Abstract 110: Carotid Plaque Instability is Associated with an Increase in the Serum Ratio of circularRNA-284 to microRNA-221

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Hernan Bazan ◽  
Ashton Brooks ◽  
Daniel Lightell ◽  
T. Cooper Woods
Keyword(s):  
Ischemic Stroke ◽  
Sensitivity And Specificity ◽  
Carotid Plaque ◽  
Plaque Rupture ◽  
Serum Levels ◽  
Circular Rna ◽  
Cerebrovascular Event ◽  
Asymptomatic Group ◽  
Plaque Instability ◽  
Non Coding Rnas

Introduction: Atherosclerotic cap thinning and plaque instability occur as a result of a decrease in vascular smooth muscle cell proliferation, which is partly regulated by alterations in the expression of non-coding RNAs in the arterial wall. We recently reported that miR-221 expression in the carotid plaque shoulder is reduced immediately following a carotid-related ischemic cerebrovascular event and returns to normal levels after seven days. We hypothesized that changes in the expression of non-coding RNAs within carotid plaques are reflected in the serum of asymptomatic and acutely symptomatic patients with carotid disease. Methods: Serum levels of microRNA (miR) -221 and a circular RNA with potential binding sites for miR-221 (circR-284), were measured using real-time polymerase chain reaction in 41 patients undergoing carotid endarterectomy. Patients were grouped into those who were asymptomatic and those with an acute ischemic cerebrovascular event within the previous 5 days (urgent). Results: miR-221 was significantly lower (0.25 ± 0.11 vs. 1.00 ± 0.31, p = 0.01) while circR-284 was significantly elevated (2.96 ± 1.16 vs. 1.00 ± 0.37, p = 0.06) in the serum of the urgent compared to the asymptomatic group. Serum levels of these RNAs alone did not exhibit favorable sensitivity and specificity for use as a biomarker indicative of carotid-related ischemic stroke. The ratio of serum circR-284:miR-221, however, was significantly elevated in the urgent group [11.7 ± 0.48 vs. 1.0 ± 0.6, p = 0.0002 (Figure, A)]. Furthermore, receiver operator curve analysis of circR-284:miR-221 ratio demonstrated favorable sensitivity and specificity (Figure, B) for detecting carotid plaque rupture and ischemic stroke. Conclusions: Increases in the ratio of serum circR-284:miR-221 has potential as a diagnostic biomarker of carotid-related ischemic stroke. This data also supports the use and development of functionally related pairs of circulating non-coding RNAs as biomarkers.

scholarly journals In Vivo Serial MRI-Based Models and Statistical Methods to Quantify Sensitivity and Specificity of Mechanical Predictors for Carotid Plaque Rupture: Location and Beyond

2011 ◽  
Vol 133 (6) ◽  
Author(s):  
Zheyang Wu ◽  
Chun Yang ◽  
Dalin Tang
Keyword(s):  
Sensitivity And Specificity ◽  
Statistical Models ◽  
Carotid Plaque ◽  
Large Scale ◽  
Plaque Rupture ◽  
Maximum Shear Stress ◽  
Risk Indicators ◽  
Serial Mri

It has been hypothesized that mechanical risk factors may be used to predict future atherosclerotic plaque rupture. Truly predictive methods for plaque rupture and methods to identify the best predictor(s) from all the candidates are lacking in the literature. A novel combination of computational and statistical models based on serial magnetic resonance imaging (MRI) was introduced to quantify sensitivity and specificity of mechanical predictors to identify the best candidate for plaque rupture site prediction. Serial in vivo MRI data of carotid plaque from one patient was acquired with follow-up scan showing ulceration. 3D computational fluid-structure interaction (FSI) models using both baseline and follow-up data were constructed and plaque wall stress (PWS) and strain (PWSn) and flow maximum shear stress (FSS) were extracted from all 600 matched nodal points (100 points per matched slice, baseline matching follow-up) on the lumen surface for analysis. Each of the 600 points was marked “ulcer” or “nonulcer” using follow-up scan. Predictive statistical models for each of the seven combinations of PWS, PWSn, and FSS were trained using the follow-up data and applied to the baseline data to assess their sensitivity and specificity using the 600 data points for ulcer predictions. Sensitivity of prediction is defined as the proportion of the true positive outcomes that are predicted to be positive. Specificity of prediction is defined as the proportion of the true negative outcomes that are correctly predicted to be negative. Using probability 0.3 as a threshold to infer ulcer occurrence at the prediction stage, the combination of PWS and PWSn provided the best predictive accuracy with (sensitivity, specificity) = (0.97, 0.958). Sensitivity and specificity given by PWS, PWSn, and FSS individually were (0.788, 0.968), (0.515, 0.968), and (0.758, 0.928), respectively. The proposed computational-statistical process provides a novel method and a framework to assess the sensitivity and specificity of various risk indicators and offers the potential to identify the optimized predictor for plaque rupture using serial MRI with follow-up scan showing ulceration as the gold standard for method validation. While serial MRI data with actual rupture are hard to acquire, this single-case study suggests that combination of multiple predictors may provide potential improvement to existing plaque assessment schemes. With large-scale patient studies, this predictive modeling process may provide more solid ground for rupture predictor selection strategies and methods for image-based plaque vulnerability assessment.

Abstract TMP60: A Prospective Study of Serum Metabolites and Risk of Ischemic Stroke

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Bing Yu ◽  
Rebecca F Gottesman ◽  
Thomas H Mosley ◽  
Eric Boerwinkle ◽  
Myriam Fornage
Keyword(s):  
Ischemic Stroke ◽  
Multiple Testing ◽  
Dicarboxylic Acids ◽  
Serum Levels ◽  
Cardioembolic Stroke ◽  
Serum Metabolites ◽  
Atherosclerosis Risk In Communities ◽  
Plaque Instability ◽  
Baseline Examination ◽  
Long Chain

Ischemic stroke (IS) is a leading cause of death and disability worldwide. Identification of novel blood-based biomarkers that aid in the early identification of high-risk patients and in the classification and diagnosis of IS may facilitate patient management and improve the understanding of stroke etiologies. In 3,904 men and women from the Atherosclerosis Risk In Communities study, we investigated the association of 245 serum metabolites measured at the baseline examination via untargeted metabolomic profiling with incident IS. First IS events occurring between the baseline examination and December 31, 2012 were ascertained by annual telephone interview and hospital surveillance, followed case adjudication by a committee of experienced physicians. Cox proportional hazard models were used to estimate the hazard ratio (HR) for IS per standard deviation of the standardized serum level of each metabolites, adjusting for baseline age, sex, race and field center (model 1); and additionally for diabetes, hypertension, current smoking, body mass index, and estimated glomerular filtration rate (model 2). Over a median follow-up of 23 years, 306 incident IS were observed. After correcting for multiple testing, we identified 12 serum metabolites associated with IS in model 1 (P<0.0002). Two long-chain dicarboxylic acids, tetradecanedioate and hexadecanedioate, remained significantly associated with IS in model 2 (HR [95%CI] = 1.13 [1.08-1.18] and 1.15 [1.09-1.20], respectively). Serum levels of these two metabolites were strongly correlated ( r 2 =0.88). Analyses by IS subtypes suggested that this association is specific to cardioembolic stroke. In summary, we identified two long-chain dicarboxylic acids associated with cardioembolic stroke independently of known risk factors. These compounds are metabolic products of fatty acids produced by ω-oxidation, a normally minor catabolic pathway, which becomes more prominent when β-oxidation is defective. These results are consistent with recent metabolomics studies of carotid plaque tissue implicating β-oxidation dysfunction in plaque instability. Further studies are needed to confirm the relationships uncovered here and shed light on possible mechanisms for these associations.

Abstract WP434: Serum MicroRNA Panel as a Candidate Biomarker of Carotid Plaque Rupture and Stroke

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Aaron M Brug ◽  
Sullivan Smith ◽  
Ashton J Brooks ◽  
Daniel J Lightell ◽  
Hernan A Bazan ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Carotid Plaque ◽  
Plaque Rupture ◽  
Rna Seq ◽  
Circulating Mirnas ◽  
Ischemic Event ◽  
Biomarker Panel ◽  
Serum Microrna ◽  
Asymptomatic Patients

Introduction: Atherosclerotic plaque vulnerability and subsequent rupture are mediated by alterations in miRNAs that promote inflammation and fibrous cap thinning, leading to an acute ischemic stroke. Release of these miRNAs from the plaque tissue into the circulation may provide a miRNA profile that serves as a biomarker panel to identify the vulnerable patient at greatest risk of plaque rupture. Methods: Using RNA-Seq methodology, serum microRNA content was compared between patients undergoing carotid endarterectomy (CEA) for 2 distinct clinical phenotypes: patients without previous neurological events but high-grade carotid stenosis (asymptomatic, n=5), and patients with an acute neurological event within 5 days of the CEA (urgent, n=7). Differential expression of miRNAs was performed using the R statistical software and the DESeq2 package. Results: A total of 695 miRNAs detected in sera on RNA-Seq, 54 were significantly different between the asymptomatic and urgent groups. 22 miRNAs were decreased and 32 were increased in the serum of urgent patient’s compared to asymptomatic patients (adjusted p-value < 0.05). Of these miRNAs, miR-21, miR-486, miR-23b, miR-27b, and let-7f were selected for validation as a biomarker panel based on a prior association with vascular disease. A pilot study (n= 6 asymptomatic and 6 urgent) measuring these miRNAs demonstrated that while miR-486 was detectable in all samples and exhibited a 9.4-fold increase (p < 0.10) in the urgent group, the other miRNAs were only detected in a fraction of the samples (33 - 75%). Furthermore, miR-486 alone did not exhibit characteristics of a good indicator of ischemic stroke. A score normalizing the expression of miR-486 to the mean expression of the detectable miRNAs from this panel, did yield a promising C-statistic (0.97 ± 0.08, p < 0.01), suggesting its potential as an indicator of an acute ischemic event. Conclusion: Carotid plaque rupture resulting in an acute ischemic event is associated with alterations in the profile of circulating miRNAs and these may be useful as biomarkers of ischemic stroke. Our pilot data suggest that the development of a score based on a panel of circulating miRNAs may allow for the diagnosis of patients experiencing plaque rupture and an acute ischemic stroke.

scholarly journals Association between carotid plaque vulnerability and high mobility group box-1 serum levels in a diabetic population

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Federico Biscetti ◽  
Giovanni Tinelli ◽  
Maria Margherita Rando ◽  
Elisabetta Nardella ◽  
Andrea Leonardo Cecchini ◽  
...  
Keyword(s):  
Carotid Plaque ◽  
Internal Carotid ◽  
High Mobility ◽  
Serum Levels ◽  
Internal Carotid Artery Stenosis ◽  
Diabetic Patients ◽  
Plaque Vulnerability ◽  
Unstable Plaque ◽  
Plaque Instability ◽  
Diabetic Population

Abstract Background Carotid atherosclerosis represents one of the complications of diabetes mellitus. In particular, plaque instability contributes to disease progression and stroke incidence. High mobility group box-1 (HMGB1) is a nuclear protein involved in promotion and progression of atherosclerosis and cardiovascular diseases. The aim of this study was to analyze the relationship between HMGB1 serum levels, main inflammatory cytokines, the presence of internal carotid stenosis and unstable plaque in a diabetic population. Research design and methods We studied 873 diabetic patients, including 347 patients with internal carotid artery stenosis (ICAS) who underwent carotid endarterectomy and 526 diabetic patients without internal carotid artery stenosis (WICAS). At baseline, HMGB1 and the main inflammatory cytokines serum levels were evaluated. For ICAS patients, the histological features of carotid plaque were also collected to differentiate them in patients with stable or unstable atherosclerotic lesions. Results We found that HMGB1 serum levels, osteoprotegerin, high-sensitivity C-reactive protein, tumor necrosis factor-alpha and interleukin-6, were significantly higher in diabetic ICAS patients compared to diabetic WICAS patients. Among ICAS patients, individuals with unstable plaque had higher levels of these cytokines, compared to patients with stable plaque. A multivariable stepwise logistic regression analysis showed that HMGB1 and osteoprotegerin remained independently associated with unstable plaque in ICAS patients. Conclusions The present study demonstrated that HMGB1 is an independent risk factor for carotid plaque vulnerability in an Italian population with diabetes mellitus, representing a promising biomarker of carotid plaque instability and a possible molecular target to treat unstable carotid plaques and to prevent stroke.

scholarly journals Association between Circulatory and Plaque Resistin Levels with Carotid Plaque Instability and Ischemic Stroke Events

2018 ◽  
Vol 21 (6) ◽  
pp. E448-E463
Author(s):  
Ivana Jurin ◽  
Frane Paić ◽  
Stela Bulimbašić ◽  
Igor Rudež ◽  
Lovorka Đerek ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Regression Analysis ◽  
Ischemic Stroke ◽  
Carotid Artery ◽  
Carotid Artery Stenosis ◽  
Carotid Plaque ◽  
High Grade ◽  
Plaque Vulnerability ◽  
Histological Features ◽  
Plaque Instability

ses of ischemic stroke. The risk of ischemic stroke increases with the degree of carotid stenosis and plaque vulnerability. The aim of this study was to investigate the association of circulating and plaque resistin levels with plaque vulnerability and ischemic stroke events in patients with moderate- to high-grade carotid artery stenosis. Methods: 40 patients with ischemic stroke events and 38 neurologically asymptomatic patients scheduled for carotid endarterectomy were recruited for this study. Fasting blood samples for laboratory analysis were collected preoperatively and serum resistin levels were measured by enzyme-linked immunosorbent assays. Carotid endarterectomy specimens were analyzed according to the gold-standard procedure of histological classification. Plaque resistin expression was determined by standard immunohistochemical procedure. Results: Serum resistin levels and resistin plaque expression were found to be significantly higher in subjects with unstable carotid plaque (P < .001) while significantly higher serum resistin levels were also present in patients with ischemic stroke events (P < .001). In univariate stepwise logistic regression analysis, higher serum resistin levels were significantly associated with plaque instability (OR 2.223, 95% CI 1.488-3.320, P < .0001) and ischemic stroke events (OR 1.237, 95% CI 1.079-1.420, P = .002). There was also a significant association between higher serum and plaque resistin expression (OR 1.663, 95% CI1.332-2.077, P < .0001). These associations remained significant in all models of multivariate logistic regression analysis. High serum and plaque resistin levels were also significantly associated with specific histological features of plaque instability. Conclusion: The results suggests that serum resistin levels may be used as a potential biomarker of plaque vulnerability and ischemic stroke events in patients with moderate- to high-grade carotid artery stenosis and highlight the possible relationship that plaque resistin expression has with histological features of plaque vulnerability.

scholarly journals COVID-19 and Risk of Acute Ischemic Stroke and Acute Lung Injury in Patients With Type II Diabetes Mellitus: The Anti-inflammatory Role of Metformin

2021 ◽  
Vol 8 ◽  
Author(s):  
Hayder M. Al-kuraishy ◽  
Ali I. Al-Gareeb ◽  
M. Alblihed ◽  
Natália Cruz-Martins ◽  
Gaber El-Saber Batiha
Keyword(s):  
Diabetes Mellitus ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Serum Levels ◽  
Type Ii Diabetes Mellitus ◽  
Diabetic Patients ◽  
Metformin Therapy ◽  
Plaque Instability ◽  
Radiological Data ◽  
Metformin Group

Background: Coronavirus disease 19 (COVID-19) is regarded as an independent risk factor for acute ischemic stroke (AIS) due to the induction of endothelial dysfunction, coagulopathy, cytokine storm, and plaque instability.Method: In this retrospective cohort study, a total of 42 COVID-19 patients with type 2 diabetes mellitus (T2DM) who presented with AIS within 1 week of displaying COVID-19 symptoms were recruited. According to the current anti-DM pharmacotherapy, patients were divided into two groups: a Metformin group of T2DM patients with COVID-19 and AIS on metformin therapy (850 mg, 3 times daily (n = 22), and a Non-metformin group of T2DM patients with COVID-19 and AIS under another anti-DM pharmacotherapy like glibenclamide and pioglitazone (n = 20). Anthropometric, biochemical, and radiological data were evaluated.Results: Ferritin serum level was lower in metformin-treated patients compared to non-metformin treated patients (365.93 ± 17.41 vs. 475.92 ± 22.78 ng/mL, p = 0.0001). CRP, LDH, and D-dimer serum levels were also lowered in metformin-treated patients compared to non-metformin treated patients (p = 0.0001). In addition, lung CT scan scores of COVID-19 patients was 30.62 ± 10.64 for metformin and 36.31 ± 5.03 for non-metformin treated patients.Conclusion: Metformin therapy in T2DM patients was linked to a lower risk of AIS during COVID-19. Further studies are needed to observe the link between AIS in COVID-19 diabetic patients and metformin therapy.

scholarly journals Clinical worsening despite intravenous thrombolysis in acute ischemic stroke secondary to carotid plaque rupture

2020 ◽  
Vol 49 (3) ◽  
pp. 497-498
Author(s):  
Fabrizio Sallustio ◽  
Domenico Samà ◽  
Alfredo Paolo Mascolo ◽  
Federico Marrama ◽  
Mauro Fresilli ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Carotid Plaque ◽  
Plaque Rupture ◽  
Intravenous Thrombolysis ◽  
Clinical Worsening

scholarly journals Omentin-1 is Associated with Carotid Plaque Instability among Ischemic Stroke Patients

2018 ◽  
Vol 25 (6) ◽  
pp. 505-511 ◽  
Author(s):  
Tian Xu ◽  
Peng Zuo ◽  
Lin Cao ◽  
Zhiwei Gao ◽  
Kaifu Ke
Keyword(s):  
Ischemic Stroke ◽  
Carotid Plaque ◽  
Stroke Patients ◽  
Plaque Instability

MicroRNAs as sentinels and protagonists of carotid artery thromboembolism

2020 ◽  
Vol 134 (2) ◽  
pp. 169-192
Author(s):  
Sneha Raju ◽  
Jason E. Fish ◽  
Kathryn L. Howe
Keyword(s):  
Carotid Artery ◽  
Atherosclerotic Plaque ◽  
Carotid Plaque ◽  
Molecular Mechanisms ◽  
Clinical Decision Making ◽  
Plaque Rupture ◽  
Cell Communication ◽  
Clinical Decision ◽  
Plaque Instability

Abstract Stroke is the leading cause of serious disability in the world and a large number of ischemic strokes are due to thromboembolism from unstable carotid artery atherosclerotic plaque. As it is difficult to predict plaque rupture and surgical treatment of asymptomatic disease carries a risk of stroke, carotid disease continues to present major challenges with regard to clinical decision-making and revascularization. There is therefore an imminent need to better understand the molecular mechanisms governing plaque instability and rupture, as this would allow for the development of biomarkers to identify at-risk asymptomatic carotid plaque prior to disease progression and stroke. Further, it would aid in creation of therapeutics to stabilize carotid plaque. MicroRNAs (miRNAs) have been implicated as key protagonists in various stages of atherosclerotic plaque initiation, development and rupture. Notably, they appear to play a crucial role in carotid artery thromboembolism. As the molecular pathways governing the role of miRNAs are being uncovered, we are learning that their involvement is complex, tissue- and stage-specific, and highly selective. Notably, miRNAs can be packaged and secreted in extracellular vesicles (EVs), where they participate in cell–cell communication. The measurement of EV-encapsulated miRNAs in the circulation may inform disease mechanisms occurring in the plaque itself, and therefore may serve as sentinels of unstable plaque as well as therapeutic targets.

Abstract WP136: Enhanced Carotid Plaque on Contrast-enhanced Ultrasound is Asociated with Plaque Instability and Symptomatic Patients

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Noriko Matsumoto ◽  
Kazumi Kimura ◽  
Masaaki Uno ◽  
Kenichirou Sakai ◽  
Yoshito Sadahira ◽  
...  
Keyword(s):  
Neurological Symptom ◽  
Carotid Plaque ◽  
Plaque Rupture ◽  
Surrogate Marker ◽  
Intraplaque Hemorrhage ◽  
Contrast Enhanced Ultrasound ◽  
Plaque Instability ◽  
Linear Pattern ◽  
Contrast Enhanced ◽  
Histopathologic Findings

Background: Presence of neovascularization in plaque was reported as a reliable maker of plaque vulnerability. Contrast-enhanced ultrasound (CEUS) can demonstrate the presence of intraplaque neovascularization. The aim of the present study was to investigate the neurological symptom and histopathologic findings of enhanced carotid plaque using CEUS. Methods: We studied consecutive 30 patients (27 men, age 68.2 ± 7.6 years) who underwent carotid endarterectomy. Enhanced plaque (enhanced group) was classified into two subgroups: a spotty pattern as moving bright spots within plaque (spotty subgroup, Figure A); and a linear pattern, where enhanced lesions appeared as a line from intima into plaque (linear subgroup, Figure B).Sonazoid, perflurobutane microbubbles, was used as the contrast agent. We investigated the association between the neurological symptom, CEUS findings and histopathologic findings. Results: CEUS revealed enhanced plaque in 22 (73.3%) of 30 patients. 10 patients were spotty subgroup, and 12 patients were linear subgroup. Symptomatic patients were more frequent in enhanced group than non-enhanced group (82.6% vs. 50%, p=0.037).The amount of neovascularization was larger in enhanced group than in non-enhanced group (6.3±4.2/2.5mm 2 vs. 1.5±1.6/2.5 mm 2 , P=0.001, Figure C). Furthermore, the enhanced group had more macrophage aggregation (11.1±12.5% vs. 4.2±1.5%, P=0.001) and intraplaque hemorrhage (20.2±15.9% vs. 9.4±12.2%, P=0.031) compared with the non-enhanced group. 11 of the linear subgroup (91.7%) had fibrous cap rupture, but this was observed in only 20% of those with a spotty subgroup (P=0.001, Figure D). Symptom and other histopathological findings were not different between the two subgroups. Conclusions: Enhanced plaque on CEUS indicates vulnerable plaque. A linear pattern of enhanced plaque indicates plaque rupture. Enhanced plaque on CEUS should become a new surrogate marker of vulnerable carotid plaque and patients.

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