-
Frontiers in Immunology 2024The CC chemokine ligand 18 (CCL18) is a chemokine highly expressed in chronic inflammation in humans. Recent observations of elevated CCL18 plasma levels in patients...
INTRODUCTION
The CC chemokine ligand 18 (CCL18) is a chemokine highly expressed in chronic inflammation in humans. Recent observations of elevated CCL18 plasma levels in patients with acute cardiovascular syndromes prompted an investigation into the role of CCL18 in the pathogenesis of human and mouse atherosclerosis.
METHODS AND RESULTS
CCL18 was profoundly upregulated in ruptured human atherosclerotic plaque, particularly within macrophages. Repeated administration of CCL18 in Western-type diet-fed mice or PCSK9-overexpressing wild type (WT) mice led to increased plaque burden, enriched in CD3 T cells. In subsequent experimental and molecular modeling studies, we identified CCR6 as a functional receptor mediating CCL18 chemotaxis, intracellular Ca flux, and downstream signaling in human Jurkat and mouse T cells. CCL18 failed to induce these effects in murine spleen T cells with CCR6 deficiency. The ability of CCR6 to act as CCL18 receptor was confirmed in an inflammation model, where subcutaneous CCL18 injection induced profound focal skin inflammation in WT but not in mice. This inflammation featured edema and marked infiltration of various leukocyte subsets, including T cells with a Th17 signature, supporting CCR6's role as a Th17 chemotactic receptor. Notably, focal overexpression of CCL18 in plaques was associated with an increased presence of CCR6 (T) cells.
DISCUSSION
Our studies are the first to identify the CCL18/CCR6 axis as a regulator of immune responses in advanced murine and human atherosclerosis.
Topics: Animals; Humans; Atherosclerosis; Mice; Receptors, CCR6; Chemokines, CC; Disease Models, Animal; Mice, Inbred C57BL; Jurkat Cells; Plaque, Atherosclerotic; Mice, Knockout; Male; T-Lymphocytes; Th17 Cells; Female; Mice, Knockout, ApoE
PubMed: 38807599
DOI: 10.3389/fimmu.2024.1327051 -
Korean Journal of Radiology Jun 2024Coronary computed tomography angiography (CCTA) has emerged as a pivotal tool for diagnosing and risk-stratifying patients with suspected coronary artery disease (CAD).... (Review)
Review
Coronary computed tomography angiography (CCTA) has emerged as a pivotal tool for diagnosing and risk-stratifying patients with suspected coronary artery disease (CAD). Recent advancements in image analysis and artificial intelligence (AI) techniques have enabled the comprehensive quantitative analysis of coronary atherosclerosis. Fully quantitative assessments of coronary stenosis and lumen attenuation have improved the accuracy of assessing stenosis severity and predicting hemodynamically significant lesions. In addition to stenosis evaluation, quantitative plaque analysis plays a crucial role in predicting and monitoring CAD progression. Studies have demonstrated that the quantitative assessment of plaque subtypes based on CT attenuation provides a nuanced understanding of plaque characteristics and their association with cardiovascular events. Quantitative analysis of serial CCTA scans offers a unique perspective on the impact of medical therapies on plaque modification. However, challenges such as time-intensive analyses and variability in software platforms still need to be addressed for broader clinical implementation. The paradigm of CCTA has shifted towards comprehensive quantitative plaque analysis facilitated by technological advancements. As these methods continue to evolve, their integration into routine clinical practice has the potential to enhance risk assessment and guide individualized patient management. This article reviews the evolving landscape of quantitative plaque analysis in CCTA and explores its applications and limitations.
Topics: Humans; Computed Tomography Angiography; Coronary Artery Disease; Coronary Angiography; Plaque, Atherosclerotic; Radiographic Image Interpretation, Computer-Assisted; Coronary Stenosis
PubMed: 38807334
DOI: 10.3348/kjr.2023.1311 -
BMC Cardiovascular Disorders May 2024Autophagy, as a regulator of cell survival, plays an important role in atherosclerosis (AS). Sperm associated antigen 5 (SPAG5) is closely associated with the classical...
BACKGROUND
Autophagy, as a regulator of cell survival, plays an important role in atherosclerosis (AS). Sperm associated antigen 5 (SPAG5) is closely associated with the classical autophagy pathway, PI3K/Akt/mTOR signaling pathway. This work attempted to investigate whether SPAG5 can affect AS development by regulating autophagy.
METHODS
Human umbilical vein endothelial cells (HUVECs) were treated with oxidized-low density lipoprotein (ox-LDL) to induce cell damage. ApoE mice were fed a Western diet to establish an AS mouse model. Haematoxylin and eosin (H&E) staining and Oil Red O staining evaluated the pathological changes and in lipid deposition in aortic tissues. CCK-8 and flow cytometry detected cell proliferation and apoptosis. Immunohistochemistry, Enzyme linked immunosorbent assay, qRT-PCR and western blotting assessed the levels of mRNA and proteins.
RESULTS
Ox-LDL treatment elevated SPAG5 expression and the expression of autophagy-related proteins, LC3-I, LC3-II, Beclin-1, and p62, in HUVECs. GFP-LC3 dots were increased in ox-LDL-treated HUVECs and LPS-treated HUVECs. SPAG5 knockdown reversed both ox-LDL and LPS treatment-mediated inhibition of cell proliferation and promotion of apoptosis in HUVECs. SPAG5 silencing further elevated autophagy and repressed the expression of PI3K, p-Akt/Akt, and p-mTOR/mTOR in ox-LDL-treated HUVECs. 3-MA (autophagy inhibitor) treatment reversed SPAG5 silencing-mediated increase of cell proliferation and decrease of apoptosis in ox-LDL-treated HUVECs. In vivo, SPAG5 knockdown reduced atherosclerotic plaques in AS mice through activating autophagy and inhibiting PI3K/Akt/mTOR signaling pathway.
CONCLUSION
This work demonstrated that SPAG5 knockdown alleviated AS development through activating autophagy. Thus, SPAG5 may be a potential target for AS therapy.
Topics: Animals; Autophagy; Human Umbilical Vein Endothelial Cells; Humans; Atherosclerosis; Signal Transduction; TOR Serine-Threonine Kinases; Disease Models, Animal; Mice, Knockout, ApoE; Apoptosis; Proto-Oncogene Proteins c-akt; Plaque, Atherosclerotic; Cell Proliferation; Aortic Diseases; Mice, Inbred C57BL; Lipoproteins, LDL; Male; Cells, Cultured; Autophagy-Related Proteins; Aorta; Phosphatidylinositol 3-Kinase; Cell Cycle Proteins; Mice; Apolipoproteins E
PubMed: 38807081
DOI: 10.1186/s12872-024-03945-5 -
Stroke and Vascular Neurology May 2024Recently, computational fluid dynamics (CFD) has been used to simulate blood flow of symptomatic intracranial atherosclerotic stenosis (sICAS) and investigate the...
BACKGROUND
Recently, computational fluid dynamics (CFD) has been used to simulate blood flow of symptomatic intracranial atherosclerotic stenosis (sICAS) and investigate the clinical implications of its haemodynamic features, which were systematically reviewed in this study.
METHODS
Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analysis of Observational Studies in Epidemiology statements, we searched PubMed and Embase up to March 2024 and screened for articles reporting clinical implications of haemodynamic parameters in sICAS derived from CFD models.
RESULTS
19 articles met the inclusion criteria, all studies recruiting patients from China. Most studies used CT angiography (CTA) as the source image for vessel segmentation, and generic boundary conditions, rigid vessel wall and Newtonian fluid assumptions for CFD modelling, in patients with 50%-99% sICAS. Pressure and wall shear stress (WSS) were quantified in almost all studies, and the translesional changes in pressure and WSS were usually quantified with a poststenotic to prestenotic pressure ratio (PR) and stenotic-throat to prestenotic WSS ratio (WSSR). Lower PR was associated with more severe stenosis, better leptomeningeal collaterals, prolonged perfusion time and internal borderzone infarcts. Higher WSSR and other WSS measures were associated with positive vessel wall remodelling, regression of luminal stenosis and artery-to-artery embolism. Lower PR and higher WSSR were both associated with the presence and severity of cerebral small vessel disease. Moreover, translesional PR and WSSR were promising predictors for stroke recurrence in medically treated patients with sICAS and outcomes after acute reperfusion therapy, which also provided indicators to assess the effects of stenting treatment on focal haemodynamics.
CONCLUSIONS
CFD is a promising tool in investigating the pathophysiology of ICAS and in risk stratification of patients with sICAS. Future studies are warranted for standardisation of the modelling methods and validation of the simulation results in sICAS, for its wider applications in clinical research and practice.
PubMed: 38806205
DOI: 10.1136/svn-2024-003202 -
PloS One 2024This study aims to evaluate the role of the peri-coronary Fat Attenuation Index (FAI) and High-Risk Plaque Characteristics (HRPC) in the assessment of coronary heart...
Peri-coronary fat attenuation index combined with high-risk plaque characteristics quantified from coronary computed tomography angiography for risk stratification in new-onset chest pain individuals without acute myocardial infarction.
This study aims to evaluate the role of the peri-coronary Fat Attenuation Index (FAI) and High-Risk Plaque Characteristics (HRPC) in the assessment of coronary heart disease risk. By conducting coronary CT angiography and coronary angiography on 217 patients with newly developed chest pain (excluding acute myocardial infarction), their degree of vascular stenosis, FAI, and the presence and quantity of HRPC were assessed. The study results demonstrate a correlation between FAI and HRPC, and the combined use of FAI and HRPC can more accurately predict the risk of major adverse cardiovascular events (MACE). Additionally, the study found that patients with high FAI were more prone to exhibit high-risk plaque characteristics, severe stenosis, and multiple vessel disease. After adjustment, the combination of FAI and HRPC improved the ability to identify and reclassify MACE. Furthermore, the study identified high FAI as an independent predictor of MACE in patients undergoing revascularization, while HRPC served as an independent predictor of MACE in patients not undergoing revascularization. These findings suggest the potential clinical value of FAI and HRPC in the assessment of coronary heart disease risk, particularly in patients with newly developed chest pain excluding acute myocardial infarction.
Topics: Humans; Male; Female; Middle Aged; Computed Tomography Angiography; Chest Pain; Plaque, Atherosclerotic; Coronary Angiography; Aged; Myocardial Infarction; Risk Assessment; Adipose Tissue; Coronary Artery Disease; Risk Factors; Coronary Vessels
PubMed: 38805487
DOI: 10.1371/journal.pone.0304137 -
Frontiers in Neurology 2024The aim of this study was to extract radiomic features from vertebrobasilar artery calcification (VBAC) on head computed tomography (CT) images and investigate its...
OBJECTIVES
The aim of this study was to extract radiomic features from vertebrobasilar artery calcification (VBAC) on head computed tomography (CT) images and investigate its diagnostic performance to identify culprit lesions responsible for acute cerebral infarctions.
METHODS
Patients with intracranial atherosclerotic disease who underwent vessel wall MRI (VW-MRI) and head CT examinations from a single center were retrospectively assessed for VBAC visual and textural analyses. Each calcified plaque was classified by the likelihood of having caused an acute cerebral infarction identified on VW-MRI as culprit or non-culprit. A predefined set of texture features extracted from VBAC segmentation was assessed using the minimum redundancy and maximum relevance method. Five key features were selected to integrate as a radiomic model using logistic regression by the Aikaike Information Criteria. The diagnostic value of the radiomic model was calculated for discriminating culprit lesions over VBAC visual assessments.
RESULTS
A total of 1,218 radiomic features were extracted from 39 culprit and 50 non-culprit plaques, respectively. In the VBAC visual assessment, culprit plaques demonstrated more observed presence of multiple calcifications, spotty calcification, and intimal predominant calcification than non-culprit lesions (all < 0.05). In the VBAC texture analysis, 55 (4.5%) of all extracted features were significantly different between culprit and non-culprit plaques (all < 0.05). The radiomic model incorporating 5 selected features outperformed multiple calcifications [AUC = 0.81 with 95% confidence interval (CI) of 0.72, 0.90 vs. AUC = 0.61 with 95% CI of 0.49, 0.73; = 0.001], intimal predominant calcification (AUC = 0.67 with 95% CI of 0.58, 0.76; = 0.04) and spotty calcification (AUC = 0.62 with 95% CI of 0.52, 0.72; = 0.005) in the identification of culprit lesions.
CONCLUSION
Culprit plaques in the vertebrobasilar artery exhibit distinct calcification radiomic features compared to non-culprit plaques. CT texture analysis of VBAC has potential value in identifying lesions responsible for acute cerebral infarctions, which may be helpful for stroke risk stratification in clinical practice.
PubMed: 38803646
DOI: 10.3389/fneur.2024.1381370 -
Cell Biology and Toxicology May 2024MYBL1 is a strong transcriptional activator involved in the cell signaling. However, there is no systematic study on the role of MYBL1 in atherosclerosis. The aim of...
MYBL1 is a strong transcriptional activator involved in the cell signaling. However, there is no systematic study on the role of MYBL1 in atherosclerosis. The aim of this study is to elucidate the role and mechanism of MYBL1 in atherosclerosis. GSE28829, GSE43292 and GSE41571 were downloaded from NCBI for differentially expressed analysis. The expression levels of MYBL1 in atherosclerotic plaque tissue and normal vessels were detected by qRT-PCR, Western blot and Immunohistochemistry. Transwell and CCK-8 were used to detect the migration and proliferation of HUVECs after silencing MYBL1. RNA-seq, Western blot, qRT-PCR, Luciferase reporter system, Immunofluorescence, Flow cytometry, ChIP and CO-IP were used to study the role and mechanism of MYBL1 in atherosclerosis. The microarray data of GSE28829, GSE43292, and GSE41571 were analyzed and intersected, and then MYBL1 were verified. MYBL1 was down-regulated in atherosclerotic plaque tissue. After silencing of MYBL1, HUVECs were damaged, and their migration and proliferation abilities were weakened. Overexpression of MYBL1 significantly enhanced the migration and proliferation of HUVECs. MYBL1 knockdown induced abnormal autophagy in HUVEC cells, suggesting that MYBL1 was involved in the regulation of HUVECs through autophagy. Mechanistic studies showed that MYBL1 knockdown inhibited autophagosome and lysosomal fusion in HUVECs by inhibiting PLEKHM1, thereby exacerbating atherosclerosis. Furthermore, MYBL1 was found to repress lipid accumulation in HUVECs after oxLDL treatment. MYBL1 knockdown in HUVECs was involved in atherosclerosis by inhibiting PLEKHM1-induced autophagy, which provided a novel target of therapy for atherosclerosis.
Topics: Animals; Humans; Atherosclerosis; Autophagy; Cell Movement; Cell Proliferation; Down-Regulation; Human Umbilical Vein Endothelial Cells; Membrane Glycoproteins; Plaque, Atherosclerotic; Trans-Activators
PubMed: 38797732
DOI: 10.1007/s10565-024-09873-6 -
Pharmaceuticals (Basel, Switzerland) May 2024Atherosclerosis is the main pathological basis of cardiovascular diseases (CVDs). Fufang Danshen Tablet (FDT) is a traditional Chinese medicine that has been clinically...
Atherosclerosis is the main pathological basis of cardiovascular diseases (CVDs). Fufang Danshen Tablet (FDT) is a traditional Chinese medicine that has been clinically used to treat CVDs for more than 40 years. Nevertheless, owing to the complexity of the ingredients, the pharmacological mechanism of FDT in the treatment of CVDs has not been fully elucidated. In this study, an integrated strategy of UFLC-Q-TOF-MS/MS, network pharmacology, molecular biology, and transcriptomics was used to elucidate the mechanisms of action of FDT in the treatment of atherosclerosis. In total, 22 absorbed constituents were identified in rat serum after oral administration of FDT. In silico, network pharmacology studies have shown that FDT regulates four key biological functional modules for the treatment of atherosclerosis: oxidative stress, cell apoptosis, energy metabolism, and immune/inflammation. In animal experiments, FDT exerted protective effects against atherosclerosis by reducing the plaque area and lipid levels in ApoE mice. Furthermore, we found that FDT inhibited inflammatory macrophage accumulation by regulating the expression of and , which are both involved in monocyte adhesion and migration. The inhibition of monocyte recruitment by FDT is a new perspective to elucidate the anti-atherosclerotic mechanism of FDT, which has not been adopted in previous studies on FDT. Our results may help to elucidate the therapeutic mechanism of FDT against CVDs and provide potential therapeutic targets.
PubMed: 38794213
DOI: 10.3390/ph17050643 -
Medicina (Kaunas, Lithuania) May 2024carotid artery stenosis contributes significantly to ischemic strokes, with management options including carotid endarterectomy (CEA) and carotid artery stenting (CAS)...
carotid artery stenosis contributes significantly to ischemic strokes, with management options including carotid endarterectomy (CEA) and carotid artery stenting (CAS) ischemic stroke risk can be reduced. Controversies persist regarding their efficacy and factors influencing complications, and understanding the relationship between atherosclerotic plaque characteristics and stent restenosis after CAS is crucial. we conducted a retrospective study involving 221 patients who underwent CAS for symptomatic or asymptomatic carotid artery stenosis. Comprehensive assessments of plaque morphology were performed using contrast-enhanced ultrasound (CEUS) before CAS. Patient demographics, including smoking status and diabetes, were also recorded. Stent restenosis was diagnosed using various imaging modalities, including ultrasound, angiography, and digital subtraction angiography (DSA). plaque analysis using CEUS revealed a significant association between plaque grade and restenosis incidence ( < 0.001), particularly with grade 0 (11.1%) and grade 2 plaques (66.7%). Smoking was notably associated with plaque vascularization and restenosis ( < 0.001), while diabetes did not significantly impact plaque characteristics or restenosis risk ( > 0.05). The mean duration of restenosis was 17.67 months. Stenting was the most frequent treatment modality for restenosis (70.6%). However, no significant relationship was found between restenosis type and plaque morphology ( = 0.268). Furthermore, while no clear relationship was observed between plaque morphology and the type of restenosis, our findings underscored the importance of plaque characterization in predicting post-CAS outcomes. this study highlights the utility of CEUS in predicting stent restenosis following CAS. There was a significant association between stent restenosis within 12-24 months after the carotid stenting procedure and an elevated grade of plaque vascularization. Moreover, one of the main factors possibly determining the grade of plaque vascularization was smoking. Further research is warranted to elucidate the underlying mechanisms and refine risk stratification in this patient population.
Topics: Humans; Retrospective Studies; Male; Female; Aged; Stents; Carotid Stenosis; Plaque, Atherosclerotic; Middle Aged; Ultrasonography; Contrast Media; Carotid Arteries; Angiography, Digital Subtraction; Aged, 80 and over; Risk Factors
PubMed: 38793019
DOI: 10.3390/medicina60050836 -
Life (Basel, Switzerland) Apr 2024An imbalance between pro- and anti-inflammatory mechanisms is indicated in the pathophysiology of atherosclerotic plaque. The coronary artery and carotid disease,...
BACKGROUND
An imbalance between pro- and anti-inflammatory mechanisms is indicated in the pathophysiology of atherosclerotic plaque. The coronary artery and carotid disease, despite sharing similar risk factors, are developed separately. The aim of this study was to analyze possible mechanisms between trace element hair-scalp concentrations and whole blood counts that favor atherosclerotic plaque progression in certain locations.
METHODS
There were 65 (36 (55%) males and 29 (45%) females) patients with a median age of 68 (61-73) years enrolled in a prospective, preliminary, multicenter analysis. The study group was composed of 13 patients with stable coronary artery disease (CAD group) referred for surgical revascularization due to multivessel coronary disease, 34 patients with carotid artery disease (carotid group) admitted for vascular procedure, and 18 patients in a control group (control group).
RESULTS
There was a significant difference between the CAD and carotid groups regarding lymphocyte ( = 0.004) counts. The biochemical comparison between the coronary and carotid groups revealed significant differences regarding chromium (Cr) ( = 0.002), copper (Cu) ( < 0.001), and zinc (Zn) ( < 0.001) concentrations. Spearman Rank Order Correlations between lymphocyte counts and trace elements in the analyzed groups were performed, revealing a strong correlation with zinc (R = 0.733, < 0.001) in the control group (non-CAD, non-carotid).
CONCLUSION
Significant differences in hair-scalp concentrations related to atherosclerosis location were observed in our analysis. The interplay between zinc concentration and lymphocyte count may play a pivotal role in cardiovascular disease development.
PubMed: 38792593
DOI: 10.3390/life14050571