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Characterizing the Mechanical Variations of Human Femoropopliteal Artery During Aging Process 人类股腘动脉在衰老过程中的力学变化特征
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2019-04-03 DOI: 10.32604/MCB.2019.06096
Shaoxiong Yang, Ying‐Xin Qi, Zong-Lai Jiang, X. Gong
Vascular diseases during aging process are closely correlated to the age-related changes of mechanical stimuli for resident cells. Characterizing the variations of mechanical environments in vessel walls with advancing age is crucial for a better understanding of vascular remodeling and pathological changes. In this study, the mechanical stress, strain, and wall stiffness of the FPAs were compared among four different age groups from adolescent to young, middle-aged, and aged subjects. The material parameters and geometries adopted in the FPA models were obtained from published experimental results. It is found that high mechanical stress appears at different layers in young and old FPA walls respectively. The characteristics of the middle-aged FPA wall suggests that it is the most capable of resisting high blood pressures and maintaining a mechanical homeostasis during the entire life span. It is demonstrated that the variations of stress and strain rather than that of wall stiffness can be used as an indicator to illustrate the profile of FPA aging. Our results could serve as an age-specific mechanical reference for vascular mechanobiological studies, and allow further exploration of cellular dysfunctions in vessel walls during aging process.
衰老过程中的血管疾病与常驻细胞机械刺激的年龄相关性变化密切相关。随着年龄的增长,描述血管壁机械环境的变化对于更好地理解血管重塑和病理变化至关重要。在这项研究中,比较了四个不同年龄组(从青少年到青年,中年和老年受试者)的fpa的机械应力,应变和壁刚度。FPA模型采用的材料参数和几何形状均来源于已发表的实验结果。研究发现,在新壁层和老壁层中,高机械应力分别出现在不同的层上。中年FPA壁的特征表明,它在整个生命周期内抵抗高血压和维持机械稳态的能力最强。结果表明,应力应变的变化比壁刚度的变化更能反映FPA的老化情况。我们的研究结果可以作为血管力学生物学研究的年龄特异性力学参考,并允许进一步探索衰老过程中血管壁的细胞功能障碍。
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引用次数: 0
Experimental Study of Aqueous Humor Flow in a Transparent Anterior Segment Phantom by Using PIV Technique 透明前段幻体房水流动的PIV实验研究
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2019-04-03 DOI: 10.32604/MCB.2019.06393
Wenjia Wang, Xiuqing Qian, Qi Li, Gong Zhang, Huangxuan Zhao, Tan Li, Yang Yu, Hongfang Song, Zhicheng Liu
Pupillary block is considered as an important cause of primary angle-closure glaucoma (PACG). In order to investigate the effect of pupillary block on the hydrodynamics of aqueous humor (AH) in anterior chamber (AC) and potential risks, a 3D printed eye model was developed to mimic the AH flow driven by fluid generation, the differential pressure between AC and posterior chambers (PC) and pupillary block. Particle image velocimetry technology was applied to visualize flow distribution. The results demonstrated obvious differences in AH flow with and without pupillary block. Under the normal condition (without pupillary block), the flow filed of AH was nearly symmetric in the AC. The highest flow velocity located at the central of AC when the differential pressure between AC and PC was under 5.83 Pa, while it appeared near the cornea and iris surface when the differential pressure was greater than 33.6 Pa. Once pupillary block occurred, two asymmetric vortices with different sizes were observed and the shear stress in the paracentral cornea and iris epithelium increased greatly. It can be concluded that the pupillary block and the elevated differential pressure between AC and PC could change the flow distribution and thus increase the risk of corneal endothelial cells detachment. This study could make a further understanding of the pathogenesis of PACG.
瞳孔阻滞被认为是原发性闭角型青光眼(PACG)的重要病因。为了研究瞳孔阻滞对前房房水(AH)流体动力学的影响及其潜在风险,建立了3D打印眼模型,模拟流体生成、前房与后房(PC)压差和瞳孔阻滞驱动的AH流动。采用粒子图像测速技术对流动分布进行可视化。结果显示,有瞳孔阻滞和无瞳孔阻滞时,血气流量有明显差异。正常情况下(无瞳孔阻塞),AH流场在AC内接近对称,当AC与PC压差在5.83 Pa以下时,流速最高的位置位于AC中心,压差大于33.6 Pa时,流速最高的位置出现在角膜和虹膜表面附近。一旦发生瞳孔阻滞,观察到两个不同大小的不对称涡旋,中央旁角膜和虹膜上皮的剪切应力大大增加。可见,瞳孔阻滞及AC和PC压差升高可改变血流分布,从而增加角膜内皮细胞脱离的风险。本研究有助于进一步了解PACG的发病机制。
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引用次数: 3
Traction Force Measurements of Human Aortic Smooth Muscle Cells Reveal a Motor-Clutch Behavior 人主动脉平滑肌细胞的牵引力测量揭示了一种马达-离合器行为
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2019-03-20 DOI: 10.32604/mcb.2019.06415
C. Petit, A. Guignandon, S. Avril
The contractile behavior of smooth muscle cells (SMCs) in the aorta is an important determinant of growth, remodeling, and homeostasis. However, quantitative values of SMC basal tone have never been characterized precisely on individual SMCs. Therefore, to address this lack, we developed an in vitro technique based on Traction Force Microscopy (TFM). Aortic SMCs from a human lineage at low passages (4-7) were cultured 2 days in conditions promoting the development of their contractile apparatus and seeded on hydrogels of varying elastic modulus (1, 4, 12 and 25 kPa) with embedded fluorescent microspheres. After complete adhesion, SMCs were artificially detached from the gel by trypsin treatment. The microbeads movement was tracked and the deformation fields were processed with a mechanical model, assuming linear elasticity, isotropic material, plane strain, to extract the traction forces formerly applied by individual SMCs on the gel. Two major interesting and original observations about SMC traction forces were deduced from the obtained results: 1. they are variable but driven by cell dynamics and show an exponential distribution, with 40% to 80% of traction forces in the range 0-10 µN. 2. They depend on the substrate stiffness: the fraction of adhesion forces below 10 µN tend to decrease when the substrate stiffness increases, whereas the fraction of higher adhesion forces increases. As these two aspects of cell adhesion (variability and stiffness dependence) and the distribution of their traction forces can be predicted by the probabilistic motor-clutch model, we conclude that this model could be applied to SMCs. Further studies will consider stimulated contractility and primary culture of cells extracted from aneurysmal human aortic tissue.
主动脉平滑肌细胞(SMCs)的收缩行为是生长、重塑和体内平衡的重要决定因素。然而,SMC基底张力的定量值从未在单个SMC上精确表征。因此,为了解决这一不足,我们开发了一种基于牵引力显微镜(TFM)的体外技术。将低传代(4-7)人主动脉SMCs在促进其收缩器官发育的条件下培养2天,并将其接种于不同弹性模量(1,4,12和25 kPa)的水凝胶上,并嵌入荧光微球。完全粘附后,用胰蛋白酶处理人工分离SMCs。采用力学模型,假设线弹性、各向同性材料、平面应变,跟踪微珠运动,处理变形场,提取单个微珠对凝胶的牵引力。从得到的结果中推导出关于SMC牵引力的两个主要有趣和原始的观察结果:1。它们是可变的,但受细胞动力学驱动,呈指数分布,40%至80%的牵引力在0-10 μ N范围内。2. 它们取决于衬底刚度:当衬底刚度增加时,低于10µN的附着力分数趋于减少,而较高附着力分数则增加。由于细胞粘附的这两个方面(可变性和刚度依赖性)及其牵引力的分布可以通过概率电机-离合器模型来预测,因此我们得出结论,该模型可以应用于SMCs。进一步的研究将考虑从动脉瘤性人主动脉组织中提取的细胞的刺激收缩性和原代培养。
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引用次数: 10
Echo-Based FSI Models to Simulate Ventricular Electrical Signal Conduction in Pig Pacemaker Models 基于回波的FSI模型模拟猪起搏器模型的心室电信号传导
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2019-02-21 DOI: 10.32604/MCB.2019.05720
Longling Fan, Jing Yao, Chun Yang, Di Xu, D. Tang
Cardiac pacing has been an effective treatment in the management of patients with arrhythmia. Different pacemaker location may have different impact on pacemaker effectiveness. A novel image-based ventricle animal modeling approach was proposed to integrate echocardiography images, propagating dynamic electric potential on ventricle surface to perform myocardial function assessment. The models will be used to simulate ventricular electrical signal conduction and optimize pacemaker location for better cardiac outcome.  One health female adult pig weight 42.5kg was used to make pacing animal model with different ventricle pacing locations. Pig health status was assessed before undergoing experimental procedures. Ventricle surface electric signal, blood pressure and echo image were acquired 15 minutes after the pacemaker was implanted.  Echo-based left ventricle (LV) fluid-structure interaction (FSI) models were constructed to perform ventricle function analysis and investigate impact of pacemaker location on cardiac outcome.  The nonlinear Mooney-Rivlin model was used for ventricle tissue material model. With the measured electric signal map from the pig associated with the actual pacemaker site, electric potential conduction of myocardium was modeled by material stiffening and softening in our model, with stiffening simulating contraction and softening simulating relaxation. Material stiffness parameters were adjusted in a cardiac cycle to match Echo-measured LV deformation and volume variations. Mapping between material stiffness and ventricle electric signal was quantified using data measured from the animal with different pacemaker locations. Ventricle model without pacemaker and three ventricle models with the following pacemaker locations were simulated: right ventricular apex (RVA), posterior interventricular septum (PIVS) and right ventricular outflow tract (RVOT). Data for ventricle volume change, ejection fraction, stress and strain, flow velocity and shear stress data were collected for comparisons. Our results demonstrating that PIVS pacing model had higher peak flow velocity and stress/strain.  It indicated that PIVS pacemaker site may be the best location.  This modeling approach could be used as “virtual surgery” to try various pacemaker locations and avoid risky and dangerous surgical experiments on real patients.
心脏起搏是治疗心律失常的一种有效方法。不同的起搏器位置可能对起搏器的效果有不同的影响。提出了一种新的基于图像的心室动物建模方法,整合超声心动图图像,在心室表面传播动态电位,进行心肌功能评估。这些模型将用于模拟心室电信号传导和优化起搏器位置,以获得更好的心脏预后。选取一只体重42.5kg的健康雌性成年猪,制作不同心室起搏位置的起搏动物模型。在进行实验程序之前评估猪的健康状况。起搏器植入15分钟后,采集心室表面电信号、血压和回声图像。建立基于回声的左心室(LV)流固相互作用(FSI)模型进行心室功能分析,探讨起搏器位置对心脏转归的影响。脑室组织材料模型采用非线性Mooney-Rivlin模型。利用实测的猪与实际起搏器部位相关联的电信号图,我们的模型采用材料的硬化和软化来模拟心肌的电位传导,硬化模拟收缩,软化模拟松弛。在心脏周期中调整材料刚度参数,以匹配echo测量的左室变形和体积变化。材料刚度与心室电信号之间的映射关系通过测量不同起搏器位置的动物的数据进行量化。模拟无起搏器的心室模型和有起搏器位置的3个心室模型:右心室尖部(RVA)、后室间隔(PIVS)和右心室流出道(RVOT)。收集心室容积变化、射血分数、应力应变、流速和剪应力数据进行比较。结果表明,PIVS起搏模型具有更高的峰值流速和应力/应变。提示PIVS起搏器部位可能是最佳位置。这种建模方法可以作为“虚拟手术”,尝试不同的起搏器位置,避免在真实患者身上进行风险和危险的手术实验。
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引用次数: 1
Biomechanical Implications of Bicuspid Pulmonary Valve Dynamic Deformation in Patients with Repaired Tetralogy of Fallot 修复法洛四联症患者双尖瓣动态变形的生物力学意义
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2019-02-21 DOI: 10.32604/MCB.2019.05745
Caili Li, Jing Yao, Chun Yang, Di Xu, Liang Wang, D. Tang
Pulmonary valve stenosis (PVS) is one common post-operative problem in patients with tetralogy of Fallot (TOF) after repair. Congenital bicuspid pulmonary valve (BPV) is a condition of valvular stenosis, and the occurrence of congenital BPV is often associated with TOF. Compared with the biomechanical simulation model of the bicuspid aortic valve, the BPV is often neglected. In this study, we developed a dynamic biomechanical model of a simulated normal pulmonary root (PR) with tri-leaflet and a model of simulated PR with BPV in patients with repaired TOF in order to describe the effect of geometric structure with BPV on the stress and strain distribution. The geometry of PR included valvular leaflets, valsalva sinuses, inter leaflet triangle and annulus. Mechanical properties of PV leaflet were obtained from biaxial testing of human PV leaflet, and characterized by an anisotropic hyperelastic material model. Our model simulated complete cardiac cycles to observe valve leaflet dynamic stress/strain behaviors. Our results indicated that stress/strain distribution patterns of normal PV and the BPV were similar on pulmonary root and valve leaflets, but their values were different. When the valve was completely closed, maximum stresses were found leaflet attachment boundary, with their values at 17.1 kPa and 17.2 kPa respectively. When the valve was fully open, maximum stresses were found at the vicinity of commissures of sinus and leaflet, that is, near the annulus, with the values at 115.0 kPa and 143.0 kPa respectively. Compared with normal PR, the valve orifice area in the completely opened position in congenital BPV is significantly reduced. Our initial results demonstrated that geometrical variations with BPV may be a potential risk factor linked to occurrence of PVS in patients with repaired TOF.  Computational models could be a useful tool in identifying possible linkage between valve disease development and biomechanical factors.  Large-scale clinical studies are needed to validate these preliminary findings.
肺动脉瓣狭窄(PVS)是法洛四联症(TOF)患者修复后常见的术后问题。先天性双尖瓣肺动脉瓣(BPV)是一种瓣膜狭窄的疾病,先天性双尖瓣肺动脉瓣的发生通常与TOF有关。与双尖瓣主动脉瓣的生物力学模拟模型相比,BPV常常被忽略。在本研究中,我们建立了三叶模拟正常肺动脉根(PR)的动态生物力学模型和修复性TOF患者模拟带BPV的PR模型,以描述带BPV的几何结构对应力和应变分布的影响。PR的几何形态包括瓣叶、瓣窦、瓣叶间三角形和瓣环。通过人体PV小叶的双轴测试获得PV小叶的力学性能,并采用各向异性超弹性材料模型表征。我们的模型模拟了完整的心脏周期,以观察瓣膜叶的动态应力/应变行为。结果表明,正常PV和BPV在肺根和瓣叶上的应力应变分布模式相似,但数值不同。当阀门完全关闭时,最大应力出现在小叶附着边界,分别为17.1 kPa和17.2 kPa。当瓣膜全开时,最大应力出现在鼻窦和小叶交界处附近,即环附近,应力值分别为115.0 kPa和143.0 kPa。与正常PR相比,先天性BPV完全打开位置的瓣口面积明显减少。我们的初步结果表明,BPV的几何变化可能是与修复TOF患者发生PVS相关的潜在危险因素。计算模型可能是识别瓣膜疾病发展与生物力学因素之间可能联系的有用工具。需要大规模的临床研究来验证这些初步发现。
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引用次数: 1
Numerical Investigation of the Hemodynamics Characteristics in Coronary Bifurcation Region with Different Dual Stent Implantation Techniques 不同双支架植入术冠状动脉分叉区血流动力学特性的数值研究
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2019-02-21 DOI: 10.32604/MCB.2019.05733
Guangyu Zhu, Wei Cai, Q. Yuan, Lianglong Chen
The prevalence of coronary bifurcation lesions (CBL) in the percutaneous coronary intervention (PCI) was reported to be approximately 15-20 % [Steigen (2006)]. The complex surgical techniques and the high incidence of restenosis make the treatment of CBL is still one of the most challenging fields in PCI. Even the single stent technique showed prognosis in most CBL treatment, dual stenting technique is still required in some cases. Our clinical follow-ups of dual stent implantation showed that the optimized provisional T-stenting (OPT) technique in CBL treatment has a lower restenosis rate compare with the Culotte stenting technique and T-stenting and small protrusion (TAP) technique. Though the local hemodynamic characteristics have been suggested as a key factor of the restenosis post PCI, the detailed hemodynamics features of the different dual stent implantation configurations are yet to be explored. In this study, the numerical simulations were performed to investigate the flow characteristics in coronary bifurcations with different dual stenting techniques.
据报道,经皮冠状动脉介入治疗(PCI)中冠状动脉分叉病变(CBL)的发生率约为15- 20% [Steigen(2006)]。复杂的手术技术和高发生率的再狭窄使得CBL的治疗仍然是PCI治疗中最具挑战性的领域之一。即使单支架技术在大多数CBL治疗中预后良好,但在某些情况下仍需要双支架技术。我们对双支架植入术的临床随访显示,优化后的临时t -支架(OPT)技术在CBL治疗中的再狭窄率较curot支架技术和t -支架小突出(TAP)技术低。虽然局部血流动力学特征已被认为是PCI后再狭窄的关键因素,但不同双支架植入构型的详细血流动力学特征尚待探讨。在本研究中,通过数值模拟研究了不同双支架术冠状动脉分叉的血流特性。
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引用次数: 1
Automatic Segmentation Methods Based on Machine Learning for Intracoronary Optical Coherence Tomography Image 基于机器学习的冠状动脉内光学相干断层图像自动分割方法
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2019-02-21 DOI: 10.32604/MCB.2019.05747
Caining Zhang, Xiaoya Guo, D. Tang, D. Molony, Chun Yang, H. Samady, Jie Zheng, G. Mintz, A. Maehara, M. Matsumura, D. Giddens
Cardiovascular diseases are closely associated with sudden rupture of atherosclerotic plaques. Previous image modalities such as magnetic resonance imaging (MRI) and intravascular ultrasound (IVUS) were unable to identify vulnerable plaques due to their limited resolution. Optical coherence tomography (OCT) is an advanced intravascular imaging technique developed in recent years which has high resolution approximately 10 microns and could provide more accurate morphology of coronary plaque. In particular, it is now possible to identify plaques with fibrous cap thickness < 65 µm, an accepted threshold value for vulnerable plaques.  However, the current segmentation of OCT images are still performed manually by physicians and the process is time consuming. Automatic segmentation and recognition of vulnerable plaques through quantification of plaque components have great clinical significance for cardiovascular research. Two segmentation methods for intracoronary OCT image based on support vector machine (SVM) and convolutional neural network (CNN) were performed to detect the lumen borders and characterize the plaque component. In vivo IVUS and OCT coronary plaque data from 5 patients were acquired at Emory University with patient’s consent obtained. Seventy-seven matched IVUS and OCT slices with good image quality and medium to large lipid cores were selected for our segmentation study.  Manual OCT segmentation was performed by experts and used as gold standard in the automatic segmentations.  VH-IVUS was used as references and guide by the experts in the manual segmentation process.  Three plaque component tissue classes were identified from OCT images in this work: lipid tissue (LT), fibrous tissue (FT) and background (BG). Procedures using two machine learning methods (CNN and SVM) were developed to segment OCT images, respectively. For CNN method, the U-Net architecture was selected due to its good performance in very different biomedical segmentation and very few annotated images. For SVM method, local binary patterns (LBPs), gray level co-occurrence matrices (GLCMs) which contains contrast, correlation, energy and homogeneity, entropy and mean value were calculated as features and assembled to feed SVM classifier. The accuracies of two segmentation methods were evaluated and compared using the OCT dataset. Segmentation accuracy is defined as the ratio of the number of pixels correctly classified over the total number of pixels. The overall classification accuracy based CNN method reached 95.8%, and the accuracies for LT, FT and BG were 86.8%, 83.4%, and 98.2%, respectively. The overall classification accuracy based SVM was 71.9%, and per-class accuracy for LT, FT and BG was 75.4%, 78.3%, and 67.0%, respectively. The two methods proposed can automatically detect the lumen borders and characterize the composition of the superficial plaque in OCT images and greatly reduce the time spent by doctors in segmenting and identifying plaques.  CNN
心血管疾病与动脉粥样硬化斑块的突然破裂密切相关。以前的成像方式,如磁共振成像(MRI)和血管内超声(IVUS)由于分辨率有限,无法识别易损斑块。光学相干断层扫描(OCT)是近年来发展起来的一种先进的血管内成像技术,其分辨率约为10微米,可以提供更准确的冠状动脉斑块形态。特别是,现在可以识别纤维帽厚度< 65µm的斑块,这是易损斑块的公认阈值。然而,目前的OCT图像分割仍然是由医生手动执行的,而且这个过程非常耗时。通过对易损斑块成分的量化,对易损斑块进行自动分割和识别,对心血管研究具有重要的临床意义。采用基于支持向量机(SVM)和卷积神经网络(CNN)的冠状动脉内OCT图像分割方法检测管腔边界,表征斑块成分。5例患者的体内IVUS和OCT冠状动脉斑块数据在获得患者同意后在Emory大学获得。选取77张影像质量良好、脂质核大小适中的IVUS和OCT切片进行分割研究。人工OCT分割由专家完成,并作为自动分割的金标准。VH-IVUS作为人工分割的参考和指导。本研究从OCT图像中确定了三种斑块组成组织:脂质组织(LT)、纤维组织(FT)和背景组织(BG)。分别使用CNN和SVM两种机器学习方法对OCT图像进行分割。对于CNN方法,由于U-Net架构在非常不同的生物医学分割中具有良好的性能,并且注释的图像很少,因此选择U-Net架构。支持向量机方法将局部二值模式(lbp)、包含对比度、相关性、能量和均匀性的灰度共生矩阵(glcm)、熵和均值作为特征进行计算,并将其组合到支持向量机分类器中。使用OCT数据集对两种分割方法的准确率进行了评估和比较。分割精度定义为正确分类的像素数与总像素数之比。基于CNN的分类方法总体准确率达到95.8%,其中LT、FT和BG的准确率分别为86.8%、83.4%和98.2%。基于SVM的总体分类准确率为71.9%,其中LT、FT和BG的分类准确率分别为75.4%、78.3%和67.0%。所提出的两种方法可以在OCT图像中自动检测腔腔边界和表征表面斑块的组成,大大减少了医生分割和识别斑块的时间。与SVM相比,CNN提供了更好的分割精度。致谢:本研究得到了美国国立卫生研究院资助项目R01 EB004759,中国国家科学基金资助项目11672001和江苏省科技厅资助项目BE2016785的部分支持。
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引用次数: 1
Papillary Muscle Related Biomechanical Properties of Mitral Valve Chordae Tendineae 二尖瓣腱索与乳头肌相关的生物力学特性
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2019-02-21 DOI: 10.32604/MCB.2019.05740
Sheng-Liang Chen, Candra Ratna Sari, P. Segers, Guixue Wang, Xingshuang Ma
. Introduction Mitral valve is a complex structure including the annulus, the anterior leaflet, the posterior leaflet, the papillary muscles (PM), and the chordae tendineae connecting the leaflets and PM. The mechanical properties of the chordae play an important role in the normal functioning of the mitral valve: the chordae assists in maintaining the opening and closing configuration of the valve during cardiac cycle. Failure of certain chordae may lead to failure of the mitral valve and in severe cases, will lead to heart disease and mortality. In some cases, the ruptured chord need to be corrected by repair or replacement. Therefore, there has been high interest in the analysis of the function, mechanical properties and shape features of the mitral apparatus to improve the surgical effect. Chordae can be distinguished by leaflet location insertion as primary and secondary chordae. These finger-like chords connect the mitral valve to either anterolateral papillary muscle (APM) or posteromedial papillary muscle (PPM). The PPM has a higher risk to necrose and rupture in myocardial ischemia and infarction in clinic, but it is underlying mechanism is still unknown. Previous studies have shown importance in maintaining the asymmetric structure and realistic material property of the mitral valve for physiological load condition, but simplified the chord as symmetric structure, which is not true. In this study, the porcine heart chords were classified and measured according to the attached PMs. The uniaxial tensile test was utilized to analyze the biomechanical properties of the papillary muscle related chordae and histology observation was carried out for microstructure analysis. This study aims to analyze the anatomical and mechanical property differences in chords based on PMs which may help to understand the mitral valve function and to optimize the design of the artificial implantation or repair. Methods and materials Studies have shown that porcine valve was identified as an appropriate model for further investigation of the mitral valve system when considering the rarity of human valve. A total of 16 fresh porcine hearts were collected, infused in 4°C PBS buffer and infiltrated in physiological saline during the experiment, 9 of which were used for tensile testing, 6 for histological section staining, and 1 for TEM scanning. Based on insert position to PM (APM or PPM) and leaflets (primary on free edge and secondary on belly), the chord were divided into the APM primary chord, APM secondary chord, and PPM primary chord, and PPM secondary chord. The chords were separated from the valve, and the chordae diameter and length were measured via microscope, Markers were added at the target area of ​​the chord for strain measurement. The sample was then fixed on an Instron1000 uniaxial tensile test machine with sandpaper. Before the experiment, the specimens were preload from 0N to2N until the displacement curves were substantially coincident
. 二尖瓣是一个复杂的结构,包括瓣环、前小叶、后小叶、乳头肌(PM)以及连接小叶和PM的腱索。二尖瓣索的力学特性在二尖瓣的正常功能中起着重要作用:在心脏周期中,二尖瓣索协助维持二尖瓣的开启和关闭构型。某些索的衰竭可能导致二尖瓣的衰竭,在严重的情况下,会导致心脏病和死亡。在某些情况下,需要通过修复或更换来纠正断裂的弦。因此,分析二尖瓣的功能、力学特性和形状特征以提高手术效果已成为人们关注的焦点。按小叶位置插入可将索科分为初级索科和次级索科。这些指状索将二尖瓣连接到前外侧乳头肌(APM)或后内侧乳头肌(PPM)。PPM在临床上具有较高的心肌缺血和梗死坏死和破裂风险,但其潜在机制尚不清楚。以往的研究认为维持二尖瓣的不对称结构和真实的材料特性对生理负荷条件很重要,但将二尖瓣弦简化为对称结构,这是不正确的。本研究根据所附的pmms对猪心弦进行了分类和测量。采用单轴拉伸试验分析乳头肌相关索的生物力学特性,并进行组织学观察进行微观结构分析。本研究旨在分析二尖瓣的解剖和力学特性差异,以帮助了解二尖瓣的功能,优化人工植入或修复的设计。方法和材料研究表明,考虑到人类瓣膜的罕见性,猪瓣膜被认为是进一步研究二尖瓣系统的合适模型。采集新鲜猪心16颗,实验过程中灌注4℃PBS缓冲液,生理盐水浸润,其中9颗做拉伸试验,6颗做组织切片染色,1颗做TEM扫描。根据对PM (APM或PPM)和小叶(主要在自由边缘,次要在腹部)的插入位置,将弦分为APM主弦、APM副弦、PPM主弦和PPM副弦。将弦与瓣膜分离,在显微镜下测量弦的直径和长度,在弦的目标区域添加标记物进行应变测量。然后用砂纸将样品固定在Instron1000单轴拉伸试验机上。试验前对试件进行0 ~ 2n的预加载,直至位移曲线基本一致,然后进行拉伸试验。传感器用于记录应力变化,CCD摄像机同步采集目标区域上标记的位移画面,直到弦样从拉力试验机上断裂或滑落。利用MATLAB代码进行成像处理,得到应力-应变曲线。组织标本用4%戊二醛固定于PO4缓冲液(pH 7.4)中5小时,用分级浓度乙醇脱水,石蜡包埋。将径向切片切至5µm厚,进行masson染色,用显微镜(ZEISS Stemi 2000-C)和相机(ZEISS AxioCam ICc5)拍照。观察胶原纤维截面积比和微血管数量。采用透射电镜(TEM)观察样品的微观结构。用2.5%戊二醛修剪固定,1%四氧化锇后固定1小时,1%醋酸铀酰在马来酸缓冲液中固定1小时,用乙醇和环氧丙烷脱水,包埋于Epon中。透射电镜观察了胶原纤维结构的差异。结果与结论各PM的弦数差异无统计学意义,但PPM弦长。Green应变- cauchy应力曲线显示,PPM副弦的切线模量(TM)大于APM副弦。APM主弦上血管数量多于PPM主弦,各PM主弦上胶原纤维面积比差异无统计学意义。本研究采用Ogden非线性应变能函数拟合实验应力-应变数据,得到材料参数。为后续采用有限元法进行动力仿真提供了理论依据。
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引用次数: 1
Systems Modeling of Cardiomyocyte Mechanobiology 心肌细胞力学生物学系统建模
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2019-02-21 DOI: 10.32604/MCB.2019.05693
Philip M. Tan, Kyle S. Buchholz, Shulin Cao, Y. Aboelkassem, J. Omens, A. McCulloch, J. Saucerman
In this article, we summarize our systems model of cardiomyocyte mechano-signaling published in PLoS Computational Biology and discuss new approaches to extending these models to predict cardiac myocyte gene expression in response to stretch.
在本文中,我们总结了我们在PLoS计算生物学上发表的心肌细胞机械信号传导系统模型,并讨论了扩展这些模型以预测心肌细胞基因表达响应拉伸的新方法。
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引用次数: 1
Effect and Mechanism of Kir2.1 Channel Overexpression on Transdifferentiation of Endothelial Progenitor Cells Kir2.1通道过表达对内皮祖细胞转分化的影响及机制
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2019-02-21 DOI: 10.32604/MCB.2019.05753
Jifeng Li, Yanting He, Xiaoyun Zhang, Hong Li, Xiumei Guan, Min Cheng, Xiaodong Cui
Objective The propose of the study is to investigate the specific effects of the mechanically sensitive channel Kir2.1 on the transdifferentiation of EPCs so as to understand the molecular mechanism of pathological vascular remodeling. Methods Endothelial progenitor cells (EPCs) were isolated from rat bone marrow and cultured in EGM2 medium in vitro. The recombinant lentiviral vectors carrying Kir2.1 (NM_017296.1) gene was designed and constructed in order to overexpress the gene. The smooth muscle cells (SMCs) molecules marker on EPCs, such as α-SMA, FSP1 and α-SM22, were detected by RT-PCR and cellular immunofluorescence. In addition, cell angiogenic capacity and migration in vitro were assessed by Matrigel and Transwell methods respectively. Moreover, neointimal thickening was evaluated in the surgery model of balloon injury of rat carotid artery in vivo. Result The results showed that the expression levels of α-SM22, FSP1 and α-SMA were up-regulated in the Kir2.1 overexpression group compared with the control. The number of migrating cells in the Kir2.1 overexpression group was significantly higher than that in the scramble group, while quantitative assessment further confirmed that the Kir2.1 overexpression strongly attenuated the ability of bone marrow-derived EPC to form tube-like structures in Matrigel assay. Compared with the control group, morphometric analysis showed ratio of intimal area/medial area (I/M) in rats was increased in rats transplanted with Lenti-Kir2.1 overexpression. Conclusion It is indicated that the overexpression of channel Kir2.1 induces EPCs transdifferentiated into mesenchymal transition SMCs (EndoMT). It may provide a potential target for the treatment or prevention of pathological vascular remodeling disease.
目的探讨机械敏感通道Kir2.1在EPCs转分化中的具体作用,以了解病理性血管重构的分子机制。方法从大鼠骨髓中分离内皮祖细胞(EPCs),体外培养于EGM2培养基中。设计并构建了携带Kir2.1 (NM_017296.1)基因的重组慢病毒载体,以过表达该基因。采用RT-PCR和细胞免疫荧光法检测EPCs上平滑肌细胞(SMCs)分子标志物α-SMA、FSP1和α-SM22。此外,分别采用Matrigel法和Transwell法评估细胞的体外血管生成能力和迁移能力。并在大鼠颈动脉球囊损伤手术模型中对其新生内膜增厚进行了评价。结果Kir2.1过表达组与对照组相比,α-SM22、FSP1和α-SMA的表达水平均上调。Kir2.1过表达组的迁移细胞数量明显高于scramble组,同时在Matrigel实验中进一步定量评估证实,Kir2.1过表达强烈减弱了骨髓源性EPC形成管状结构的能力。形态计量学分析显示,与对照组相比,lentii - kir2.1过表达移植大鼠的内膜面积/内侧面积(I/M)比增加。结论过表达Kir2.1通道可诱导EPCs向间充质过渡型SMCs (EndoMT)转化。它可能为治疗或预防病理性血管重构疾病提供一个潜在的靶点。
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引用次数: 1
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Molecular & Cellular Biomechanics
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