Remodeling of the transverse tubular system after myocardial infarction in rabbit correlates with local fibrosis: A potential role of biomechanics.
Remodeling of the transverse tubular system after myocardial infarction in rabbit correlates with local fibrosis: A potential role of biomechanics.
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DOI：
10.1016/j.pbiomolbio.2017.07.006
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发表时间：
2017-11
影响因子：
3.8
通讯作者：
Sachse FB
中科院分区：
文献类型：
--
作者：
Seidel T;Sankarankutty AC;Sachse FB
心室肌细胞的横管系统（t系统）对于有效的兴奋-收缩偶联至关重要。在心脏疾病中，如心力衰竭，t系统的重塑导致心脏收缩力降低。然而，t系统重塑的机制还不完全清楚。先前的研究表明，与改变心脏生物力学和基因表达的疾病。由于纤维化可能会改变组织的生物力学，我们研究了局部微观关联的t-系统重塑与纤维化的兔模型心肌梗死（MI）。从6个梗塞心脏和6个对照心脏的MI边缘区进行活检。使用共聚焦显微镜和自动图像分析，我们定量的t-系统的完整性（ITT）和细胞外基质（fECM）的局部分数。在对照组中，fECM为18± 0.3%。ITT为高且均匀（0.07±0.006），与fECM无关（R2=0.05±0.02）。MI边界区在距梗死瘢痕3 mm内表现出fECM增加（30± 3.5%，p<0.01 vs对照），表明纤维化。MI边缘区的肌细胞表现出显著的t系统重塑，具有扩张的片状成分，导致ITT较低（0.03±0.008，p<0.001 vs对照）。虽然fECM和t系统重塑都随着梗死距离的增加而降低，但ITT与fECM降低的相关性（R2=0.44）比与梗死距离（R2=0.24，p<0.05）更好。我们的研究结果表明，在兔心肌梗死边缘区的t-系统重塑类似于以前在人类心力衰竭中描述的表型。T系统重塑与局部纤维化的量相关，已知局部纤维化会破坏心脏组织，但在无纤维化的区域未发现。因此，局部改变的组织力学可能有助于t系统重塑。
The transverse tubular system (t-system) of ventricular cardiomyocytes is essential for efficient excitation-contraction coupling. In cardiac diseases, such as heart failure, remodeling of the t-system contributes to reduced cardiac contractility. However, mechanisms of t-system remodeling are incompletely understood. Prior studies suggested an association with altered cardiac biomechanics and gene expression in disease. Since fibrosis may alter tissue biomechanics, we investigated the local microscopic association of t-system remodeling with fibrosis in a rabbit model of myocardial infarction (MI). Biopsies were taken from the MI border zone of 6 infarcted hearts and from 6 control hearts. Using confocal microscopy and automated image analysis, we quantified t-system integrity (ITT) and the local fraction of extracellular matrix (fECM). In control, fECM was 18±0.3%. ITT was high and homogeneous (0.07±0.006), and did not correlate with fECM (R2=0.05±0.02). The MI border zone exhibited increased fECM within 3mm from the infarct scar (30±3.5%, p<0.01 vs control), indicating fibrosis. Myocytes in the MI border zone exhibited significant t-system remodeling, with dilated, sheet-like components, resulting in low ITT (0.03±0.008, p<0.001 vs control). While both fECM and t-system remodeling decreased with infarct distance, ITT correlated better with decreasing fECM (R2=0.44) than with infarct distance (R2=0.24, p<0.05). Our results show that t-system remodeling in the rabbit MI border zone resembles a phenotype previously described in human heart failure. T-system remodeling correlated with the amount of local fibrosis, which is known to stiffen cardiac tissue, but was not found in regions without fibrosis. Thus, locally altered tissue mechanics may contribute to t-system remodeling.
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影响因子：
20.1
作者：
Heinzel, FR;Bito, V;Sipido, KR
通讯作者：
Sipido, KR
影响因子：
10.8
作者：
Frisk M;Ruud M;Espe EK;Aronsen JM;Røe ÅT;Zhang L;Norseng PA;Sejersted OM;Christensen GA;Sjaastad I;Louch WE
通讯作者：
Louch WE
影响因子：
4.3
作者：
Driesen, Ronald B.;Verheyen, Fons K.;Borgers, Marcel
通讯作者：
Borgers, Marcel
影响因子：
37.8
作者：
CONRAD, CH;BROOKS, WW;BING, OHL
通讯作者：
BING, OHL
影响因子：
3.7
作者：
Biesmans L;Macquaide N;Heinzel FR;Bito V;Smith GL;Sipido KR
通讯作者：
Sipido KR