Spatial distribution and network morphology of epicardial, endocardial, interstitial, and Purkinje cell-associated elastin fibers in porcine left ventricle

Shi, Xiaodan; Zhang, Song; Liu, Yue; Brazile, Bryn; Cooley, A J; Butler, J. L.; McMahan, Sara R.; Perez, Karla L.; Xu, Jiazhu; Eastep, Timothy; Nguyen, Kytai T.; Bajona, Pietro; Peltz, Matthias; Gao, Huajian; Hong, Yi; Liao, Jun

doi:10.1016/j.bioactmat.2022.04.019

Cited by 3 publications

(1 citation statement)

References 58 publications

(84 reference statements)

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“…In Williams-Beuren syndrome, impairment of the elastin ELN gene results in four out of five patients having cardiovascular abnormalities ( 89 ), with mutations also resulting in congenital heart disease ( 90 ). Elastin fibres are crucial for the proper functioning of Purkinje’s fibres ( 91 ) and blood vessels ( 92 ), and impairment can cause arrhythmias ( 93 ) or altered blood flow respectively, again impacting heart function.…”

Section: Discussionmentioning

confidence: 99%

AAV9-mediated SMN gene therapy rescues cardiac desmin but not lamin A/C and elastin dysregulation in Smn 2B/− spinal muscular atrophy mice

Brown

Šoltić

Synowsky

et al. 2023

Human Molecular Genetics

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Structural, functional and molecular cardiac defects have been reported in spinal muscular atrophy (SMA) patients and mouse models. Previous quantitative proteomics analyses demonstrated widespread molecular defects in the severe Taiwanese SMA mouse model. Whether such changes are conserved across different mouse models, including less severe forms of the disease, has yet to be established. Here, using the same high-resolution proteomics approach in the less-severe Smn2B/− SMA mouse model, 277 proteins were found to be differentially abundant at a symptomatic timepoint (post-natal day (P) 18), 50 of which were similarly dysregulated in severe Taiwanese SMA mice. Bioinformatics analysis linked many of the differentially abundant proteins to cardiovascular development and function, with intermediate filaments highlighted as an enriched cellular compartment in both datasets. Lamin A/C was increased in cardiac tissue whilst another intermediate filament protein, desmin, was reduced. The extracellular matrix (ECM) protein, elastin, was also robustly decreased in the heart of Smn2B/− mice. AAV9-SMN1-mediated gene therapy rectified low levels of survival motor neuron (SMN) protein and restored desmin levels in heart tissues of Smn2B/− mice. In contrast AAV9-SMN1 therapy failed to correct lamin A/C or elastin levels. Intermediate filament proteins and the ECM have key roles in cardiac function and their dysregulation may explain cardiac impairment in SMA, especially since mutations in genes encoding these proteins cause other diseases with cardiac aberration. Cardiac pathology may need to be considered in the long-term care of SMA patients, as it is unclear whether currently available treatments can fully rescue peripheral pathology in SMA.

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Section: Discussionmentioning

confidence: 99%

AAV9-mediated SMN gene therapy rescues cardiac desmin but not lamin A/C and elastin dysregulation in Smn 2B/− spinal muscular atrophy mice

Brown

Šoltić

Synowsky

et al. 2023

Human Molecular Genetics

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show abstract

Role of elastic fiber degradation in disease pathogenesis

Halsey¹,

Sinha²,

Dhital³

et al. 2023

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Distribution characteristics of Purkinje fibres in the canine left ventricle

Li,

Zhang,

Meng

et al. 2024

J Cellular Molecular Medi

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Purkinje‐related ventricular arrhythmias have been increasingly reported, and with the development of catheter ablation techniques, intervention for Purkinje‐related arrhythmias has been shown to be effective. The characteristics of Purkinje fibres orientation in the 12 canine left ventricles were observed at a gross level by staining the endocardium with Lugol's solution. Purkinje fibres were observed microscopically by HE, Masson's, PAS glycogen, and Cx40 immunohistochemical staining. Staining was successful, and the transverse orientation characteristics of Purkinje fibres were observed by Lugol's staining, and the longitudinal distribution was observed microscopically. The distribution of Purkinje fibres in the canine left ventricle is ‘graded’, ‘layered’, and ‘networked’, which can guide catheter ablation of Purkinje‐related ventricular arrhythmia.

show abstract

Spatial distribution and network morphology of epicardial, endocardial, interstitial, and Purkinje cell-associated elastin fibers in porcine left ventricle

Cited by 3 publications

References 58 publications

AAV9-mediated SMN gene therapy rescues cardiac desmin but not lamin A/C and elastin dysregulation in Smn 2B/− spinal muscular atrophy mice

AAV9-mediated SMN gene therapy rescues cardiac desmin but not lamin A/C and elastin dysregulation in Smn 2B/− spinal muscular atrophy mice

Role of elastic fiber degradation in disease pathogenesis

Distribution characteristics of Purkinje fibres in the canine left ventricle

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