Deletion of ACTA2 in mice promotes angiotensin II induced pathogenesis of thoracic aortic aneurysms and dissections

Cheng, Jiancheng; Zhou, Xianwu; Jiang, Xin; Sun, Tucheng

doi:10.21037/jtd.2018.07.75

Cited by 22 publications

(16 citation statements)

References 22 publications

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“…Although aortic lesions that arise in the AngII-infused ApoE −/− mouse do not phenocopy human dissections in many regards -they occur in the abdominal, not thoracic, aorta near major branch sites, they occur at the interface between the media and adventitia rather than within the media, they do not result from a connective tissue disorder, and they do not appear to involve focal accumulations of glycosaminoglycans -they nevertheless represent an important model for study. Recent studies have used this model to gain insight into various molecular components of aortic dissection, including lymphocyte adaptor protein deficiency 36 , smooth muscle α-actin deficiency 37 , ciprofloxacin treatment 38 , and transforming growth factor-β-SMAD3 signaling 39,40 .…”

Section: Discussionmentioning

confidence: 99%

Multimodality Imaging-Based Characterization of Regional Material Properties in a Murine Model of Aortic Dissection

Bersi

Santamaría

Marback

et al. 2020

Sci Rep

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chronic infusion of angiotensin-ii in atheroprone (ApoE −/−) mice provides a reproducible model of dissection in the suprarenal abdominal aorta, often with a false lumen and intramural thrombus that thickens the wall. Such lesions exhibit complex morphologies, with different regions characterized by localized changes in wall composition, microstructure, and properties. We sought to quantify the multiaxial mechanical properties of murine dissecting aneurysm samples by combining in vitro extension-distension data with full-field multimodality measurements of wall strain and thickness to inform an inverse material characterization using the virtual fields method. A key advance is the use of a digital volume correlation approach that allows for characterization of properties not only along and around the lesion, but also across its wall. Specifically, deformations are measured at the adventitial surface by tracking motions of a speckle pattern using a custom panoramic digital image correlation technique while deformations throughout the wall and thrombus are inferred from optical coherence tomography. These measurements are registered and combined in 3D to reconstruct the reference geometry and compute the 3D finite strain fields in response to pressurization. Results reveal dramatic regional variations in material stiffness and strain energy, which reflect local changes in constituent area fractions obtained from histology but emphasize the complexity of lesion morphology and damage within the dissected wall. This is the first point-wise biomechanical characterization of such complex, heterogeneous arterial segments. Because matrix remodeling is critical to the formation and growth of these lesions, we submit that quantification of regional material properties will increase the understanding of pathological mechanical mechanisms underlying aortic dissection.

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Section: Discussionmentioning

confidence: 99%

Multimodality Imaging-Based Characterization of Regional Material Properties in a Murine Model of Aortic Dissection

Bersi

Santamaría

Marback

et al. 2020

Sci Rep

View full text Add to dashboard Cite

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“…ACTA2 encodes alpha smooth muscle actin (alpha-SMA).Bergeron et al modeled two human ACTA2 mutants P.(Asn117Thr) and P.(Arg118Gln) in yeast actin, a mutant highly similar to smooth muscle actin 42 . ACTA2 knockout promotes progressive cavity expansion, apoptosis and phenotypic regulation of Vascular Smooth Muscle Cells (VSMCs) in mice 43 . Studies of ACTA2 gene mutations have shown that mutation carriers exhibit a variety of vascular lesions, including early-onset coronary artery disease (CAD), early-onset ischemic stroke (including moyamoya disease), and familial thoracic aortic aneurysms and dissecting aneurysms (TAADs) 44 .…”

Section: Discussionmentioning

confidence: 99%

10×Genomics Single-cell Sequencing Reveals Differential Cell Types in Skin Tissues of Liaoning Cashmere Goats and Key Genes Related Potentially to the Fineness of Cashmere Fiber

Zheng

Wang

Hui

et al. 2020

Preprint

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Cashmere fineness is one of the important factors determining cashmere quality, however, our understanding about the cells that make up the cashmere fineness is limited. Here, we used single-cell RNA sequencing (scRNA-seq) and computational models to identify 13 skin cell types in Liaoning Cashmere Goats. We also analyzed the molecular changes by Pseudo-Timeline Analysis in the development process and revealed the maturation process in gene expression profile in Liaoning Cashmere Goats. Weighted gene co-expression network analysis (WGCNA) explored hub genes in cell clusters related to cashmere formation. Secondary hair follicle dermal papilla cells (SDPCs) play an important role in the growth and density of cashmere. ACTA2, a marker gene of SDPCs, was selected for immunofluorescence (IF) and western blot (WB) verification. It was proved that it was mainly expressed in SDPCs, and WB results showed different expression levels. COL1A1 is a high expression gene in SDPCs, which was verified by IF and WB. Then select the function gene CXCL8 of SDPCs to verify, and prove the differential expression in the coarse type and the fine type of Liaoning Cashmere Goats. Therefore, COL1A1 may involve in regulated skin development and CXCL8 gene may regulate cashmere fineness. These genes may be involved in regulating the fineness of cashmere in goat secondary hair follicle dermal papilla cells, our research will provide new insights into the mechanism of cashmere growth and cashmere fineness regulation by cells.

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“…So necessary understanding of the molecular mechanism may provide new insights into therapeutic targets for TAD. Dysregulated extracellular matrix (ECM) protein like elastin and collagen and depletion of vascular smooth muscle cells (VSMCs) of the aortic wall are believed as the main histopathological findings [3][4][5]. However, still little is known about the genetics of the disease.…”

Section: Introductionmentioning

confidence: 99%

Integration of Gene Expression Profile Data to Verify Hub Genes of Patients with Stanford A Aortic Dissection

Wang

et al. 2019

BioMed Research International

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Thoracic aortic dissection (TAD) is a catastrophic disease worldwide, but the pathogenic genes and pathways are largely unclear. This study aims at integrating two gene expression profile datasets and verifying hub genes and pathways involved in TAD as well as exploring potential molecular mechanisms. We will combine our mRNAs expression profile (6 TAD tissues versus 6 non-TAD tissues) and GSE52093 downloaded from the Gene Expression Omnibus (GEO) database. The two mRNAs expression profiles contained 13 TAD aortic tissues and 11 non-TAD tissues. The two expression profile datasets were integrated and we found out coexpression of differentially expressed genes (DEGs) using bioinformatics methods. The gene ontology and pathway enrichment of DEGs were performed by DAVID and Kyoto Encyclopedia of Genes and Genomes online analyses, respectively. The protein-protein interaction networks of the DEGs were constructed according to the data from the STRING database. Cytohubber calculating result shows the top 10 hub genes with CDC20, AURKA, RFC4, MCM4, TYMS, MCM2, DLGAP5, FANCI, BIRC5, and POLE2. Module analysis revealed that TAD was associated with significant pathways including cell cycle, vascular smooth muscle contraction, and adrenergic signaling in cardiomyocytes. The qRT-PCR result showed that the expression levels of all the hub genes were significantly increased in OA samples (p < 0.05), and these candidate genes could be used as potential diagnostic biomarkers and therapeutic targets of TAD.

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Deletion of ACTA2 in mice promotes angiotensin II induced pathogenesis of thoracic aortic aneurysms and dissections

Abstract: Knockout of ACTA2 promoted AngII induced progressive lumen dilation of the aortas, apoptosis, and the phenotypic modulation in VSMCs in mice.

Cited by 22 publications

References 22 publications

Multimodality Imaging-Based Characterization of Regional Material Properties in a Murine Model of Aortic Dissection

Multimodality Imaging-Based Characterization of Regional Material Properties in a Murine Model of Aortic Dissection

10×Genomics Single-cell Sequencing Reveals Differential Cell Types in Skin Tissues of Liaoning Cashmere Goats and Key Genes Related Potentially to the Fineness of Cashmere Fiber

Integration of Gene Expression Profile Data to Verify Hub Genes of Patients with Stanford A Aortic Dissection

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