Hydrogen Sulfide Attenuates Aortic Remodeling in Aortic Dissection Associating with Moderated Inflammation and Oxidative Stress through a NO-Dependent Pathway

Lu, Hsin Ying; Hsu, Hung Lung; Li, Chih Han; Li, Shao Jung; Lin, Shing Jong; Shih, Chün Ming; Shih, Chun Che

doi:10.3390/antiox10050682

Cited by 14 publications

(8 citation statements)

References 38 publications

(40 reference statements)

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“…ACTA2, is a smooth muscle actin, ranks first among the four algorithms. The mutation of ACTA2 is closely related to aortic dissection ( Cooper and Brown, 2017 ; van de Laar et al, 2019 ).The second key gene IL6, encodes a cytokine that functions in inflammation and the maturation of B cells, the inflammatory mechanism plays a key role in the development and progression of AD ( Lu et al, 2021 ).CTGF, is a Protein Coding gene, and has important pro-inflammatory and pro-fibrotic characteristic ( Morales et al, 2018 ), which play an important role in the progression of AD ( Bode-Jänisch et al, 2012 ; Bersi et al, 2017 ; Zhao and Bie, 2020 ). BGN, encodes a member of the small leucine-rich proteoglycan (SLRP) family of proteins, which plays a role in bone growth, muscle development and regeneration, and collagen fibril assembly in multiple tissues ( Fisher et al, 1991 ; Didangelos et al, 2010 ).…”

Section: Discussionmentioning

confidence: 99%

Single-Cell RNA Sequencing Reveals Smooth Muscle Cells Heterogeneity in Experimental Aortic Dissection

Liu

Fang

et al. 2022

Front. Genet.

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Purpose: This study aims to illustrate the cellular landscape in the aorta of experimental aortic dissection (AD) and elaborate on the smooth muscle cells (SMCs) heterogeneity and functions among various cell types.Methods: Male Apolipoprotein deficient (ApoE−/−) mice at 28 weeks of age were infused with Ang II (2,500 ng/kg/min) to induce AD. Aortas from euthanized mice were harvested after 7 days for 10×Genomics single-cell RNA sequencing (scRNA-seq), followed by the identification of cell types and differentially expressed genes (DEGs). Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was conducted.Results: AD was successfully induced in ApoE−/− mice. scRNA-seq identified 15 cell clusters and nine cell types, including non-immune cells (endothelials, fibroblasts, and SMCs) and immune cells (B cells, natural killer T cell, macrophages, dendritic cells, neutrophils, and mast cells). The relative numbers of SMCs were remarkably changed, and seven core DEGs (ACTA2,IL6,CTGF,BGN,ITGA8,THBS1, and CDH5) were identified in SMCs. Moreover, we found SMCs can differentiate into 8 different subtypes through single-cell trajectory analysis.Conclusion: scRNA-seq technology can successfully identify unique cell composition in experimental AD. To our knowledge, this is the first study that provided the complete cellular landscape in AD tissues from mice, seven core DEGs and eight subtypes of SMCs were identified, and the SMCs have evolution from matrix type to inflammatory type.

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Section: Discussionmentioning

confidence: 99%

Single-Cell RNA Sequencing Reveals Smooth Muscle Cells Heterogeneity in Experimental Aortic Dissection

Liu

Fang

et al. 2022

Front. Genet.

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“…Recent report indicates that molecular pathways and indexes that regulate the transition of VSMC phenotype might impact the development of AD [ 26 ]. In eukaryocytes, the metabolism of phosphoinositol is the core of regulating cell homeostasis [ 27 ], among which PI3P family is one of the most abundant lipids and play a critical role in endocytosis and autophagosome membrane dynamics in cells [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

C/EBPα-Mediated Transcriptional Activation of PIK3C2A Regulates Autophagy, Matrix Metalloproteinase Expression, and Phenotypic of Vascular Smooth Muscle Cells in Aortic Dissection

Lü

Chen

et al. 2022

Journal of Immunology Research

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Purpose. To investigate the function of C/EBPα in the development of aortic dissection (AD) and the underlying mechanism. Methods. Aortic vascular smooth muscle cells (VSMCs) were isolated, cultured, and identified from AD rats. Then, C/EBPα and PIK3C2A were knockdown or overexpressed by siRNA or plasmid transfection, respectively. Rapamycin or 3-MA was utilized to stimulate and restrain autophagy of VSMCs, respectively. Western blot was used to evaluate the expression levels of C/EBPα, PIK3C2A, LC3, Beclin-1, p62, MMP-2, MMP-9, α-SMA, SM-MHC, and OPN. The pathological status of aortic ring was evaluated by stretch stress, and ChIP assay was used to analyze the binding between C/EBPα and PIK3C2A. C/EBPα shRNA was injected into tail vein to observe the effect of C/EBPα knockdown in vivo on phenotype, autophagy of aortic vascular tissue by immunohistochemical staining and Western blot. Results. The protein levels of C/EBPα, PIK3C2A, MMP-2, MMP-9, and LC3 in the aorta of AD rats were all upregulated significantly. C/EBPα and rapamycin promoted notable upregulation of the synthesized proteins (OPN), PIK3C2A, matrix metalloproteinases, LC3, and Beclin-1 in VSMCs, while suppressed contractile proteins (α-SMA and SM-MHC) and p62. The opposite results were observed in the C/EBPα-knockdown VSMCs, PIK3C2A-knockdown VSMCs, or VSMCs treated with 3-MA. C/EBPα, PIK3C2A, and LC3 were dramatically upregulated by the stimulation of 3 g and 5 g stretch stress. The downregulated contractile proteins, upregulated synthetic proteins, activated autophagy, and aggravated pathological state in 5 g stretch stress-treated aortic rings were significantly reversed by the knockdown of C/EBPα. ChIP results indicated that there was a binding site for C/EBPα in the promoter of PIK3C2A. C/EBPα also downregulated α-SMA level and upregulated OPN levels in AD rats in vivo. Conclusion. Our data indicated that during the development of AD, C/EBPα regulated the transition of VSMC phenotype and extracellular matrix remodeling by activating autophagy through regulating the transcriptional activity of PIK3C2A promoter.

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“…Emerging data indicate that H 2 S improves diabetic endothelial dysfunction, 34 inhibits myocardial apoptosis after myocardial infarction, 35 and inhibits VSMC proliferation and migration induced by hyperglycaemia 27 ; recent data from our laboratory and others revealed that exogenous H 2 S attenuates angiotensin II (Ang II)–induced VSMC phenotypic switch and vascular remodeling. 12 , 36 However, there are no published literature on the potential effect of exogenous H 2 S on AF activation. Our study found that TGF-β1 induced AF phenotype switching, proliferation, and migration, which were ameliorated by exogenous H 2 S administration.…”

Section: Discussionmentioning

confidence: 99%

Hydrogen Sulfide Diminishes Activation of Adventitial Fibroblasts Through the Inhibition of Mitochondrial Fission

Guo

Yang

et al. 2022

Journal of Cardiovascular Pharmacology

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: Activation of adventitial fibroblasts (AFs) on vascular injury contributes to vascular remodeling. Hydrogen sulfide (H 2 S), a gaseous signal molecule, modulates various cardiovascular functions. The aim of this study was to explore whether exogenous H 2 S ameliorates transforming growth factor-β1 (TGF-β1)–induced activation of AFs and, if so, to determine the underlying molecular mechanisms. Immunofluorescent staining and western blot were used to determine the expression of collagen I and α-smooth muscle actin. The proliferation and migration of AFs were performed by using cell counting Kit-8 and transwell assay, respectively. The mitochondrial morphology was assessed by using MitoTracker Red staining. The activation of signaling pathway was evaluated by western blot. The mitochondrial reactive oxygen species and mitochondrial membrane potential were determined by MitoSOX and JC-1 (5,5′,6,6′-tetrachloro-1,1,3,3′-tetraethylbenzimidazolyl carbocyanine iodide) staining. Our study demonstrated exogenous H 2 S treatment dramatically suppressed TGF-β1–induced AF proliferation, migration, and phenotypic transition by blockage of dynamin-related protein 1 (Drp1)–mediated mitochondrial fission and regulated mitochondrial reactive oxygen species generation. Moreover, exogenous H 2 S reversed TGF-β1–induced mitochondrial fission and AF activation by modulating Rho-associated protein kinase 1–dependent phosphorylation of Drp1. In conclusion, our results suggested that exogenous H 2 S attenuates TGF-β1–induced AF activation through suppression of Drp1-mediated mitochondrial fission in a Rho-associated protein kinase 1–dependent fashion.

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Hydrogen Sulfide Attenuates Aortic Remodeling in Aortic Dissection Associating with Moderated Inflammation and Oxidative Stress through a NO-Dependent Pathway

Cited by 14 publications

References 38 publications

Single-Cell RNA Sequencing Reveals Smooth Muscle Cells Heterogeneity in Experimental Aortic Dissection

Single-Cell RNA Sequencing Reveals Smooth Muscle Cells Heterogeneity in Experimental Aortic Dissection

C/EBPα-Mediated Transcriptional Activation of PIK3C2A Regulates Autophagy, Matrix Metalloproteinase Expression, and Phenotypic of Vascular Smooth Muscle Cells in Aortic Dissection

Hydrogen Sulfide Diminishes Activation of Adventitial Fibroblasts Through the Inhibition of Mitochondrial Fission

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