Carotid revascularisation versus medical treatment for asymptomatic carotid artery stenosis.

OBJECTIVES: This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To compare the safety and efficacy of carotid revascularisation plus best medical treatment with best medical treatment alone in people with asymptomatic carotid artery stenosis.

Qualifying Event and Recurrence of Ischemic Stroke in Symptomatic Artery Occlusion: A Post Hoc Analysis of CMOSS.

BACKGROUND: The authors aimed to elucidate the relationship between latest ischemic event and the incidence of subsequent ischemic stroke in patients with symptomatic artery occlusion. METHODS AND RESULTS: We analyzed the association between qualifying event-the latest ischemic event (transient ischemic attack [TIA] or stroke)-and the incidence of ipsilateral ischemic stroke in patients with symptomatic artery occlusion treated with medical therapy alone in CMOSS (Carotid or Middle Cerebral Artery Occlusion Surgery Study). The incidence of CMOSS primary outcomes, including any stroke or death within 30 days after randomization or ipsilateral ischemic stroke between 30 days and 2 years, between the bypass surgical and medical groups, stratified by qualifying events, was also compared. Of the 165 patients treated with medical therapy alone, 75 had a TIA and 90 had a stroke as their qualifying event. The incidence of ipsilateral ischemic stroke did not significantly differ between patients with a TIA and those with a stroke as their qualifying event (13.3% versus 6.7%, P=0.17). In multivariate analysis, the qualifying event was not associated with the incidence of ipsilateral ischemic stroke. There were no significant differences in the CMOSS primary outcomes between the surgical and medical groups, regardless of the qualifying event being TIA (10.1% versus 12.2%, P=0.86) or stroke (6.7% versus 8.9%, P=0.55). CONCLUSIONS: Among patients with symptomatic artery occlusion and hemodynamic insufficiency, the risk of subsequent ipsilateral ischemic stroke does not appear to be lower in patients presenting with a TIA compared with those with a stroke. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01758614.

Potential of body mass index as a screening indicator for extracranial-intracranial bypass surgery in patients with symptomatic artery occlusion: a post-hoc analysis of the CMOSS trial.

BACKGROUND: To investigate the association between body mass index (BMI) and the incidence of ischemic stroke in patients with symptomatic artery occlusion, and further to evaluate the utility of BMI as a screening tool for identifying candidates for extracranial-intracranial bypass surgery. MATERIALS AND METHODS: We analyzed the relationship between BMI and the occurrence of ipsilateral ischemic stroke (IIS) among patients receiving only medical management in the Carotid or Middle cerebral artery Occlusion Surgery Study (CMOSS). Additionally, we compared the primary endpoint of CMOSS-stroke or death within 30 days, or IIS after 30 days up to two years-among patients with varying BMIs who underwent either surgery or medical treatment. RESULTS: Of the 165 patients who treated medically only, 16 (9.7%) suffered an IIS within two years. BMI was independently associated with the incidence of IIS (hazard ratio: 1.16 per kg/m2; 95% confidence interval: 1.06-1.27). The optimal BMI cutoff for predicting IIS was 24.5 kg/m2. Patients with BMI ≥24.5 kg/m2 experienced a higher incidence of IIS compared to those with BMI <24.5 kg/m2 (17.4% vs. 0.0%, P<0.01). The incidence of the CMOSS primary endpoint was significantly different between the surgical and medical groups for patients with BMI ≥24.5 kg/m2 (5.3% vs. 19.8%, P<0.01) and those with BMI <24.5 kg/m2 (10.6% vs. 1.4%; P=0.02). Surgical intervention was independently associated with a reduced rate of the CMOSS primary endpoint in patients with BMI ≥24.5 kg/m2. CONCLUSION: Data from the CMOSS trial indicate that patients with BMI ≥24.5 kg/m2 are at a higher risk of IIS when treated medically only and appear to derive greater benefit from bypass surgery compared to those with lower BMIs. Given the small sample size and the inherent limitations of retrospective analyses, further large-scale, prospective studies are necessary to confirm these findings.

eIF2α-mediated integrated stress response links multiple intracellular signaling pathways to reprogram vascular smooth muscle cell fate in carotid artery plaque.

Background: Carotid arterial atherosclerotic stenosis is a well-recognized pathological basis of ischemic stroke; however, its underlying molecular mechanisms remain unknown. Vascular smooth muscle cells (VSMCs) play fundamental roles in the initiation and progression of atherosclerosis. Organelle dynamics have been reported to affect atherosclerosis development. However, the association between organelle dynamics and various cellular stresses in atherosclerotic progression remain ambiguous. Methods: In this study, we conducted transcriptomics and bioinformatics analyses of stable and vulnerable carotid plaques. Primary VSMCs were isolated from carotid plaques and subjected to histopathological staining to determine their expression profiles. Endoplasmic reticulum (ER), mitochondria, and lysosome dynamics were observed in primary VSMCs and VSMC cell lines using live-cell imaging. Moreover, the mechanisms underlying disordered organelle dynamics were investigated using comprehensive biological approaches. Results: ER whorls, a representative structural change under ER stress, are prominent dynamic reconstructions of VSMCs between vulnerable and stable plaques, followed by fragmented mitochondria and enlarged lysosomes, suggesting mitochondrial stress and lysosomal defects, respectively. Induction of mitochondrial stress alleviated ER stress and autophagy in an eukaryotic translation initiation factor (eIF)-2α-dependent manner. Furthermore, the effects of eIF2α on ER stress, mitochondrial stress, and lysosomal defects were validated using clinical samples. Conclusion: Our results indicate that morphological and functional changes in VSMC organelles, especially in ER whorls, can be used as reliable biomarkers for atherosclerotic progression. Moreover, eIF2α plays an important role in integrating multiple stress-signaling pathways to determine the behavior and fate of VSMCs.

Incidence and predictors of restenosis following successful recanalization of non-acute internal carotid artery occlusion in 252 cases.

BACKGROUND: Data concerning restenosis following successful recanalization of non-acute internal carotid artery occlusion (ICAO) are scarce. This study was conducted to identify the incidence and predictors of restenosis following successful recanalization of non-acute ICAO. METHODS: We reviewed the incidence of restenosis (defined as >70% restenosis or reocclusion) among 252 consecutive patients with successful recanalization of non-acute ICAO. Baseline, imaging, and surgery-related characteristics were analyzed to assess their association with restenosis. A scoring system was developed to identify high-risk patients for restenosis. RESULTS: During a median follow-up of 12.6 months, restenosis occurred in 56 patients (22.2%), including 39 with reocclusion and 17 with >70% restenosis. The cumulative restenosis rate was 18.0% at 12 months and 24.1% at 24 months. The incidence of stroke was higher in patients with restenosis (25.0% vs 1.5%, P<0.01). Multivariate analysis showed occlusion length (5-10 cm vs <5 cm (hazard ratio (HR) 3.15, 95% confidence interval (95% CI) 1.07 to 9.29); ≥ 10 cm vs <5 cm (HR 5.01, 95% CI 1.73 to 14.49)), residual stenosis ≥30% (HR 3.08, 95% CI 1.79 to 5.30), and internal carotid artery (ICA) wall collapse (HR 1.96, 95% CI 1.12 to 3.44) as independent predictors of restenosis. Point scores proportional to model coefficients were assigned, with scores ranging from 0 to 6. Patients scoring 3-6 had a 4.00 times higher chance of developing restenosis (95% CI 2.35 to 6.79) compared with those scoring 0-2. CONCLUSIONS: Nearly one in five patients experienced restenosis following successful recanalization of non-acute ICAO. Occlusion length, residual stenosis ≥30%, and ICA wall collapse were independently associated with restenosis.

First-in-human experience of sirolimus coated balloon for symptomatic intracranial artery stenosis.

BACKGROUND: The drug coated balloon is a promising endovascular therapy for intracranial atherosclerosis (ICAS), potentially combining the advantages of primary angioplasty and antiproliferative drugs. Previous studies have focused on the paclitaxel coated balloon, revealing promising outcomes in the treatment of ICAS, while concerns about the neurotoxicity of paclitaxel were reported. Sirolimus was shown to have less neurotoxicity in the canine cerebral vasculature. The feasibility and safety of a sirolimus coated balloon (SCB) for ICAS have never been evaluated in humans. We assessed the first-in-human feasibility and safety of SCBs for treating symptomatic patients with severe ICAS. METHODS: This prospective, open label, single arm cohort study was designed to enroll patients with transient ischemic attacks or non-disabling, non-perforator territory ischemic stroke caused by severe ICAS (70-99%) and following at least 3 weeks after the onset of ischemic symptoms. The primary outcome was stroke or death within 30 days. All patients were followed up to detect restenosis at 6 months. RESULTS: A total of 60 eligible patients were enrolled with an average age of 59.4±10.8 years. The technical success rate of SCBs for ICAS was 100%. Seven patients (11.7%) required stenting because of flow limited dissections or elastic retraction. Three patients (5.0%) had 30 day strokes, including two ischemic strokes and one hemorrhagic stroke. An additional three patients had recurrent stroke or death during follow-up. Ten patients had restenosis but only two had symptoms. CONCLUSIONS: SCBs may be feasible and safe in selected patients with symptomatic ICAS, with high grade stenosis (70-99%). Further studies are warranted.

PCSK9 increases vulnerability of carotid plaque by promoting mitochondrial dysfunction and apoptosis of vascular smooth muscle cells.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) has been recognized as a novel lipid-lowing target. Recent clinical studies suggested the value of inhibiting PCSK9 in decreasing the vulnerability of coronary plaques. However, the evidence of PCSK9-regulated evolution of unstable carotid plaques is unclear, which has limited the use of PCSK9 inhibitor in carotid plaques. This study aimed to determine the effect and molecular mechanisms of PCSK9 on vulnerability of carotid plaques, to provide potential therapeutic targets for stabilizing carotid plaques. METHODS: The expression of PCSK9 in stable and unstable carotid plaques were examined in tissue and plasma. Human aortic vascular smooth muscle cells (VSMCs) and carotid VSMCs were employed to transfect lentivirus for overexpression and knockdown of PCSK9, respectively. Morphological and functional changes of mitochondria were observed by live-cell imaging. Cell apoptosis was evaluated by propidium iodide staining. RNA-sequencing and biological examinations were performed to explore and validate the underlying mechanisms. Truncated plasmids were employed to identify the functional domain of PCSK9 in regulation of VSMCs' mitochondrial morphology, function and apoptosis. RESULTS: Clinically, PCSK9 was closely related with vulnerability of human carotid plaques. Increased expression of PCSK9 in human VSMCs was accompanied by higher level of apoptosis. At subcellular level of VSMCs, the morphology of mitochondria was shifted toward the fission state, followed by mitochondrial dysfunction. Inhibition of p38 MAPK activation partially rescued the above morphological and behavioral changes caused by PCSK9. Furthermore, inhibiting of dynamin-related protein 1 (DRP1) attenuated PCSK9-related mitochondrial dysfunction and cell apoptosis. The 1-149aa domain of PCSK9 protein was essential to achieve functional regulation to VSMCs. CONCLUSION: Our findings demonstrated that PCSK9 induced morphology-related mitochondrial dysfunction and apoptosis of VSMCs, which may be related to increased vulnerability of carotid plaque.

Impact of acute silent ischemic lesions on clinical outcomes of carotid revascularization.

BACKGROUND: Previous literature has established an association between acute silent ischemic lesions (ASILs) and elevated susceptibility to future adverse clinical outcomes. The present study endeavors to scrutinize the prognostic significance of preprocedural ASILs, as detected through diffusion-weighted imaging and apparent diffusion coefficient metrics, in relation to subsequent adverse events-namely, stroke, myocardial infarction, and all-cause death-following carotid revascularization in a cohort of patients with symptomatic carotid stenosis. MATERIALS AND METHODS: Subjects were extracted from a comprehensive retrospective dataset involving symptomatic carotid stenosis cases that underwent carotid revascularization at a tertiary healthcare institution in China, spanning January 2019 to March 2022. Of the 2663 initially screened patients (symptomatic carotid stenosis=1600; asymptomatic carotid stenosis=1063), a total of 1172 individuals with symptomatic carotid stenosis were retained for subsequent analysis. Stratification was implemented based on the presence or absence of ASILs. The primary endpoint constituted a composite measure of in-hospital stroke, myocardial infarction, or all-cause death. Both carotid endarterectomy (CEA) and carotid artery stenting (CAS) treatment modalities were individually subjected to propensity score-matched analyses. RESULTS: Among the 584 subjects who underwent CEA, 91 ASIL-positive and 91 ASIL-negative (NASIL) cases were propensity score-matched. Notably, the ASIL cohort demonstrated a statistically significant augmentation in the risk of primary outcomes relative to the NASIL group [10.99 vs. 1.10%; absolute risk difference, 9.89% (95% CI: 3.12-16.66%); RR, 10.00 (95% CI: 1.31-76.52); P =0.01]. Similarly, within the 588 CAS-treated patients, 107 ASIL-positive and 107 NASIL cases were matched, revealing a correspondingly elevated risk of primary outcomes in the ASIL group [9.35 vs. 1.87%; absolute risk difference, 7.48% (95% CI: 1.39-13.56%); RR, 5.00 (95% CI: 1.12-22.28); P =0.02]. CONCLUSIONS: ASILs portend an elevated risk for grave adverse events postcarotid revascularization, irrespective of the specific revascularization technique employed-be it CEA or CAS. Thus, ASILs may serve as a potent biomarker for procedural risk stratification in the context of carotid revascularization.

Comparison of drug-coated balloon angioplasty versus standard medical therapy on recurrent stroke and mortality rates among patients with symptomatic intracranial atherosclerotic stenosis: protocol for a systematic review and meta-analysis.

INTRODUCTION: Stroke remains the second leading cause of death worldwide, a common cause of which is intracranial atherosclerotic stenosis (ICAS). Medical treatment is recommended as first-line therapy for treating ICAS, but the recurrence rate remains high. Drug-coated balloon (DCB) angioplasty has been designed to lower the risk of recurrent stenosis, holding therapeutic promise in the treatment of ICAS. However, the benefits of DCB require further evaluation. METHODS AND ANALYSIS: The Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols was followed to develop this protocol. We will systematically search online databases including Cochrane Central Register of Controlled Trials, PubMed, Web of Science, EMBASE, China Biological Medicine Database, ClinicalTrials.gov and WHO ICTRP from 1 January 2011 to the date of search. This will be supplemented by a manual search of unpublished and ongoing trials to manually select articles for inclusion. Inclusion criteria are randomised or quasi-randomised clinical trials and observational studies that investigated DCB or medical treatment for patients with a symptomatic ICAS of 50%-99%. The primary outcome is short-term composite safety including death of any cause, or non-fatal stroke. Secondary outcomes include long-term death or stroke, restenosis, neurological rehabilitation, quality of life and other complications. The available data will be analysed using meta-analysis, if appropriate. The evaluation of heterogeneity and biases will be guided by the Cochrane Handbook for Systematic Reviews of Interventions. ETHICS AND DISSEMINATION: This systematic review does not require ethical approval as all available data from eligible studies will be anonymous with no concerns regarding privacy. Our findings will be disseminated through international conferences and peer-reviewed publications. Additional data from the study are available on request to corresponding authors via email. PROSPERO REGISTRATION NUMBER: CRD42022341607.

Potential of unilateral combined bypass surgery to accelerate contralateral radiological progression in pediatric moyamoya disease.

Background: Surgical cerebral revascularization is recommended for treating pediatric moyamoya disease (MMD). However, whether unilateral combined bypass surgery can cause disease progression on the contralateral side is uncertain. The study aimed to investigate the vascular architecture and regional cerebral blood flow (rCBF) status of patients with pediatric MMD after successful unilateral combined bypass surgery and to identify the possible risk factors. Methods: Pediatric patients diagnosed with MMD and admitted to Xuanwu Hospital who underwent combined bypass surgery between 2019 and 2021 were enrolled. Digital subtraction angiography (DSA) and magnetic resonance imaging (MRI) with arterial spin labeling (ASL) were performed to investigate the vascular architecture and rCBF during surgery and at short-term follow-up. Suzuki's angiographic staging and moyamoya vessel grading system were both used. Progression was defined as an increase in either Suzuki stage or moyamoya vessel grade detected after unilateral surgery. All analyses were performed with conventional statistic methods. Results: A total of 27 successive patients with a median age of 8 [interquartile range (IQR), 5-14] years old were identified. On the non-operated (non-OP) side, 11 (40.7%) patients demonstrated progression, all of whom showed an increase in the moyamoya vessel grade, and 5 also displayed Suzuki stage progression during the median 4.7 (IQR, 3.7-5.7) months follow-up. However, rCBF barely changed on the non-OP side compared to preoperation [preoperation: median, 49.6, (IQR, 42.9-61.1) mL/100 g/min; postoperation: median, 50.2, (IQR, 43.5-59.3) mL/100 g/min; P=0.445]. Conclusions: Combined bypass surgery might accelerate the radiological progression on the contralateral side, which occurs before the decline of rCBF. Those with earlier Suzuki stage MMD of the non-OP side are prone to rapid progression after unilateral combined revascularization.

Knowledge fields and emerging trends about extracellular matrix in carotid artery disease from 1990 to 2021: analysis of the scientific literature.

BACKGROUND: Stroke is a heavy burden in modern society, and carotid artery disease is a major cause. The role of the extracellular matrix (ECM) in the development and progression of carotid artery disease has become a popular research focus. However, there is no published bibliometric analysis to derive the main publication features and trends in this scientific area. We aim to conduct a bibliometric analysis to reveal current status of ECM in carotid artery disease and to predict future hot spots. METHODS: We searched and downloaded articles from the Web of Science Core Collection with "Carotid" and "Extracellular Matrix" as subject words from 1990 to 2021. The complete bibliographic data were analyzed by Bibliometrics, BICOMB, gCLUTO and CiteSpace softwares. RESULTS: Since 1990, the United States has been the leader in the number of publications in the field of ECM in carotid artery disease, followed by China, Japan and Germany. Among institutions, Institut National De La Sante Et De La Recherche Medicale Inserm, University of Washington Seattle and Harvard University are in the top 3. "Arteriosclerosis Thrombosis and Vascular Biology" is the most popular journal and "Circulation" is the most cited journal. "Clowes AW", "Hedin Ulf" and "Nilsson Jan" are the top three authors of published articles. Finally, we investigated the frontiers through the strongest citation bursts, conducted keyword biclustering analysis, and discovered five clusters of research hotspots. Our research provided a comprehensive analysis of the fundamental data, knowledge organization, and dynamic evolution of research about ECM in carotid artery disease. CONCLUSIONS: The field of ECM in carotid artery disease has received increasing attention. We summarized the history of the field and predicted five future hotspots through bibliometric analysis. This study provided a reference for researchers in this fields, and the methodology can be extended to other fields.

Correlations between intravascular pressure gradients and cerebral blood flow in patients with symptomatic, medically refractory, anterior circulation artery stenosis: an exploratory study.

BACKGROUND: Fractional flow reserve is widely used in coronary disease management, with a threshold of 0.80. However, similar thresholds are unclear in functional assessment of intracranial atherosclerotic stenosis (ICAS). OBJECTIVE: To investigate the potential threshold values in functional assessment of ICAS by studying the relation between pressure-derived indexes and perfusion parameters derived from arterial spin labeling (ASL). METHODS: Patients were consecutively screened between June 2019 and December 2020. The translesional gradient indices were measured by pressure guidewire under resting-state conditions and recorded as mean distal/proximal pressure ratios (Pd/Pa) and translesional pressure difference (Pa-Pd). Preoperative and postoperative cerebral blood flow (CBF) bilaterally and the relative cerebral blood flow ratio (rCBF) were measured and recorded by ASL imaging. Patients were defined as having reversible hemodynamic insufficiency only if the preoperative rCBF was <0.9 and the postoperative rCBF≥0.9. Preoperative and postoperative Pd/Pa or Pa-Pd values of those patients were used to calculate the threshold. RESULTS: Twenty-five patients (19 men, 6 women) with a mean age of 56.7±9.4 years were analyzed. Seventeen patients (68%) had lesions at the M1 segment of the middle cerebral artery, eight patients (32%) had lesions in the intracranial internal carotid artery. In 14 of the 25 patients, the preoperative rCBF was <0.9 and the postoperative rCBF≥0.9. Cut-off values of Pd/Pa=0.81 and Pa-Pd=8 mm Hg were suggested to be associated with hemodynamic insufficiency. CONCLUSIONS: In a highly selected subgroup with ICAS, cut-off values of translesional pressure gradients (Pd/Pa=0.81 or Pa-Pd=8 mm Hg) were preliminarily established, which may facilitate clinical decision-making in the management of ICAS.

Transcarotid versus transfemoral access for cerebrovascular intervention: protocol for a systematic review and meta-analysis.

INTRODUCTION: Cerebrovascular intervention is an excellent option to treat cerebrovascular diseases. Interventional access is a prerequisite and a foundation for cerebrovascular intervention, which is crucial to the success of an intervention. Although transfemoral arterial access (TFA) has become a popular and acceptable method of access for cerebrovascular angiography and intervention in clinical practice, it has some drawbacks that limit the usage in cerebrovascular interventions. Therefore, transcarotid arterial access (TCA) has been developed in cerebrovascular interventions. We aim to conduct a systematic review to compare the safety and efficacy of TCA with TFA for cerebrovascular intervention. METHODS AND ANALYSIS: In this protocol, Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols were followed. PubMed, Embase, Web of Science and the Cochrane Central Register of Controlled Trials will be searched mainly from 1 January 2004, to the formal search date. Additionally, reference lists and clinical trial registries will be searched. We will include clinical trials with more than 30 participants, which reported the endpoints of stroke, death and myocardial infarction. Two investigators will independently select studies, extract data and assess bias risk. A standardised mean difference with 95% CI will be presented for continuous data, and a risk ratio with 95% CI will be presented for dichotomous data. On inclusion of sufficient studies, subgroup analysis and sensitivity analysis will be conducted. The funnel plot and Egger's test will be used to assess publication bias. ETHICS AND DISSEMINATION: As only published sources will be used in this review, ethical approval is not required. We will publish the results in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42022316468.

Stenting versus medical therapy alone for symptomatic intracranial arterial stenosis: protocol for a systematic review and individual patient data meta-analysis.

INTRODUCTION: Intracranial atherosclerotic stenosis (ICAS) is a common cause of stroke worldwide. However, whether the treatment options for symptomatic ICAS is stent placement or medical therapy alone is still controversial. At present, three multicentre randomised controlled trials (RCTs) have been published, but their research designs are also slightly different and the conclusions are not completely consistent. Therefore, we plan to conduct a systematic review and individual patient data (IPD) meta-analysis of randomised clinical trials to ascertain safety and efficacy of stenting versus medical therapy alone for symptomatic patients with intracranial arterial stenosis. METHODS AND ANALYSES: We will identify RCTs comparing stenting vs medical therapy alone in patients with symptomatic ICAS stenosis (70%-99%) through a systematic search, mainly including PubMed, MEDLINE, EMBASE, the Cochrane Library and ClinicalTrials.gov. Individual-level patient data for a prespecified list of variables will be sought from authors of all eligible studies. The primary outcome was a composite of stroke or death within 30 days, or stroke in territory of qualifying artery beyond 30 days after randomisation. IPD meta-analysis will be conducted with a one-stage approach. ETHICS AND DISSEMINATION: Ethical approval and individual patient consent will not be required in most cases since this IPD meta-analysis will use pseudoanonymised data from RCTs. Results will be disseminated through peer-reviewed journals and international conferences. PROSPERO REGISTRATION NUMBER: CRD42022369922.

Circular RNA as biomarkers for acute ischemic stroke: A systematic review and meta-analysis.

BACKGROUND: Rapid diagnosis of acute ischemic stroke (AIS) patients is still challenging, and reliable biomarkers are needed. Noncoding RNAs are important for many physiological activities, among which circular RNAs (circRNAs) have been proven to be more tissue-specific and conservative. Many recent studies found the potential of circRNAs as biomarkers for many diseases, including cardiovascular diseases, cancers, and ischemic stroke. This systemic review and meta-analysis aimed to identify circRNAs as potential biomarkers for AIS. METHODS: This study has been prospectively registered in PROSPERO (Registration No. 11 CRD42021288033). Published literature comparing circRNA expression profiles between AIS and non-AIS in human and animal models were retrieved from the articles published by January 2023 in major databases. We descriptively summarized the included studies, conducted meta-analysis under a random effects model, and did bioinformatics analysis including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. RESULTS: Totally 23 studies were included, reporting 18 distinctive upregulated and 20 distinctive downregulated circRNAs. Diagnostic meta-analysis indicated discriminative ability of the circRNAs. Furthermore, circRNA HECTD1, circRNA DLGAP4, circRNA CDC14A, circRNA SCMH1, and circRNA TLK1 were reported with the same regulation trend in more than one study (animal studies included). GO and KEGG enrichment analyses indicated that the target genes of these five circRNAs were enriched in regulating cell proliferation, apoptosis, and oxidative stress. CONCLUSIONS: This study demonstrates that circRNAs (circRNA HECTD1, circRNA DLGAP4, circRNA CDC14A, circRNA SCMH1, and circRNA TLK1) generally are promising as potential biomarkers for AIS. However, due to the limited number of studies, diagnostic value of individual circRNA could not be validated. More in vitro and in vivo functional studies are needed.

Membrane contact sites orchestrate cholesterol homeostasis that is central to vascular aging.

Chronological age causes structural and functional vascular deterioration and is a well-established risk factor for the development of cardiovascular diseases, leading to more than 40% of all deaths in the elderly. The etiology of vascular aging is complex; a significant impact arises from impaired cholesterol homeostasis. Cholesterol level is balanced through synthesis, uptake, transport, and esterification, the processes executed by multiple organelles. Moreover, organelles responsible for cholesterol homeostasis are spatially and functionally coordinated instead of isolated by forming the membrane contact sites. Membrane contact, mediated by specific protein-protein interaction, pulls opposing organelles together and creates the hybrid place for cholesterol transfer and further signaling. The membrane contact-dependent cholesterol transfer, together with the vesicular transport, maintains cholesterol homeostasis and has intimate implications in a growing list of diseases, including vascular aging-related diseases. Here, we summarized the latest advances regarding cholesterol homeostasis by highlighting the membrane contact-based regulatory mechanism. We also describe the downstream signaling under cholesterol homeostasis perturbations, prominently in cholesterol-rich conditions, stimulating age-dependent organelle dysfunction and vascular aging. Finally, we discuss potential cholesterol-targeting strategies for therapists regarding vascular aging-related diseases. This article is categorized under: Cardiovascular Diseases > Molecular and Cellular Physiology.

Patterns and implications of artery remodeling based on high-resolution vessel wall imaging in symptomatic severe basilar artery stenosis.

Background: Knowledge regarding the influence of arterial remodeling patterns on plaque characteristics and postoperative outcomes in patients with severe basilar artery (BA) stenosis after endovascular treatment is lacking. The purpose of this study was to investigate plaque characteristics, remodeling patterns, and perioperative outcomes in patients with severe BA stenosis. Methods: A prospective cohort study was conducted on symptomatic patients with severe BA stenosis who underwent high-resolution MRI before endovascular treatment. The remodeling index, plaque burden, and area of stenosis were evaluated for each plaque. Based on the remodeling index calculated by high-resolution MRI, remodeling patterns were classified as negative remodeling (NR) or non-negative remodeling (non-NR). Baseline demographics, plaque features, and treatment characteristics were compared between the NR and non-NR groups. Correlations between the remodeling index, plaque burden, and stenosis severity were also examined. Results: In total, 140 eligible patients were included and analyzed, including 91 non-NR cases and 49 NR cases. A strong correlation existed between the remodeling index and plaque burden (r=0.973, P<0.001), and a marginal correlation was observed between the remodeling index and degree of stenosis by area (r=-0.261, P=0.0019). There was no significant difference between the two groups in terms of perioperative complications related to ischemic events and new ischemic cerebral lesions (NICLs). Conclusions: Under the current submaximal angioplasty and/or stenting treatment paradigms, remodeling patterns may not influence the outcome of ischemic events and NICLs. However, the remodeling index is strongly associated with plaque burden, which may provide insight for the evaluation of severe BA stenosis. Further research is warranted.

Endovascular therapy versus medical treatment for symptomatic intracranial artery stenosis.

BACKGROUND: Intracranial artery stenosis (ICAS) is an arterial narrowing in the brain that can cause stroke. Endovascular therapy (ET) and conventional medical treatment (CMT) may prevent recurrent ischaemic stroke caused by ICAS. However, there is no consensus on the best treatment for people with ICAS. OBJECTIVES: To evaluate the safety and efficacy of endovascular therapy plus conventional medical treatment compared with conventional medical treatment alone for the management of symptomatic intracranial artery stenosis. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register, CENTRAL, MEDLINE, Embase, four other databases, and three trials registries on 16 August 2022. We contacted study authors and researchers when we required additional information. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing ET plus CMT with CMT alone for the treatment of symptomatic ICAS. ET modalities included angioplasty alone, balloon-mounted stent, and angioplasty followed by placement of a self-expanding stent. CMT included antiplatelet therapy in addition to control of risk factors such as hypertension, hyperlipidaemia, and diabetes. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the records to select eligible RCTs, then extracted data from them. We resolved any disagreements through discussion, reaching consensus decisions among the full team. We assessed risk of bias and applied the GRADE approach to assess the certainty of the evidence. The primary outcome was death by any cause or non-fatal stroke of any type within three months of randomisation. Secondary outcomes included all-cause death or non-fatal stroke of any type occurring more than three months after randomisation, ipsilateral stroke, transient ischaemic attack, ischaemic stroke, haemorrhagic stroke, death, restenosis, dependency, and health-related quality of life. MAIN RESULTS: We included four RCTs with 989 participants who had symptomatic ICAS, with an age range of 18 to 85 years. We identified two ongoing RTCs. All trials had high risk of performance bias, as it was impossible to blind participants and personnel to the intervention. Three trials were terminated early. One trial was at high risk of attrition bias because of substantial loss to follow-up after one year and a high proportion of participants transferring from ET to CMT. The certainty of evidence ranged from low to moderate; we downgraded for imprecision. Compared to CMT alone, ET plus CMT probably increases the risk of short-term death or stroke (risk ratio (RR) 2.93, 95% confidence interval (CI) 1.81 to 4.75; 4 RCTs, 989 participants; moderate certainty), short-term ipsilateral stroke (RR 3.26, 95% CI 1.94 to 5.48; 4 RCTs, 989 participants; moderate certainty), short-term ischaemic stroke (RR 2.24, 95% CI 1.30 to 3.87; 4 RCTs, 989 participants; moderate certainty), and long-term death or stroke (RR 1.49, 95% CI 1.12 to 1.99; 4 RCTs, 970 participants; moderate certainty). Compared to CMT alone, ET plus CMT may increase the risk of short-term haemorrhagic stroke (RR 13.49, 95% CI 2.59 to 70.15; 4 RCTs, 989 participants; low certainty), short-term death (RR 5.43, 95% CI 1.21 to 24.40; 4 RCTs, 989 participants; low certainty), and long-term haemorrhagic stroke (RR 7.81, 95% CI 1.43 to 42.59; 3 RCTs, 879 participants; low certainty). It is unclear if ET plus CMT compared with CMT alone has an effect on the risk of short-term transient ischaemic attack (RR 0.79, 95% CI 0.30 to 2.07; 3 RCTs, 344 participants; moderate certainty), long-term transient ischaemic attack (RR 1.05, 95% CI 0.50 to 2.19; 3 RCTs, 335 participants; moderate certainty), long-term ipsilateral stroke (RR 1.78, 95% CI 1.00 to 3.17; 4 RCTs, 970 participants; moderate certainty), long-term ischaemic stroke (RR 1.56, 95% CI 0.77 to 3.16; 4 RCTs, 970 participants; moderate certainty), long-term death (RR 1.61, 95% CI 0.77 to 3.38; 4 RCTs, 951 participants; moderate certainty), and long-term dependency (RR 1.51, 95% CI 0.93 to 2.45; 4 RCTs, 947 participants; moderate certainty). No subgroup analyses significantly modified the effect of ET plus CMT versus CMT alone. The trials included no data on restenosis or health-related quality of life. AUTHORS' CONCLUSIONS: This review provides moderate-certainty evidence that ET plus CMT compared with CMT alone increases the risk of short-term stroke and death in people with recent symptomatic severe ICAS. This effect was still apparent at long-term follow-up but appeared to be due to the early risks of ET; therefore, there may be no clear difference between the interventions in terms of their effects on long-term stroke and death. The impact of delayed ET intervention (more than three weeks after a qualifying event) warrants further study.

Mechanism of oxidized phospholipid-related inflammatory response in vascular ageing.

Vascular ageing is an important factor in the morbidity and mortality of the elderly. Atherosclerosis is a characteristic disease of vascular ageing, which is closely related to the enhancement of vascular inflammation. Phospholipid oxidation products are important factors in inducing cellular inflammation. Through interactions with vascular cells and immune cells, they regulate intracellular signaling pathways, activate the expression of various cytokines, and affect cell behavior, such as metabolic level, proliferation, apoptosis, etc. Intervention in lipid metabolism and anti-inflammation are the two key pathways of drugs for the treatment of atherosclerosis. This review aims to sort out the signaling pathway of oxidized phospholipids-induced inflammatory factors in vascular cells and immune cells and the mechanism leading to changes in cell behavior, and summarize the therapeutic targets in the inflammatory signaling pathway for the development of atherosclerosis drugs.

Optical Coherence Tomography in Cerebrovascular Disease: Open up New Horizons.

Optical coherence tomography (OCT), based on the backscattering or reflection of near-infrared light, enables an ultra-high resolution of up to 10 µm. The successful application of OCT in coronary artery diseases has sparked increasing interest in its implementation in cerebrovascular diseases. OCT has shown promising potential in the atherosclerotic plaque structure characterization, plaque rupture risk stratification, pre-stenting and post-stenting evaluation, and long-term follow-up in extracranial and intracranial atherosclerotic stenosis (ICAS). In hemorrhagic cerebrovascular diseases, OCT plays an important role in the structure evaluation, rupture risk stratification, and healing and occlusion evaluation following initial treatment in intracranial aneurysms (IAs). In this study, we summarized the applications of OCT in the diagnosis, treatment, and follow-up of cerebrovascular diseases, especially in ICAS and IAs. The current limitations and future directions of OCT in the endovascular treatment of cerebrovascular diseases were also discussed.