RESUMO
The phenotypic switch of vascular smooth cells (VSMCs) from a contractile to a synthetic state is associated with the development and progression of aortic aneurysm (AA). However, the mechanism underlying this process remains unclear. In this issue of the JCI, Song et al. identified SLC44A2 as a regulator of the phenotypic switch in VSMCs. Inhibition of SLC44A2 facilitated the switch to the synthetic state, contributing to the development of AA. Mechanistically, SLC44A2 interacted with NRP1 and ITGB3 to activate the TGF-ß/SMAD signaling pathway, resulting in VSMCs with a contractile phenotype. Furthermore, VSMC-specific SLC44A2 overexpression by genetic or pharmacological manipulation reduced AA in mouse models. These findings suggest the potential of targeting the SLC44A2 signaling pathway for AA prevention and treatment.
Assuntos
Aneurisma Aórtico , Músculo Liso Vascular , Miócitos de Músculo Liso , Transdução de Sinais , Animais , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Aneurisma Aórtico/metabolismo , Aneurisma Aórtico/patologia , Aneurisma Aórtico/genética , Camundongos , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Humanos , Fenótipo , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta/genética , Integrina beta3/metabolismo , Integrina beta3/genética , Proteínas de Membrana Transportadoras/metabolismo , Proteínas de Membrana Transportadoras/genética , Neuropilina-1/metabolismo , Neuropilina-1/genéticaRESUMO
OBJECTIVE: Malignant cerebral edema (MCE) is a life-threatening complication of ischemic stroke. Few studies have evaluated MCE in patients with acute basilar artery occlusion (BAO) receiving endovascular treatment (EVT). Therefore, the authors investigated the incidence, predictors, and functional outcomes of MCE in BAO patients undergoing EVT. METHODS: This was a post hoc analysis of the Endovascular Treatment for Acute Basilar Artery Occlusion (ATTENTION) trial, a prospective, randomized, multicenter clinical trial that compared endovascular treatment with conventional care of patients with BAO at 36 centers in China. Brain edema was retrospectively assessed using the Jauss score for all available follow-up scans, and patients with a Jauss score ≥ 4 were classified as having MCE. Clinical functional independence was defined as a modified Rankin Scale (mRS) score of 0-2, and a good outcome was defined as an mRS score of 0-3 at the 90-day follow-up. Univariate and multivariate analyses were used to explore the predictors of MCE and the impact of MCE on prognosis. RESULTS: A total of 189 patients were analyzed, and 13.2% of patients developed MCE. Multivariate analysis showed that the baseline Glasgow Coma Scale (GCS) score (OR 0.722, 95% CI 0.548-0.950; p = 0.020) and the number of procedures (OR 1.594, 95% CI 1.051-2.419; p = 0.028) were significantly associated with MCE. After adjusting for confounding factors, the presence of MCE was significantly associated with a lower rate of functional independence (OR 0.115, 95% CI 0.023-0.563; p = 0.008), a lower rate of good outcome (OR 0.092, 95% CI 0.023-0.360; p = 0.001), and a higher rate of mortality (OR 5.373, 95% CI 2.055-14.052; p = 0.001) at the 90-day follow-up. CONCLUSIONS: MCE is not uncommon in BAO patients undergoing EVT and is associated with poor outcomes. Baseline GCS score and the number of procedures were predictors of MCE. In clinical practice, it is crucial that physicians identifying MCE after EVT in patients with BAO and identification of MCE will help in the selection of an appropriate pharmacological treatment strategy and close monitoring.
RESUMO
OBJECTIVES: A higher reperfusion grade after endovascular thrombectomy (EVT) is associated with a good prognosis. However, the effect of the number of retrievals has not yet been investigated in vertebrobasilar occlusion (VBAO). Therefore, the aim of this study was to investigate whether to continue retrieval after early modified thrombolysis in cerebral infarction (mTICI) 2b to achieve a better reperfusion grade. METHODS: We retrospectively analyzed the data of patients who underwent EVT caused by VBAO in a multicenter registry dataset. Patients who underwent successful reperfusion were included (mTICI 2b/3). Regression models were used to analyze the correlation of different reperfusion grades stratified by the number of retrieval attempts with clinical prognosis and hemorrhage transition. RESULTS: We included 432 patients: 34.5% (n = 149) had a final mTICI score of 2b and 65.5% (n = 283) had a final mTICI score of 3. Patients who obtained a mTICI of 3 after the first pass had significantly increased odds of having a good prognosis. As the number of passes increases, the chances of obtaining a good prognosis decreases. After three or more passes, the odds of achieving functional independence and favorable outcomes were comparable to those of the first mTICI 2b, regardless of the 90-day (OR 1.132 95% CI 0.367-3.487 p = 0.829; OR 1.070 95% CI 0.375-3.047 p = 0.900) or 1-year follow-up (OR 1.217 95% CI 0.407-3.637 p = 0.725; OR 1.068 95% CI 0.359-3.173 p = 0.906). INTERPRETATION: Within two retrieval attempts, mTICI 3 was better than the first retrieval to mTICI 2b. After early mTICI 2b, each retrieval should be undertaken with caution to pursue a higher reperfusion grade.