Thoracic aortic aneurysm and dissection (TAAD) is a life-threatening condition characterized by medial layer degeneration of the thoracic aorta. A thorough understanding of the regulator changes during pathogenesis is essential for medical therapy development. To delineate the cellular and molecular changes during the development of TAAD, we performed single-cell RNA sequencing of thoracic aortic cells from β-aminopropionitrile-induced TAAD mouse models at three time points that spanned from the early to the advanced stages of the disease. Comparative analyses were performed to delineate the temporal dynamics of changes in cellular composition, lineage-specific regulation, and cell–cell communications. Excessive activation of stress-responsive and Toll-like receptor signaling pathways contributed to the smooth muscle cell senescence at the early stage. Three subpopulations of aortic macrophages were identified, i.e., Lyve1+ resident-like, Cd74high antigen-presenting, and Il1rn+/Trem1+ pro-inflammatory macrophages. In both mice and humans, the pro-inflammatory macrophage subpopulation was found to represent the predominant source of most detrimental molecules. Suppression of macrophage accumulation in the aorta with Ki20227 could significantly decrease the incidence of TAAD and aortic rupture in mice. Targeting the Il1rn+/Trem1+ macrophage subpopulation via blockade of Trem1 using mLR12 could significantly decrease the aortic rupture rate in mice. We present the first comprehensive analysis of the cellular and molecular changes during the development of TAAD at single-cell resolution. Our results highlight the importance of anti-inflammation therapy in TAAD, and pinpoint the macrophage subpopulation as the predominant source of detrimental molecules for TAAD. Targeting the IL1RN+/TREM1+ macrophage subpopulation via blockade of TREM1 may represent a promising medical treatment.
Background: Revascularization of the supra-aortic major branches in thoracic endovascular aortic repair (TEVAR) is challenging owing to the complex anatomic configuration of aortic arch pathologies. This study aims to evaluate the feasibility, effectiveness, and safety of three major techniques—chimney, fenestrated, and in-situ fenestration—for patients with aortic arch pathologies. Methods: A retrospective analysis was performed involving 234 patients with aortic arch lesions, who underwent TEVAR with adaptations in technique (chimney, fenestrated, or in-situ fenestration) between January 2016 and December 2017. Results: One hundred and twenty-six patients underwent the chimney technique (98 single chimneys, 24 double chimneys, and four triple chimneys); one hundred and two patients (102/234) were treated with on-the-table fenestration technique (92 single fenestrations, nine double fenestrations, and one double fenestration plus innominate artery chimney); and the remaining six patients underwent in-situ needle fenestration technique. Overall, indications included aortic dissections (99/234), aortic arch aneurysms (60/234), penetrating aortic ulcers (72/234), and re-interventions (3/234). The technical success rates were 99.6%. There were five cases of early all-cause mortality. The patency rates of overall branches were 99.6%. There were 15 cases with type Ia endoleak—14 in the chimney group (11.1%) and one in the on-the-table fenestration group (1%). Five patients underwent re-interventions. The median follow-up time for all patients was 28 (range, 16–41) months. Conclusions: Our experience suggests that chimney, on-the-table fenestration, and in-situ needle fenestration techniques are feasible, effective, and safe treatment options for aortic arch pathologies with encouraging mid-term results. Long-term durability concerns require further evaluation.
1 October 2021 in Diabetes Research and Clinical Practice
Purpose: To evaluate the safety and feasibility of the in situ needle fenestration (ISNF) technique for reconstruction of the left subclavian artery (LSA) during thoracic endovascular aortic repair (TEVAR) of complicated aortic arch pathologies. Materials and Methods: A retrospective review was conducted from January 2014 to December 2019 of 50 patients (mean age 60.2±11.1; 45 men) who underwent ISNF to revascularize the LSA during TEVAR. Twenty-one of the patients also required revascularization of the left common carotid artery (LCCA; n=19) and innominate artery (IA; n=2) using physician-modified in vitro fenestration. Overall, 73 supra-aortic branches were targeted for revascularization. Results: ISNF was successful in 48 patients (96%); one LSA could not be stented and a tortuous LSA prevented the needle from fenestrating the graft. No perioperative major adverse event occurred. There were no type I and 4 type III endoleaks (8%), 3 of which occurred among the first 20 cases. Types II and IV endoleaks were found in 3 (6%) and 6 (12%) cases, respectively; all disappeared during a median follow-up of 15 months (range 3–66). One death (2%) occurred within 12 months due to cerebral hemorrhage. Two patients (4%) required open reinterventions at 6 and 62 months. Conclusion: ISNF for revascularization of the LSA during TEVAR seems to be feasible with acceptable midterm outcomes. The learning curve and evolving patient selection criteria affected technical success, complications, and the need for reinterventions. Long-term durability requires further evaluation.
The aortic dissection (AD) is a life-threatening disease. The transcatheter endovascular aortic repair (EVAR) affords a minimally invasive technique to save the lives of these critical patients, and an appropriate stent-graft gets to be the key medical device during an EVAR procedure. Herein, we report a trilayer stent-graft and corresponding delivery system used for the treatment of the AD disease. The stent-graft is made of nitinol stents with an asymmetric Z-wave design and two expanded polytetrafluoroethylene (ePTFE) membranes. Each of the inner and outer surfaces of the stent-graft was covered by an ePTFE membrane, and the two membranes were then sintered together. The biological studies of the sintered ePTFE membranes indicated that the stent-graft had excellent cytocompatibility and hemocompatibility in vitro. Both the stent-graft and the delivery system exhibited satisfactory mechanical properties and operability. The safety and efficacy of this stent-graft and the corresponding delivery system were demonstrated in vivo. In nine canine experiments, the blood vessels of the animals implanted with the stent-grafts were of good patency, and there were no thrombus and obvious stenosis by angiography after implantation for 6 months. Furthermore, all of the nine clinical cases experienced successful implantation using the stent-graft and its postrelease delivery system, and the 1-year follow-ups indicated the preliminary safety and efficacy of the trilayer stent-graft with an asymmetric Z-wave design for interventional treatment.