RESUMO
Increased fluid shear stress (FSS) is a key initiating stimulus for arteriogenesis, the outward remodeling of collateral arterioles in response to upstream occlusion. Placental growth factor (PLGF) is an important arteriogenic mediator. We previously showed that elevated FSS increases PLGF in a reactive oxygen species (ROS)-dependent fashion both in vitro and ex vivo. Heme oxygenase 1 (HO-1) is a cytoprotective enzyme that is upregulated by stress and has arteriogenic effects. In the current study, we used isolated murine mesentery arterioles and co-cultures of human coronary artery endothelial cells (EC) and smooth muscle cells (SMC) to test the hypothesis that HO-1 mediates the effects of FSS on PLGF. HO-1 mRNA was increased by conditions of increased flow and shear stress in both co-cultures and vessels. Both inhibition of HO-1 with zinc protoporphyrin and HO-1 knockdown abolished the effect of FSS on PLGF. Conversely, induction of HO-1 activity increased PLGF. To determine which HO-1 product upregulates PLGF, co-cultures were treated with a CO donor (CORM-A1), biliverdin, ferric ammonium citrate (FAC), or iron-nitrilotriacetic acid (iron-NTA). Of these FAC and iron-NTA induced an increase PLGF expression. This study demonstrates that FSS acts through iron to induce pro-arteriogenic PLGF, suggesting iron supplementation as a novel potential treatment for revascularization.
Assuntos
Circulação Sanguínea/fisiologia , Heme Oxigenase-1/metabolismo , Heme Oxigenase-1/fisiologia , Ferro/metabolismo , Fator de Crescimento Placentário/metabolismo , Resistência ao Cisalhamento/fisiologia , Animais , Células Cultivadas , Técnicas de Cocultura , Vasos Coronários , Células Endoteliais/metabolismo , Expressão Gênica , Heme Oxigenase-1/genética , Humanos , Artérias Mesentéricas , Camundongos , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , RNA Mensageiro/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
AIM: We examined the effect of modulating the shear stress (SS) profile using forearm warming and cooling on subsequent endothelial function in the brachial artery (BA) during exercise. METHODS: Twelve healthy young subjects immersed their right forearm in water (15 â or 42 â) during a leg cycling exercise at 120-130 bpm for 60 min. The same exercise without water immersion served as a control. The BA diameter and blood velocity were simultaneously recorded using Doppler ultrasonography to evaluate the antegrade, retrograde, and mean shear rates (SRs, an estimate of SS) before, during, and after exercise. The endothelial function in the right BA was evaluated using flow-mediated dilation (FMD) (%) using two-dimensional high-resolution ultrasonography before (baseline) and 15 and 60 min after exercise. RESULTS: During exercise, compared with the control trial, higher antegrade and mean SRs and lower retrograde SRs were observed in the warm trial; conversely, lower antegrade and mean SRs and higher retrograde SRs were observed in the cool trial. At 15 min postexercise, no significant change was observed in the FMD from baseline in the warm (Δ%FMD: +1.6%, tendency to increase; p = 0.08) and control trials (Δ%FMD: +1.1%). However, in the cool trial, the postexercise FMD at 60 min decreased from baseline (Δ%FMD: -2.7%) and was lower than that of the warm (Δ%FMD: +1.5%) and control (Δ%FMD: +1.2%) trials. Accumulated changes in each SR during and after exercise were significantly correlated with postexercise FMD changes. CONCLUSION: Modulation of shear profiles in the BA during exercise appears to be associated with subsequent endothelial function.
Assuntos
Artéria Braquial/fisiologia , Crioterapia , Exercício Físico/fisiologia , Antebraço , Hipertermia Induzida , Perna (Membro) , Velocidade do Fluxo Sanguíneo/fisiologia , Endotélio Vascular/fisiologia , Feminino , Humanos , Masculino , Valores de Referência , Fluxo Sanguíneo Regional/fisiologia , Resistência ao Cisalhamento/fisiologia , Estresse Mecânico , Ultrassonografia Doppler , Vasodilatação/fisiologia , Adulto JovemRESUMO
A non-invasive method for measurement of the bladder wall nonlinear elastic behavior is presented. The method is based on acoustoelasticity modeling of the elasticity changes in bladder tissue modulus at different volumetric strain levels. At each volume, tissue strain is obtained from the real-time ultrasound images. Using acoustic radiation force, a transient Lamb wave is excited on the bladder wall and instantaneous modulus of shear elasticity is obtained from the 2-D Fourier analysis of the spatial-temporal dispersion maps. Measured elasticity and strain data are then used in an acoustoelasticity formulation to obtain the third order elastic coefficient, referred to as nonlinearity parameter A, and initial resting elasticity µ0. The method was tested in ex vivo porcine bladder samples (N = 9) before and after treatment with formalin. The estimated nonlinearity parameter, A, was significantly higher in the treated samples compared to intact (p < 0.00062). The proposed method was also applied on 16 patients with neurogenic bladders (10 compliant and 6 non-compliant subjects). The estimated nonlinearity parameter A was significantly higher in the non-compliant cases compared to the compliant (p < 0.0293). These preliminary results promise a new method for non-invasive evaluation of the bladder tissue nonlinearity which may serve as a new diagnostic and prognostic biomarker for management of the patients with neurogenic bladders.
Assuntos
Técnicas de Imagem por Elasticidade/métodos , Bexiga Urinaria Neurogênica/diagnóstico , Bexiga Urinaria Neurogênica/patologia , Bexiga Urinária/diagnóstico por imagem , Bexiga Urinária/patologia , Estimulação Acústica/métodos , Estimulação Acústica/veterinária , Animais , Estudos de Casos e Controles , Módulo de Elasticidade , Elasticidade , Técnicas de Imagem por Elasticidade/veterinária , Humanos , Fenômenos Mecânicos , Tamanho do Órgão , Prognóstico , Resistência ao Cisalhamento/fisiologia , Som , Suínos , Ultrassonografia , Bexiga Urinária/fisiologia , Bexiga Urinaria Neurogênica/fisiopatologiaRESUMO
Shear-induced platelet activation may cause life-threatening thrombosis, particularly in patients with mechanical support devices or coronary atherosclerosis. The majority of present anti-platelet agents target or interfere with biochemical, rather than physical mechanisms of platelet activation. Less data and understanding exists with regard to pharmacologic modulation of shear-mediated platelet activation. In this work, we hypothesized that modulating cell membrane properties, via alteration of membrane composition through addition of exogenous lipid moieties, would alter platelet responsiveness to shear. Here we tested fatty acids, lecithin and cholesterol as additive lipid compounds. We demonstrated that incorporation of fatty acids (DHA/EPA) or lecithin into the platelet membrane triggered enhanced sensitivity of platelets to shear-mediated activation. On the other hand, cholesterol incorporation provides significant protection, limiting the effect of shear on platelet activation. These findings provide valuable insight for the development of therapeutic strategies that can modulate shear-mediated platelet activation.
Assuntos
Plaquetas/metabolismo , Metabolismo dos Lipídeos/fisiologia , Ativação Plaquetária/fisiologia , Resistência ao Cisalhamento/fisiologia , Adulto , Membrana Celular/metabolismo , Colesterol/metabolismo , Ácidos Graxos/metabolismo , Hemodinâmica , Humanos , Lecitinas/metabolismoRESUMO
Apatite (Ap), laminin-apatite composite (L5Ap, L10Ap, L20Ap and L40Ap) and albumin-apatite (AlbAp) composite layers were prepared on titanium (Ti) using a supersaturated calcium phosphate solution supplemented with laminin (0, 5, 10, 20 and 40 µg ml(-1)) or albumin (800 µg ml(-1)). With an increase in the concentrations of laminin in the supersaturated calcium phosphate solutions, the amounts of laminin immobilized on the Ti increased. The number of human umbilical vein endothelial cells (HUVECs) adhered to the laminin-apatite composite layers were remarkably higher than those to the untreated Ti, Ap layer and AlbAp composite layer. The number of cells adhered to the L40Ap was 4.3 times the untreated Ti. Moreover, cells adhered to the laminin-apatite composite layers showed significantly higher cell retention under the physiological shear stress for 1 h and 2 h than those to the untreated Ti, Ap layer and AlbAp composite layer. The number of cells remaining on the L40Ap under the physiological shear stress for 2 h was 9.5 times that of the untreated Ti. The laminin-apatite composite layer is a promising interfacial layer for endothelialization of blood-contacting materials.
Assuntos
Apatitas/química , Materiais Biocompatíveis , Biotecnologia/métodos , Adesão Celular/fisiologia , Células Endoteliais da Veia Umbilical Humana/fisiologia , Laminina/química , Resistência ao Cisalhamento/fisiologia , Albuminas/química , Humanos , Titânio/químicaRESUMO
This study examined a potential cellular basis for strain hardening of fascial tissues: an increase in stiffness induced by stretch and subsequent rest. Mice lumbodorsal fascia were isometrically stretched for 15 min followed by 30 min rest (n=16). An increase in stiffness was observed in the majority of samples, including the nonviable control samples. Investigations with porcine lumbar fascia explored hydration changes as an explanation (n=24). Subject to similar loading procedures, tissues showed decreases in fluid content immediately post-stretch and increases during rest phases. When allowed sufficient resting time, a super-compensation phenomenon was observed, characterised by matrix hydration higher than initial levels and increases in tissue stiffness. Therefore, fascial strain hardening does not seem to rely on cellular contraction, but rather on this super-compensation. Given a comparable occurrence of this behaviour in vivo, clinical application of routines for injury prevention merit exploration.