Notch signaling in descending thoracic aortic aneurysm and dissection

BACKGROUND: Descending thoracic aortic aneurysm and dissection (DTAAD) is characterized by progressive medial degeneration, which may result from excessive tissue destruction and insufficient repair. Resistance to tissue destruction and aortic self-repair are critical in preventing medial degeneration. The signaling pathways that control these processes in DTAAD are poorly understood. Because Notch signaling is a critical pathway for cell survival, proliferation, and tissue repair, we examined its activation in DTAAD. METHODS: We studied descending thoracic aortic tissue from patients with sporadic thoracic aortic aneurysm (TAA; n = 14) or chronic thoracic aortic dissection (TAD; n = 16) and from age-matched organ donors (n = 12). Using western blot, real-time RT-PCR, and immunofluorescence staining, we examined aortic tissue samples for the Notch ligands Delta-like 1, Delta-like 4 (DLL1/4), and Jagged1; the Notch receptor 1 (Notch1); the Notch1 intracellular domain (NICD); and Hes1, a downstream target of Notch signaling. RESULTS: Western blots and RT-PCR showed higher levels of the Notch1 protein and mRNA and the NICD and Hes1 proteins in both TAA and TAD tissues than in control tissue. However, immunofluorescence staining showed a complex pattern of Notch signaling in the diseased tissue. The ligand DLL1/4 and Notch1 were significantly decreased and NICD and Hes1 were rarely detected in medial vascular smooth muscle cells (VSMCs) in both TAA and TAD tissues, indicating downregulation of Notch signaling in aortic VSMCs. Interestingly Jagged1, NICD, and Hes1 were highly present in CD34+ stem cells and Stro-1+ stem cells in aortas from TAA and TAD patients. NICD and Hes1 were also detected in most fibroblasts and macrophages that accumulated in the aortic wall of DTAAD patients. CONCLUSIONS: Notch signaling exhibits a complex pattern in DTAAD. The Notch pathway is impaired in medial VSMCs but activated in stem cells, fibroblasts, and macrophages

Open repair of thoracoabdominal aortic aneurysms in experienced centers

Objective: We performed a systematic review and meta-analysis aiming to assess the mortality and morbidity of all published case series on thoracoabdominal aortic aneurysms (TAAAs) in experienced centers treated with open repair. Methods: A systematic search of the literature published until April 2017 was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Separate meta-analyses were conducted for overall in-hospital mortality for TAAA, mortality according to the type of TAAA, spinal cord ischemia, paraplegia and paraparesis, cardiac events, stroke, acute kidney failure, and bowel ischemia. A metaregression analysis was performed with volume of the center, percentage of ruptured cases among the series, length of in-hospital stay, and publication year as covariates. Results: A total of 30 articles were included in the meta-analysis, corresponding to a total of 9963 patients who underwent open repair for TAAAs (543 ruptured). The pooled mortality rate among all studies was 11.26% (95% confidence interval [CI], 9.56-13.09). Mortality was 6.97% (95% CI, 3.75-10.90), 10.32% (95% CI, 7.39-13.63), 8.02% (95% CI, 6.37-9.81), and 7.20% (95% CI, 4.19-10.84) for Crawford types I, II, III, and IV, respectively. Pooled spinal cord ischemia rate was estimated at 8.26% (95% CI, 6.95-9.67), whereas paraparesis and paraplegia rates were 3.61% (95% CI, 2.25-5.25) and 5% (95% CI, 4.36-5.68), respectively. We estimated a pooled cardiac event rate of 4.41% (95% CI, 1.84-7.95) and a stroke rate of 3.11% (95% CI, 2.36-3.94), whereas the need for permanent dialysis rate was 7.92% (95% CI, 5.34-10.92). Respiratory complications after surgery were as high as 23.01% (95% CI, 14.73-32.49). Metaregression analysis evidenced a statistically significant inverse association between mortality and the volume of cases performed in the vascular center (t = −2.00; P =.005). Interestingly, a more recent year of study publication tended to be associated with decreased in-hospital mortality (t = −1.35; P =.19). Conclusions: Our study showed that despite the advances in open surgical techniques, the morbidity and mortality of the technique continue to remain considerable. Despite the focus on mortality and spinal cord ischemia, respiratory complications, permanent postoperative renal dialysis, stroke rate, and cardiac events also affect the outcome. The estimated trend of lower mortality in high-volume centers suggests that perhaps this type of service should be provided in a few reference centers that have an established record and experience in the management of these patients. © 2018 Society for Vascular Surger