Progression Of Aortic Dissection Research Articles

Transketolase drives the development of aortic dissection by impairing mitochondrial bioenergetics.

Aortic dissection (AD) is a disease with rapid onset but with no effective therapeutic drugs yet. Previous studies have suggested that glucose metabolism plays a critical role in the progression of AD. Transketolase (TKT) is an essential bridge between glycolysis and the pentose phosphate pathway. However, its role in the development of AD has not yet been elucidated. In this study, we aimed to explore the role of TKT in AD. We collected AD patients' aortic tissues and used high-throughput proteome sequencing to analyze the main factors influencing AD development. We generated an AD model using BAPN in combination with angiotensin II (Ang II) and pharmacological inhibitors to reduce TKT expression. The effects of TKT and its downstream mediators on AD were elucidated using human aortic vascular smooth muscle cells (HAVSMCs). We found that glucose metabolism plays an important role in the development of AD and that TKT is upregulated in patients with AD. Western blot and immunohistochemistry confirmed that TKT expression was upregulated in mice with AD. Reduced TKT expression attenuated AD incidence and mortality, maintained the structural integrity of the aorta, aligned elastic fibers, and reduced collagen deposition. Mechanistically, TKT was positively associated with impaired mitochondrial bioenergetics by upregulating AKT/MDM2 expression, ultimately contributing to NDUFS1 downregulation. Our results provide new insights into the role of TKT in mitochondrial bioenergetics and AD progression. These findings provide new intervention options for the treatment of AD.

Downregulation of LILRB4 Promotes Human Aortic Smooth Muscle Cell Contractile Phenotypic Switch and Apoptosis in Aortic Dissection.

Aortic dissection (AD) is a severe vascular disease with high rates of mortality and morbidity. However, the underlying molecular mechanisms of AD remain unclear. Differentially expressed genes (DEGs) were screened by bioinformatics methods. Alterations of histopathology and inflammatory factor levels in β-aminopropionitrile (BAPN)-induced AD mouse model were evaluated through Hematoxylin-Eosin (HE) staining and Enzyme-linked immunosorbent assay (ELISA), respectively. Reverse transcription quantitative real-time polymerase chain reaction was performed to detect DEGs expression. Furthermore, the role of LILRB4 in AD was investigated through Cell Counting Kit-8 (CCK-8), wound healing, and flow cytometry. Western blotting was employed to assess the phenotypic switch and extracellular matrix (ECM)-associated protein expressions in platelet-derived growth factor-BB (PDGF-BB)-stimulated in vitro model of AD. In the AD mouse model, distinct dissection formation was observed. TNF-α, IL-1β, IL-8, and IL-6 levels were higher in the AD mouse model than in the controls. Six hub genes were identified, including LILRB4, TIMP1, CCR5, CCL7, MSR1, and CLEC4D, all of which were highly expressed. Further exploration revealed that LILRB4 knockdown inhibited the cell vitality and migration of PDGF-BB-induced HASMCs while promoting apoptosis and G0/G1 phase ratio. More importantly, LILRB4 knockdown promoted the protein expression of α-SMA and SM22α, while decreasing the expression of Co1, MMP2, and CTGF, which suggested that LILRB4 silencing promoted contractile phenotypic transition and ECM stability. LILRB4 knockdown inhibits the progression of AD. Our study provides a new potential target for the clinical treatment of AD.

Abstract 13284: New Elastic Fiber Formation by Non-Smooth Muscle Lineage Cells During the Progression of Aortic Dissections

Introduction: Aortic dissection (AD) is a life-threatening vascular disease displaying the disruption of the extracellular matrix (ECM). Elastic fibers are a major component of ECM and confer structural integrity to the aortic wall. Normally, elastic fibers are minimally synthesized in adulthood. However, it remains unknown whether and how elastic fibers are synthesized following ADs. Methods and Results: AD was induced by administration of β-aminopropionitrile (BAPN, 0.5% wt/vol) to male C57BL/6J mice at 4 weeks of age. Thoracic aortas were collected after 4 or 12 weeks of BAPN administration. False lumen formation with fresh hematomas was observed at 4 weeks of BAPN administration, indicating development of acute ADs. The false lumen developed striking remodeling at 12 weeks, suggesting progression to the chronic phase. RT-qPCR revealed that mRNA abundance of tropoelastin, a precursor of elastic fibers, was increased significantly at the chronic phase of ADs, but not at the acute phase. Tropoelastin mRNA was observed primarily in the vascular wall of the false lumen, as evidenced by in situ hybridization. Of interest, elastic fibers were formed in the wall of the false lumen in chronic ADs. These data suggest that elastic fibers were newly synthesized during the progression of ADs. Immunostaining revealed that the walls of true and false lumens of chronic ADs were mainly composed of cells expressing both αSMA (encoding by Acta2 ) and MYH11, common markers for smooth muscle cells (SMCs). However, in a lineage tracing study, the walls of the false lumen of chronic ADs were negative for the Acta2 lineage, suggesting that cells in the wall of the false lumen were derived from a non-SMC lineage but acquired SMC properties during AD progression. Bulk RNA sequencing identified the increased abundance of 2,799 genes in chronic ADs and 102 transcription factors were predicted to regulate these genes. Among them, JunB was the most abundant molecule that can be aligned in the promotor region of tropoelastin. Of note, JunB was expressed adjacent to both αSMA-positive cells and new elastic fibers in the dissected aortas. Conclusion: ADs exhibit vascular remodeling with newly elastic fiber formation by non-SMC lineage cells during the disease progression.

Abstract 13229: Coiled-Coil Domain-Containing Protein 80 Protects Against Aortic Dissection by Maintaining the Contractile Smooth Muscle Cell Phenotype

Background: Aortic dissection (AD) is a life-threatening medical emergency characterized by adverse vascular remodeling. Effective prevention and treatment options are lacking for AD. Coiled-coil domain-containing protein 80 (CCDC80) plays an essential role in regulating vascular remodeling. In the present study, we aimed to define the role of CCDC80 in the formation and development of AD. Methods: The expression and subcellular localization of CCDC80 were determined in human and mouse AD. CCDC80 knockout mice (CCDC80 –/– ) and vascular smooth muscle cell (VSMC)-specific CCDC80 knockout mice (CCDC80 fl/fl SM22α Cre + ) were treated with angiotensin II (Ang II) or Ang II combined with β-aminopropionitrile monofumarate (BAPN) to induce AD models. RNA-Seq analysis combined with immunoprecipitation and blockage of the JAK2/STAT3 signaling pathway in CCDC80 –/– mice were used to evaluate the effect of CCDC80 deficiency on this pathway. Results: CCDC80 was downregulated in VSMCs in human and mouse AD. CCDC80 – / – mice challenged with Ang II and BAPN developed AD with higher frequency and severity compared with their littermate controls (66.7% vs. 100%, p < 0.05). Remarkably, compared with littermate controls treated with Ang II, CCDC80 –/– mice (8.3% vs. 87.5%, p < 0.05) and CCDC80 fl/fl SM22α Cre + mice (12.5% vs. 80%, p < 0.05) frequently developed AD with severe elastin fragmentation and collagen deposition. CCDC80 interacted with JAK2; CCDC80 deficiency could promote VSMC phenotype switching, proliferation, and migration as well as matrix metalloproteinase production by activating the JAK2/STAT3 signaling pathway. The JAK2/STAT3 pathway-specific inhibitor ameliorated adverse vascular remodeling and reduced AD formation (90% vs. 55%, p < 0.05) in CCDC80 knockout mice. Conclusion: CCDC80 deficiency exacerbates the progression of AD by activating the JAK2/STAT3 pathway involved in regulating the phenotype switching and function of VSMCs. Our findings suggest that CCDC80 is a potential target for the prevention and treatment of AD.

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.

Gut Microbiota-Derived Tryptophan Metabolite Indole-3-aldehyde Ameliorates Aortic Dissection.

Tryptophan, an essential dietary amino acid, is metabolized into various metabolites within both gut microbiota and tissue cells. These metabolites have demonstrated potential associations with panvascular diseases. However, the specific relationship between tryptophan metabolism, particularly Indole-3-aldehyde (3-IAId), and the occurrence of aortic dissection (AD) remains unclear. 3-IAId showed an inverse association with advanced atherosclerosis, a risk factor for AD. In this study, we employed a well-established β-aminopropionitrile monofumarate (BAPN)-induced AD murine model to investigate the impact of 3-IAId treatment on the progression of AD. Our results reveal compelling evidence that the administration of 3-IAId significantly mitigated aortic dissection and rupture rates (BAPN + 3-IAId vs. BAPN, 45% vs. 90%) and led to a notable reduction in mortality rates (BAPN + 3-IAId vs. BAPN, 20% vs. 55%). Furthermore, our study elucidates that 3-IAId exerts its beneficial effects by inhibiting the phenotype transition of vascular smooth muscle cells (VSMCs) from a contractile to a synthetic state. It also mitigates extracellular matrix degradation, attenuates macrophage infiltration, and suppresses the expression of inflammatory cytokines, collectively contributing to the attenuation of AD development. Our findings underscore the potential of 3-IAId as a promising intervention strategy for the prevention of thoracic aortic dissection, thus providing valuable insights into the realm of vascular disease management.

Preoperative Immature Neutrophils Predict Clinical Outcomes in Patients with Uncomplicated Type-B Aortic Dissection After Thoracic Endovascular Aortic Repair.

Inflammation is a hallmark of the initial development and progression of aortic dissection. This study aimed to investigate the predictive value of preoperative neutrophils in aorta-related adverse events (AAEs) after thoracic endovascular aortic repair (TEVAR) for type B aortic dissection (TBAD). A total of 80 patients with TBAD undergoing TEVAR were enrolled in our hospital. Preoperative inflammatory markers, including white blood cells (WBCs), neutrophils, neutrophil-to-lymphocyte ratio (NLR) and plasma high-sensitivity C-reactive protein (hs-CRP), were measured. Circulating neutrophil subpopulation was determined by flow cytometry. Kaplan-Meier curve was performed to determine whether neutrophil subsets independently predicted aorta-related adverse events (AAEs) after TEVAR. Compared with control group, the prevalence of hypertension and the levels of inflammatory indicators including WBCs, total neutrophils, NLR, immature neutrophils and hs-CRP were significantly higher in TBAD patients. Receiver operating characteristic (ROC) curve showed that NLR, absolute number of total neutrophils and percent CD10- immature neutrophils had excellent area under curves. During the 18-month follow-up, 16 (20.0%) were reported to occur AAEs, while 4 deaths (5.0%) were documented. Percent immature neutrophil was markedly higher in TBAD patients experiencing AAEs as compared with those without AAEs. Kaplan-Meier curve and Cox regression analysis demonstrated that percent immature neutrophil was the only predictor correlated with the occurrence of AAEs (hazard ratio 7.66, 95% CI: 2.91, 20.17, P = 0.018). Increased CD10- immature neutrophils could act as a potential biomarker related to long-term adverse outcomes in TBAD patients following TEVAR.

An application of soliton solutions of a differential equation in the progression of aortic dissection

Aortic dissection is a serious pathology involving the vessel wall of the aorta with significant societal impact. To understand aortic dissection, we explain the role of the dynamic pathology in the absence or presence of structural and/or functional abnormalities. We frame a differential equation to evaluate the impact of mean blood pressure on the aortic wall and prove the existence and uniqueness of its solution for homeostatic recoil and relaxation for infinitesimal aortic tissue. We model and analyze a generalized (3 + 1)‐dimensional nonlinear partial differential equation for aortic wave dynamics. We use the Lie group of transformations on this nonlinear evolution equation to obtain invariant solutions, traveling wave solutions including solitons. We find that abnormalities in the dynamic pathology of aortic dissection act as triggers for the progression of disease in the early stage through the formation of soliton‐like pulses and their interaction. We address the role of unstable wavefields in waveform dynamics when waves are unidirectional. Moreover, the notion of dynamic pathology within the domain of vascular geometry may explain the evolution of aneurysms in cerebral arteries and cardiomyopathies even in the absence of anatomical and physiological abnormalities.

Bestrophin3 Deficiency in Vascular Smooth Muscle Cells Activates MEKK2/3-MAPK Signaling to Trigger Spontaneous Aortic Dissection.

Aortic dissection (AD) is a fatal cardiovascular disorder without effective medications due to unclear pathogenic mechanisms. Bestrophin3 (Best3), the predominant isoform of bestrophin family in vessels, has emerged as critical for vascular pathological processes. However, the contribution of Best3 to vascular diseases remains elusive. Smooth muscle cell-specific and endothelial cell-specific Best3 knockout mice (Best3SMKO and Best3ECKO, respectively) were engineered to investigate the role of Best3 in vascular pathophysiology. Functional studies, single-cell RNA sequencing, proteomics analysis, and coimmunoprecipitation coupled with mass spectrometry were performed to evaluate the function of Best3 in vessels. Best3 expression in aortas of human AD samples and mouse AD models was decreased. Best3SMKO but not Best3ECKO mice spontaneously developed AD with age, and the incidence reached 48% at 72 weeks of age. Reanalysis of single-cell transcriptome data revealed that reduction of fibromyocytes, a fibroblast-like smooth muscle cell cluster, was a typical feature of human ascending AD and aneurysm. Consistently, Best3 deficiency in smooth muscle cells decreased the number of fibromyocytes. Mechanistically, Best3 interacted with both MEKK2 and MEKK3, and this interaction inhibited phosphorylation of MEKK2 at serine153 and MEKK3 at serine61. Best3 deficiency induced phosphorylation-dependent inhibition of ubiquitination and protein turnover of MEKK2/3, thereby activating the downstream mitogen-activated protein kinase signaling cascade. Furthermore, restoration of Best3 or inhibition of MEKK2/3 prevented AD progression in angiotensin II-infused Best3SMKO and ApoE-/- mice. These findings unveil a critical role of Best3 in regulating smooth muscle cell phenotypic switch and aortic structural integrity through controlling MEKK2/3 degradation. Best3-MEKK2/3 signaling represents a novel therapeutic target for AD.

Circ_0022920 Maintains the Contractile Phenotype of Human Aortic Vascular Smooth Muscle Cells Via Sponging microRNA-650 and Promoting Transforming Growth Factor Beta Receptor 1 Expression in Angiotensin II-Induced Models for Aortic Dissection.

Background Abnormal regulation of vascular smooth muscle cells is regarded as the iconic pathological change of aortic dissection (AD). Herein, we aim to identify circ_0022920 as a crucial regulator in AD. Methods and Results Microarray analysis of circular RNAs, messenger RNAs, and micro RNAs in patients with AD was performed, and we identified that circ_0022920 was significantly downregulated in these patients. The Pearson correlation analysis uncovered the negative correlation between miR-650 and circ_0022920 or TGFβR1 (transforming growth factor beta receptor 1). Angiotensin II was used to treat human aortic vascular smooth muscle cells (HASMCs) and mice as models for AD. Hematoxylin and eosin and Masson's trichrome staining were used to analyze AD histopathology. Cell proliferation was analyzed with Cell Counting Kit-8 assay and EdU incorporation. Cell migration was assessed with transwell and wound healing assays. Enhanced circ_0022920 expression dramatically inhibited HASMC proliferation and migration and maintained contractile marker expression induced by angiotensin II, whereas miR-650 exerted opposite effects. MiR-650 was a target of circ_0022920. MiR-650 targeted IRF1 (interferon regulatory factor 1) and thus negatively regulated TGFβR1 expression to promote HASMC proliferation and migration and inhibit contractile marker expression. Circ_0022920 suppressed the progression of AD in vivo. Conclusions Circ_0022920 modulates the contractile phenotype of HASMCs via regulating the miR-650-IRF1-TGFβR1 axis in angiotensin II-induced models for AD, which provides potential therapeutic targets for AD.

11S Proteasome Activator REGγ Promotes Aortic Dissection by Inhibiting RBM3 (RNA Binding Motif Protein 3) Pathway.

Aortic dissection (AD) is a life-threatening cardiovascular disorder with high mortality and lacking underlying mechanisms or effective treatments. REGγ, the 11S proteasome activator known to promote the degradation of cellular proteins in a ubiquitin- and ATP-independent manner, emerges as a new regulator in the cardiovascular system. Using β-aminopropionitrile (BAPN)-subjected REGγ knockout AD mice and Ang II (angiotensin II)-treated REGγ deficiency vascular smooth muscle cells (VSMCs) to explore the effect of REGγ in AD progression. REGγ was upregulated in mouse aorta of β-aminopropionitrile-induced AD model in vivo and Ang II-treated VSMCs in vitro. REGγ deficiency ameliorated AD progression in β-aminopropionitrile-induced mice by protecting against the switch in VSMCs from contractile to synthetic phenotype through suppressing RBM3 (RNA-binding motif protein 3) decay. Mechanically, REGγ interacted with and degraded the RNA-binding protein RBM3 directly, leading to decreased mRNA stability, lowered expression and transcriptional activity of transcription factor SRF (serum response factor), subsequently reduced transcription of VSMCs-specific contractile genes, α-SMA (alpha-smooth muscle actin) and SM22α (smooth muscle 22 alpha), caused the switch in VSMCs from contractile to synthetic phenotype and associated AD progression. Ablation of endogenous SRF or RBM3, or overexpressing exogenous RBM3 in VSMCs significantly blocked or reestablished the REGγ-dependent action on VSMCs phenotypic switch of Ang II stimulation in vitro. Furthermore, exogenously introducing RBM3 improved the switch in VSMCs from contractile to synthetic phenotype and associated AD features caused by REGγ in vivo. Our results demonstrated that REGγ promoted the switch in VSMCs from contractile to synthetic phenotype and AD progression by inhibiting RBM3-SRF pathway, indicated that modulating REGγ-proteasome activity may be a potential therapeutic approach for AD-associated cardiovascular dysfunction.

Upregulation of miR-222-3p alleviates the symptom of aortic dissection through targeting STAT3

ObjectiveThis study sought to investigate the differentially expressed miRNAs in Aortic dissection (AD) and explore the downstream mechanisms in regulating AD. MethodsExosomes of AD patients and healthy people were isolated by differential centrifugation, and the differentially expressed miRNAs were evaluated by RNA sequencing. The downstream target of miR-222-3p was predicted by bioinformatics method and validated by dual-luciferase assay. Angiotensin II and Promethazine were used to establish AD mouse model and platelet-derived growth factor BB (PDGF-BB) was used to induce human vascular smooth muscle cells (HVSMCs) to elucidate the effect of miR-222-3p upregulation on AD in vivo and in vitro. The relative level of miR-222-3p was evaluated by RT-qPCR. The level of several proteins was investigated by Western blot. Immunofluorescence staining was used to detect the stress fiber formation. Cell migration was evaluated by wound healing and Transwell assay. The proliferation, cell cycle and apoptosis of HVSMCs were assessed by CCK-8 and flow cytometry, respectively. ResultsMiR-222-3p was downregulated in AD and PDGF-BB induced HVSMCs. The upregulation of miR-222-3p alleviated the symptom of AD in vivo by targeting STAT3, and inhibited stress fiber formation, abnormal migration, proliferation and apoptosis of HVSMCs induced by PDGF-BB by regulating the expression of α-SMA, SM22α, MMP2, MMP9 and p-Smad2. ConclusionThe upregulation of miR-222-3p attenuates the progression of AD. Our study provides a theoretical basis for exploring new strategies against AD.

Preoperative systemic inflammatory response index predicts long-term outcomes in type B aortic dissection after endovascular repair.

ObjectivesInflammation is a hallmark of the initial development and progression of aortic dissection. This study aimed to investigate the value of preoperative inflammatory biomarkers in predicting aorta-related adverse events (AAEs) after thoracic endovascular aortic repair (TEVAR) for type B aortic dissection.MethodsWe included all patients who underwent TEVAR for type B aortic dissection between November 2016 and November 2020 in this single-center, retrospective cohort study. Patients were divided into two groups: the AAEs group (n = 75) and the non-AAEs group (n = 126). Preoperative inflammatory biomarkers were recorded, including neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic immune inflammation index (SII), and systemic inflammatory response index (SIRI). Patients were followed-up for the development of AAEs. Prediction accuracy of inflammatory biomarkers for AAEs were evaluated using the area under the receiver operating characteristic curves.ResultsThis study included 201 patients, of whom 80.0% were men, with a mean age of 59.1 ± 12.5 years. A total of 75 patients developed AAEs after TEVAR. The AUCs of NLR, MLR, PLR, SII, and SIRI for AAEs were.746,.782,.534,.625 and.807, respectively. Age and SIRI were independent risk factors for the AAEs after TEVAR (HR 3.264, p <.001; HR 4.281, p <.001, respectively). Survival analysis revealed significantly lower AAE-free status in patients with preoperative SIRI > = 4 (p <.001).ConclusionIncreased preoperative SIRI and age are independent risk factors for AAEs after TEVAR in type B aortic dissection.

MiR-335-5p regulates the proliferation, migration and phenotypic switching of vascular smooth muscle cells in aortic dissection by directly regulating SP1.

Uncontrolled proliferation, migration and phenotypic switching of vascular smooth muscle cells (VSMCs) are important steps in the development and progression of aortic dissection (AD). The function and potential mechanism of miR-335-5p in the pathogenesis of AD are explored in this study. Specifically, the biological function of miR-335-5p is explored in vitro through CCK-8, Transwell, immunofluorescence, EdU, wound-healing, RT-qPCR and western blotting assays. In addition, an AD model induced by angiotensin II is used to investigate the function of miR-335-5p in vivo. A dual-luciferase assay is performed to verify the targeting relationship between miR-335-5p and specificity protein 1 (SP1). Experiments involving the loss of SP1 function are performed to demonstrate the function of SP1 in the miR-335-5p-mediated regulation of human aortic-VSMCs (HA-VSMCs). AD tissues and platelet-derived growth factor BB (PDGF-BB)-stimulated HA-VSMCs show significant downregulation of miR-335-5p expression and upregulated SP1 expression. Overexpression of miR-335-5p effectively suppresses cell proliferation, migration and synthetic phenotype markers and enhances contractile phenotype markers induced by PDGF-BB treatment. Additionally, SP1 is identified as a target gene downstream of miR-335-5p, and its expression is negatively correlated with miR-335-5p in AD. Upregulation of SP1 partially reverses the inhibitory effect of miR-335-5p on HA-VSMCs, whereas the downregulation of SP1 has the opposite effect. Furthermore, Ad-miR-335-5p clearly suppresses aorta dilatation and vascular media degeneration in the AD model. Our results suggest that miR-335-5p inhibits HA-VSMC proliferation, migration and phenotypic switching by negatively regulating SP1, and indicate that miR-335-5p may be a potential therapeutic target in AD.

Distal Reoperations after Repair of Acute Type A Aortic Dissection—Incidence, Causes and Outcomes

Background and Aim of the Study: In patients with acute type A aortic dissection (A-AAD) whether initial repair should include also aortic arch replacement is still debated. We aimed to assess if extensive aortic repair prevents from reoperations patients with A-AAD. Methods: Outcomes after distal reoperation following repair of A-AAD (n = 285; 1977 to 2018) were analysed in 22 of 226 who underwent ascending aorta/hemiarch replacement (Group 1R) and 7 of 59 who had ascending aorta/arch replacement (Group 2R). Results: Distal reoperation was more common in Group 1R (n = 22) than in Group 2R (n = 0) (p &lt; 0.001) while thoracic endovascular stenting was more frequent in Group 2R (7 vs 3, p &lt; 0.001). Indications for reoperation were pseudoaneurysm at distal anastomosis (n = 4, 18%) and progression of aortic dissection (n = 18, 82%) in Group 1R. Indication for thoracic endovascular stenting was progressive aortic dissection in 3 patients of Group 1R and in 6 of Group 2R. Second reoperation was required in 2 patients from Group 1R (2%) during a mean follow-up of 5 years. Median follow-up was 4 years in Group 1R and 7 years in Group 2R (p = 0.36). Hospital mortality was 14% in Group 1R and 0% in Group 2R (p = 0.3). Actuarial survival is 68 ± 10%, and 62 ± 11% for Group 1R and 100% for Group 2R at 5 and 10 years (p = 0.076). Conclusions: Distal reoperations after A-AAD repair have an acceptable mortality. An extensive initial repair has lower rate of reoperation and better mid-term survival and should be indicated especially for young patients in experienced centers.

Serum Oxylipin Profiles Identify Potential Biomarkers in Patients with Acute Aortic Dissection.

Aortic dissection (AD) is a life-threatening cardiovascular disease with a dismal prognosis. Inflammation plays an important role in AD. Oxylipins are bioactive lipids involved in the modulation of inflammation and may be involved in the pathogenesis and progression of AD. This study aims to identify possible metabolites related to AD. A total of 10 type A Aortic dissection (TAAD) patients, 10 type B Aortic dissection (TBAD) patients and 10 healthy controls were included in this study. Over 100 oxylipin species were identified and quantified by liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis. Our investigation demonstrated substantial alterations in 91 oxylipins between AD and healthy individuals. Patients with TAAD had 89 entries accessible compared to healthy controls. According to orthogonal partial least squares discriminant analysis (OPLS-DA), fitness (R2X = 0.362 and R2Y = 0.807, p = 0.03) and predictability (Q2 = 0.517, p = 0.005) are the validation parameters between the two groups. Using multivariate logistic regression, 13-HOTrE and 16(17)-EpDPE were the risk factors in the aortic patients group compared to healthy people (OR = 2.467, 95%CI:1.256–7.245, p = 0.035; OR = 0.015, 95%CI:0.0002–0.3240, p = 0.016, respectively). In KEGG enrichment of differential metabolites, the arachidonic acid metabolism pathway has the most metabolites involved. We established a diagnostic model in distinguishing between AD and healthy people. The AUC was 0.905. Oxylipins were significantly altered in AD patients, suggesting oxylipin profile is expected to exploit a novel, non-invasive, objective diagnosis for AD.

Monocyte to high-density lipoprotein ratio at hospital admission predicts intrahospital mortality in patients with Stanford type-A dissection.

Immune inflammatory mechanisms have crucial roles not only in the presence but also in the progression of aortic dissection (AD). Monocyte count to high-density lipoprotein ratio (MHR) has recently emerged as an indicator of inflammation and oxidative stress. Thus, we aimed to examine the prognostic value of MHR in patients with AD. A total of 204 consecutive patients with Stanford type-A dissection who managed surgically were retrospectively enrolled in the present study. Recruited patients were divided into two groups according to the occurrence of intrahospital death; Group 1 consisted of 165 patients who were discharged alive, and Group 2 consisted of 39 patients who died during index hospitalization. Two groups were compared with respect to baseline clinical data and admission laboratory parameters including MHR. The mean age of the Group 1 was 55.2 ± 12.3 years, while the mean age of the Group 2 was 60.6 ± 10.8 years (p = .012). The patients who were discharged alive (Group 1) had significantly lower MHR than the deceased patients (Group 2) (0.02099 ± 0.00140 vs. 0.02848 ± 0.01513, p = .004). At receiver operating characteristics curve analysis, MHR = 0.020699 had 67% sensitivity and 59% specificity in predicting intrahospital mortality among patients with AD. In multivariate analysis, MHR was found to be an independent risk factor of intrahospital mortality among those (β = 1.094, p = .011). MHR is an inexpensive and easily calculated biomarker, which is useful to predict intrahospital mortality in patients with Stanford type-A dissection who managed surgically.

Attitudes and behavioral intentions of aortic dissection survivors towards exercise: an application of the health action process approach framework.

Exercise can help patients with aortic dissection (AD) control blood pressure, prevent further progression of AD, promote mental health, improve the prognosis of cardiovascular disease, and improve their overall quality of life. However, it is not clear what the attitudes and behavioral intentions of AD survivors are towards exercise. This exploratory qualitative research was based on the Health Action Process Approach (HAPA) theory to explore the cognition, attitude, motivational factors, behavior intention, barriers and facilitators of exercise in patients with AD. Face-to-face and telephone semi-structured interviews were conducted in 24 AD patients from the Department of Cardio-Vascular Surgery of third-grade Class A hospitals in Wuhan, China from April 2021 to June 2021. The patient's current stage of behavior was evaluated according to the Patient-Centered Assessment and Counseling for Exercise (PACE) questionnaire. Among the 24 participants interviewed, 9 (37.5%) were in the pre-intention stage, 8 (33.3%) were in the intention stage, and 7 (29.2%) were in the action stage. The three groups were significantly different in terms of their history of previous cardiac surgery (Fisher's exact test, p = 0.043) and in the type of interview conducted (Fisher's exact test, p < 0.001). In-patients with a history of cardiac surgery were more likely to be in the pre-intention stage (post-hoc test, p < 0.05). Patients from different stages had different structures. AD patients in the pre-intention stage were more likely to express risk perception and negative results for exercise. The self-efficacy of this group was often low, and lacked exercise intention and clear action plans (post-hoc test, p < 0.05). More attention should be paid to in-patients with a history of cardiac surgery, including health advice on exercise after discharge and promotion of changes in their health behavior. Guidelines based on the available exercise data in AD patients should be established to provide recommendations for individualized exercise programs. This should provide a basis for promoting patient rehabilitation and improving postoperative quality of life.

Aortic Agatston score correlates with the progression of acute type A aortic dissection.

Aortic calcification in the tunica media is correlated with aortic stiffness, elastin degradation, and wall shear stress. The study aim was to determine if aortic calcifications influence disease progression in patients with acute type A aortic dissection (ATAAD). We retrospectively reviewed a total of 103 consecutive patients who had undergone surgery for ATAAD at our institution between January 2009 and December 2019. Of these, 85 patients who had preoperatively undergone plain computed tomography angiography (CTA) for evaluation of their aortic calcification were included. Moreover, we assessed the progression of aortic dissection after surgery via postoperative CTA. Using a classification and regression tree to identify aortic Agatston score thresholds predictive of disease progression, the patients were classified into high-score (Agatston score ≥ 3344; n = 36) and low-score (<3344; n = 49) groups. Correlations between aortic Agatston scores and CTA variables were assessed. Higher aortic Agatston scores were significantly correlated with the smaller distal extent of aortic dissection (p < 0.001), larger true lumen areas of the ascending (p = 0.009) and descending aorta (p = 0.002), and smaller false lumen areas of the descending aorta (p = 0.028). Patients in the high-score group were more likely to have DeBakey type II dissection (p = 0.001) and false lumen thrombosis (p = 0.027) than those in the low-score group, thereby confirming the correlations. Aortic dissection in the high-score group was significantly less distally extended (p < 0.001). A higher aortic Agatston score correlates with the larger true lumen area of the ascending and descending aorta and the less distal progression of aortic dissection in patients with ATAAD. Interestingly, the findings before and after surgery were consistent. Hence, aortic Agatston scores are associated with aortic dissection progression and may help predict postoperative residual dissected aorta remodeling.

Pharmacologic IRE1α kinase inhibition alleviates aortic dissection by decreasing vascular smooth muscle cells apoptosis.

Aortic dissection (AD) is a rare but catastrophic disorder, and associated with significant morbidity among survivors. This study aimed to target IRE1α-XBP1s pathway pharmacologically, and evaluate its therapeutic potential in the occurrence and progression of AD. Western Blot and immunohistochemistry results showed that expression of XBP1s was significantly increased in the human aorta samples of AD group in compared with the control group, and exclusively in aortic vascular smooth muscle cells (VSMCs). Further in vitro study revealed that Angiotensin II (Ang II) could increase the expression of XBP1s and promote its nuclear translocation in cultured VSMCs, which leads to numerous gene transcription, including gp91phox, Chop, Cleaved-caspase 3, Bax, and Bcl-2. These genes contribute to the production of reactive oxygen species (ROS), VMSCs phenotypic switch and apoptosis. Whereas an IRE1α endoribonuclease domain inhibitor MKC-3946 could reverse it. Finally, the efficacy of MKC-3946 was tested in a mouse AD model. As shown in vitro, MKC-3946 could reduce the expression of XBP1s and protect against AD by suppressing XBP1s associated ROS production and apoptosis in VSMCs in vivo. The current study revealed the relevant role of IRE1α-XBP1s signaling pathway in AD occurrence and progression. MKC-3946 could be of great potential in clinical application.