Pathogenesis Of Aortic Dissection Research Articles

The role of cellular senescence in aortic dissection

Abstract Background Aortic dissection (AD) is a catastrophic disease with high mortality. Survived patients frequently suffer from serious complications due to progressive destruction of the aortic walls. Recently we have reported that cell proliferation precedes the inflammatory response which is important in AD development and progression. Since cell proliferation promotes cellular senescence that can induce inflammatory response through SASP (senescence-associated secretary phenotype), we hypothesized that cellular senescence plays a critical role in AD pathogenesis. Purpose To investigate if cellular senescence contributes to AD pathogenesis in mouse AD model. Methods and Results A mouse AD model was created by the continuous infusion of beta-aminopropionitrile and angiotensin II (BAPN+AngII) for 14days. BAPN+AngII infusion induced senescence markers and senescent cells in mouse AD model. Senescent cells, as demonstrated by the expression of senescence-associated beta-galactosidase, were evident in intimal endothelial cells, medial smooth muscle cells, adventitial macrophages, and fibroblasts. Rapamycin, an inhibitor of mTOR pathway, suppressed the expression of senescent cells on the aortic tissue and the senescent marker protein expression. To examine the role of cellular senescence in AD, we orally administrated ABT263 known as "senolytics" that eliminates senescent cells. ABT263 treatment prevented cellular senescence in mouse AD model. The AD mortality of ABT263 group was 35%, which was lower than that of vehicle group (66.7%, P < 0.05 by log-rank test). The severity of AD, as assessed by the lesion length in vehicle group was 33.2 ± 3.1mm, whereas that in ABT263 group was 24.6 ± 1.8mm (P < 0.05). Transcriptome analysis revealed that ABT263 treatment suppressed the immune and inflammatory response in the aorta before AD onset. Quantitative RT-PCR confirmed that ABT263 treatment prevented the induction of p21Cip1, interleukin-6, several chemokines and M1 macrophage marker CD80 and CD86. It is known that Jnk activation induces SASP and accelerates cellular senescence. Western blotting confirmed that ABT263 reduced the ratio of pJnk to total Jnk, which was induced by BAPN + AngⅡ. Moreover, aortic smooth muscle cells（SMCs）remained contractile phenotype in ABT263 group, whereas BAPN+AngII reduced that phenotype in vehicle group. Conclusions Cell proliferation via mTOR pathway causes cellular senescence in mouse AD model. Jnk activation was confirmed in mouse AD model. Cellular senescence contributes to AD progression and death associated with inflammatory responses including SASP, the differentiation to M1 macrophage, and the phenotype change of SMCs.Cellular senescence represents a potential predictor and a therapeutic target for AD.

Role of macrophages in aortic dissection pathogenesis: insights from preclinical studies to translational prospective.

Aortic dissection is a critical vascular disease that is characterized by a high mortality rate and inflammation significantly influences its onset and progression. Recent studies highlight the integral role of macrophages, key players in the immune system, in the pathological landscape of aortic dissection. These cells are involved in crucial processes, such as the remodeling of the extracellular matrix, immunocyte infiltration, and phenotypic switching of smooth muscle cells, which are essential for the structural integrity and functional dynamics of the aortic wall. Despite these insights, the specific contributions of macrophages to the development and progression of aortic dissection remains unclear. This review explores the pathogenesis of aortic dissection with a focus on macrophages and describes their origins, phenotypic variations, and potential roles based on the most recent research findings. Furthermore, we discuss key molecules related to macrophages during aortic dissection, their interactions with other cellular components within the aorta, and the implications of these interactions for future therapeutic strategies. This comprehensive analysis aimed to improve our understanding of macrophages in aortic dissection and promote the development of targeted interventions.

Cell Type-Specific Relationships Among Immune Cells in Human Aortic Dissection Tissue.

Although recent studies have revealed the importance of inflammation in the pathogenesis of aortic dissection (AD), little is known about the relationships among inflammatory cells in human AD tissue. We assessed the relationships among various immune cell types, including neutrophils, macrophages (M1 and M2), B cells, and helper T cells (Th1, Th2, Th17, Treg and Tfh ) in human AD tissue. AD tissues displayed abundant infiltration of immune cells. Correlation analysis revealed two groups of highly correlated cell types: a group of neutrophils and M1 and M2 macrophages, and another group consisting of B cells and helper T cells. In one particular case of AD, we were able to analyze the correlations between neutrophils and M1 and M2 macrophages in the entry, border, and intact zones of the AD lesions. Neutrophils showed significant correlations with M1 and M2 macrophages in the border zones. The entry and border zones showed M1-dominant polarization, whereas the intact zone showed M2-dominant polarization. These findings indicate the existence of cell type-specific and site-specific interactions among immune cell types in human AD tissues.

Uncovering Druggable Targets in Aortic Dissection: An Association Study Integrating Mendelian Randomization, pQTL, and Protein-Protein Interaction Network.

Aortic dissection (AD) is a life-threatening acute aortic syndrome. There are limitations and challenges in the discovery and application of biomarkers and drug targets for AD. Mendelian randomization (MR) analysis is a reliable analytical method to identify effective therapeutic targets. We aimed to identify novel therapeutic targets for AD and investigate their potential side-effects based on MR analysis. Data from protein quantitative trait loci (pQTLs) were used for MR analyses to identify potential therapeutic targets. We probed druggable proteins involved in the pathogenesis of aortic dissection from deCODE. In this study, a two-sample MR analysis was conducted, with druggable proteins as the exposure factor and data on genome-wide association studies (GWAS) of AD as the outcome. After conducting a two-sample MR, summary data-based Mendelian randomization (SMR) analysis and colocalization analysis were performed. A protein-protein interaction (PPI) network was also constructed to delve into the interactions between identified proteins. After MR analysis and the Steiger test, we identified five proteins as potential therapeutic targets for AD. SMR analysis and colocalization analysis also confirmed our findings. Finally, we identified ASPN (OR = 1.36, 95% CI: 1.20, 1.54, p = 4.22 × 10-5) and SPOCK2 (OR = 0.57, 95% CI: 0.41, 0.78, p = 4.52 × 10-4) as the core therapeutic targets. Through PPI network analysis, we identified six druggable targets, enabling the subsequent identification of six promising drugs from DrugBank for treating AD. This discovery of specific proteins as novel therapeutic targets represents a significant advancement in AD treatment. These findings provide more effective treatment options for AD.

The role of RUNX1/NF-κB in regulating PVAT inflammation in aortic dissection

The pathogenesis of aortic dissection (AD), an aortic disease associated with high mortality, involves significant vascular inflammatory infiltration. However, the precise relationship between perivascular adipose tissue (PVAT) and aortic dissection remains incompletely understood. The objective of this study is to investigate the role of PVAT inflammation in the pathogenesis of aortic dissection and identify novel therapeutic targets for this disease. The mouse model of aortic dissection was established in this study through intraperitoneal injection of Ang II and administration of BAPN in drinking water. Additionally, control groups were established at different time points including the 2-week group, 3-week group, and 4-week group. qPCR and immunohistochemistry techniques were employed to detect the expression of inflammatory markers and RUNX1 in PVAT surrounding the thoracic aorta in mice. Additionally, an aortic dissection model was established using RUNX1 knockout mice, and the aforementioned indicators were assessed. The 3T3-L1 cells were induced to differentiate into mature adipocytes in vitro, followed by lentivirus transfection for the knockdown or overexpression of RUNX1. The study aimed to investigate the potential cell-to-cell interactions by co-culturing 3T3-L1 cells with A7r5 or RAW264.7 cells. Subsequently, human aortic PVAT samples were obtained through clinical surgery and the aforementioned indicators were detected. In comparison to the control group, the aortic dissection model group exhibited decreased expression of MMP-2 and NF-κB in PVAT, while TNF-α and RUNX1 expression increased. Suppression of RUNX1 expression resulted in increased MMP-2 and NF-κB expression in PVAT, along with decreased TNF-α expression. Overexpression of RUNX1 upregulated the expression levels of NF-Κb, MMP-2, and TNF-α in adipocytes, whereas knockdown of RUNX1 exerted an opposite effect. Macrophages co-cultured with adipocytes overexpressing RUNX1 exhibited enhanced CD86 expression, while vascular smooth muscle cells co-cultured with these adipocytes showed reduced α-SMA expression. In human samples, there was an increase in both RUNX1 and MMP-2 expression levels, accompanied by a decrease in TNF-α and NF-Κb expression. The presence of aortic dissection is accompanied by evident inflammatory alterations in the PVAT, and this phenomenon appears to be associated with the involvement of RUNX1. It is plausible that the regulation of PVAT's inflammatory changes by RUNX1/NF-κB signaling pathway plays a role in the pathogenesis of aortic dissection.

Unraveling the Enigma of Aortic Dissection: From Genetics to Innovative Therapies.

Aortic dissection (AD) presents a critical medical emergency characterized by a tear in the aortic wall, necessitating prompt recognition and management to mitigate catastrophic complications. Despite advancements in medical technology and therapeutic interventions, AD remains a formidable challenge, often resulting in severe morbidity and mortality. This narrative review provides a comprehensive overview of AD, encompassing its clinical presentation, diagnostic modalities, and management strategies, while also exploring emerging trends and innovations in its management. Genetic predispositions significantly influence AD pathogenesis, with over 30 contributory genes identified, emphasizing the importance of genetic screening and counseling. Classification systems such as Stanford and DeBakey, alongside their revised counterparts, aid in categorizing AD and guiding treatment decisions. Advancements in diagnostic imaging, including transesophageal echocardiography and computed tomography angiography, have enhanced diagnostic precision, augmented by artificial intelligence and machine learning algorithms. Pharmacological innovations focus on optimizing medical therapy, while surgical and endovascular approaches offer minimally invasive treatment options. Hybrid procedures and aortic valve-sparing techniques broaden treatment avenues, while bioresorbable stent grafts hold promise for tissue regeneration. Collaborative efforts and ongoing research are essential to address remaining challenges and improve outcomes in managing AD. This review contributes to the understanding of AD's complexity and facilitates informed decision-making in clinical practice, underscoring the imperative for continued innovation and research in AD management.

Identification of Key Immune Infiltration Related Genes Involved in Aortic Dissection Using Bioinformatic Analyses and Experimental Verification.

Immune microenvironment plays an important role in aortic dissection (AD). Therefore, novel immune biomarkers may facilitate AD prevention, diagnosis, and treatment. This study aimed at mining key immune-related genes and relevant mechanisms involved in AD pathogenesis. Key immune cells in AD were identified by ssGESA algorithm. Next, genes associated with key immune cells were screened by weighted gene coexpression network analysis (WGCNA). Then hub immune genes were picked from protein-protein interaction network of overlapped genes from differential expression and WGCNA analyses by cytohubba plug-in. Their diagnostic potential was evaluated in two independent cohorts from GEO database. In addition, the expressions of hub immune genes were determined by quantitative RT-PCR, immunohistochemistry, and Western blotting in dissected and normal aortic tissues. Activated B cells, CD56dim natural killer cells, eosinophils, gamma delta T cells, immature B cells, natural killer cells and type 17 T helper cells were identified as key immune cells in AD. Thereafter, a gene module significantly correlated with key immune cells were found by WGCNA method. Subsequently, KDR, IGF1, NOS3, PECAM1, GAPDH, FLT1, DLL4, CDH5, VWF, and TEK were identified as hub immune cell related genes by PPI network analysis, which may be potential diagnostic markers for AD, as evidenced by ROC curves. Moreover, the decreased expression of VWF in AD was validated at both mRNA and protein levels, and its expression was significantly positive correlated with the marker of smooth muscle cells, ACTA2, in AD. Further immunofluorescent results showed that VWF was colocalized with ACTA2 in aortic tissues. We identified key immune cells and hub immune cell-related genes involved in AD. Moreover, we found that VWF was co-expressed with the smooth muscle cell marker ACTA2, indicating the important role of VWF in smooth muscle cell loss in AD pathogenesis.

Roles of pyroptosis and immune infiltration in aortic dissection.

Introduction: Aortic dissection (AD) is often fatal, and its pathogenesis involves immune infiltration and pyroptosis, though the molecular pathways connecting these processes remain unclear. This study aimed to investigate the role of immune infiltration and pyroptosis in AD pathogenesis using bioinformatics analysis. Methods: Two Gene Expression Omnibus datasets and a Gene Cards dataset of pyroptosis-related genes (PRGs) were utilized. Immunological infiltration was assessed using CIBERSORT, and AD diagnostic markers were identified through univariate logistic regression and least absolute shrinkage and selection operator regression. Interaction networks were constructed using STRING, and weighted gene correlation network analysis (WGCNA) was employed to identify important modules and essential genes. Single-sample gene set enrichment analysis determined immune infiltration, and Pearson correlation analysis assessed the association of key genes with infiltrating immune cells. Results: Thirty-one PRGs associated with inflammatory response, vascular epidermal growth factor receptor, and Rap1 signaling pathways were identified. WGCNA revealed seven important genes within a critical module. CIBERSORT detected immune cell infiltration, indicating significant changes in immune cell infiltration and pyroptosis genes in AD and their connections. Discussion: Our findings suggest that key PRGs may serve as indicators for AD or high-risk individuals. Understanding the role of pyroptosis and immune cell infiltration in AD pathogenesis may lead to the development of novel molecular-targeted therapies for AD. Conclusion: This study provides insights into the molecular mechanisms underlying AD pathogenesis, highlighting the importance of immune infiltration and pyroptosis. Identification of diagnostic markers and potential therapeutic targets may improve the management of AD and reduce associated morbidity and mortality.

Untargeted metabolomics identifies indole-3-propionic acid to relieve Ang II-induced endothelial dysfunction in aortic dissection.

Indole-3-propionic acid (IPA), a gut microbiota-derived metabolite of tryptophan, has been proven to fulfill an essential function in cardiovascular disease (CVD) and nerve regeneration disease. However, the role of IPA in aortic dissection (AD) has not been revealed. We aimed to investigate the role of IPA in the pathogenesis of AD and the underlying mechanisms of IPA in endothelial dysfunction. Untargeted metabolomics has been employed to screen the plasma metabolic profile of AD patients in comparison with healthy individuals. Network pharmacology provides insights into the potential molecular mechanisms underlying IPA. 3-aminopropionitrile fumarate (BAPN) and angiotensin II (Ang II) were administered to induce AD in mice, while human umbilical vein endothelial cells (HUVECs) were employed for in vitro validation of the signaling pathways predicted by network pharmacology. A total of 224 potentially differential plasma metabolites were identified in the AD patients, with 110 up-regulated metabolites and 114 down-regulated metabolites. IPA was the most significantly decreased metabolite involved in tryptophan metabolism. Bcl2, caspase3, and AKT1 were predicted as the target genes of IPA by network pharmacology and molecular docking. IPA suppressed Ang II-induced apoptosis, intracellular ROS generation, inflammation, and endothelial tight junction (TJ) loss. Animal experiments demonstrated that administration of IPA alleviated the occurrence and severity of AD in mice. Taken together, we identified a previously unexplored association between tryptophan metabolite IPA and AD, providing a novel perspective on the underlying mechanism through which IPA mitigates endothelial dysfunction to protect against AD.

Abstract 16322: Role of Spleen Tyrosine Kinase in Pathomechanism of Aortic Dissection

Background: Aortic dissection (AD) is a fatal aortic disease of which molecular pathogenesis has not been elucidated. In our previous studies, we found that systemic inhibition of Syk, spleen tyrosine kinase, exacerbates AD leading and sudden death in model mice. However, cell type-specific role of the AD pathogenesis is unknown. Subject: How does Syk contribute to the pathogenesis of AD. And what cells in the aorta contribute to the pathogenesis of AD. Methods and results: Mouse AD model was created by continuous infusion of β-aminopropionitrile and angiotensin II (BAPN+AngII) for 14 days as previously reported. Iba1 and αSMA, markers of activated macrophage (Mϕ) and smooth muscle cell (Sm), respectively, were double-stained with p-Syk in the mouse AD model. As a results, we found that both Mϕ and Sm are activated in the same region as Syk. This suggests that Syk contributes in some way to Mϕ and Sm in the pathogenesis of AD. Mϕ-specific Syk knockout mice were generated using the Cre-LoxP system. Phenotype effects were compared in the controls and Mϕ-specific Syk knockout groups, but there were no significant differences in AD lesion length and mortality. Sm-specific Syk knockout mice were generated using the tamoxifen-induced CreERT2 system to avoid alteration of aortic phenotypic at the baseline. Ten-week-old mice with loxP sequences at both ends of the Syk gene in Sm were injected with 1 mg/day of tamoxifen for 5 days, and In Situ Hybridization showed that p-Syk was reduced in the aortic tunica media after 2 weeks. Phenotypic comparisons with controls what did not receive tamoxifen showed no significant differences in AD lesion length and mortality. These results differ from previous findings that systemic Syk inhibition increases AD. Conclusions: We found that systemic inhibition of Syk exacerbates the pathogenesis and mortality of AD, and that Syk has some activation in Mϕ and Sm. However, deletion of Syk in Mϕ or Sm alone had no apparent effect on the pathogenesis of AD. These results suggest that the action of Syk in AD pathogenesis is not solely due to Mϕ and Sm, but is due to a more complex mechanism involving multiple cells interactions.

Abstract 17622: CCN3 Deficiency in Myeloid Cells Exacerbates Aortic Dissection by Governing a Proinflammatory Program in Macrophages

Introduction: Aortic dissection (AD) is a fatal disease. Macrophages are known central regulators of aortic inflammation and elastic fiber disruption, two major hallmarks of AD. Cellular communication network factor 3 (CCN3/NOV) is a matricellular protein associated with various biological cellular functions in cardiovascular disease and cancers. Emerging evidence strongly implicates a protective role of CCN3 against several types of vascular pathologies, however its role in AD remains unknown. Hypothesis: CCN3 deficiency in myeloid cells promotes AD development in murine models through the modulation of macrophage phenotype. Aims: We investigated the causal role of CCN3 loss in AD pathogenesis, focusing on its role in macrophages. Methods: 3-4-week-old male myeloid-specific CCN3 knockout mice (CCN3F/F;LysMCre) and control mice (LysMCre) were given BAPN (β-aminopropionitrile monofumarate; 0.2%) in their drinking water for 4 weeks for AD modeling. Mouse survival rate and histological changes of the aorta were assessed. Single cell RNA sequencing analysis was performed to recapitulate cellular transcriptome profile changes. Finally, gain and loss of function studies in bone marrow-derived macrophages (BMDMs) were performed to decipher the underlying mechanism by which CCN3 controls macrophage plasticity. Results: Following BAPN administration, myeloid-specific CCN3 knockout mice had a higher mortality rate due to AD formation and aortic rupture. In accordance with this phenotype, vascular media thickness was markedly reduced, and elastic fiber fragmentation and macrophage infiltration were elevated in myeloid-specific CCN3 knockout mice. Using single-cell RNA-seq, we found that myeloid-deficiency of CCN3 was associated with a pathogenic pro-inflammatory phenotype of perivascular tissue-resident macrophages, which promoted deleterious aortic wall remodeling at early stages. Furthermore, CCN3 deficient BMDMs are prone to M1 macrophage polarization, an effect dependent on the activation of the JAK/STAT1 signaling pathway. Conclusions: Myeloid-deficiency of CCN3 drives vascular macrophages toward an M1-like, pathogenic phenotype and promotes dissecting aortic aneurysm.

Abstract 12710: The Role of Cellular Senescence in Aortic Dissection

Background: Aortic dissection (AD) is a catastrophic disease with high mortality and serious complications, and its molecular pathogenesis is largely unknown. The importance of inflammation in AD has been reported. Recently we found that cell proliferation precedes the inflammatory response in AD. Cell proliferation causes cellular senescence that induces inflammatory response, however, role of cellular senescence in AD has not been elucidated. Objective: We investigated if cellular senescence contributes to AD pathogenesis in mouse AD model. Methods and Results: A mouse AD model was created by continuous infusion of beta-aminopropionitrile and angiotensin II (BAPN+AngII) for 14days. BAPN+AngII infusion induced senescence markers from day 3, before AD onset, and persisted until day14. Senescent cells, as demonstrated by the expression of senescence-associated beta-galactosidase, were evident in intimal endothelial cells, medial smooth muscle cells, adventitial macrophages, and fibroblasts. To examine role of cellular senescence in AD, we orally administrated ABT263 known as “senolytics” that eliminates senescent cells. ABT263 treatment reduced the expression of the senescence markers. The AD mortality of ABT263 group was 35%, which was lower than that of vehicle group(66.7%, P < 0.05 by log-rank test). The severity of AD, as assessed by the lesion length in vehicle group was 33.2 ± 3.1mm, whereas that in ABT263 group was 24.6 ± 1.8mm (P < 0.05). Transcriptome analysis revealed that ABT263 treatment suppressed the immune and inflammatory response in the aorta before AD onset. Quantitative RT-PCR confirmed that ABT263 treatment prevented the induction of p21Cip1, interleukin-6 and several chemokines. Bioplex analysis of mice’s serum showed that ABT263 decreased inflammatory molecules in mice’s serum compared to vehicle group. Moreover, aortic smooth muscle cells(SMCs)remained contractile phenotype in ABT263 group, whereas BAPN+AngII reduced the phenotype in vehicle group. Conclusions: Elimination of senescent cells prevented AD progression and death in mice. ABT263 suppressed the inflammatory response and contributed to retain the SMCs phenotype. Cellular senescence represents a potential predictor and a therapeutic target for AD.

Independent and Interactive Roles of Immunity and Metabolism in Aortic Dissection.

Aortic dissection (AD) is a cardiovascular disease that seriously endangers the lives of patients. The mortality rate of this disease is high, and the incidence is increasing annually, but the pathogenesis of AD is complicated. In recent years, an increasing number of studies have shown that immune cell infiltration in the media and adventitia of the aorta is a novel hallmark of AD. These cells contribute to changes in the immune microenvironment, which can affect their own metabolism and that of parenchymal cells in the aortic wall, which are essential factors that induce degeneration and remodeling of the vascular wall and play important roles in the formation and development of AD. Accordingly, this review focuses on the independent and interactive roles of immunity and metabolism in AD to provide further insights into the pathogenesis, novel ideas for diagnosis and new strategies for treatment or early prevention of AD.

PiRNA-823 is a novel potential therapeutic target in aortic dissection

Aortic dissection (AD) presents a medical challenge for clinicians. Here, to determine the role of a novel small non-coding piRNA-823 (piR-823) in AD, murine and human aorta from patients with AD were used. A high expression levels of piR-823 were found in patients with AD. Using performed loss- and gain-of-function assays in vitro and in vivo, we explore the regulatory effect of piR-823 on vascular smooth muscle cells (VSMCs) and AD. piR-823 obviously facilitates the proliferation, migration, and phenotypic transformation of VSMCs with or without nicotine treatment. piR-823 directly binds and suppresses histone deacetylase 1 (HDAC1) expression, and regulates the acetylation of histone 3 (H3) via H3K9ac and H3K27ac, eventually, VSMC functions and AD. To consolidate our findings, AD murine model was performed, and we observed that piR-823 antagomir strongly inhibited the pathogenesis of AD through regulating vascular remodeling. Thus, our study finds a potential target for the prevention and treatment strategy for nicotine-induced AD.

Identification of co-diagnostic effect genes for aortic dissection and metabolic syndrome by multiple machine learning algorithms

Aortic dissection (AD) is a life-threatening condition in which the inner layer of the aorta tears. It has been reported that metabolic syndrome (MS) has a close linkage with aortic dissection. However, the inter-relational mechanisms between them were still unclear. This article explored the hub gene signatures and potential molecular mechanisms in AD and MS. We obtained five bulk RNA-seq datasets of AD, one single cell RNA-seq (scRNA-seq) dataset of ascending thoracic aortic aneurysm (ATAA), and one bulk RNA-seq dataset of MS from the gene expression omnibus (GEO) database. Identification of differentially expressed genes (DEGs) and key modules via weighted gene co-expression network analysis (WGCNA), functional enrichment analysis, and machine learning algorithms (Random Forest and LASSO regression) were used to identify hub genes for diagnosing AD with MS. XGBoost further improved the diagnostic performance of the model. The receiver operating characteristic (ROC) and precision-recall (PR) curves were developed to assess the diagnostic value. Then, immune cell infiltration and metabolism-associated pathways analyses were created to investigate immune cell and metabolism-associated pathway dysregulation in AD and MS. Finally, the scRNA-seq dataset was performed to confirm the expression levels of identified hub genes. 406 common DEGs were identified between the merged AD and MS datasets. Functional enrichment analysis revealed these DEGs were enriched for applicable terms of metabolism, cellular processes, organismal systems, and human diseases. Besides, the positively related key modules of AD and MS were mainly enriched in transcription factor binding and inflammatory response. In contrast, the negatively related modules were significantly associated with adaptive immune response and regulation of nuclease activity. Through machine learning, nine genes with common diagnostic effects were found in AD and MS, including MAD2L2, IMP4, PRPF4, CHSY1, SLC20A1, SLC9A1, TIPRL, DPYD, and MAPKAPK2. In the training set, the AUC of the hub gene on RP and RR curves was 1. In the AD verification set, the AUC of the Hub gene on RP and RR curves were 0.946 and 0.955, respectively. In the MS set, the AUC of the Hub gene on RP and RR curves were 0.978 and 0.98, respectively. scRNA-seq analysis revealed that the SLC20A1 was found to be relevant in fatty acid metabolic pathways and expressed in endothelial cells. Our study revealed the common pathogenesis of AD and MS. These common pathways and hub genes might provide new ideas for further mechanism research.

Potential biomarkers of aortic dissection based on expression network analysis

BackgroundAortic dissection (AD) is a rare disease with severe morbidity and high mortality. Presently, the pathogenesis of aortic dissection is still not completely clear, and studying its pathogenesis will have important clinical significance.MethodsWe downloaded 28 samples from the Gene Expression Omnibus (GEO) database (Accession numbers: GSE147026 and GSE190635), including 14 aortic dissection samples and 14 healthy controls (HC) samples. The Limma package was used to screen differentially expressed genes. The StarBasev2.0 tool was used to predict the upstream molecular circRNA of the selected miRNAs, and Cytoscape software was used to process the obtained data. STRING database was used to analyze the interacting protein pairs of differentially expressed genes under medium filtration conditions. The R package "org.hs.eg.db" was used for functional enrichment analysis.ResultsTwo hundred genes associated with aortic dissection were screened. Functional enrichment analysis was performed based on these 200 genes. At the same time, 2720 paired miRNAs were predicted based on these 200 genes, among which hsa-miR-650, hsa-miR-625-5p, hsa-miR-491-5p and hsa-miR-760 paired mRNAs were the most. Based on these four miRNAs, 7106 pairs of circRNAs were predicted to be paired with them. The genes most related to these four miRNAs were screened from 200 differentially expressed genes (CDH2, AKT1, WNT5A, ADRB2, GNAI1, GNAI2, HGF, MCAM, DKK2, ISL1).ConclusionsThe study demonstrates that miRNA-associated circRNA-mRNA networks are altered in AD, implying that miRNA may play a crucial role in regulating the onset and progression of AD. It may become a potential biomarker for the diagnosis and treatment of AD.

Research advances of inflammatory cells and aortic intrinsic cells in the pathogenesis of aortic dissection

主动脉夹层是指主动脉内膜撕裂，血液经内膜撕裂口进入主动脉壁造成正常主动脉壁分离，形成真假腔的一种凶险的心血管疾病。常见于中老年人群，尽管发病率低，但发病突然，且病死率极高。主动脉夹层的诱因错综复杂，发病机制尚未完全明确，主要与主动脉壁结构异常、血管壁炎症反应和血流动力学有关。该文重点整理了炎性细胞和主动脉固有细胞在主动脉夹层发生发展过程中的作用，为该疾病的治疗提供新思路。.

Emerging Role of Non-Coding RNAs in Aortic Dissection.

Aortic dissection (AD) is a fatal cardiovascular acute disease with high incidence and mortality, and it seriously threatens patients’ lives and health. The pathogenesis of AD mainly includes vascular inflammation, extracellular matrix degradation, and phenotypic conversion as well as apoptosis of vascular smooth muscle cells (VSMCs); however, its detailed mechanisms are still not fully elucidated. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are an emerging class of RNA molecules without protein-coding ability, and they play crucial roles in the progression of many diseases, including AD. A growing number of studies have shown that the dysregulation of ncRNAs contributes to the occurrence and development of AD by modulating the expression of specific target genes or the activity of related proteins. In addition, some ncRNAs exhibit great potential as promising biomarkers and therapeutic targets in AD treatment. In this review, we systematically summarize the recent findings on the underlying mechanism of ncRNA involved in AD regulation and highlight their clinical application as biomarkers and therapeutic targets in AD treatment. The information reviewed here will be of great benefit to the development of ncRNA-based therapeutic strategies for AD patients.

Activation of AMP-activated protein kinase ablated the formation of aortic dissection by suppressing vascular inflammation and phenotypic switching of vascular smooth muscle cells

BackgroundAortic dissection (AD) is a fatal vascular disease in absence of effective pharmaceutical therapy. Adenosine monophosphate-activated protein kinase α (AMPKα) plays a critical role in various cardiovascular diseases. Whether AMPKα is involved in the pathogenesis of aortic dissection remains unknown. We aimed to determine whether activation of AMPKα prevents the formation of AD. Methods and resultsReduced expression of phosphorylated AMPKα (Thr172) and exacerbated phenotypic switching were observed in human aortic tissues from aortic dissection patients compared with those in tissues from controls. In vivo, the formation of aortic dissection in ApoE-/- mice was successfully induced by continuous infusion of angiotensin II (AngII) for two weeks, characterized by the activation of vascular inflammation, infiltration of macrophages and phenotypic switching of vascular smooth muscle cells (VSMCs). rAAV2-mediated overexpression of constitutively active AMPKα (CA-AMPKα) enhanced the expression of phosphorylated AMPKα (Thr172) and attenuated AngII-induced occurrence of aortic dissection by suppressing the infiltration of macrophages, activation of vascular inflammation and phenotypic switching of VSMCs. The pathogenesis above was conversely exacerbated by rAAV2-mediated overexpression of dominant negative AMPKα2 (DN-AMPKα). In vitro, we demonstrated that the administration of an AMPK agonist (AICAR) or transfection of CA-AMPKα induced the activation of AMPKα and then ameliorated AngII-induced phenotypic switching in the VSMCs and inflammation in the bone marrow-derived macrophages (BMDMs). This could be reversed by the addition of AMPK inhibitor compound C or transfection of DN-AMPKα. ConclusionImpaired activation of AMPKα may increase the susceptibility to aortic dissection. Our findings verified the protective effects of AMPKα on the formation of aortic dissection and may provide evidence for clinical prevention or treatment.

Nutritional Management Mode of Early Cardiac Rehabilitation in Patients with Stanford Type A Aortic Dissection.

Malnutrition and metabolic disorders are common problems faced by patients with Stanford type A aortic dissection after surgery. Some patients have dietary problems such as malnutrition, unbalanced diet, and poor eating habits before surgery. Therefore, the nutritional management of early heart health can improve the nutritional support for perioperative recovery, to improve the pertinence. Therefore, active nutritional support after surgery will help to change malnutrition and metabolism and is of great significance to postoperative recovery and quality of life. This paper is aimed at studying the nutritional management mode of early cardiac rehabilitation in patients with Stanford type A aortic dissection. Based on the analysis of the pathogenesis of aortic dissection and the diagnosis of aortic dissection, two groups of patients were given individualized nutritional management scheme and routine nutritional scheme, respectively, and the nutritional risk differences between the two groups under different schemes were compared. The results showed that there was a statistical difference between the two groups at discharge. The NRS-2002 score of 14 cases in the observation group was less than 3 after nutritional intervention, indicating that there was no nutritional risk at discharge.