Background: Intraplaque neovascularisation (IPN) increases the vulnerability of plaques, which makes them more likely to rupture and increases the risk of vascular events. However, it is unclear whether IPN can predict future vascular events (stroke recurrence and cardiovascular events). Previous studies on IPN have focused on patients with severe stenosis but overlooked patients with mild and moderate stenosis. This study aimed to investigate whether IPN assessed by contrast-enhanced ultrasonography (CEUS) in patients with mild and moderate degrees of stenosis is associated with future vascular events. Methods: One hundred and twenty-one patients participated in this study. 76 patients who met the inclusion and exclusion criteria were included in the final dataset of the study. IPN was graded from 0 to 2 according to the extent of the microbubbles assessed using CEUS. The degree of carotid stenosis was graded as mild, moderate, or severe. We recorded future vascular events during the follow-up. Univariate and multivariate logistic regression analyses were used to evaluate risk factors for future vascular events. Results: After a follow-up period of 30 ± 6 months, 30 patients (39.5%) experienced subsequent vascular events. Compared with the ‘non-recurrent’ group, the ‘recurrent’ group showed a higher proportion of grade 2 neovascularisation ( p < 0.05), and it was an independent predictor of subsequent vascular events (odds ratio 6.066, 95% confidence interval 1.565–23.512, p < 0.05). Furthermore, in patients with mild and moderate stenosis, future vascular events occurred in an unexpectedly high proportion (up to 42.9%). In the ‘recurrent’ group, 55% of patients with mild and moderate stenosis had grade 2 neovascularisation. Conclusion: IPN by CEUS was an independent predictor of future vascular events in patients with recent ischemic stroke, and the high proportion of neovascularisation in patients with mild and moderate stenosis requires more attention.

Objective: Intraplaque neovascularization is a marker of plaque vulnerability and is used to predict the risk of future vascular events in patients with symptomatic carotid stenosis; however, its association with asymptomatic carotid stenosis has not been prospectively evaluated. Therefore, this study aimed to explore the association between intraplaque neovascularization assessed using contrast-enhanced ultrasound and the occurrence of future ischemic events in asymptomatic patients diagnosed with carotid stenosis.Methods: We recruited patients with asymptomatic carotid stenosis from our center. Contrast-enhanced ultrasound was performed at baseline. The outcomes were ischemic stroke and cardiovascular events. We plotted Kaplan-Meier survival curves and performed a log-rank test to compare endpoint event probability in patients with and without grade 2 intraplaque neovascularization. Univariate and multivariate Cox proportional hazards models were used to assess predictors of future vascular events.Results: The data of 50 participants were included in the analysis (median follow-up, 43.7 months). Endpoint events occurred in 12 participants (24%). The Kaplan-Meier survival curves showed that patients with grade 2 intraplaque neovascularization had a higher probability of future vascular events than those with grades 0 and 1 (p &lt; .05). Grade 2 intraplaque neovascularization (hazard ratio: 4.530, 95% confidence interval, 1.337–15.343, p &lt; .05) was an independent predictor of future vascular events in patients with asymptomatic carotid stenosis.Conclusion: Grade 2 intraplaque neovascularization assessed using contrast-enhanced ultrasound independently predicted future ischemic events in patients with asymptomatic carotid stenosis, and contrast-enhanced ultrasound may be an effective screening method to identify high-risk subgroups of patients with asymptomatic carotid stenosis.

: Hypoxia-inducible factor-1 (HIF-1) is a heterodimer protein composed of an oxygen-regulated functional subunit, HIF-1α, and a structural subunit, HIF-1β, belonging to the basic helix-loop-helix family. Strict regulation of HIF-1 protein stability and subsequent transcriptional activity involves various molecular interactions and is primarily controlled by post-transcriptional modifications. Hypoxia, owing to impaired cerebral blood flow, has been implicated in a range of central nervous system (CNS) diseases by exerting a deleterious effect on brain function. As a master oxygen-sensitive transcription regulator, HIF-1 is responsible for upregulating a broad spectrum of target genes involved in glucose metabolism, angiogenesis, and erythropoiesis to generate the adaptive response to avoid or minimize hypoxic brain injury. However, prolonged, severe oxygen deprivation may directly contribute to the role-conversion of HIF-1, namely. From neuroprotection to the promotion of cell death. Currently, an increasing number of studies support the fact HIF-1 is involved in a variety of CNS-related diseases, such as intracranial atherosclerosis, stroke, and neurodegenerative diseases. This review article chiefly focuses on the effect of HIF-1 on the pathogenesis and mechanism of progression of numerous CNS-related disorders by mediating the expression of various downstream genes and extensive biological functional events. It presents robust evidence that HIF-1 may represent a potential therapeutic target for CNS-related diseases.

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Background: Intraplaque neovascularisation (IPN) is a component of vulnerable atherosclerotic plaque, which is a biomarker of cardiovascular events. However, the identification of patients with high probability of ischaemic events after carotid artery stenting (CAS) is mainly based on vascular risk factors. Prospective studies on the development of plaques are lacking. Objectives: The purpose of this study was to investigate whether IPN detected by contrast-enhanced ultrasound is related to the occurrence of ischaemic events after CAS. Methods: Sixty consecutive patients receiving CAS were prospectively enrolled in our centre. The patients were evaluated using contrast-enhanced ultrasound before CAS. According to the degree of microbubble enhancement, IPN was graded from 0 to 2. Endpoint events, including ischaemic stroke and other cardiovascular events, were recorded during follow-up. Kaplan–Meier survival curves and Cox proportional-hazards models were used to evaluate the risk factors for endpoint events. At a median follow-up of 30 months, 13 patients (28.9%) experienced endpoint events. Kaplan–Meier survival curves showed that patients with grade 2 IPN had a higher risk of future ischaemic events than those with grade 0 or 1 IPN ( p < 0.05). Cox proportional-hazards models showed that grade 2 IPN [adjusted hazard ratio (HR), 4.049; 95% confidence interval (CI), 1.078–15.202] was a significant predictor of endpoint events ( p < 0.05). Conclusion: Grade 2 IPN evaluated by contrast-enhanced ultrasound has predictive value for ischaemic events in patients after CAS and may help clinicians identify high-risk patients who need close follow-up. Plain Language Summary Neovascularisation and carotid artery stenting Introduction: Introduction: It is unclear whether intraplaque neovascularisation (IPN) can be used as an biomarker of high probability ischemic events after carotid artery stenting (CAS). Materials and methods: We enrolled 60 patients who underwent CAS, all of whom underwent CEUS before CAS. We recorded ischaemic events during follow-up. Cox proportional-hazards models were used to evaluate the risk factors for ischaemic events. Results: We found that grade 2 IPN was an independent predictor (hazard ratio, 4.049; 95% confidence interval, 1.078–15.202; p < 0.05) of ischaemic events in patients after CAS. Conclusion: This may help clinicians identify high-risk patients who need close follow-up.