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Osteoarthritic synovial fluid rheology and correlations with protein concentration. 骨关节炎滑液流变学及其与蛋白浓度的相关性。
IF 1.1 4区 医学 Q4 BIOPHYSICS Pub Date : 2016-11-09 DOI: 10.3233/BIR-15078
A. Madkhali, Michael Chernos, D. Grecov, E. Kwok
BACKGROUNDOsteoarthritis is a common, localized joint disease that causes pain, stiffness and reduced mobility. Osteoarthritis is particularly common in the knees. The effects of osteoarthritis on the rheology of synovial fluid in the knees are not fully understood and consequently require further study.OBJECTIVEThe purpose of this study is to investigate the effects of protein content on synovial fluid shear rheology. A secondary study outcome will include study of the temperature dependence of synovial fluid behaviour.METHODS38 osteoarthritic synovial fluid samples were studied under shear flow. Shear properties were correlated with protein concentration. Viscosupplement was used as a comparison and to verify measurement reliability. The effects of temperature were investigated at 20, 29 and 37°C.RESULTSShear rheological properties were found to vary widely between samples, however all samples demonstrated clear non-Newtonian shear thinning behaviour. In general viscoelastic properties were lower in osteoarthritic samples than previously studied healthy synovial fluid. A moderate correlation was observed between synovial fluid dynamic moduli at a frequency of 2.5 Hz and protein concentration. Temperature was found to affect the rheology of osteoarthritic synovial fluid and was fitted with the Arrhenius model.CONCLUSIONSIncreased protein concentration has been correlated with decreased shear rheological parameters. Temperature dependence of synovial fluid was also demonstrated and modelled for use in Part 2 of this article.
背景:骨关节炎是一种常见的局部关节疾病,可引起疼痛、僵硬和活动能力降低。骨关节炎在膝盖上尤为常见。骨关节炎对膝关节滑液流变学的影响尚不完全清楚,因此需要进一步研究。目的探讨蛋白质含量对滑液剪切流变学的影响。第二个研究结果将包括滑液行为的温度依赖性研究。方法对38例骨关节炎滑膜液进行剪切流动研究。剪切性能与蛋白质浓度相关。用粘剂作为对照,验证测量的可靠性。在20、29和37℃时考察了温度的影响。结果发现剪切流变特性在样品之间差异很大,但所有样品都表现出明显的非牛顿剪切变薄行为。一般来说,骨关节炎样本的粘弹性性能低于先前研究的健康滑液。在2.5 Hz频率下观察到滑液动力模量与蛋白质浓度之间存在适度的相关性。发现温度对骨关节炎滑膜液流变学有影响,并采用Arrhenius模型拟合。结论蛋白浓度升高与剪切流变参数降低相关。滑液的温度依赖性也被证明和建模用于本文的第2部分。
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引用次数: 17
Rheological effects of macromolecular interactions in synovial fluid. 滑液中大分子相互作用的流变效应。
IF 1.1 4区 医学 Q4 BIOPHYSICS Pub Date : 2016-07-29 DOI: 10.3233/BIR-15104
L Martin-Alarcon, T A Schmidt

The rheological properties of synovial fluid (SF) are largely attributed to the presence of high molecular weight hyaluronan (HA). However, rheological differences between SF and pure HA solutions suggest that SF proteins actively contribute towards the bulk viscoelasticity of this biological fluid. Due to various experimental challenges involved with the rheometry of low-viscosity biological fluids, the macromolecular interactions in SF and their relative rheological importance are still a matter of active discussion. Interestingly however, recent evidence suggests that the concentration and structure of proteoglycan 4 (PRG4, also known as lubricin) can directly modulate the viscoelastic properties of HA-PRG4 solutions. The objective of this review is to highlight recent rheological studies that examine the macromolecular interactions between HA and proteins in SF. First, a general overview of the chemical composition of SF and the molecular structure of its key constituents HA and PRG4 is provided. Subsequently, diverse rheological experimental techniques that have been developed to characterize HA solutions are discussed. Finally, rheological investigations of macromolecular interactions between HA, serum proteins, and PRG4 are examined. This review illustrates how diverse rheological techniques can expand our understanding of the composition-structure-function relationships in SF.

滑液(SF)的流变特性很大程度上归因于高分子量透明质酸(HA)的存在。然而,SF和纯HA溶液之间的流变学差异表明,SF蛋白积极地促进了这种生物流体的总体粘弹性。由于涉及低粘度生物流体流变学的各种实验挑战,SF中的大分子相互作用及其相对流变学重要性仍然是一个积极讨论的问题。然而,有趣的是,最近的证据表明,蛋白多糖4 (PRG4,也称为润滑素)的浓度和结构可以直接调节HA-PRG4溶液的粘弹性。这篇综述的目的是强调最近的流变学研究,研究了SF中HA和蛋白质之间的大分子相互作用。首先,概述了SF的化学组成及其关键成分HA和PRG4的分子结构。随后,讨论了已开发的用于表征HA溶液的各种流变实验技术。最后,研究了HA、血清蛋白和PRG4之间大分子相互作用的流变学研究。这篇综述说明了不同的流变学技术如何扩展我们对SF中成分-结构-功能关系的理解。
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引用次数: 35
Heterogeneous phase fibrinolysis rates by damped oscillation rheometry. 阻尼振荡流变法测定非均相纤维蛋白溶解率。
IF 1.1 4区 医学 Q4 BIOPHYSICS Pub Date : 2016-07-29 DOI: 10.3233/BIR-15089
Jae-Suk Lee, Makoto Kaibara, Edgar A O'Rear

Background: Devices gauging viscoelastic properties of blood during coagulation like the thromboelastograph support fundamental research as well as point of care needs. Associated fibrinolysis data are based on endogenous species or plasminogen activator added to a homogeneous sample prior to clot formation. Digestion in a monolithic structure differs from the physical situation of thrombolytic therapy where surface reactions dominate.

Objective: This study aims to develop rheological testing for heterogeneous phase fibrinolysis.

Method: Fibrinolysis rates were determined by phase change of a solid clot induced by autologous plasma/streptokinase (SK) in a rheometer sensitive to viscous damping.

Results: Initial slope or overall change in the logarithmic damping factor indicated fibrinolytic rates. Rates depended on clot geometry, phase volumes, clot composition and SK concentration.

Conclusion: The damped oscillation rheometer can be adapted to determine relative rates of heterogeneous fibrinolysis in vitro.

背景:测量凝血过程中血液粘弹性特性的设备,如血栓弹性仪,支持基础研究和护理点需求。相关的纤溶数据是基于内源性物种或纤溶酶原激活剂在血栓形成之前添加到均匀样品中。整体结构的消化不同于表面反应占主导地位的溶栓治疗的物理情况。目的:建立非均相纤溶的流变学检测方法。方法:在黏性阻尼敏感流变仪中,采用自体血浆/链激酶(SK)诱导的固体凝块的相变法测定纤维蛋白溶解率。结果:对数阻尼因子的初始斜率或总体变化指示纤溶率。速率取决于凝块几何形状、相体积、凝块组成和SK浓度。结论:阻尼振荡流变仪可用于体外测定非均质纤溶的相对速率。
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引用次数: 0
Relationship between arterial blood pressure and blood viscosity in spontaneously hypertensive rats treated with pentoxifylline. 己酮茶碱对自发性高血压大鼠动脉血压和血液粘度的影响。
IF 1.1 4区 医学 Q4 BIOPHYSICS Pub Date : 2016-07-26 DOI: 10.3233/BIR-15100
Mark B Plotnikov, Oleg I Aliev, Alexey V Nosarev, Alexander Y Shamanaev, Anastasia V Sidekhmenova, Yana Anfinogenova, Anna M Anishchenko, Ekaterina V Pushkina

Background: Systemic arterial pressure (AP) depends on two physiological variables: cardiac output (CO) and total peripheral resistance (TPR). The latter depends on vascular hindrance and blood viscosity (BV). However, the relative contributions of the vascular and rheological factors to TPR remain unclear.

Objective: The aim of our work was to study the haemodynamic and haemorheologic effects of a treatment course with pentoxifylline (PTX) in SHRs in an effort to assess the impact of the rheological factor on TPR and AP.

Methods: The effects of the treatment course with PTX (100 mg/kg/day p.o. for six weeks) on BV, plasma viscosity, haematocrit, erythrocyte aggregation and deformability, mean AP (MAP), stroke volume (SV), CO, and TPR were studied in SHRs and in control Wistar Kyoto (WKY) rats.

Results: PTX-treated SHRs had a lower BV, lower erythrocyte aggregation, and higher erythrocyte deformability index compared with the controls. The TPR level was higher by 43% compared with that in WKY rats and did not differ from the values obtained from control SHRs. In SHRs, moderate and strong positive correlations were found between BV and MAP and between BV and TPR. PTX-treated SHRs did not have any significant correlations between the above mentioned parameters.

Conclusions: Treatment with PTX attenuated whole blood viscosity, but did not affect the AP and hemodynamic parameters in the experimental SHRs compared with the control SHRs. The magnitude of the rheologic effects of PTX was insufficient to cause appreciable decreases in TPR and AP.

背景:全身动脉压(AP)取决于两个生理变量:心输出量(CO)和总外周阻力(TPR)。后者取决于血管阻塞和血液粘度(BV)。然而,血管和流变学因素对TPR的相对影响尚不清楚。目的:我们的工作的目的是研究血液动力学的疗程和haemorheologic效果与pentoxifylline (PTX)月为了评估流变的影响因素对TPR和AP.Methods:疗程的影响与PTX(100毫克/公斤/天以上六个星期)BV,血浆粘度、血细胞压积,红细胞聚集和可变形性,意味着美联社(MAP),中风量(SV)、CO和TPR研究萎缩和控制纯种京都WKY大鼠。结果:与对照组相比,ptx治疗的SHRs BV较低,红细胞聚集较低,红细胞变形指数较高。TPR水平比WKY大鼠高43%,与对照SHRs值无差异。在SHRs中,BV与MAP、BV与TPR之间存在中强正相关。ptx处理的SHRs在上述参数之间无显著相关性。结论:与对照组相比,PTX治疗降低了全血黏度,但不影响实验SHRs的AP和血流动力学参数。PTX的流变效应不足以引起TPR和AP的明显降低。
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引用次数: 9
Atrial natriuretic peptide down-regulates neutrophil recruitment on inflamed endothelium by reducing cell deformability and resistance to detachment force. 心房利钠肽通过降低细胞的变形能力和对脱离力的抵抗,下调炎症内皮的中性粒细胞募集。
IF 1.1 4区 医学 Q4 BIOPHYSICS Pub Date : 2016-07-04 DOI: 10.3233/BIR-15067
V. Morikis, Chris Radecke, Yanyan Jiang, V. Heinrich, F. Curry, S. Simon
BACKGROUND Recombinant atrial natriuretic peptide (ANP) is administered in patients with acute heart failure in Japan to improve renal function and hemodynamics, but its anti-inflammatory effect on activated leukocytes may also contribute to its therapeutic efficacy. OBJECTIVE Examine unconventional role of ANP in neutrophil adhesion to inflamed endothelium. METHODS Human neutrophils were perfused over endothelial monolayers in a microfluidic lab-chip assay. Cell rheology was assessed by micropipette aspiration to assess changes in cortical tension and viscosity. Fluorescence microscopy was applied to measure adhesive contact area and β2-integrin focal bond formation. RESULTS ANP inhibited neutrophil rolling and firm adhesion without influencing the upregulation of cellular adhesion molecules on endothelium or the regulation of high affinity CD18 and shedding of L-selectin during neutrophil activation. Exposed to fluid shear, integrin mediated arrest was disrupted with ANP treatment, which elicited formation of long tethers and diminished cell spreading and contact. This correlated with a ∼40% increase in neutrophil viscosity and a reduction in the adhesive footprint. CONCLUSIONS A decrease in cell deformation and neutrophil flattening with ANP results in fewer integrin bond clusters, which translates to higher tensile forces and impaired adhesion strengthening and cell detachment.
在日本,联合心房钠素肽(ANP)用于急性心力衰竭患者以改善肾功能和血流动力学,但其对活化白细胞的抗炎作用也可能有助于其治疗效果。目的探讨ANP在中性粒细胞粘附炎症内皮中的作用。方法采用微流控芯片法将人中性粒细胞灌注到内皮单层细胞上。细胞流变学通过微管抽吸评估皮质张力和黏度的变化。采用荧光显微镜测量黏着接触面积和β2-整联素焦点键形成情况。结果sanp抑制中性粒细胞滚动和牢固粘附,但不影响内皮细胞粘附分子的上调,也不影响中性粒细胞活化过程中高亲和CD18的表达和l -选择素的脱落。暴露于流体剪切下,整合素介导的阻滞被ANP破坏,引发长系链的形成,减少细胞的扩散和接触。这与中性粒细胞粘度增加~ 40%和粘合剂足迹减少相关。结论ANP减少细胞变形和中性粒细胞扁平,导致整合素键簇减少,从而导致拉伸力增加,粘附增强和细胞脱离受损。
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引用次数: 10
Atrial natriuretic peptide down-regulates neutrophil recruitment on inflamed endothelium by reducing cell deformability and resistance to detachment force. 心房利钠肽通过降低细胞的变形能力和对脱离力的抵抗,下调炎症内皮的中性粒细胞募集。
IF 1.1 4区 医学 Q4 BIOPHYSICS Pub Date : 2016-07-04 DOI: 10.3233/BIR-15067A
Vasilios A Morikis, Chris Radecke, Yanyan Jiang, Volkmar Heinrich, Fitz-Roy Curry, Scott I Simon
2 BACKGROUND: In Japan, Recombinant atrial natriuretic peptide (ANP) is administered in 3 patients with acute heart failure in Japan to improve renal function and hemodynamics, but its anti-inflammatory effect on activated leukocytes may also contribute to its therapeutic efficacy OBJECTIVE: Examine unconventional role of ANP in neutrophil adhesion to inflamed endothelium. METHODS: Human neutrophils were perfused over endothelial monolayers in a microfluidic 10 lab-chip assay. Cell rheology was assessed by micropipette aspiration to assess changes in 11 cortical tension and viscosity. Fluorescence microscopy was applied to measure adhesive contact 12 area and β 2 -integrin focal bond formation. 13 14 RESULTS: ANP inhibited neutrophil rolling and firm adhesion without influencing the 15 upregulation of cellular adhesion molecules on endothelium or the regulation of high affinity 16 CD18 and shedding of L-selectin during neutrophil activation. Conversion Exposed to fluid 17 shear, to shear resistant integrin mediated arrest was disrupted with ANP treatment, which 18 elicited formation of long tethers and diminished cell spreading and contact. This correlated with 19 an ~40% increase in neutrophil viscosity and a reduction in the adhesive footprint. CONCLUSIONS: A decrease in cell deformation and PMN neutrophil flattening with ANP 22 results in fewer integrin bond clusters, which translates to higher tensile forces and impaired 23 adhesion strengthening and cell detachment. prior to measurement. ANP did not alter the up-regulation of β 2 -integrin or 21 the shedding of L-selectin when compared to untreated control (n=3). PMN F-actin was measured using Phalloidin with and without IL-8 stimulation after simultaneous fixing and 23 permeabilization. Data shows replicates for n=3 donors with no significant effect of ANP 24 observed.
{"title":"Atrial natriuretic peptide down-regulates neutrophil recruitment on inflamed endothelium by reducing cell deformability and resistance to detachment force.","authors":"Vasilios A Morikis,&nbsp;Chris Radecke,&nbsp;Yanyan Jiang,&nbsp;Volkmar Heinrich,&nbsp;Fitz-Roy Curry,&nbsp;Scott I Simon","doi":"10.3233/BIR-15067A","DOIUrl":"https://doi.org/10.3233/BIR-15067A","url":null,"abstract":"2 BACKGROUND: In Japan, Recombinant atrial natriuretic peptide (ANP) is administered in 3 patients with acute heart failure in Japan to improve renal function and hemodynamics, but its anti-inflammatory effect on activated leukocytes may also contribute to its therapeutic efficacy OBJECTIVE: Examine unconventional role of ANP in neutrophil adhesion to inflamed endothelium. METHODS: Human neutrophils were perfused over endothelial monolayers in a microfluidic 10 lab-chip assay. Cell rheology was assessed by micropipette aspiration to assess changes in 11 cortical tension and viscosity. Fluorescence microscopy was applied to measure adhesive contact 12 area and β 2 -integrin focal bond formation. 13 14 RESULTS: ANP inhibited neutrophil rolling and firm adhesion without influencing the 15 upregulation of cellular adhesion molecules on endothelium or the regulation of high affinity 16 CD18 and shedding of L-selectin during neutrophil activation. Conversion Exposed to fluid 17 shear, to shear resistant integrin mediated arrest was disrupted with ANP treatment, which 18 elicited formation of long tethers and diminished cell spreading and contact. This correlated with 19 an ~40% increase in neutrophil viscosity and a reduction in the adhesive footprint. CONCLUSIONS: A decrease in cell deformation and PMN neutrophil flattening with ANP 22 results in fewer integrin bond clusters, which translates to higher tensile forces and impaired 23 adhesion strengthening and cell detachment. prior to measurement. ANP did not alter the up-regulation of β 2 -integrin or 21 the shedding of L-selectin when compared to untreated control (n=3). PMN F-actin was measured using Phalloidin with and without IL-8 stimulation after simultaneous fixing and 23 permeabilization. Data shows replicates for n=3 donors with no significant effect of ANP 24 observed.","PeriodicalId":9167,"journal":{"name":"Biorheology","volume":"53 2","pages":"109"},"PeriodicalIF":1.1,"publicationDate":"2016-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/BIR-15067A","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34713796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Optical twisting to monitor the rheology of single cells. 光学扭曲监测单个细胞的流变。
IF 1.1 4区 医学 Q4 BIOPHYSICS Pub Date : 2016-05-26 DOI: 10.3233/BIR-15084
Matthieu Robert de Saint Vincent

Background: Biological cells exhibit complex mechanical properties which determine their responses to applied force.

Objective: We developed an optical method to probe the temporal evolution of power-law rheology of single cells.

Methods: The method consisted in applying optically a constant mechanical torque to a birefringent microparticle bound to the cell membrane, and observing dynamics of the particle's in-plane rotation.

Results: The deformation dynamics of the membrane followed a power law of time, which directly relates to cytoskeletal prestress as reported in the literature. The temporal evolution of this rheological behaviour, over time scales of several minutes, showed strong variations of the exponent on single adherent cells not subject to any specific treatment.

Conclusions: The consistent observation of variations in the exponent suggests that, in their normal activity, living cells modulate their prestress by up to three orders of magnitude within minutes.

背景:生物细胞表现出复杂的机械特性,这决定了它们对施加的力的反应。目的:研究单细胞幂律流变学的时间演化过程。方法:将恒定的机械扭矩施加于与细胞膜结合的双折射微粒上,观察微粒的平面内旋转动力学。结果:膜的变形动力学遵循时间的幂律,这与文献报道的细胞骨架预应力直接相关。这种流变行为的时间演变,在几分钟的时间尺度上,显示出不受任何特定处理的单个贴壁细胞指数的强烈变化。结论:对指数变化的一致观察表明,在其正常活动中,活细胞在几分钟内将其预应力调节了三个数量级。
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引用次数: 1
Effects of vessel size, cell sedimentation and haematocrit on the adhesion of leukocytes and platelets from flowing blood. 血管大小、细胞沉降和红细胞压积对血液中白细胞和血小板粘附的影响。
IF 1.1 4区 医学 Q4 BIOPHYSICS Pub Date : 2016-02-10 DOI: 10.3233/BIR-15043
Tim Watts, M. Barigou, G. Nash
BACKGROUNDLeukocytes and platelets typically fulfil their functions through adhesion to the walls of vessels with different size, haematocrit and shear rate.OBJECTIVEWe aimed to investigate differential effects of these variables on leukocyte and platelet adhesion.METHODSBlood with varying haematocrit was perfused at a range of wall shear rates through capillaries of depth 100 or 300 µm coated with P-selectin or collagen.RESULTSAdhesion of leukocytes was much more efficient in the smaller capillaries, but was equal on the upper and lower surfaces and showed nearly identical shear rate dependence for either size of vessel. Platelets also adhered more efficiently in the smaller vessels (although the effect of size was not so great), and equally on upper and lower surfaces, but their adhesion was much less sensitive to increasing shear rate. In previous studies using vertically-orientated capillaries, leukocyte adhesion increased with increasing haematocrit (Am. J. Physiol.285 (2003), H229-H240). Here, in horizontal 100 µm capillaries, leukocyte adhesion was highly efficient at haematocrit of 10% but restricted to the lower surface. Adhesion decreased initially as haematocrit was increased to 30% and then increased slightly again at 40% haematocrit. Increasing haematocrit supported a monotonic increase in platelet adhesion in the horizontal capillaries.CONCLUSIONSPlatelets adhere efficiently over a wider range of sizes and shear rates, and at high haematocrit. Leukocytes adhere better in smaller vessels and at low haematocrit in horizontal vessels. The different behaviours may represent 'rheological adaptation' to functions in inflammation vs. haemostasis.
白细胞和血小板通常通过粘附不同大小、红细胞压积和剪切速率的血管壁来实现其功能。目的探讨这些变量对白细胞和血小板粘附的不同影响。方法将不同红细胞压积的血液以一定的壁剪切速率灌注到深度为100或300µm的涂有p -选择素或胶原的毛细血管中。结果白细胞的粘附在较小的毛细血管中更有效,但在上下表面上是相等的,并且对血管大小表现出几乎相同的剪切速率依赖。血小板在小血管中的粘附效率也更高(尽管大小的影响不是那么大),上下表面的粘附效率同样高,但它们的粘附对剪切速率的增加不太敏感。在先前使用垂直定向毛细血管的研究中,白细胞粘附随着红细胞压积的增加而增加。[j] .生物医学工程学报,2009,33(2):559 - 564。在水平的100µm毛细血管中,白细胞粘附在10%的红细胞压积时非常有效,但仅限于下表面。当红细胞压积增加到30%时,粘附力开始下降,然后在红细胞压积增加到40%时,粘附力又略有增加。红细胞压积的增加支持水平毛细血管中血小板粘附的单调增加。结论血小板在更大的尺寸和剪切速率范围内有效粘附,并具有较高的红细胞压积。白细胞在小血管中粘附较好,水平血管中红细胞压积较低。不同的行为可能代表了对炎症和止血功能的“流变适应”。
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引用次数: 7
Proteolytic receptor cleavage in the pathogenesis of blood rheology and co-morbidities in metabolic syndrome. Early forms of autodigestion. 蛋白水解受体裂解在血液流变学的发病机制和代谢综合征的合并症。早期形式的自体消化。
IF 1.1 4区 医学 Q4 BIOPHYSICS Pub Date : 2016-02-10 DOI: 10.3233/BIR-15045
R. Mazor, G. Schmid-Schönbein
Abnormal blood rheological properties seldom occur in isolation and instead are accompanied by other complications, often designated as co-morbidities. In the metabolic syndrome with complications like hypertension, diabetes and lack of normal microvascular blood flow, the underlying molecular mechanisms that simultaneously lead to elevated blood pressure and diabetes as well as abnormal microvascular rheology and other cell dysfunctions have remained largely unknown. In this review, we propose a new hypothesis for the origin of abnormal cell functions as well as multiple co-morbidities. Utilizing experimental models for the metabolic disease with diverse co-morbidities we summarize evidence for the presence of an uncontrolled extracellular proteolytic activity that causes ectodomain receptor cleavage and loss of their associated cell function. We summarize evidence for unchecked degrading proteinase activity, e.g. due to matrix metalloproteases, in patients with hypertension, Type II diabetes and obesity, in addition to evidence for receptor cleavage in the form of receptor fragments and decreased extracellular membrane expression levels. The evidence suggest that a shift in blood rheological properties and other co-morbidities may in fact be derived from a common mechanism that is due to uncontrolled proteolytic activity, i.e. an early form of autodigestion. Identification of the particular proteases involved and the mechanisms of their activation may open the door to treatment that simultaneously targets multiple co-morbidities in the metabolic syndrome.
异常血液流变学特性很少单独发生,而是伴有其他并发症,通常被称为合并症。在伴有高血压、糖尿病和微血管血流不足等并发症的代谢综合征中,同时导致血压升高和糖尿病以及微血管流变学异常和其他细胞功能障碍的潜在分子机制在很大程度上仍然未知。在这篇综述中,我们提出了一个新的假设的起源异常细胞功能和多种合并症。利用具有多种合并症的代谢性疾病的实验模型,我们总结了存在不受控制的细胞外蛋白水解活性的证据,该活性导致外胞结构域受体切割和相关细胞功能丧失。我们总结了在高血压、II型糖尿病和肥胖患者中不受控制的降解蛋白酶活性的证据,例如由于基质金属蛋白酶,以及受体片段形式的切割和细胞外膜表达水平降低的证据。有证据表明,血液流变学特性的改变和其他合并症实际上可能源于一种共同的机制,即不受控制的蛋白质水解活性,即早期形式的自体消化。对所涉及的特定蛋白酶及其激活机制的鉴定可能为同时针对代谢综合征中的多种合并症的治疗打开大门。
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引用次数: 10
Laudatio for Harry Goldsmith. 为哈里·戈德史密斯鼓掌。
IF 1.1 4区 医学 Q4 BIOPHYSICS Pub Date : 2016-02-10 DOI: 10.3233/BIR-150676
G. Cokelet
and branch points with different angles. They identified the spiraling vortexes with flow separation and reattachment points, which are the sites prone to atherogenesis. Their fundamental discoveries provided an important foundation for our research on the differential behaviors of endothelial cells in response to pulsatile or laminar flow vs. disturbed flow in athero-protective vs. atheroprone regions of the arterial tree, respectively.
以及不同角度的分支点。他们确定了具有流动分离和再附着点的螺旋涡,这是易于发生动脉粥样硬化的部位。他们的基本发现为我们研究内皮细胞对动脉树动脉粥样硬化保护区和动脉粥样硬化易发区搏动或层流与干扰血流的差异行为提供了重要的基础。
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引用次数: 0
期刊
Biorheology
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