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International Journal of Stroke :... Jun 2024Microcalcification and macrocalcification are critical processes in atherosclerotic plaque progression, though how these processes relate to the risk of stroke...
BACKGROUND
Microcalcification and macrocalcification are critical processes in atherosclerotic plaque progression, though how these processes relate to the risk of stroke recurrence in symptomatic carotid atherosclerosis is poorly understood.
METHODS
We performed a post-hoc analysis of data from the ICARUSS study, where individuals with acute ischemic stroke originating from ipsilateral carotid stenosis of ≥50% underwent 18F-sodium fluoride-positron emission tomography (NaF-PET) to measure microcalcification. Tracer uptake was quantified using maximum tissue-to-background ratio (TBRmax). Macrocalcification was measured on computed tomography (CT) using Agatston scoring. Patients were followed up for six months for recurrent ipsilateral neurovascular events.
RESULTS
Five (27.8%) of 18 individuals had a recurrent ischemic stroke or transient ischemic attack. Ipsilateral carotid plaque NaF uptake at baseline was higher in those with recurrent events compared to those without, and this association remained after adjustment for other vascular risk factors (OR 1.24, 1.03-1.50). Macrocalcification score in the symptomatic artery was also significantly independently associated with ipsilateral recurrence, but the effect size was relatively smaller (OR 1.12, 1.06-1.17 for each 100 unit increase).
CONCLUSIONS
Our findings indicate that microcalcification in symptomatic carotid plaques is independently associated with ipsilateral ischemic stroke recurrence. Furthermore, differences in the extent of active microcalcification in macrocalcified plaques may help explain variation in the relationship between calcified carotid plaques and stroke recurrence reported in the literature. Our pilot study indicates that evaluation of carotid artery microcalcification using NaF-PET may be a useful method for risk-stratification of carotid atherosclerosis, though our findings require confirmation in larger cohorts.
PubMed: 38888039
DOI: 10.1177/17474930241264734 -
Acta Pharmacologica Sinica Jun 2024Urolithin A (UroA), a dietary phytochemical, is produced by gut bacteria from fruits rich in natural polyphenols ellagitannins (ETs). The efficiency of ETs metabolism to...
Urolithin A (UroA), a dietary phytochemical, is produced by gut bacteria from fruits rich in natural polyphenols ellagitannins (ETs). The efficiency of ETs metabolism to UroA in humans depends on gut microbiota. UroA has shown a variety of pharmacological activities. In this study we investigated the effects of UroA on atherosclerotic lesion development and stability. Apolipoprotein E-deficient (ApoE) mice were fed a high-fat and high-cholesterol diet for 3 months to establish atherosclerosis model. Meanwhile the mice were administered UroA (50 mg·kg·d, i.g.). We showed that UroA administration significantly decreased diet-induced atherosclerotic lesions in brachiocephalic arteries, macrophage content in plaques, expression of endothelial adhesion molecules, intraplaque hemorrhage and size of necrotic core, while increased the expression of smooth muscle actin and the thickness of fibrous cap, implying features of plaque stabilization. The underlying mechanisms were elucidated using TNF-α-stimulated human endothelial cells. Pretreatment with UroA (10, 25, 50 μM) dose-dependently inhibited TNF-α-induced endothelial cell activation and monocyte adhesion. However, the anti-inflammatory effects of UroA in TNF-α-stimulated human umbilical vein endothelial cells (HUVECs) were independent of NF-κB p65 pathway. We conducted RNA-sequencing profiling analysis to identify the differential expression of genes (DEGs) associated with vascular function, inflammatory responses, cell adhesion and thrombosis in UroA-pretreated HUVECs. Human disease enrichment analysis revealed that the DEGs were significantly correlated with cardiovascular diseases. We demonstrated that UroA pretreatment mitigated endothelial inflammation by promoting NO production and decreasing YAP/TAZ protein expression and TEAD transcriptional activity in TNF-α-stimulated HUVECs. On the other hand, we found that UroA administration modulated the transcription and cleavage of lipogenic transcription factors SREBP1/2 in the liver to ameliorate cholesterol metabolism in ApoE mice. This study provides an experimental basis for new dietary therapeutic option to prevent atherosclerosis.
PubMed: 38886550
DOI: 10.1038/s41401-024-01317-5 -
Phytotherapy Research : PTR Jun 2024Atherosclerosis represents the major cause of mortality worldwide and triggers higher risk of acute cardiovascular events. Pericytes-endothelial cells (ECs)...
Atherosclerosis represents the major cause of mortality worldwide and triggers higher risk of acute cardiovascular events. Pericytes-endothelial cells (ECs) communication is orchestrated by ligand-receptor interaction generating a microenvironment which results in intraplaque neovascularization, that is closely associated with atherosclerotic plaque instability. Notoginsenoside R (R) exhibits anti-atherosclerotic bioactivity, but its effect on angiogenesis in atherosclerotic plaque remains elusive. The aim of our study is to explore the therapeutic effect of R on vulnerable plaque and investigate its potential mechanism against intraplaque neovascularization. The impacts of R on plaque stability and intraplaque neovascularization were assessed in ApoE mice induced by high-fat diet. Pericytes-ECs direct or non-direct contact co-cultured with VEGF-A stimulation were used as the in vitro angiogenesis models. Overexpressing Ang1 in pericytes was performed to investigate the underlying mechanism. In vivo experiments, R treatment reversed atherosclerotic plaque vulnerability and decreased the presence of neovessels in ApoE mice. Additionally, R reduced the expression of Ang1 in pericytes. In vitro experiments demonstrated that R suppressed pro-angiogenic behavior of ECs induced by pericytes cultured with VEGF-A. Mechanistic studies revealed that the anti-angiogenic effect of R was dependent on the inhibition of Ang1 and Tie2 expression, as the effects were partially reversed after Ang1 overexpressing in pericytes. Our study demonstrated that R treatment inhibited intraplaque neovascularization by governing pericyte-EC association via suppressing Ang1-Tie2/PI3K-AKT paracrine signaling pathway. R represents a novel therapeutic strategy for atherosclerotic vulnerable plaques in clinical application.
PubMed: 38886264
DOI: 10.1002/ptr.8257 -
Journal of Ethnopharmacology Jun 2024Zhishi Xiebai Guizhi Decoction (ZSXBGZD) is a traditional herbal manuscript used to treat cardiovascular disease, including atherosclerosis and coronary heart disease....
ETHNOPHARMACOLOGICAL RELEVANCE
Zhishi Xiebai Guizhi Decoction (ZSXBGZD) is a traditional herbal manuscript used to treat cardiovascular disease, including atherosclerosis and coronary heart disease. The decoction has demonstrated its capability to protect arteries and resist atherosclerosis. Its mechanisms for anti-atherosclerosis effect, nevertheless, remain unknown.
AIMS OF THE STUDY
The goal of the present study is to explore the effectiveness of ZSXBGZD acting on atherosclerosis and its key components based on experimental verification and network pharmacology analysis.
MATERIALS AND METHODS
The ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and databases were used to identify chemical components in ZSXBGZD. Network pharmacological analysis and molecular docking were implemented in order to reveal the possible therapeutic targets of ZSXBGZD. To form the model of atherosclerosis, we gave Apolipoprotein E knocked out mice a high-fat diet. H&E staining was performed to observe the effects of ZSXBGZD on atherosclerosis. Immunofluorescence and Western blot were used to investigate whether ZSXBGZD could affect autophagy, apoptosis, AGE-RAGE signaling pathway and other related mechanisms.
RESULTS
In total, 30 core compounds were screened through intersecting UPLC-Q-TOF-MS and the databases. The anti-atherosclerotic effect of ZSXBGZD might relate to the AGE-RAGE signaling pathway via network pharmacology analysis. ZSXBGZD could inhibit apoptosis, activate autophagy and ease inflammation by modifying AGE-RAGE signaling pathway to reduce the area of atherosclerotic plaque.
CONCLUSION
ZSXBGZD could treat atherosclerosis by regulating autophagy and apoptosis via adjusting the AGE-RAGE signaling pathway.
PubMed: 38885915
DOI: 10.1016/j.jep.2024.118466 -
The British Journal of Radiology Jun 2024To explore the role of quantitative evaluation using carotid ultrasonography (US)-based high-frame-rate vector flow (V Flow) imaging in patients with low carotid...
OBJECTIVE
To explore the role of quantitative evaluation using carotid ultrasonography (US)-based high-frame-rate vector flow (V Flow) imaging in patients with low carotid stenosis.
METHODS
This single-center cross-sectional study consecutively recruited volunteers without carotid plaque and patients with low carotid stenosis from August 2022 to May 2023. Patients were divided into symptomatic and asymptomatic groups according to their head CT or MRI results within eight weeks. All V Flow imaging examinations were performed using a Mindray Resona R9 US system. The wall shear stress (WSS) values, oscillatory shear index (OSI) values and turbulence (Tur) indexes in the normal common carotid artery (CCA), normal carotid bifurcation (CB), and on the upstream and downstream surface of carotid plaque were measured. Pearson Chi-square test and Fisher exact test were used for counting data according to their type. For measurement data, independent sample t test and non-parametric rank sum test were used.
RESULTS
The results proved that patients have higher WSS values and Tur indexes of CB than volunteers, and higher WSS values were detected on the surface of the plaques in symptomatic patients. What's more, the downstream side of the plaque was more vulnerable to plaque rupture than the upstream side due to more dynamic blood flow.
CONCLUSION
Therefore, carotid US-based high-frame-rate V Flow imaging provides reliable mechanical biomarkers for assessing the hemodynamic change in patients with low stenosis. Our study may provide a new imaging tool for monitoring the progression of atherosclerosis and aiding the management of early atherosclerotic patients.
PubMed: 38885374
DOI: 10.1093/bjr/tqae115 -
Clinical Cardiology Jun 2024The coronary artery disease-reporting and data system (CAD-RADS) 2.0 is used to standardize the reporting of coronary computed tomography angiography (CCTA) results....
The Plaque Analysis Classifies the Coronary Artery Disease-Reporting and Data System (CAD-RADS) Stenosis and Plaque Burden Categories: Association of the Plaque Features, Fat Attenuation Index, Coronary Computed Tomography Fractional Flow Reserve, and the Combination of Stenosis and Calcification.
BACKGROUND
The coronary artery disease-reporting and data system (CAD-RADS) 2.0 is used to standardize the reporting of coronary computed tomography angiography (CCTA) results. Artificial intelligence software can quantify the plaque composition, fat attenuation index, and fractional flow reserve.
OBJECTIVE
To analyze plaque features of varying severity in patients with a combination of CAD-RADS stenosis and plaque burden categorization and establish a random forest classification model.
METHODS
The data of 100 patients treated between April 2021 and February 2022 were retrospectively collected. The most severe plaque observed in each patient was the target lesion. Patients were categorized into three groups according to CAD-RADS: CAD-RADS 1-2 + P0-2, CAD-RADS 3-4B + P0-2, and CAD-RADS 3-4B + P3-4. Differences and correlations between variables were assessed between groups. AUC, accuracy, precision, recall, and F1 score were used to evaluate the diagnostic performance.
RESULTS
A total of 100 patients and 178 arteries were included. The differences of computed tomography fractional flow reserve (CT-FFR) (H = 23.921, p < 0.001), the volume of lipid component (H = 12.996, p = 0.002), the volume of fibro-lipid component (H = 8.692, p = 0.013), the proportion of lipid component volume (H = 22.038, p < 0.001), the proportion of fibro-lipid component volume (H = 11.731, p = 0.003), the proportion of calcification component volume (H = 11.049, p = 0.004), and plaque type (χ = 18.110, p = 0.001) was statistically significant.
CONCLUSION
CT-FFR, volume and proportion of lipid and fibro-lipid components of plaques, the proportion of calcified components, and plaque type were valuable for CAD-RADS stenosis + plaque burden classification, especially CT-FFR, volume, and proportion of lipid and fibro-lipid components. The model built using the random forest was better than the clinical model (AUC: 0.874 vs. 0.647).
Topics: Humans; Male; Female; Fractional Flow Reserve, Myocardial; Plaque, Atherosclerotic; Retrospective Studies; Computed Tomography Angiography; Middle Aged; Coronary Angiography; Coronary Stenosis; Severity of Illness Index; Coronary Artery Disease; Coronary Vessels; Vascular Calcification; Aged
PubMed: 38884449
DOI: 10.1002/clc.24305 -
Frontiers in Endocrinology 2024The global prevalence of cardiovascular diseases (CVD) continues to rise steadily, making it a leading cause of mortality worldwide. Atherosclerosis (AS) serves as a... (Review)
Review
The global prevalence of cardiovascular diseases (CVD) continues to rise steadily, making it a leading cause of mortality worldwide. Atherosclerosis (AS) serves as a primary driver of these conditions, commencing silently at an early age and culminating in adverse cardiovascular events that severely impact patients' quality of life or lead to fatality. Dyslipidemia, particularly elevated levels of low-density lipoprotein cholesterol (LDL-C), plays a pivotal role in AS pathogenesis as an independent risk factor. Research indicates that abnormal LDL-C accumulation within arterial walls acts as a crucial trigger for atherosclerotic plaque formation. As the disease progresses, plaque accumulation may rupture or dislodge, resulting in thrombus formation and complete blood supply obstruction, ultimately causing myocardial infarction, cerebral infarction, and other common adverse cardiovascular events. Despite adequate pharmacologic therapy targeting LDL-C reduction, patients with cardiometabolic abnormalities remain at high risk for disease recurrence, highlighting the importance of addressing lipid risk factors beyond LDL-C. Recent attention has focused on the causal relationship between triglycerides, triglyceride-rich lipoproteins (TRLs), and their remnants in AS risk. Genetic, epidemiologic, and clinical studies suggest a causal relationship between TRLs and their remnants and the increased risk of AS, and this dyslipidemia may be an independent risk factor for adverse cardiovascular events. Particularly in patients with obesity, metabolic syndrome, diabetes, and chronic kidney disease, disordered TRLs and its remnants levels significantly increase the risk of atherosclerosis and cardiovascular disease development. Accumulation of over-synthesized TRLs in plasma, impaired function of enzymes involved in TRLs lipolysis, and impaired hepatic clearance of cholesterol-rich TRLs remnants can lead to arterial deposition of TRLs and its remnants, promoting foam cell formation and arterial wall inflammation. Therefore, understanding the pathogenesis of TRLs-induced AS and targeting it therapeutically could slow or impede AS progression, thereby reducing cardiovascular disease morbidity and mortality, particularly coronary atherosclerotic heart disease.
Topics: Humans; Cardiovascular Diseases; Lipoproteins; Triglycerides; Atherosclerosis; Animals; Dyslipidemias; Risk Factors
PubMed: 38883601
DOI: 10.3389/fendo.2024.1409653 -
European Journal of Radiology Open Jun 2024To determine the value of an algorithm for reducing stair-step artifacts for advanced coronary analyses in sequential mode coronary CT angiography (CCTA).
Increasing the rate of datasets amenable to CT and quantitative plaque analysis: Value of software for reducing stair-step artifacts demonstrated in photon-counting detector CT.
PURPOSE
To determine the value of an algorithm for reducing stair-step artifacts for advanced coronary analyses in sequential mode coronary CT angiography (CCTA).
METHODS
Forty patients undergoing sequential mode photon-counting detector CCTA with at least one stair-step artifact were included. Twenty patients (14 males; mean age 57±17years) with 45 segments showing stair-step artifacts and without atherosclerosis were included for CT analysis. Twenty patients (20 males; mean age 74±13years) with 22 segments showing stair-step artifacts crossing an atherosclerotic plaque were included for quantitative plaque analysis. Artifacts were graded, and CT and quantitative coronary plaque analyses were performed in standard reconstructions and in those reconstructed with a software (entitled ) for artifact reduction.
RESULTS
Stair-step artifacts were significantly reduced in compared to standard reconstructions (p<0.05). In standard reconstructions, CT was not feasible in 3/45 (7 %) segments but was feasible in all reconstructions. In 9/45 (20 %) segments without atherosclerosis, the algorithm led to a change of CT values from pathologic in standard to physiologic values in reconstructions. In one segment (1/22, 5 %), quantitative plaque analysis was not feasible in standard but only in reconstruction. The mean overall plaque volume (111±60 mm), the calcific (77±47 mm), fibrotic (31±28 mm), and lipidic (4±3 mm) plaque components were higher in standard than in reconstructions (overall 75±50 mm, p<0.001; calcific 51±42 mm, p<0.001; fibrotic 22±19 mm, p<0.05; lipidic 3±3 mm, p=0.055).
CONCLUSION
Despite the lack of reference standard modalities for CT and coronary plaque analysis, initial evidence indicates that an algorithm for reducing stair-step artifacts in sequential mode CCTA increases the rate and quality of datasets amenable to advanced coronary artery analysis, hereby potentially improving patient management.
PubMed: 38882632
DOI: 10.1016/j.ejro.2024.100574 -
Circulation Jun 2024Thromboembolic events, including myocardial infarction (MI) or stroke, caused by the rupture or erosion of unstable atherosclerotic plaques are the leading cause of...
BACKGROUND
Thromboembolic events, including myocardial infarction (MI) or stroke, caused by the rupture or erosion of unstable atherosclerotic plaques are the leading cause of death worldwide. Although most mouse models of atherosclerosis develop lesions in the aorta and carotid arteries, they do not develop advanced coronary artery lesions. Moreover, they do not undergo spontaneous plaque rupture with MI and stroke or do so at such a low frequency that they are not viable experimental models to study late-stage thrombotic events or to identify novel therapeutic approaches for treating atherosclerotic disease. This has stymied the development of more effective therapeutic approaches for reducing these events beyond what has been achieved with aggressive lipid lowering. Here, we describe a diet-inducible mouse model that develops widespread advanced atherosclerosis in coronary, brachiocephalic, and carotid arteries with plaque rupture, MI, and stroke.
METHODS
We characterized a novel mouse model with a C-terminal mutation in the scavenger receptor class B, type 1 (SR-BI), combined with knockout (designated SR-BI/). Mice were fed Western diet (WD) for 26 weeks and analyzed for MI and stroke. Coronary, brachiocephalic, and carotid arteries were analyzed for atherosclerotic lesions and indices of plaque stability. To validate the utility of this model, SR-BI/ mice were treated with the drug candidate AZM198, which inhibits myeloperoxidase, an enzyme produced by activated neutrophils that predicts rupture of human atherosclerotic lesions.
RESULTS
SR-BI/ mice show high (>80%) mortality rates after 26 weeks of WD feeding because of major adverse cardiovascular events, including spontaneous plaque rupture with MI and stroke. Moreover, WD-fed SR-BI/ mice displayed elevated circulating high-sensitivity cardiac troponin I and increased neutrophil extracellular trap formation within lesions compared with control mice. Treatment of WD-fed SR-BI/ mice with AZM198 showed remarkable benefits, including >90% improvement in survival and >60% decrease in the incidence of plaque rupture, MI, and stroke, in conjunction with decreased circulating high-sensitivity cardiac troponin I and reduced neutrophil extracellular trap formation within lesions.
CONCLUSIONS
WD-fed SR-BI/ mice more closely replicate late-stage clinical events of advanced human atherosclerotic disease than previous models and can be used to identify and test potential new therapeutic agents to prevent major adverse cardiac events.
PubMed: 38881440
DOI: 10.1161/CIRCULATIONAHA.123.067931 -
Zhonghua Xin Xue Guan Bing Za Zhi Jun 2024To analyze plaque characteristics of non-culprit coronary lesions with cholesterol crystals in patients with acute myocardial infarction(AMI) by using optical coherence...
To analyze plaque characteristics of non-culprit coronary lesions with cholesterol crystals in patients with acute myocardial infarction(AMI) by using optical coherence tomography(OCT). We also investigated the potential association between cholesterol crystals with plaque rupture and healed plaque at non-culprit segment. This study was a retrospective cohort study. Between January 2017 and December 2017, patients with AMI who underwent 3-vessel OCT imaging were included in this study. Patients were divided into two groups according to the presence or absence of cholesterol crystals at the non-culprit lesions. All patients underwent coronary angiography and OCT examination, and non-culprit plaque characteristics were compared between the two groups. The generalized estimating equation log-binomial multirariate regression model was used to assess the relationship between non-culprit lesions with cholesterol crystals and plaque rupture and plaque healing. The follow-up data collection ended in October 2023. Kaplan-Meier survival curves were plotted, and log-rank tests were used to compare the cumulative incidence of major adverse cardiovascular events between the two groups. A total of 173 AMI patients were included (aged (56.8±11.6) years; 124 men (71.7%)). Among 710 non-culprit lesions identified by OCT, there were 102 (14.4%) in cholesterol crystals group and 608 (85.6%) in non-cholesterol crystals group. Compared with non-culprit lesions without cholesterol crystals, those with cholesterol crystals had smaller minimum lumen diameter, severer diameter stenosis, and longer lesion length (all 0.01). The prevalence of plaque rupture (17.6% (18/102) vs. 4.9% (30/608), =0.001) and thin-cap fibroatheroma (31.4% (32/102) vs. 11.5% (70/608), <0.01) was higher in the cholesterol crystals groups than in the non-cholesterol crystals group. In addition, vulnerable plaque characteristics such as (44.1% (45/102) vs. 25.8% (157/608), <0.01), macrophages were more frequently observed in non-culprit lesions with cholesterol crystals. The generalized estimating equation log-binomial multivariate regression analyses showed that non-culprit cholesterol crystals were positively correlated with healed plaque (=1.583, 95%: 1.004-2.495, =0.048). Conversely, cholesterol crystals were not associated with plaque rupture (=1.632, 95%: 0.745-3.576, =0.221). The follow-up time was 2 142 (1 880, 2 198) days. Non-culprit cholesterol crystals were not related to the major adverse cardiovascular events in patients with AMI (log-rank =0.558). Among AMI patients, non-culprit lesions with cholesterol crystals presented with severer luminal stenosis and increased plaque vulnerability. The presence of non-culprit cholesterol crystals was associated with rather than plaque rupture.
Topics: Humans; Male; Middle Aged; Female; Cholesterol; Plaque, Atherosclerotic; Retrospective Studies; Tomography, Optical Coherence; Myocardial Infarction; Crystallization; Coronary Vessels; Coronary Angiography; Aged
PubMed: 38880745
DOI: 10.3760/cma.j.cn112148-20240228-00116