LncRNA Sox2ot modulates the progression of thoracic aortic aneurysm by regulating miR-330-5p/Myh11

Xiao, Weizhang; Li, Xing; Ji, Cheng; Shi, Jiahai; Pan, Youmin

doi:10.1042/bsr20194040

Cited by 14 publications

(5 citation statements)

References 25 publications

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“…The mechanism of such phenomenon could be explained by the oligogenic model [19]. Markedly decreased cell apoptosis and increased proliferation were found in the aortic SMCs of Myh11 −/− mice [20], and the case with arterial stenosis in the intracranial vessel involvement caused by variants of MYH11 has been reported recently [21], indicating that there are other potential mechanisms of variants in MYH11 which remain to be explored. The mechanism by which variants in MYH11 result in TAAD/PDA is complex, and the genotype-phenotype correlation of MYH11 has not been clearly determined.…”

Section: Discussionmentioning

confidence: 94%

Complex genotype–phenotype correlation of MYH11: new insights from monozygotic twins with highly variable expressivity and outcomes

Wei,

Ma,

Xie

et al. 2024

BMC Med Genomics

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Background Thoracic aortic aneurysm/dissection (TAAD) and patent ductus arteriosus (PDA) are serious autosomal-dominant diseases affecting the cardiovascular system. They are mainly caused by variants in the MYH11 gene, which encodes the heavy chain of myosin 11. The aim of this study was to evaluate the genotype–phenotype correlation of MYH11 from a distinctive perspective based on a pair of monozygotic twins. Methods The detailed phenotypic characteristics of the monozygotic twins from the early fetal stage to the infancy stage were traced and compared with each other and with those of previously documented cases. Whole-exome and Sanger sequencing techniques were used to identify and validate the candidate variants, facilitating the analysis of the genotype–phenotype correlation of MYH11. Results The monozygotic twins were premature and presented with PDA, pulmonary hypoplasia, and pulmonary hypertension. The proband developed heart and brain abnormalities during the fetal stage and died at 18 days after birth, whereas his sibling was discharged after being cured and developed normally post follow-up. A novel variant c.766 A > G p. (Ile256Val) in MYH11 (NM_002474.2) was identified in the monozygotic twins and classified as a likely pathogenic variant according to the American College of Medical Genetics/Association for Molecular Pathology guidelines. Reviewing the reported cases (n = 102) showed that the penetrance of MYH11 was 82.35%, and the most common feature was TAAD (41.18%), followed by PDA (22.55%), compound TAAD and PDA (9.80%), and other vascular abnormalities (8.82%). The constituent ratios of null variants among the cases with TAAD (8.60%), PDA (43.8%), or compound TAAD and PDA (28.6%) were significantly different (P = 0.01). Further pairwise comparison of the ratios among these groups showed that there were significant differences between the TAAD and PDA groups (P = 0.006). Conclusion This study expands the mutational spectrum of MYH11 and provides new insights into the genotype–phenotype correlation of MYH11 based on the monozygotic twins with variable clinical features and outcomes, indicating that cryptic modifiers and complex mechanisms beside the genetic variants may be involved in the condition.

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Section: Discussionmentioning

confidence: 94%

Complex genotype–phenotype correlation of MYH11: new insights from monozygotic twins with highly variable expressivity and outcomes

Wei,

Ma,

Xie

et al. 2024

BMC Med Genomics

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“…MYH11 gene is involved in vascular contractility and vascular wall stability ( 43 , 44 ). For instance, it can decrease the proliferation and enhance the apoptosis of SMCs ( 45 ). Numerous studies on MYH11 and thoracic AD have been reported, and it is found that the heterozygous mutations of MYH11 are more susceptible to AD ( 7 , 46 ).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of Key m6A Modification Related Genes and Immune Infiltrates in Human Aortic Dissection

Yin

Zhang

Guo

et al. 2022

Front. Cardiovasc. Med.

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ObjectiveTo identify the feature of N6-methyladenosine (m6A) methylation modification genes in acute aortic dissection (AAD) and explore their relationships with immune infiltration.MethodsThe GSE52093 dataset including gene expression data from patients with AAD and healthy controls was downloaded from Gene Expression Omnibus (GEO) database in order to obtain the differentially expressed genes (DEGs). The differentially methylated m6A genes were obtained from the GSE147027 dataset. The differentially expressed m6A-related genes were obtained based on the intersection results. Meanwhile, the protein-protein interaction (PPI) network of differentially expressed m6A-related genes was constructed, and hub genes with close relationships in the network were selected. Later, hub genes were verified by using the GSE153434 dataset. Thereafter, the relationships between these genes and immune cells infiltration were analyzed.ResultsA total of 279 differentially expressed m6A-related genes were identified in the GSE52093 and GSE147027 datasets. Among them, 94 genes were up-regulated in aortic dissection (AD), while the remaining 185 were down-regulated. As indicated by Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, these genes were mainly associated with extracellular matrix (ECM) and smooth muscle cells (SMCs). The seven hub genes, namely, DDX17, CTGF, FLNA, SPP1, MYH11, ITGA5 and CACNA1C, were all confirmed as the potential biomarkers for AD. According to immune infiltration analysis, it was found that hub genes were related to some immune cells. For instance, DDX17, FLNA and MYH11 were correlated with Macrophages M2.ConclusionOur study identifies hub genes of AD that may serve as the potential biomarkers, illustrates of the molecular mechanism of AD, and provides support for subsequent research and treatment development.

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“…Fbn1 C1041G/+ mice: This mouse model of Marfan syndrome represents the most commonly used genetic model in investigating TAA [40,52,[75][76][77][78][79][80][81][82][83][84][85][86][87]. Fbn1 C1041G/+ mice, also known as Fbn1 C1039G/+ mice, are generated by substitution of cysteine with glycine at amino acid 1041 (C1041G) in exon 25 of fibrillin-1 (previously identified in the literature as C1039G) [88].…”

Section: Genetic Taa Models In Rodentsmentioning

confidence: 99%

Animal Models, Pathogenesis, and Potential Treatment of Thoracic Aortic Aneurysm

Wang,

Panicker,

Anesi

et al. 2024

IJMS

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Thoracic aortic aneurysm (TAA) has a prevalence of 0.16–0.34% and an incidence of 7.6 per 100,000 person-years, accounting for 1–2% of all deaths in Western countries. Currently, no effective pharmacological therapies have been identified to slow TAA development and prevent TAA rupture. Large TAAs are treated with open surgical repair and less invasive thoracic endovascular aortic repair, both of which have high perioperative mortality risk. Therefore, there is an urgent medical need to identify the cellular and molecular mechanisms underlying TAA development and rupture to develop new therapies. In this review, we summarize animal TAA models including recent developments in porcine and zebrafish models: porcine models can assess new therapeutic devices or intervention strategies in a large mammal and zebrafish models can employ large-scale small-molecule suppressor screening in microwells. The second part of the review covers current views of TAA pathogenesis, derived from recent studies using these animal models, with a focus on the roles of the transforming growth factor-beta (TGFβ) pathway and the vascular smooth muscle cell (VSMC)-elastin-contractile unit. The last part discusses TAA treatment options as they emerge from recent preclinical studies.

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LncRNA Sox2ot modulates the progression of thoracic aortic aneurysm by regulating miR-330-5p/Myh11

Cited by 14 publications

References 25 publications

Complex genotype–phenotype correlation of MYH11: new insights from monozygotic twins with highly variable expressivity and outcomes

Complex genotype–phenotype correlation of MYH11: new insights from monozygotic twins with highly variable expressivity and outcomes

Comprehensive Analysis of Key m6A Modification Related Genes and Immune Infiltrates in Human Aortic Dissection

Animal Models, Pathogenesis, and Potential Treatment of Thoracic Aortic Aneurysm

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