Aneurysms and dissections represent some of the most serious cardiovascular diseases. The prevailing theory posits that mechanical overloading of the vessel wall is the underlying cause. Inspired by Barkhordarian et al, the authors present matrix metalloproteinases (MMPs) and their inhibitors in immunohistological analyses as contributing factors in the pathophysiology of aortic aneurysms (AA). Data analysis of MMP-1, MMP-9, tissue inhibitors of metalloproteinases (TIMPs), including TIMP-1 and TIMP-2 expression reveals a varied distribution between the adventitia and media and a non-uniform expression of the investigated markers. These elements, as key components of the extracellular matrix (ECM), indicate that the formation of AA is not solely driven by endoluminal pressure loading of the aortic wall. Instead, degenerative processes within ECM elements contribute significantly. Importantly, AA do not necessarily imply dissection. Tissue destruction, allowing blood flow entry, arises from reduced oxygen supply to the media, primarily due to incomplete capillarization or neocapillarization.

• Matrix metalloproteinases
• Tissue inhibitor of metalloproteinases
• Acute aortic dissection
• Aortic aneurysm
• Extracellular matrix remodeling
• Pathogenesis

• Acute aortic dissection
• Chronobiological patterns
• Incidence rate
• Northwest China

• Humans
• Aortic Dissection/epidemiology
• Male
• Female
• Middle Aged
• Retrospective Studies
• China/epidemiology
• Seasons
• Acute Disease
• Aged
• Circadian Rhythm/physiology
• Incidence
• Prevalence
• Adult
• Aortic Aneurysm/epidemiology
• Aortic Aneurysm, Thoracic/epidemiology
• East Asian People

• connective tissue disease
• histological and genetic findings
• thoracic proximal aneurysm and dissection

• no number Open Access Publishing Fund of the Philipps University of Marburg

Treatment of aortic arch aneurysms and dissections require highly complex surgical procedures with devastating complications and mortality rates. Currently, repair of the complete arch until the proximal descending thoracic aorta consists of a two-stage procedure, called elephant trunk (ET) technique, or a single stage a single-stage technique referred to as frozen elephant trunk (FET). There is conflicting evidence about the perioperative results of ET in comparison with FET. We carried out a meta-analysis to investigate possible differences in perioperative and early (up to 30 days) outcomes of ET vs. FET, particularly for mortality, spinal cord injury (SCI), stroke, and renal failure. We also performed a meta-regression to explore the effects of age and sex as possible cofactors. Twenty-one studies containing data from interventions conducted between 1997 and 2019 and published between 2008 and 2021 with 3153 patients (68.5% male) were included. ET was applied to 1,693 patients (53.7%) and FET to 1460 (46.3%). Overall mortality after ET was 250/1693 (14.8%) and after FET 116/1460 (7.9%). Relative risk (RR) and 95% confidence interval (CI) were 1.37 [1.04 to 1.81], p = 0.027. There was no significant effect of age and sex. SCI occurrence after the second stage of ET was 45/1693 (2.7%) and after FET 70/1,460 patients (4.8%) RR 0.53 [0.35 to 0.81], p = 0.004. Age and sex were not associated with the risk of SCI. No significant differences were observed between ET and FET in the incidence of stroke and renal failure. Our results indicate that ET is associated with higher early mortality but lower incidence of SCI compared to FET. When studies published in the last 5 years were analyzed, no significant differences in mortality or SCI were found between ET and FET. This difference is attributed to a decrease in mortality after ET, as the mortality after FET did not change significantly over time.

Thoracic aortic aneurysm/dissection (TAA/D) are complicated vascular disorders with rapid development and high mortality. Vascular smooth muscle cells (VSMCs) phenotype switching plays an important role in the pathological process of TAA/D. Previous studies have indicated a potential correlation between long non-coding RNA (lncRNA) RP11-465L10.10 and matrix metallopeptidase 9 (MMP9) involved in the development of TAA/D. This study aims to investigate the role of lncRNA RP11-465L10.10 in VSMCs phenotype switching and the molecular mechanism in regulating MMP9 expression.

The expression of RP11-465L10.10 in vascular tissues and in VMSCs was detected by RT-qPCR. To investigate the role of RP11-465L10.10 on VSMCs phenotype switching, an RP11-465L10.10-overexpressed lentiviral vector was constructed and transfected into VSMCs. Through EdU staining, migration assay, flow cytometry analysis, the roles of RP11-465L10.10 were estimated. Bioinformatics indicated that RP11-465L10.10 upregulating MMP9 expression via NF-κB signaling, and SN50 (a specific inhibitor of NF-κB pathway) was used to inhibit the NF-κB pathway activation, then the expression of MMP9 was detected in RP11-465L10.10 overexpressed VMSCs.

In this study, we found RP11-465L10.10 and MMP9 were highly increased in TAD patient tissues, which was consistent in angiotensin II-induced VSMCs phenotype switching. RP11-465L10.10 overexpression facilitated VSMCs phenotype switching and MMP9 expression. Mechanismly, NF-κB signal pathway was involved in RP11-465L10.10 induced VSMCs phenotype switching and MMP9 expression by transcriptome data analysis and experimental confirm.

This study demonstrated that RP11-465L10.10 induces VSMCs phenotype switching and MMP9 expression via the NF-κB signal pathway, suggesting that RP11-465L10.10 might be a potential therapeutic target for TAA/D treatment.

• NF-κB pathway
• RP11-465L10.10
• matrix metallopeptidase 9 (MMP9)
• phenotype switching
• vascular smooth muscle cells (VSMCs)

• aortic arch
• aortic dissection
• mortality
• predictors

Matrix metalloproteinase-9 (MMP9) has been reported to play a key role in the pathogenesis of aortic aneurysm. However, few studies have assessed serum MMP9 levels in both abdominal aortic aneurysm (AAA) and thoracic aortic aneurysm (TAA). In this study, we investigated the serum levels of MMP9 in aortic aneurysm to evaluate its predictive and diagnostic efficacy for AAA and TAA, and explored the association of MMP9 with circulating laboratory markers.

A total of 296 subjects were enrolled, including 105 AAA patients, 79 TAA patients and 112 healthy controls. The levels of serum MMP9 were detected by enzyme-linked immunosorbent assay (ELISA).

Compared to control group, both AAA and TAA patients had higher serum MMP9 levels in the overall comparison and subgroup analysis based on subjects aged<65 years, either male or female, hypertension, non-diabetes and non-hyperlipidemia (all P<0.05). Moreover, MMP9 levels were significantly higher in TAA group than those in AAA group in the total comparison, and this discrepancy was also found in the non-diabetes, non-hyperlipidemia and aortic diameter ≥ 5.5 cm subgroup analysis. Serum MMP9 levels were influenced by age and hypertension. There was a positive association of serum MMP9 with CRP (r = 0.33, P < 0.001) and Hcy (r = 0.199, P = 0.033). Multiple logistic analyses showed that serum MMP9 was an independent risk factor for AAA and TAA. Based on receiver operating characteristic (ROC) analysis, the area under the curve (AUC) of MMP9 for predicting TAA was 0.83 with 70% sensitivity and 91% specificity, while the AUC of MMP9 to detect AAA was 0.69 and the sensitivity and specificity were 50% and 88%.

Serum MMP9 was closely related to the existence of aortic aneurysms and could be a valuable marker for the discrimination of aortic aneurysm, especially for TAA.

• Abdominal aortic aneurysm
• C- reactive protein
• Matrix metalloproteinase-9
• Thoracic aortic aneurysm

• Stanford A acute aortic dissection
• early outcomes
• hypertension
• long-term outcomes
• mortality

• Long non-coding RNA
• Microarray
• Thoracic aortic aneurysm

• Inter-arm blood pressure
• atherosclerosis
• calcium score
• coronary artery
• difference

• Arm/physiopathology
• Blood Pressure
• Calcium/metabolism
• Coronary Artery Disease/physiopathology
• Cost of Illness
• Female
• Humans
• Logistic Models
• Male
• Middle Aged
• Multivariate Analysis
• ROC Curve
• Risk Factors
• Systole

• aortic aneurysm
• extracellular matrix
• matrix metalloproteinase
• polymorphism

• Anesthesia
• Cerebral ischemia
• Endovascular aortic repair (EVAR)
• Endovascular procedures
• Monitoring
• Risk assessment
• Spinal cord ischemia
• Thoracic endovascular aortic repair (TEVAR)

• All-cause mortality
• Cardiovascular mortality
• Inter-arm systolic blood pressure difference
• Meta-analysis

• acute aortic dissection
• cardiovascular mortality
• electrocardiography
• fragmented QRS

• Aneurysm
• Anévrysme
• Aorta
• Aorte
• Arteritis
• Artérite
• Graft
• Pontage
• Takayasu