from the perspective of energy input to avoid the analysis of the material deformation mechanism and improve the prediction accuracy.

5.
J Mech Behav Biomed Mater ; 109: 103842, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32543409

RESUMO

In this work, TC4/TNTZO multi-layered composite as well as TNTZO and TC4 alloys were prepared by direct laser deposition (DLD) to investigate the microstructure, mechanical properties and in vitro bioactivity. The microstructure characterization shows that the multi-layered material is free of cracks and intermetallics while the interface is metallurgically bonded. The fine microstructure was observed in TC4 layer of the TC4/TNTZO multi-layered material, and a large amount of α' martensite exists in the transition zone. Different from the single ß phase cellular arrays in the DLD-ed TNTZO alloy, α″ martensite with high volume content formed at the cellular grain boundary in TNTZO zone of DLD-ed TC4/TNTZO. The elastic modulus of the DLD-ed TC4/TNTZO is 64 GPa, decreased about 45% compared to the DLD-ed TC4. The tensile yield strength and elongation along the printing direction are up to 789 MPa and 7%, which are 12% higher than the tensile yield strength of DLD-ed TNTZO and 61% higher than the elongation of DLD-ed TC4 respectively. Moreover, the DLD-ed TC4/TNTZO shows good in vitro bioactivity. The TC4/TNTZO multi-layered composite fabricated by DLD can be regarded as a potential candidate to integrate the advantages of the two Ti-base alloys for application in the biomedical field.


Assuntos
Ligas , Titânio , Módulo de Elasticidade , Lasers , Teste de Materiais , Resistência à Tração
6.
ACS Appl Mater Interfaces ; 12(16): 19194-19200, 2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32223253

RESUMO

The manipulation of liquid droplets on a specific surface with reversible wettability is of great importance for various applications from science to industry. Herein, the concept of a smart, flexible photodriven droplet motion (PDM) device with programmable wettability is designed using the 2D material of MXene film. Because of the MXene photothermal property, the Vaseline layer in the device is in transition between solid and liquid states under the heat transformation due to light illumination, thus attractively producing a reversible wettability for liquid motion with respect to sliding and pinning. Multifarious pathways for liquid motion could be designed through the flexibility of light illumination, which is a revolutionary enhancement in diverse liquid motion to form the desired pathways. In addition, we demonstrated liquid motion under illumination of the back face, which has a profound influence on applications, such as microfluidic systems, microengines, and liquid manipulation.

7.
Materials (Basel) ; 12(5)2019 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-30845716

RESUMO

Increasing the ingot size of GH4720Li superalloys makes it difficult to control their microstructure, and the withdrawal rate is an important factor in controlling and refining the microstructure of GH4720Li superalloys. In this study, GH4720Li superalloy samples were prepared via Bridgman-type directional solidification with different withdrawal rates. The morphology and average size of the dendrites in the stable growth zone during directional solidification in each sample, morphology and average size of the γ' phases, and microsegregation of each alloying element were analyzed using optical microscopy, Photoshop, Image Pro Plus, field emission scanning electron microscopy, and electron probe microanalysis. Increasing the withdrawal rate significantly helped in refining the superalloy microstructure; the average secondary dendrite arm spacing decreased from 133 to 79 µm, whereas the average sizes of the γ' phases in the dendrite arms and the interdendritic regions decreased from 1.02 and 2.15 µm to 0.69 and 1.26 µm, respectively. Moreover, the γ' phase distribution became more uniform. The microsegregation of Al, Ti, Cr, and Co decreased with the increase in the withdrawal rate; the segregation coefficients of Al, Cr, and Co approached 1 at higher withdrawal rates, whereas that of Ti remained above 2.2 at all the withdrawal rates.

8.
Materials (Basel) ; 11(9)2018 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-30217019

RESUMO

The characteristics and formation mechanisms of intragranular acicular ferrite (IAF) in steel with MgO nanoparticle additions were systematically investigated for different isothermal heat-treatment temperatures, and its influence on mechanical properties was also clarified. The results indicate that the inclusions were finely dispersed and refined after adding MgO nanoparticles. In addition, with decreasing heat-treatment temperature, the microstructure changed from grain boundary ferrite (GBF) and polygonal ferrite (PF) to intragranular acicular ferrite. Moreover, the steel with MgO additions had excellent mechanical properties in the temperature range of 973 to 823 K and an average Charpy absorbed energies value of around 174 J at 873 K due to the significant refinement of the microstructure and nucleation of intragranular acicular ferrite.

9.
Materials (Basel) ; 11(10)2018 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-30261696

RESUMO

The choice of melting technique is crucial for controlling the purity of a superalloy, which is especially important because purity has come to limit progress in the superalloy field. In this study, double- and triple-melting techniques were used to refine the GH4738 superalloy. Elemental analyses, inductively coupled plasma-atomic emission spectroscopy, X-ray diffraction analysis, scanning electron microscopy with energy-dispersive spectroscopy, high-temperature cupping machine, high-temperature fatigue testing machine, and Image-Pro Plus software were used to analyze and compare the contents of specific elements, the types and sizes of inclusions, the mechanical properties, and the probabilities of white spot formation using the two melting techniques. The effects of the different melting processes on the purity of the superalloy were systematically studied. In terms of controlling the presence of impurities, the triple-melting process resulted in lower levels of harmful N, S, and O impurities in the superalloy, the triple-melted superalloy also contained fewer types of inclusion of smaller sizes and in smaller amounts than the double-melted alloy. Triple melting also promotes tensile strength and fatigue life, and minimizes the probability of forming defects in the superalloy.

10.
Thromb Res ; 159: 58-64, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28982031

RESUMO

INTRODUCTION: The multifunctional serine protease thrombin exerts proinflammatory and profibrotic cellular effects that may contribute to cardiac remodeling. This study was designed to investigate whether direct thrombin inhibition with dabigatran attenuates myocardial injury in the setting of pressure overload-induced heart failure. MATERIAL AND METHODS: Transverse aortic constriction (TAC) surgery was performed on C57Bl/6J male mice to elicit cardiac hypertrophy. TAC, or sham, mice were randomly assigned to receive chow supplemented with the oral anticoagulant, dabigatran etexilate, or placebo. RESULTS: Dabigatran did not affect cardiac hypertrophy, as measured by heart weight-to-body weight or the heart weight-to-tibia length, although a non-significant reduction in myocardial hypertrophic markers (ANP, BNP and MHC) occurred. Dabigatran reduced perivascular fibrosis by 25%, interstitial fibrosis by 54%, and the expression of myocardial fibrosis markers collagen I & III, MMP9, SMA, and PAR-1. These changes were associated with significant improvement in both coronary flow reserve and global left ventricular function. In cultured cardiac fibroblasts, dabigatran decreased thrombin and PAR-1-mediated collagen deposition by 30% and 37%, respectively. CONCLUSIONS: Dabigatran attenuates cardiac fibrosis in the setting of pressure overload and improves coronary flow reserve and global cardiac function possibly by inhibiting thrombin activity and down-regulating PAR-1 expression in the absence of an effect on cardiomyocyte hypertrophy.


Assuntos
Dabigatrana/uso terapêutico , Fibrose/patologia , Miocárdio/patologia , Trombina/antagonistas & inibidores , Animais , Dabigatrana/farmacologia , Modelos Animais de Doenças , Humanos , Masculino , Camundongos
11.
Materials (Basel) ; 10(8)2017 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-28829393

RESUMO

The microstructure of continuously hot-dip galvanizing Zn-Mg coating was investigated in order to obtain the mechanism of the effects of Mg on the corrosion resistance. In this paper, the vertical section of the Zn-0.20 wt % Al-Mg ternary phase diagram near the Al-low corner was calculated. The results indicates that the phase composition of the Zn-0.20 wt % Al-Mg ternary phase diagram near the Al-low corner is the same as Zn-Mg binary phase diagram, suggesting Al in the Zn-Mg (ZM) coatings mainly concentrates on the interfacial layer between the coating and steel substrate. The microstructure of continuously hot-dip galvanizing ZM coatings with 0.20 wt % Al containing 1.0-3.0 wt % Mg was investigated using tunneling electron microscopy (TEM). The morphology of Zn in the coating changes from bulk to strip and finally to mesh-like, and the MgZn2 changes from rod-like to mesh-like with the Mg content increasing. Al in the ZM coatings mainly segregates at the Fe2Al5 inhibition layer and the Mg added to the Zn bath makes this inhibition layer thinner and uneven. Compared to GI coating, the time of the first red rust appears increases by more than two-fold and expansion rate of red rust reduces by more than four-fold in terms of salt spray experiment. The ZM coating containing 2.0 wt % Mg has the best corrosion resistance. The enhanced corrosion resistance of ZM coatings mainly depends on different corrosion products.

12.
Materials (Basel) ; 10(9)2017 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-28850088

RESUMO

The formation mechanism of TiC particles in a Ni-Ti-C system were revealed by using differential thermal analysis (DTA), XRD, and SEM to identify the reaction products in different temperature ranges. The results indicated that the synthesis mechanism of TiC in Ni-Ti-C system was complex; several reactions were involved in the combustion synthesis of TiC-Ni composite. The Ni-Ti intermediate phases play important roles during the formation of TiC. Moreover, the influence of heating rate on the size range of TiC was also discussed.

13.
JACC Basic Transl Sci ; 1(7): 633-643, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30167547

RESUMO

PF-1355 is an oral myeloperoxidase (MPO) inhibitor that successfully decreased elevated MPO activity in mouse myocardial infarction models. Short duration PF-1355 treatment for 7 days decreased the number of inflammatory cells and attenuated left ventricular dilation. Cardiac function and remodeling improved when treatment was increased to 21 days. Better therapeutic effect was further achieved with early compared with delayed treatment initiation (1 h vs. 24 h after infarction). In conclusion, PF-1355 treatment protected a mouse heart from acute and chronic effects of MI, and this study paves the way for future translational studies investigating this class of drugs in cardiovascular diseases.

14.
Materials (Basel) ; 9(11)2016 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-28774050

RESUMO

Freckle defects usually appear on the surface of castings and industrial ingots during the directional solidification process and most of them are located near the interface between the shell mold and superalloys. Ceramic cores create more interfaces in the directionally solidified (DS) and single crystal (SX) hollow turbine blades. In order to investigate the location of freckle occurrence in superalloys, superalloy CM247 LC was directionally solidified in an industrial-sized Bridgman furnace. Instead of ceramic cores, Alumina tubes were used inside of the casting specimens. It was found that freckles occur not only on the casting external surfaces, but also appear near the internal interfaces between the ceramic core and superalloys. Meanwhile, the size, initial position, and area of freckle were investigated in various diameters of the specimens. The initial position of the freckle chain reduces when the diameter of the rods increase. Freckle area follows a linear relationship in various diameters and the average freckle fraction is 1.1% of cross sectional area of casting specimens. The flow of liquid metal near the interfaces was stronger than that in the interdendritic region in the mushy zone, and explained why freckle tends to occur on the outer or inner surfaces of castings. This new phenomenon suggests that freckles are more likely to occur on the outer or inner surfaces of the hollow turbine blades.

15.
Am J Physiol Heart Circ Physiol ; 307(10): H1529-38, 2014 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-25239803

RESUMO

Bone marrow-derived inflammatory cells, including platelets, may contribute to the progression of pressure overload-induced left ventricular hypertrophy (LVH). However, the underlying mechanisms for this are still unclear. One potential mechanism is through release of granule cargo. Unc13-d(Jinx) (Jinx) mice, which lack Munc13-4, a limiting factor in vesicular priming and fusion, have granule secretion defects in a variety of hematopoietic cells, including platelets. In the current study, we investigated the role of granule secretion in the development of LVH and cardiac remodeling using chimeric mice specifically lacking Munc13-4 in marrow-derived cells. Pressure overload was elicited by transverse aortic constriction (TAC). Chimeric mice were created by bone marrow transplantation. Echocardiography, histology staining, immunohistochemistry, real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and mass spectrometry were used to study LVH progression and inflammatory responses. Wild-type (WT) mice that were transplanted with WT bone marrow (WT→WT) and WT mice that received Jinx bone marrow (Jinx→WT) developed LVH and a classic fetal reprogramming response early (7 days) after TAC. However, at late times (5 wk), mice lacking Munc13-4 in bone marrow-derived cells (Jinx→WT) failed to sustain the cardiac hypertrophy observed in WT chimeric mice. No difference in cardiac fibrosis was observed at early or late time points. Reinjection of WT platelets or platelet releasate partially restored cardiac hypertrophy in Jinx chimeric mice. These results suggest that sustained LVH in the setting of pressure overload depends on one or more factors secreted from bone marrow-derived cells, possibly from platelets. Inhibiting granule cargo release may represent a novel target for preventing sustained LVH.


Assuntos
Plaquetas/metabolismo , Células da Medula Óssea/metabolismo , Hipertrofia Ventricular Esquerda/metabolismo , Proteínas de Membrana/metabolismo , Miocárdio/metabolismo , Vesículas Secretórias/metabolismo , Animais , Transplante de Medula Óssea , Modelos Animais de Doenças , Hipertensão/complicações , Hipertrofia Ventricular Esquerda/etiologia , Hipertrofia Ventricular Esquerda/patologia , Hipertrofia Ventricular Esquerda/prevenção & controle , Proteínas de Membrana/deficiência , Proteínas de Membrana/genética , Camundongos Endogâmicos C57BL , Camundongos Knockout , Miocárdio/patologia , Transfusão de Plaquetas , Fatores de Tempo , Função Ventricular Esquerda , Remodelação Ventricular
16.
J Lipid Res ; 54(10): 2775-84, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23948545

RESUMO

Lysophosphatidic acid (LPA) is a bioactive lipid mediator. Concentrations of the major LPA species in mouse plasma decreased uniformly following administration of a potent selective inhibitor of the LPA-generating lysophospholipase D autotaxin, identifying an active mechanism for removal of LPA from the circulation. LPA, akylglycerol phosphate (AGP), sphingosine 1-phosphate (S1P), and a variety of structural mimetics of these lipids, including phosphatase-resistant phosphonate analogs of LPA, were rapidly eliminated (t1/2 < 30 s) from the circulation of mice following intravenous administration of a single bolus dose without significant metabolism in situ in the blood. These lipids accumulated in the liver. Elimination of intravenously administered LPA was blunted by ligation of the hepatic circulation, and ∼90% of LPA administered through the portal vein was accumulated by the isolated perfused mouse liver at first pass. At early times following intravenous administration, more LPA was associated with a nonparenchymal liver cell fraction than with hepatocytes. Primary cultures of nonparenchymal liver cells rapidly assimilated exogenously provided LPA. Our results identify hepatic uptake as an important determinant of the bioavailability of LPA and bioactive lysophospholipid mimetics and suggest a mechanism to explain changes in circulating LPA levels that have been associated with liver dysfunction in humans.


Assuntos
Metabolismo dos Lipídeos , Lisofosfolipídeos/sangue , Animais , Benzoxazóis/farmacologia , Células Cultivadas , Meia-Vida , Hepatócitos/metabolismo , Fígado/metabolismo , Lisofosfolipídeos/farmacocinética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Inibidores de Fosfodiesterase/farmacologia , Diester Fosfórico Hidrolases/metabolismo , Piperazinas/farmacologia , Espectrometria de Massas em Tandem , Distribuição Tecidual
17.
Arterioscler Thromb Vasc Biol ; 33(1): 52-9, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23104851

RESUMO

OBJECTIVE: The lipid phosphate phosphatase 3 (LPP3) degrades bioactive lysophospholipids, including lysophosphatidic acid and sphingosine-1-phosphate, and thereby terminates their signaling effects. Although emerging evidence links lysophosphatidic acid to atherosclerosis and vascular injury responses, little is known about the role of vascular LPP3. The goal of this study was to determine the role of LPP3 in the development of vascular neointima formation and smooth muscle cells (SMC) responses. METHODS AND RESULTS: We report that LPP3 is expressed in vascular SMC after experimental arterial injury. Using gain- and loss-of-function approaches, we establish that a major function of LPP3 in isolated SMC cells is to attenuate proliferation (extracellular signal-regulated kinases) activity, Rho activation, and migration in response to serum and lysophosphatidic acid. These effects are at least partially a consequence of LPP3-catalyzed lysophosphatidic acid hydrolysis. Mice with selective inactivation of LPP3 in SMC display an exaggerated neointimal response to injury. CONCLUSIONS: Our observations suggest that LPP3 serves as an intrinsic negative regulator of SMC phenotypic modulation and inflammation after vascular injury, in part, by regulating lysophospholipid signaling. These findings may provide a mechanistic link to explain the association between a PPAP2B polymorphism and coronary artery disease risk.


Assuntos
Lesões das Artérias Carótidas/prevenção & controle , Proliferação de Células , Músculo Liso Vascular/enzimologia , Miócitos de Músculo Liso/enzimologia , Fosfatidato Fosfatase/metabolismo , Animais , Lesões das Artérias Carótidas/enzimologia , Lesões das Artérias Carótidas/genética , Lesões das Artérias Carótidas/patologia , Artéria Carótida Primitiva/enzimologia , Artéria Carótida Primitiva/patologia , Movimento Celular , Modelos Animais de Doenças , Ativação Enzimática , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Regulação da Expressão Gênica , Genótipo , Células HEK293 , Humanos , Hidrólise , Hiperplasia , Lisofosfolipídeos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/patologia , Neointima , Fenótipo , Fosfatidato Fosfatase/deficiência , Fosfatidato Fosfatase/genética , Transdução de Sinais , Fatores de Tempo , Transfecção , Quinases Associadas a rho/metabolismo
18.
Adv Hematol ; 2012: 924042, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22919395

RESUMO

Anemia and resultant red blood cell transfusion may be associated with adverse long-term clinical outcomes. To investigate the mechanism(s) responsible, we profiled inflammatory biomarkers and circulating levels of the bioactive lysophospholipid mediator sphingosine-1-phosphate (S1P) in control and anemic mice with or without LPS-induced systemic inflammation. Acute anemia or lipopolysaccharide (LPS) challenge alone triggered an increase of circulating levels of the inflammatory markers IL-6 and keratinocyte-derived chemokine (CXCL1/KC). Moreover, administration of LPS to anemic mice reduced circulating S1P levels and augmented lung injury and pulmonary vascular permeability. Transfusion of aged, but not fresh, red blood cells (RBCs) worsened pulmonary vascular leak. S1P levels decline markedly during storage of mouse RBCs. Loading stored murine RBCs with S1P prior to transfusion partially attenuated anemia-associated acute pulmonary vascular leak. Taken together, our results indicate that anemia and systemic inflammation can alter the S1P buffering capacity of RBCs, suggesting possible strategies for alleviating transfusion-related lung injury in clinical practice.

19.
PLoS One ; 7(8): e40196, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22916095

RESUMO

Left ventricular hypertrophy (LVH) is usually accompanied by intensive interstitial and perivascular fibrosis, which may contribute to arrhythmogenic sudden cardiac death. The mechanisms underlying the development of cardiac fibrosis are incompletely understood. To investigate the role of perivascular inflammation in coronary artery remodeling and cardiac fibrosis during hypertrophic ventricular remodeling, we used a well-established mouse model of LVH (transverse aortic constriction [TAC]). Three days after pressure overload, macrophages and T lymphocytes accumulated around and along left coronary arteries in association with luminal platelet deposition. Consistent with these histological findings, cardiac expression of IL-10 was upregulated and in the systemic circulation, platelet white blood cell aggregates tended to be higher in TAC animals compared to sham controls. Since platelets can dynamically modulate perivascular inflammation, we investigated the impact of thrombocytopenia on the response to TAC. Immunodepletion of platelets decreased early perivascular T lymphocytes' accumulation and altered subsequent coronary artery remodeling. The contribution of lymphocytes were examined in Rag1(-/-) mice, which displayed significantly more intimal hyperplasia and perivascular fibrosis compared to wild-type mice following TAC. Collectively, our studies support a role of early perivascular accumulation of platelets and T lymphocytes in pressure overload-induced inflammation.


Assuntos
Plaquetas/fisiologia , Vasos Coronários/patologia , Ventrículos do Coração/patologia , Macrófagos/fisiologia , Modelos Biológicos , Linfócitos T/fisiologia , Animais , Ecocardiografia Doppler , Citometria de Fluxo , Ventrículos do Coração/fisiopatologia , Camundongos , Camundongos Transgênicos , Reação em Cadeia da Polimerase
20.
Arterioscler Thromb Vasc Biol ; 32(1): 24-32, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22015657

RESUMO

OBJECTIVE: Lysophosphatidic acid (LPA) is a bioactive lipid molecule produced by the plasma lysophospholipase D enzyme autotaxin that is present at ≥100 nmol/L in plasma. Local administration of LPA promotes systemic arterial remodeling in rodents. To determine whether LPA contributes to remodeling of the pulmonary vasculature, we examined responses in mice with alterations in LPA signaling and metabolism. METHODS AND RESULTS: Enpp2(+/-) mice, which are heterozygous for the autotaxin-encoding gene and which have reduced expression of autotaxin/lysophospholipase D and approximately half normal plasma LPA, were hyperresponsive to hypoxia-induced vasoconstriction and remodeling, as evidenced by the development of higher right ventricular (RV) systolic pressure, greater decline in peak flow velocity across the pulmonary valve, and a higher percentage of muscularized arterioles. Mice lacking LPA(1) and LPA(2), 2 LPA receptors abundantly expressed in the vasculature, also had enhanced hypoxia-induced pulmonary remodeling. With age, Lpar1(-/-)2(-/-) mice spontaneously developed elevated RV systolic pressure and RV hypertrophy that was not observed in Lpar1(-/-) mice or Lpar2(-/-) mice. Expression of endothelin-1, a potent vasoconstrictor, was elevated in lungs of Lpar1(-/-)2(-/-) mice, and expression of endothelin(B) receptor, which promotes vasodilation and clears endothelin, was reduced in Enpp2(+/-) and Lpar1(-/-)2(-/-) mice. CONCLUSIONS: Our findings indicate that LPA may negatively regulate pulmonary vascular pressure through LPA(1) and LPA(2) receptors and that in the absence of LPA signaling, upregulation in the endothelin system favors remodeling.


Assuntos
Hipóxia/patologia , Hipóxia/fisiopatologia , Lisofosfolipídeos/fisiologia , Artéria Pulmonar/patologia , Artéria Pulmonar/fisiopatologia , Animais , Pressão Sanguínea/fisiologia , Endotelina-1/fisiologia , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/patologia , Hipertensão Pulmonar/fisiopatologia , Hipertrofia Ventricular Direita/etiologia , Hipertrofia Ventricular Direita/patologia , Hipertrofia Ventricular Direita/fisiopatologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Diester Fosfórico Hidrolases/deficiência , Diester Fosfórico Hidrolases/genética , Diester Fosfórico Hidrolases/fisiologia , Receptores de Ácidos Lisofosfatídicos/deficiência , Receptores de Ácidos Lisofosfatídicos/genética , Receptores de Ácidos Lisofosfatídicos/fisiologia , Transdução de Sinais
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