Myofibril orientation as a metric for characterizing heart disease.
Myofibril orientation as a metric for characterizing heart disease.
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DOI：
10.1016/j.bpj.2022.01.009
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发表时间：
2022-02-15
影响因子：
3.4
通讯作者：
Irving T
中科院分区：
文献类型：
--
作者：
Ma W;Gong H;Jani V;Lee KH;Landim-Vieira M;Papadaki M;Pinto JR;Aslam MI;Cammarato A;Irving T
心肌细胞紊乱是许多心脏疾病的特征。然而，个体肌原纤维和肌丝取向的改变与疾病进展之间的关系在很大程度上还没有得到充分的研究。这种疏忽主要是因为缺乏客观和定量的分析方法。在这里，我们介绍了一种新的、较少偏见的方法来量化近生理条件下心肌中的肌原纤维和肌丝取向，并展示了与传统组织学评估相比的优越性。利用小角X射线衍射，我们首先通过评估1，0赤道反射的角度扩散(σ角)，研究了从左心室通透性的、松弛的、野生型的小鼠心肌中，随着肌节长度的增加，肌原纤维取向的变化。当肌节长度为1.9rad时，σ角为0.23±0.01rad，当肌节长度为2.1rad时，角度μ减小到0.19±0.01rad，当肌节长度为2.3rad时，角度μ进一步减小到0.15±0.01rad(p<0.0001)。在MYH7型肥厚型心肌病模型R403Q中，猪心肌的σ角(0.24±0.01rad)明显大于野生型心肌(0.14±0.005 rad；p<0.0001)；人心衰组织(0.19±0.006 rad)明显大于正常心肌(0.17±0.007 rad；p<0.01)。这些数据表明，与健康对照组相比，患病心肌有更大的肌原纤维定向障碍。最后，我们证明了传统的、基于组织学的混乱分析可能会受到用户偏见和/或抽样误差的影响，并导致假阳性。我们的直接评估肌原纤维取向的方法避免了传统组织学方法评估肌细胞取向而仅间接评估肌纤维取向的伪影，并为心肌表型特征提供了准确和客观的衡量标准。从冷冻的人体心肌中获得优秀的X射线衍射图的能力为研究与心脏疾病相关的结构异常提供了新的工具。
Myocyte disarray is a hallmark of many cardiac disorders. However, the relationship between alterations in the orientation of individual myofibrils and myofilaments to disease progression has been largely underexplored. This oversight has predominantly been because of a paucity of methods for objective and quantitative analysis. Here, we introduce a novel, less-biased approach to quantify myofibrillar and myofilament orientation in cardiac muscle under near-physiological conditions and demonstrate its superiority as compared with conventional histological assessments. Using small-angle x-ray diffraction, we first investigated changes in myofibrillar orientation at increasing sarcomere lengths in permeabilized, relaxed, wild-type mouse myocardium from the left ventricle by assessing the angular spread of the 1,0 equatorial reflection (angle σ). At a sarcomere length of 1.9 μm, the angle σ was 0.23 ± 0.01 rad, decreased to 0.19 ± 0.01 rad at a sarcomere length of 2.1 μm, and further decreased to 0.15 ± 0.01 rad at a sarcomere length of 2.3 μm (p < 0.0001). Angle σ was significantly larger in R403Q, a MYH7 hypertrophic cardiomyopathy model, porcine myocardium (0.24 ± 0.01 rad) compared with wild-type myocardium (0.14 ± 0.005 rad; p < 0.0001), as well as in human heart failure tissue (0.19 ± 0.006 rad) when compared with nonfailing samples (0.17 ± 0.007 rad; p = 0.01). These data indicate that diseased myocardium suffers from greater myofibrillar disorientation compared with healthy controls. Finally, we showed that conventional, histology-based analysis of disarray can be subject to user bias and/or sampling error and lead to false positives. Our method for directly assessing myofibrillar orientation avoids the artifacts introduced by conventional histological approaches that assess myocyte orientation and only indirectly evaluate myofibrillar orientation, and provides a precise and objective metric for phenotypically characterizing myocardium. The ability to obtain excellent x-ray diffraction patterns from frozen human myocardium provides a new tool for investigating structural anomalies associated with cardiac diseases.
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DOI：
10.1073/pnas.1809540115
发表时间：
2018-08-28
影响因子：
11.1
作者：
Anderson, Robert L.;Trivedi, Darshan V.;Spudich, James A.
通讯作者：
Spudich, James A.
影响因子：
13.6
作者：
Kawana M;Sarkar SS;Sutton S;Ruppel KM;Spudich JA
通讯作者：
Spudich JA
影响因子：
64.5
作者：
GEISTERFERLOWRANCE, AAT;KASS, S;SEIDMAN, JG
通讯作者：
SEIDMAN, JG
影响因子：
4.5
作者：
Fukuda, N;Wu, YM;Granzier, H
通讯作者：
Granzier, H
DOI：
10.1083/jcb.118.6.1411
发表时间：
1992-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
Danowski BA;Imanaka-Yoshida K;Sanger JM;Sanger JW
通讯作者：
Sanger JW