RESUMO
Moyamoya disease (MMD) is closely associated with the Ring Finger Protein 213 (RNF213), a susceptibility gene for MMD. However, its biological function remains unclear. We aimed to elucidate the role of RNF213 in the damage incurred by human endothelial cells under oxygen-glucose deprivation (OGD). We analyzed autophagy in peripheral blood mononuclear cells (PBMCs) derived from patients carrying either RNF213 wildtype (WT) or variant (p.R4810K). Subsequently, human umbilical vein endothelial cells (HUVECs) were transfected with RNF213 WT (HUVECWT) or p.R4810K (HUVECR4810K) and exposed to OGD for 2 h. Immunoblotting was used to analyze autophagy marker proteins, and endothelial function was analyzed by tube formation assay. Autophagic vesicles were observed using transmission electron microscopy. Post-OGD exposure, we administered rapamycin and cilostazol as potential autophagy inducers. The RNF213 variant group during post-OGD exposure (vs. pre-OGD) showed autophagy inhibition, increased protein expression of SQSTM1/p62 (p < 0.0001) and LC3-II (p = 0.0039), and impaired endothelial function (p = 0.0252). HUVECR4810K during post-OGD exposure (versus pre-OGD) showed a remarkable increase in autophagic vesicles. Administration of rapamycin and cilostazol notably restored the function of HUVECR4810K and autophagy. Our findings support the pivotal role of autophagy impaired by the RNF213 variant in MMD-induced endothelial cell dysfunction.
RESUMO
BACKGROUND: Vertebral artery dissections (VADs) may extend from the extracranial to the intracranial vasculature (e+iVAD). We evaluated how the characteristics of e+iVAD differed from those of intracranial VAD (iVAD). METHODS AND RESULTS: From 2002 to 2019, among consecutive patients with cervicocephalic dissection, those with iVAD and e+iVAD were included, and their clinical characteristics were compared. In patients with unruptured dissections, a composite clinical outcome of subsequent ischemic events, subsequent hemorrhagic stroke, or mortality was evaluated. High-resolution magnetic resonance images were analyzed to evaluate intracranial remodeling index. Among 347 patients, 51 (14.7%) had e+iVAD and 296 (85.3%) had iVAD. The hemorrhagic presentation occurred solely in iVAD (0.0% versus 19.3%), whereas e+iVAD exhibited higher ischemic presentation (84.3% versus 27.4%; P<0.001). e+iVAD predominantly presented steno-occlusive morphology (88.2% versus 27.7%) compared with dilatation patterns (11.8% versus 72.3%; P<0.001) of iVAD. The ischemic presentation was significantly associated with e+iVAD (iVAD as a reference; adjusted odds ratio, 3.97 [95% CI, 1.67-9.45]; P=0.002]). Patients with unruptured VAD showed no differences in the rate of composite clinical outcome between the groups (log-rank, P=0.996). e+iVAD had a lower intracranial remodeling index (1.4±0.3 versus 1.6±0.4; P<0.032) and a shorter distance from dural entry to the maximal dissecting segment (6.9±8.4 versus 15.7±7.4; P<0.001). CONCLUSIONS: e+iVAD is associated with lower rates of hemorrhages and higher rates of ischemia than iVAD at the time of admission. This may be explained by a lower intracranial remodeling index and less deep intrusion of the dissecting segment into the intracranial space.
Assuntos
Dissecação da Artéria Vertebral , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral Hemorrágico , Imageamento por Ressonância Magnética , Estudos Retrospectivos , Fatores de Risco , Artéria Vertebral/diagnóstico por imagem , Dissecação da Artéria Vertebral/diagnóstico por imagemRESUMO
BACKGROUND: Transdural collaterals, originating mainly from the extracalvarial superficial temporal artery and intracalvarial middle meningeal artery via the external carotid artery (ECA), have been observed after revascularisation surgery. However, the origin of these collaterals in patients with stroke with perfusion insufficiency is not yet known. Therefore, we studied the revascularisation patterns and characteristics based on the origin of these collaterals. METHODS: We employed erythropoietin pretreatment and performed multiple burr holes under local anaesthesia to achieve transdural revascularisation in patients with acute stroke with perfusion insufficiency. After 6 months, we reassessed the transfemoral cerebral angiography to evaluate the revascularisation patterns. The collaterals were categorised into intracalvarial ECA-dominant (originating from the middle meningeal artery), extracalvarial ECA-dominant (originating from the superficial temporal or occipital artery) and balanced groups. We compared various imaging parameters among these groups. RESULTS: Overall, 87 patients with 103 treated hemispheres were involved. Among them, 57.3% were classified as intracalvarial ECA-dominant, 20.4% as extracalvarial ECA-dominant and 22.3% as balanced. Most of the hemispheres with intracalvarial or extracalvarial collaterals (vs balanced collaterals) showed successful revascularisation (78/80 (97.5%) vs 12/23 (52.1%)), p<0.001). In ultrasonographic haemodynamic changes according to revascularisation pattern, only the intracalvarial ECA-dominant revascularisation was significantly associated with specific changes in ECA blood flow, leading to the conversion to a low-resistance ECA Doppler sonography waveform. CONCLUSIONS: Our findings suggest that intracalvarial ECA-dominant revascularisation plays a crucial role in the formation of transdural collaterals following combined therapy. These distinct changes in ECA haemodynamics can be non-invasively identified through bedside ultrasound studies.
RESUMO
BACKGROUND: Mechanical thrombectomy is an effective treatment method for large-vessel occlusion stroke (LVOS); however, it has limited efficacy for intracranial atherosclerotic disease (ICAD)-related LVOS. We investigated the use of cerebral blood volume (CBV) maps for identifying ICAD as the underlying cause of LVOS before the initiation of endovascular treatment (EVT). METHODS AND RESULTS: We reviewed clinical and imaging data from patients who presented with LVOS and underwent endovascular treatment between January 2011 and May 2021. The CBV patterns were analyzed to identify an increase in CBV within the hypoperfused area and estimate infarct patterns within the area of decreased CBV. Comparisons were made between the patients with an increase in CBV and those without, and among the estimated infarct patterns: territorial, cortical wedge, basal ganglia-only, subcortical, and normal CBV. Overall, 243 patients were included. CBV increase in the hypoperfused area was observed in 23.5% of patients. A significantly higher proportion of ICAD was observed in those with increased CBV than in those without (56.4% versus 19.8%; P<0.001). Regarding the estimated infarct patterns on the CBV, ICAD was most frequently observed in the normal CBV group (territorial, 14.9%; cortical wedge, 10.0%; basal ganglia-only, 43.8%; subcortical, 35.7%; normal, 61.7%). CBV parameters, including "an increase in CBV," "normal CBV infarct pattern," and "an increase in CBV or normal CBV infarct pattern composite," were independently associated with ICAD. CONCLUSIONS: An increased CBV or normal CBV pattern may be associated with ICAD LVOS on the pretreatment perfusion imaging.