Background Aortic aneurysms (AA) are pathological dilations of the aorta, associated with an overall mortality rate up to 90% in case of rupture. In addition to dilation, the aortic layers can separate by a tear within the layers, defined as aortic dissections (AD). Vascular smooth muscle cells (vSMC) are the predominant cell type within the aortic wall and dysregulation of vSMC functions contributes to AA and AD development and progression. However, since the exact underlying mechanism is poorly understood, finding potential therapeutic targets for AA and AD is challenging and surgery remains the only treatment option. Methods In this review, we summarize current knowledge about vSMC functions within the aortic wall and give an overview of how vSMC functions are altered in AA and AD pathogenesis, organized per anatomical location (abdominal or thoracic aorta). Results Important functions of vSMC in healthy or diseased conditions are apoptosis, phenotypic switch, extracellular matrix regeneration and degradation, proliferation and contractility. Stressors within the aortic wall, including inflammatory cell infiltration and (epi)genetic changes, modulate vSMC functions and cause disturbance of processes within vSMC, such as changes in TGF‐β signalling and regulatory RNA expression. Conclusion This review underscores a central role of vSMC dysfunction in abdominal and thoracic AA and AD development and progression. Further research focused on vSMC dysfunction in the aortic wall is necessary to find potential targets for noninvasive AA and AD treatment options.
Purpose: To report the outcomes from the observational SURPASS registry, which was created to assess the performance of the Conformable TAG (CTAG) stent-graft with the Active Control System (ACS) in patients undergoing thoracic endovascular aortic repair (TEVAR) in a real-world setting. Materials and Methods: The SURPASS registry ( ClinicalTrials.gov; identifier NCT03286400) was an observational, prospective, single-arm, post-market, international study that enrolled patients undergoing TEVAR using the CTAG with ACS for both acute and chronic thoracic aortic disease between October 2017 and July 2018. The CTAG with ACS features 2-stage deployment of the stent-graft and an optional angulation mechanism that modifies only the proximal end of the stent-graft. During the observation period, 127 patients (mean age 67.1±12.1 years, range 27–86; 92 men) were enrolled and treated for an array of aortic pathologies, including chronic and acute lesions and 4 ruptured descending thoracic aneurysms. The primary outcome of this study was technical success; secondary outcomes were clinical success and major adverse events at 30 days and 12 months. The numbers of 2-stage device deployments and applications of the angulation mechanism were recorded, along with the reasons for use. Results: Technical success of the TEVAR was 97.6% owing to unintentional partial coverage of supra-aortic branches in 3 cases (the vessels were patent on imaging). The stent-graft was repositioned at its intermediate diameter in 79 patients (62.2%), and the angulation feature was applied in 64 cases (50.4%), mainly to improve proximal wall apposition and orthogonality in the aorta. The desired effect was achieved in 60 cases (93.8%). There was no device compression, bird-beak configuration, fracture, or graft occlusion. The 30-day and 12-month clinical success rates were 97.6% and 92.9%, respectively. There were 3 aorta-related deaths at 30 days and a further 3 at 12 months. Fatalities were due to a retrograde type A dissection (0.8%), paraplegia, bowel ischemia, sepsis in the setting of a mycotic aneurysm, aneurysm rupture post aortoesophageal fistula, and multiorgan dysfunction syndrome. Three endoleaks (2 type Ia and 1 type III) required reintervention. Conclusion: In the SURPASS registry, the use of the CTAG device with ACS showed promising outcomes despite the challenging pathologies. The new delivery system enables a controlled staged delivery with in situ adjustments during positioning, facilitating the treatment of complex aortic disease.
Objectives: This study compared very long-term follow-up (12-15 years) results after endovascular or conventional open abdominal aneurysm repair.Methods: The DREAM trial included 351 patients between 2000 and 2003, of whom 178 were randomized for endovascular repair and 173 for conventional open aneurysm repair. We evaluated follow-up results after 12 to 15 years by using medical records and approaching patients, relatives, and general practioners to obtain details on survival status and possible reinterventions. Values are presented as median and interquartile range (IQR). Overall survival and freedom from reintervention was analyzed on an intention-to-treat basis using Kaplan-Meier statistics and log-rank test for comparisons (SPSS 23).Results: Median age at randomization was 70 years (IQR 66-75 years), 91.7% were male, and 43.9% had concomitant cardiovascular disease. Median duration of follow-up was 10.2 years (IQR, 5.0-12.5 years). The completeness of follow-up was 98%. Five patients (2.8%) were lost to followup after endovascular repair compared to 4 patients (2.3%) after open repair. At 12 years after randomization, the cumulative overall survival rates were 41.7% for open repair and 38.4% for endovascular repair (3.3% difference; 95% confidence interval [CI], À7.1 to 13.7; P ¼ .48 ; Fig upper panel). Freedom from reintervention was 86.4% after open repair vs 65.1% after endovascular repair (21.3% difference; 95% CI, 11.2-31.4 ; P ¼ .001; Fig, lower panel). Conclusions: No difference in overall survival between endovascular and conventional open repair was found 12 to 15 years after randomization. Still, an almost threefold increased risk of reintervention after endovascular compared to open repair persisted over the same period.
Aortic aneurysms (AA) are pathological dilatations of the aorta. Pathogenic variants in genes encoding for proteins of the contractile machinery of vascular smooth muscle cells (VSMC), genes encoding proteins of the TGFβ signaling pathway, and extracellular matrix (ECM) homeostasis play a role in the weakening of the aortic wall. These variants affect the functioning of VSMC, the predominant cell type in the aorta. Many variants have unknown clinical significance, with unknown consequences on VSMC function and AA development. Our goal was to develop functional assays that show the effects of pathogenic variants in aneurysm related genes. We used a previously developed fibroblast transdifferentiation protocol to induce VSMC-like cells which are used for all assays. We compared transdifferentiated VSMC-like cells of patients with a pathogenic variant in genes encoding for components of VSMC contractility (ACTA2, MYH11), TGFβ signaling (SMAD3) and a dominant negative (DN) and two haploinsuficient variants (HI) in the extracellular matrix elastic laminae (FBN1) to those of healthy controls. The transdifferentiation efficiency, structural integrity of the cytoskeleton, TGFβ signaling profile, migration velocity and maximum contraction were measured. Transdifferentiation efficiency was strongly reduced in SMAD3 and FBN1 DN patients. ACTA2 and FBN1 DN showed a decrease in SMAD2 phosphorylation. Migration velocity was impaired for ACTA2 and MYH11. ACTA2 cells showed reduced contractility. In conclusion, these assays for showing effects of pathogenic variants may be a promising tool to help reclassification of variants of unknown clinical significance in AA related genes.
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