Vulnerable Plaque, Characteristics, Detection, and Potential Therapies.
Ontology highlight
ABSTRACT:
SUBMITTER: Hafiane A
PROVIDER: S-EPMC6787609 | biostudies-literature | 2019 Jul
REPOSITORIES: biostudies-literature
Publications
Vulnerable Plaque, Characteristics, Detection, and Potential Therapies.
Journal of cardiovascular development and disease 20190727 3
Plaque development and rupture are hallmarks of atherosclerotic vascular disease. Despite current therapeutic developments, there is an unmet necessity in the prevention of atherosclerotic vascular disease. It remains a challenge to determine at an early stage if atherosclerotic plaque will become unstable and vulnerable. The arrival of molecular imaging is receiving more attention, considering it allows for a better understanding of the biology of human plaque and vulnerabilities. Various plaqu ...[more]
Similar Datasets
Project description:Background This cross-sectional study sought to explore the possible risk factors assessed with magnetic resonance (MR) vessel wall imaging for hemodynamic instability (HI) during carotid artery stenting (CAS). Methods Patients with carotid stenosis who were referred for CAS from January 2017 to December 2019 were recruited and underwent carotid MR vessel wall imaging. The vulnerable plaque features, including lipid-rich necrotic core (LRNC), intraplaque hemorrhage (IPH), fibrous cap rupture, and plaque morphology, were evaluated. The HI was defined as a drop of systolic blood pressure (SBP) of ≥30 mmHg or the lowest SBP measurement of <90 mmHg after stent implantation. The carotid plaque characteristics were compared between the HI and non-HI groups. The association between carotid plaque characteristics and HI was analyzed. Results A total of 56 participants (mean age 68.7±8.3 years; 44 males) were recruited. Patients in the HI group (n=26, 46%) had a significantly greater wall area [median 43.2 (IQR, 34.9–50.5) vs. 35.9 (IQR, 32.3–39.4) mm2; P=0.008], total vessel area (79.7±17.2 vs. 69.9±17.3 mm2; P=0.03), prevalence of IPH (62% vs. 30%; P=0.02), prevalence of vulnerable plaque (77% vs. 43%; P=0.01), and volume of LRNC [median 344.7 (IQR, 155.1–665.7) vs. 103.1 (IQR, 53.9–162.9) mm3; P=0.001] in carotid plaque compared to those in non-HI group (n=30, 54%). Carotid LRNC volume (OR =1.005, 95% CI: 1.001–1.009; P=0.01) and presence of vulnerable plaque (OR =4.038, 95% CI: 0.955–17.070; P=0.06) were significantly and marginally associated with HI, respectively. Conclusions Carotid plaque burden and vulnerable plaque features, particularly a larger LRNC, might be effective predictors for HI during the CAS procedure.
| S-EPMC10240037 | biostudies-literature
Project description:Carotid atherosclerotic plaque rupture and thrombosis are independent risk factors for acute ischemic cerebrovascular disease. Timely identification of vulnerable plaque can help prevent stroke and provide evidence for clinical treatment. Advanced invasive and non-invasive imaging modalities such as computed tomography, magnetic resonance imaging, intravascular ultrasound, optical coherence tomography, and near-infrared spectroscopy can be employed to image and classify carotid atherosclerotic plaques to provide clinically relevant predictors used for patient risk stratification. This study compares existing clinical imaging methods, and the advantages and limitations of different imaging techniques for identifying vulnerable carotid plaque are reviewed to effectively prevent and treat cerebrovascular diseases.
| S-EPMC9515377 | biostudies-literature
Project description:Not only the degree of luminal narrowing but also the plaque morphology and composition play an important role in risk stratification of carotid atherosclerotic lesions. During the last few years, carotid contrast-enhanced ultrasound (CEUS) has emerged as a valuable imaging tool to assess such vulnerable carotid plaques. This review article discussed the use of CEUS for the detection of carotid plaque irregularities and ulcerations as well as the quantification of intraplaque neovascularization and its correlation with histology and inflammatory biomarkers. Apart from evaluating for markers of vulnerable carotid plaques, CEUS enhancement is directly associated with past cerebrovascular events. More importantly, preliminary evidence has shown that CEUS could be used to predict future cerebrovascular and cardiovascular events. Despite the progress in CEUS imaging for carotid atherosclerotic disease, past studies still suffer from the retrospective nature, small sample size, and a lack of matched, well controlled prospective studies. In the future, large multi-center prospective studies addressing the relationship between CEUS findings and patient clinical outcomes in carotid atherosclerotic disease are warranted.
| S-EPMC7487408 | biostudies-literature
Project description:Plaque rupture and subsequent thrombus formation is responsible for the majority of clinical complications of atherosclerosis and nonetheless our understanding of what underlies plaque vulnerability and rupture is still sparse and mostly deductively based on animal models and in vitro studies. We adopted five different -omics platforms to compare ruptured atherosclerotic and advanced-stable tissue within the same carotid plaque specimen from 24 carotid endarterectomy patients. Segments designated as stable feature either a fibrous cap atheroma or pathological intimal thickening. Segments designated as ruptured include a thrombus and/or presented intraplaque hemorrhage. For the present study only those samples were selected for further analysis that were flanked by two segments of identical classification, be it stable (S) or ruptured (R); and were derived from CEA specimen that contained plaque segments of both classifications.
2014-05-17 | E-MTAB-2055 | biostudies-arrayexpress
Project description:Current risk stratification for stroke is still based upon percentage of carotid stenosis, despite this measure providing minimal patient-specific information on the actual risk of stroke for both symptomatic individuals without significant carotid artery stenosis as well as asymptomatic carotid stenosis patients. A continuously growing body of literature suggests that the identification and quantification of certain carotid plaque characteristics, including lipid-rich necrotic core (LRNC), thin/ruptured fibrous cap (FC), and intraplaque hemorrhage (IPH), provide a superior means of predicting future stroke. These characteristics are identifiable via magnetic resonance imaging (MRI), with most features detectable using commercially available coils and sequences utilized in routine clinical practice in as little as 4 minutes. The presence of LRNC, a thin/ruptured FC, and IPH is associated with increased risk of future stroke or TIA. Plaques with greater than 40% LRNC with a thin overlying FC are prone to rupture. LRNC is T2 hypointense and lacks enhancement on contrast enhanced T1 weighted images. Increasing LRNC size is associated with the development of new ulceration, FC rupture, increasing plaque burden, as well as fatal and nonfatal myocardial infarction, ischemic stroke, hospitalization for acute coronary syndrome (ACS), and symptom-driven revascularization, allowing for MR biomarkers of carotid plaque vulnerability to be utilized for systemic athero-thrombotic risk and not just stroke/TIA. LRNC typically shrinks with appropriate statin therapy, with PCSK9 inhibitors possibly playing a role in patients with inadequate response. Carotid plaques with IPH represent a more advanced stage of atherosclerotic disease. IPH is detectable with field strengths of both 3.0 T and 1.5 T and will demonstrate high signal on all T1 weighted imaging sequences. The presence of IPH increases the risk of future stroke in both symptomatic and asymptomatic patients, with multivariate analysis identifying IPH as a predictor of stroke, independent of percent stenosis, with no statistical difference in men vs. women, demonstrating that simple carotid stenosis measurements and traditional risk factor analysis may be inadequate in identifying patients at the highest risk for adverse cerebrovascular events. In the evaluation for recurrent stroke in recently symptomatic patients with >50% carotid stenosis, the estimated annual stroke risk is 23.2% in IPH+ patients and only 0.6% in IPH- patients, calling into question the current risk-benefit assessment for CEA. Additionally, a recent meta-analysis suggests that IPH+ plaque in patients with symptomatic <50% stenosis may be the etiology of embolic strokes previously labeled as "embolic stroke of undetermined source" (ESUS). There are no prospective drug trials testing the ability of any lipid-lowering therapies to decrease IPH and/or total plaque volume (TPV). Given the continuously increasing evidence of IPH as a significant predictor of carotid plaque progression and future adverse vascular events, trials aimed at targeted therapy for IPH represents a significant need.
| S-EPMC7487401 | biostudies-literature
Project description:Early detection and treatment of rupture-prone vulnerable atherosclerotic plaques is critical to reducing patient mortality associated with cardiovascular disease. The combination of reflectance, fluorescence, and Raman spectroscopy-termed multimodal spectroscopy (MMS)-provides detailed biochemical information about tissue and can detect vulnerable plaque features: thin fibrous cap (TFC), necrotic core (NC), superficial foam cells (SFC), and thrombus. Ex vivo MMS spectra are collected from 12 patients that underwent carotid endarterectomy or femoral bypass surgery. Data are collected by means of a unitary MMS optical fiber probe and a portable clinical instrument. Blinded histopathological analysis is used to assess the vulnerability of each spectrally evaluated artery lesion. Modeling of the ex vivo MMS spectra produce objective parameters that correlate with the presence of vulnerable plaque features: TFC with fluorescence parameters indicative of collagen presence; NC∕SFC with a combination of diffuse reflectance β-carotene∕ceroid absorption and the Raman spectral signature of lipids; and thrombus with its Raman signature. Using these parameters, suspected vulnerable plaques can be detected with a sensitivity of 96% and specificity of 72%. These encouraging results warrant the continued development of MMS as a catheter-based clinical diagnostic technique for early detection of vulnerable plaques.
| S-EPMC3041241 | biostudies-other
Project description:Atherosclerotic plaque growth requires angiogenesis, and acute coronary syndrome (ACS) is usually triggered by the rupture of unstable atherosclerotic plaques. Previous studies have identified typically circulating microRNA (miRNA/miR) profiles in patients with ACS. miRNAs serve important roles in the pathophysiology of atherosclerotic plaque progression. The present study aimed to investigate the potential role and mechanism of miR?19b in plaque stability. miRNA array data indicated that 28 miRNAs were differentially expressed in the plasma of patients with unstable angina (UA; n=12) compared with in control individuals (n=12), and miR?19b exhibited the most marked upregulation. Circulating miR?19b levels were further validated in another independent cohort, which consisted of 34 patients with UA and 24 controls, by quantitative polymerase chain reaction. Gene Ontology annotations of the predicted target genes of miR?19b suggested that miR?19b may be involved in endothelial cell (EC) proliferation, migration and angiogenesis, which was confirmed by Cell Counting kit?8, wound healing and tube formation assays in the present study. Finally, the present study indicated that miR?19b may suppress signal transducer and activator of transcription 3 (STAT3) tyrosine phosphorylation and transcriptional activity in ECs, as determined by western blot analysis and luciferase reporter assay. In conclusion, the present study revealed that increased miR?19b expression may delay unstable plaque progression in patients with UA by inhibiting EC proliferation, migration and angiogenesis via the suppression of STAT3 transcriptional activity.
| S-EPMC5752162 | biostudies-literature
Project description:Despite major advances in pharmacotherapy and interventional procedures, coronary artery disease (CAD) remains a principal cause of morbidity and mortality worldwide. Invasive coronary imaging along with the computation of hemodynamic forces, primarily endothelial shear stress and plaque structural stress, have enabled a comprehensive identification of atherosclerotic plaque components, providing a unique insight into the understanding of plaque vulnerability and progression, which may help guide patient treatment. However, the invasive-only approach to CAD has failed to show high predictive value. Meanwhile, it is becoming increasingly evident that along with the "vulnerable plaque", the presence of a "vulnerable patient" state is also necessary to precipitate an acute coronary thrombotic event. Non-invasive imaging techniques have also evolved, providing new opportunities for the identification of high-risk plaques, the study of atherosclerosis in asymptomatic individuals, and general population screening. Additionally, risk stratification scores, circulating biomarkers, immunology, and genetics also complete the armamentarium of a broader "vulnerable plaque and patient" concept approach. In the current review article, the invasive and non-invasive modalities used for the detection of high-risk plaques in patients with CAD are summarized and critically appraised. The challenges of the vulnerable plaque concept are also discussed, highlighting the need to shift towards a more interdisciplinary approach that can identify the "vulnerable plaque" in a "vulnerable patient".
| S-EPMC10052113 | biostudies-literature
Project description:Recent successes in targeted immune and cell-based therapies have driven new directions for pharmaceutical research. With the rise of these new therapies there is an unfilled need for companion diagnostics to assess patients' potential for therapeutic response. Targeted nanomaterials have been widely investigated to fill this niche; however, in contrast to small molecule or peptide-based targeted agents, binding affinities are not reported for nanomaterials, and to date there has been no standard, quantitative measure for the interaction of targeted nanoparticle agents with their targets. Without a standard measure, accurate comparisons between systems and optimization of targeting behavior are challenging. Here, we demonstrate a method for quantitative assessment of the binding affinity for targeted nanoparticles to cell surface receptors in living systems and apply it to optimize the development of a novel targeted nanoprobe for imaging vulnerable atherosclerotic plaques. In this work, we developed sulfated dextran-coated iron oxide nanoparticles with specific targeting to macrophages, a cell type whose density strongly correlates with plaque vulnerability. Detailed quantitative, in vitro characterizations of (111)In(3+) radiolabeled probes show high-affinity binding to the macrophage scavenger receptor A (SR-A). Cell uptake studies illustrate that higher surface sulfation levels result in much higher uptake efficiency by macrophages. We use a modified Scatchard analysis to quantitatively describe nanoparticle binding to targeted receptors. This characterization represents a potential new standard metric for targeted nanomaterials.
| S-EPMC6066368 | biostudies-literature
Project description:Background and objectivesFormation and progression of atherosclerotic vulnerable plaque (VP) is the primary cause of many cardio-cerebrovascular diseases such as acute coronary syndrome and stroke. It has been reported that bone marrow mesenchymal stem cells (MSC) exhibit protective effects against many kinds of diseases including myocardial infarction. Here, we examined the effects of intravenous MSC infusion on a VP model and provide novel evidence of its influence as a therapy in this animal disease model.Subjects and methodsThirty healthy male New Zealand white rabbits were randomly divided into a MSC, VP or stable plaque (SP) group (n = 10/group) and received high fat diet and cold-induced common carotid artery intimal injury with liquid nitrogen to form atherosclerotic plaques. Serum hs-CRP, TNF-?, IL-6 and IL-10 levels were measured by ELISA at 1, 2, 3, 7, 14, 21 and 28 days after MSC transplantation. The animals were sacrificed at 4 weeks after MSC transplantation. Lesions in the right common carotid were observed using H&E and Masson staining, and the fibrous cap/lipid core ratio of atherosclerotic plaques were calculated. The expression of nuclear factor ?B (NF-?B) and matrix metalloproteinase 1, 2, 9 (MMP-1,2,9) in the plaque were detected using immunohistochemistry, and apoptotic cells in the plaques were detected by TUNEL. In addition, the level of TNF-? stimulated gene/protein 6 (TSG-6) mRNA and protein were measured by quantitative Real-Time PCR and Western blotting, respectively.ResultsTwo rabbits in the VP group died of lung infection and cerebral infarction respectively at 1 week after plaque injury by liquid nitrogen. Both H&E and Masson staining revealed that the plaques from the SP and MSC groups had more stable morphological structure and a larger fibrous cap/lipid core ratio than the VP group. Serum hs-CRP, TNF-? and IL-6 were significantly down-regulated, whereas IL-10 was significantly up-regulated in the MSC group compared with the VP group. .Immunohistochemistry analysis revealed that NF-?B and MMP expression was reduced in the MSC and SP groups compared to the VP group. Cell apoptosis decreased significantly in both the MSC and SP groups in comparison to the VP group. TSG-6 mRNA and protein expression were higher in the plaques of the MSC group compared to the VP and SP groups.ConclusionsOur study results suggest that MSC transplantation can effectively stabilize vulnerable plaques in atherosclerotic rabbits. This may potentially offer a new clinical application of MSC in atherosclerosis.
| S-EPMC4546153 | biostudies-literature