Carotid Atherosclerotic Plaques Research Articles

Polymorphisms of the apolipoprotein E gene affect response to atorvastatin therapy in acute ischemic stroke.

Polymorphisms of the apolipoprotein E (APOE) gene are related to the efficacy of statin therapy. The biological functions of the APOE subtypes determine the metabolism of blood plasma lipids and the progression of atherosclerosis. This study aimed to explore the impact of APOE gene polymorphisms on the effect of atorvastatin on lipid regulation and plaque stabilization. The study was a prospective cohort study that consecutively included patients with acute ischemic stroke (AIS) in the Department of Neurology, Shanghai Tenth People's Hospital, from December 2018 to December 2019. The patients were divided into E2, E3, and E4 groups according to their APOE genotype. Atorvastatin (20 mg) was administrated to all patients. Changes in blood lipid levels over 3 months and plaque size and stability over 12 months were analyzed. We enrolled 253 consecutive patients with AIS, of whom, 136 had carotid atherosclerotic plaques. Two patients with genotype E2/E4 were excluded. There were 30 patients in the E2 group (12.0%), 191 patients in the E3 group (76.0%), and 30 patients in the E4 group (12.0%). The lowest percentage reduction in low-density lipoprotein cholesterol (LDL-C) was observed in the E4 group (41.2%), while the highest percentage reduction was observed in the E2 group (17.6%). The plaques in the E2 group showed slower progression, while those in the E4 group showed more rapid progression. APOE gene polymorphisms affect the biological functions of atorvastatin. Compared to the ε3 or ε4 allele, the ε2 allele exerted a greater lipid-lowering effect on LDL-C levels, enhanced the ability of atorvastatin to stabilize carotid artery plaques, and slowed carotid artery plaque progression.

Diagnostic Performance of Contrast-Enhanced Ultrasound and High-Resolution Magnetic Resonance Imaging for Carotid Atherosclerotic Plaques: A Systematic Review and Meta-Analysis.

The aim of this meta-analysis was to evaluate the diagnostic value of contrast-enhanced ultrasound (CEUS) and high-resolution magnetic resonance imaging (HR-MRI) in patients with carotid vulnerable plaques. A systematic review was conducted in PubMed, Embase, Cochrane Library, and Web of Science using the search terms carotid artery, atherosclerotic plaque, CEUS, contrast-enhanced ultrasound, HR-MRI, and high-resolution magnetic resonance. Studies published since the establishment of the library until December 2021 were retrieved. The statistical analyses were performed with Meta-DiSc version 1.4. Beyond that, the potential sources of heterogeneity for CEUS and HR-MRI were explored. Nine articles were included in this study. For CEUS, the pooled sensitivity and specificity for detecting carotid vulnerable plaques 91% (95% confidence interval [CI]: 84%, 95%) and 67% (95% CI: 54%, 79%), respectively. For HR-MRI, the pooled sensitivity and specificity were 78% (95% CI: 72%, 83%) and 65% (95% CI, 56%, 73%), respectively. The area under the summary receiver operating characteristic curve for CEUS and HR-MRI were 0.9218 and 0.8129, respectively. However, the difference in diagnostic accuracy between CEUS and HR-MRI diagnostic accuracy was not statistically significant. The study shows that the sensitivity of CEUS was higher than that of HR-MRI, and the specificity was similar to HR-MRI. CEUS and HR-MRI provide a similar diagnostic yield in detecting a vulnerable plaque. Thus, CEUS may be a useful tool for the diagnosis of carotid vulnerable plaques.

The Assessment of Carotid Atherosclerotic Plaque among Young Patients with Familial Hypercholesterolemia.

Objective Few data exist regarding when atherosclerotic changes occur among patients with familial hypercholesterolemia (FH). Carotid ultrasonography is a non-invasive method of evaluating this issue. The present study (1) compared the clinical utilities of carotid intima-media thickness (cIMT) and carotid plaque score (cPS) and (2) estimated the onset and progression of carotid atherosclerosis among patients with heterozygous FH (HeFH). Methods We retrospectively analyzed 511 patients under 30 years old who underwent carotid ultrasonography at our hospital from 2006 to 2019. We classified them into the HeFH group (n=78, 21.4±5.9 years old) and non-FH group (n=433, 23.4±6.0 years old) based on the clinical diagnosis and compared their cIMT and cPS values. In addition, we estimated the onset and progression of carotid atherosclerosis among young HeFH patients. Results There was no significant difference in the cIMT between the HeFH and non-FH groups (0.44 mm vs. 0.42 mm, p=0.25). In contrast, the cPS was significantly higher in the HeFH group than in the non-FH group (1.11 vs. 0.26, p=0.002). The regression equation for cPS of HeFH group was Y=-2.05+0.15X (r=0.37, p<0.001). Conclusion An assessment based on the cPS rather than the cIMT appears to be better to capture the progress of carotid atherosclerosis among young HeFH patients. Carotid atherosclerosis may start to develop at 14 years old in patients with HeFH.

A retrospective study of immunoglobulin E as a biomarker for the diagnosis of acute ischemic stroke with carotid atherosclerotic plaques.

ObjectiveIn this study, serum markers of acute ischemic stroke (AICS) with carotid artery plaque were retrospectively evaluated to establish a basis for discovering serological indicators for early warning of acute ischemic stroke (AICS).MethodsA total of 248 patients with AICS were enrolled in Lanzhou University Second Hospital from January 2019 to December 2020. The study population included 136 males and 112 females, 64 ± 11 years of age. Of these, there were 90 patients with a transient ischemic attack (TIA), including 60 males and 30 females, aged 64 ± 8 years old. Patients with AICS were stratified by carotid ultrasound into a plaque group (n = 154) and a non-plaque group (n = 94). A total of 160 healthy subjects were selected as the control group. Serum lipoprotein-associated phospholipase A2 (Lp-PLA2), amyloid A (SAA), immunoglobulin E (IgE), D-dimer (D-D), total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) were collected from all subjects. Multivariate logistic regression was used to analyze the risk factors of AICS with carotid plaque. ROC curve was used to analyze the diagnostic efficacy of AICS with carotid plaque.ResultsThe IgE, Lp-PLA2, SAA, LDL-C, TC, TG, and D-D levels in the AICS group were higher than those in the TIA group and healthy control group (P < 0.05). The IgE level was significantly higher than that in the healthy control group and TIA group. The IgE level in the AICS plaque group was significantly higher than that in the AICS non-plaque group (P < 0.01), and the Lp-PLA2 level was also different (P < 0.05). The incidence of AICS was positively correlated with Lp-PLA2, TC, IgE, TG, D-D, SAA and LDL-C (r = 0.611, 0.499, 0.478, 0.431, 0.386, 0.332, 0.280, all P < 0.05). The incidence of AICS with plaque was only positively correlated with IgE and Lp-PLA2 (r = 0.588, 0.246, P < 0.05). Logistic regression analysis showed that IgE and Lp-PLA2 were independent risk factors for predicting the occurrence of AICS with carotid plaque (P < 0.05). ROC curve analysis showed that the AUC of IgE (0.849) was significantly higher than other indicators; its sensitivity and specificity were also the highest, indicating that IgE can improve the diagnostic efficiency of AICS with carotid plaque.ConclusionIgE is a serum laboratory indicator used to diagnose AICS disease with carotid plaque, which lays a foundation for further research on potential early warning indicators of AICS disease.

Vascular Imaging Follow‐Up in Carotid Webs: Is There Vascular Remodeling?

Vascular Imaging Follow‐Up in Carotid Webs: Is There Vascular Remodeling?

Advances in Noninvasive Carotid Wall Imaging with Ultrasound: A Narrative Review.

Carotid atherosclerosis is a major cause for stroke, with significant associated disease burden morbidity and mortality in Western societies. Diagnosis, grading and follow-up of carotid atherosclerotic disease relies on imaging, specifically ultrasound (US) as the initial modality of choice. Traditionally, the degree of carotid lumen stenosis was considered the sole risk factor to predict brain ischemia. However, modern research has shown that a variety of other imaging biomarkers, such as plaque echogenicity, surface morphology, intraplaque neovascularization and vasa vasorum contribute to the risk for rupture of carotid atheromas with subsequent cerebrovascular events. Furthermore, the majority of embolic strokes of undetermined origin are probably arteriogenic and are associated with nonstenosing atheromas. Therefore, a state-of-the-art US scan of the carotid arteries should take advantage of recent technical developments and should provide detailed information about potential thrombogenic (/) and emboligenic arterial wall features. This manuscript reviews recent advances in ultrasonographic assessment of vulnerable carotid atherosclerotic plaques and highlights the fields of future development in multiparametric arterial wall imaging, in an attempt to convey the most important take-home messages for clinicians performing carotid ultrasound.

Identifying Hub Genes and Immune Cell Infiltration for the Progression of Carotid Atherosclerotic Plaques in the Context of Predictive and Preventive Using Integrative Bioinformatics Approaches and Machine-Learning Strategies.

Emerging evidence shows that carotid atherosclerosis is related to the activation of immune-related pathways and inflammatory cell infiltration. However, the immune-linked pathways that helped in the advancement of the carotid atherosclerotic plaque and the association of such plaques with the infiltration status of the body's immune cells still unclear. Here, the expression profiles of the genes expressed during the progression of the carotid atherosclerotic plaques were retrieved from the Gene Expression Omnibus database and 178 differentially expressed genes were examined. The Weighted Gene Coexpression Network Analysis technique identified one of the brown modules showed the greatest correlation with carotid atherosclerotic plaques. In total, 66 intersecting genes could be detected after combining the DEGs. LASSO regression analysis was subsequently performed to obtain five hub genes as potential biomarkers for carotid atherosclerotic plaques. The functional analysis emphasized the vital roles played by the inflammation- and immune system-related pathways in this disease. The immune cell infiltration results highlighted the significant correlation among the CD4+ T cells, B cells, macrophages, and CD8+ T cells. Thereafter, the gene expression levels and the diagnostic values related to every hub gene were further validated. The above results indicated that macrophages, B cells, CD4+ T cells, and CD8 + T cells were closely related to the formation of the advanced-stage carotid atherosclerotic plaques. Based on the results, it could be hypothesized that the expression of hub genes (C3AR1, SLAMF8, TMEM176A, FERMT3, and GIMAP4) assisted in the advancement of the early-stage to advanced-stage carotid atherosclerotic plaque through immune-related signaling pathways. This may help to provide novel strategies for the treatment of carotid plaque in the context of predictive, preventive, and personalized medicine.

Biomechanical Assessment of Macro-Calcification in Human Carotid Atherosclerosis and Its Impact on Smooth Muscle Cell Phenotype.

Intimal calcification and vascular stiffening are predominant features of end-stage atherosclerosis. However, their role in atherosclerotic plaque instability and how the extent and spatial distribution of calcification influence plaque biology remain unclear. We recently showed that extensive macro calcification can be a stabilizing feature of late-stage human lesions, associated with a reacquisition of more differentiated properties of plaque smooth muscle cells (SMCs) and extracellular matrix (ECM) remodeling. Here, we hypothesized that biomechanical forces related to macro-calcification within plaques influence SMC phenotype and contribute to plaque stabilization. We generated a finite element modeling (FEM) pipeline to assess plaque tissue stretch based on image analysis of preoperative computed tomography angiography (CTA) of carotid atherosclerotic plaques to visualize calcification and soft tissues (lipids and extracellular matrix) within the lesions. Biomechanical stretch was significantly reduced in tissues in close proximity to macro calcification, while increased levels were observed within distant soft tissues. Applying this data to an in vitro stretch model on primary vascular SMCs revealed upregulation of typical markers for differentiated SMCs and contractility under low stretch conditions but also impeded SMC alignment. In contrast, high stretch conditions in combination with calcifying conditions induced SMC apoptosis. Our findings suggest that the load bearing capacities of macro calcifications influence SMC differentiation and survival and contribute to atherosclerotic plaque stabilization.

A novel integrated angioscope-laser system for atherosclerotic carotid artery occlusion: Feasibility and techniques.

IntroductionAtherosclerotic extracranial carotid artery stenosis accounts for about 20%–30% of all strokes, which is one of the leading causes of adult morbidity and mortality. Although carotid endarterectomy (CEA) is still the mainly operational manner for atherosclerotic carotid artery stenosis/occlusion (ACAS/ACAO), and carotid angioplasty and stenting (CAS) have been used as an alternative, both CEA and CAS have limitations of their own, such as extensive invasiveness and in-stent restenosis.MethodsIn this study we established a novel interventional system in vitro to take advantage of both CEA and CAS. Twenty consecutive carotid atherosclerotic plaques were harvested from the patients who underwent CEA. The plaques were randomized into two groups and inserted into the pruned and sutured descending aortas of the swine in vitro. The ZebraScope™ was modified with a protective device on its flexible tip, so that the plaque could be dissected from the wall of parent carotid artery and ablated completely without damage to the carotid artery. The holmium:YAG (Ho:YAG) and thulium fiber laser (TFL) generators were alternately used when needed.ResultsAll the carotid atherosclerotic plaques were completely ablated by Ho:YAG laser and/or TFL. The Ho:YAG laser was more effective for the atherosclerotic plaques with severe calcification, while the TFL was more suitable for those with moderate calcification. There were still some thermal injury spots on the inner wall of the parent carotid artery caused by the laser in the non-protected group B. In the protected group A, on the contrary, there was no even a thermal injury spot was found on the relevant location except for one sample. The difference of ablating duration was statistically significant between group A (36.5 ± 4.79 min) and group B (63.4 ± 6.55 min) (P < 0.01).ConclusionAccording to our knowledge, this is the first attempt to ablate carotid atherosclerotic plaques assisted by the ZebraScope™ in vitro. The protective and dissecting device on the tip of the angioscope makes it safe and visible when the ablation is performed to carotid atherosclerotic plaques. The Ho:YAG laser and TFL are effective and safe for ablating the plaque in vitro.

Spectral analysis of ultrasound backscatter for non-invasive measurement of plaque composition

Carotid atherosclerotic plaque composition may be an important indication of patient risk for future cerebrovascular events. Ultrasound spectral analysis has the potential to provide a robust measure of plaque composition in vivo if the backscatter transfer function can be sufficiently isolated from the effects of attenuation from overlying tissue, receive and transmit transfer functions from the ultrasound system and transducer, and diffraction. This study examines the usefulness of the nonlinearly generated second harmonic portion of the backscatter signal and the effects of a variety of attenuation compensation techniques for noninvasively characterizing human carotid plaque using spectral analysis and machine learning. Post-beamformed ultrasound backscatter radiofrequency (RF) data were acquired from 6 normal subjects and 119 carotid endarterectomy patients prior to surgery. Plaque obtained following surgery was histologically processed, and regions of interest (ROI) corresponding to homogenous tissue types (fibrous/fibro-lipidic, hemorrhagic and/or necrotic core and calcified) were selected from RF data. Both the harmonic and fundamental power spectra for each ROI was obtained and normalized by data from a uniform phantom (0.5 dB/cm-MHz slope of attenuation). Additional attenuation compensation approaches were compared to simply using the reference phantom: (1) optimum power spectral shift estimation, (2) one-step adventitial, or (3) two-step adventitial. Spectral parameters extracted from both the fundamental and harmonic estimates of the backscatter transfer function of 363 ROI’s from 152 plaque specimens were used to train and test random forest and support vector machine classification models. The best results came from using spectral parameters derived from both the fundamental and second harmonic bands with a predictive accuracy of 65–68%, kappa statistic of 0.49–0.54, and accuracies of 84% for fibrous, 68–74% for hemorrhagic and/or necrotic core, and 78–81% for calcified ROI’s. The result indicated that the nonlinearly generated second harmonic portion of backscatter is useful for carotid plaque tissue characterization and that a reference phantom approach with a 0.5 dB/cm-MHz slope of attenuation works as well as more complicated approaches.

Identification of potential drug targets for vascular dementia and carotid plaques by analyzing underlying molecular signatures shared by them.

BackgroundVascular dementia (VaD) and carotid atherosclerotic plaques are common in the elderly population, conferring a heavy burden on families and society. Accumulating evidence indicates carotid atherosclerotic plaques to be a risk factor for VaD. However, the underlying mechanisms for this association are mainly unknown.Materials and methodsWe analyzed temporal cortex gene expression data of the GSE122063 dataset and gene expression data of the GSE163154 dataset to identify commonly differentially expressed genes (DEGs). Then we performed functional enrichment analysis, immune cell infiltration and evaluation, correlation analysis between differentially expressed immune-related genes (DEIRGs) and immune cells, receiver operating characteristic (ROC) analysis, and drug-gene analysis.ResultsWe identified 41 overlapped DEGs between the VaD and carotid atherosclerosis plaque datasets. Functional enrichment analyses revealed that these overlapped DEGs were mainly enriched in inflammatory and immune-related processes. Immunocyte infiltration and evaluation results showed that M0 macrophages, M2 macrophages, and T cells gamma delta had a dominant abundance in carotid atherosclerosis plaque samples, and M0 macrophages showed a significantly different infiltration percentage between the early and advanced stage plaques group. Resting CD4 memory T cells, M2 macrophages, and naive B cells were the top three highest infiltrating fractions in VaD. Furthermore, B cells and NK cells showed a different infiltration percentage between VaD and matched controls. We identified 12 DEIRGs, and the result of correlation analysis revealed that these DEIRGs were closely related to differentially expressed immune cells. We identified five key DEIRGs based on ROC analysis. The drug-gene interaction analysis showed that four drugs (avacopan, CCX354, BMS-817399, and ASK-8007) could be potential drugs for VaD and carotid atherosclerotic plaques treatment.ConclusionCollectively, these findings indicated that inflammatory and immune-related processes be a crucial common pathophysiological mechanism shared by VaD and carotid plaques. This study might provide new insights into common molecular mechanisms between VaD and carotid plaques and potential targets for the treatment.

Radiofrequency thermal balloon angioplasty of vulnerable atherosclerotic plaque accompanied by delta-aminolevulinic acid photodynamic therapy and catheter-based samarium-153 brachytherapy

Abstract Background The balloon angioplasty methods that are currently in use, cause to inflammation and subsequent neoatherosclerosis. Purpose The aim of this study was to evaluate the effect of combined photodynamic therapy and brachytherapy on inflammation and intimal hyperplasia reduction after radiofrequency thermal balloon angioplasty of carotid artery in an animal model of thin fibrous cap atheromatous plaque, wherein a high resolution diagnostic ultrasound is adjuncted with angioplasty and combination therapy system, with a goal of increased safety. Methods Briefly, New Zealand white rabbits were submitted to carotid artery vulnerable atherosclerotic plaque by primary intravascular balloon injury followed by a 1.5% cholesterol-rich diet for eight weeks. Histopathology results showed the formation of advanced atherosclerosis with a foam cell-rich atheromatous plaque, resulted in severe stenosis (&amp;gt;70%) in all of the rabbits' arteries. Then treatment group underwent B-mode ultrasound-guided radiofrequency thermal balloon angioplasty followed by catheter-based samarium-153 brachytherapy (153Sm, 18 Gy, β particles) and photosensitizer delta-aminolevulinic acid (delta-ALA)-mediated fiber optic catheter-based polarized light-emitting diodes (LEDs) violet light (λ±Δλ = 405±5 nm, E/A = 120 J/cm2) photodynamic therapy. Results Results from ultrasonography and histopathology showed a significant reduction in the mean value for macrophages, lymphocytes, mast cells, foam cells and hyperplastic vascular smooth muscle cells density after angioplasty in the treatment group compared with the other groups (p&amp;lt;0.05). Conclusion Apoptotic effect of brachytherapy in combination with cytotoxic and anti-inflammatory effect of delta-ALA photodynamic therapy on immune cells and hyperplastic vascular smooth muscle cells, can cause to reduce the neoatherosclerosis in the intimal layer. These findings provide the basis for developing of combined brachytherapy and photodynamic therapy for a successful clinical application in the inhibition of neoatherosclerosis after radiofrequency thermal balloon angioplasty. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Mehrad Research Lab

INTIMA-MEDIA THICKNESS OF CAROTID ARTERY IN PATIENTS WITH BEHÇET DISEASE

SESSION TITLE: Chest Infections and Disorders of the Pleura Abstract PostersSESSION TYPE: Original Investigation PostersPRESENTED ON: 10/18/2022 01:30 pm - 02:30 pmPURPOSE: Behcet's disease (BD) is systemic vasculitis, which affects all types and sizes of vessels. Increased carotid intima-media thickness (IMT) is parameter associated with subclinical atherosclerosis.To evaluate the IMT of carotid artery in patients with BDMETHODS: The study includes 95 patient with BD 45 healthy controls matched for age and gender. IMT were assessed by using high-resolution B-mode ultrasonography. High-sensitivity C-reactive protein (Hs CRP) concentration in the serum samples were measured by immunonephelometric assay (BN-100 Analyzer; Dade Behring).RESULTS: The male-to-female ratio was 3,7:1, the mean age of pts was 29.7 (23-35) yrs, the mean age at the disease onset - 19,9 (14-25) yrs, the mean disease duration - 9,6 (4-15) yrs. Arterial hypertension, smoked, diabetes mellitus, lipid profile, mean IMT carotid artery, IMT > 0,5-0,89 mm, IMT - 0,9 - 1,2 mm, IMT > 1,2 mm (plaques) were similar in BD pts compared with controls. In pts thinning IMT and concentration of hs CRP were significantly higher compared with controls (IMT <0,5 mm - 31,6% vs. 6,6%, p<0,05), (hs CRP 2,42 +-21,0 vs. 0,3 +-0,63, p <0,05). IMT correlate with age of pts, concentration of total cholesterol, LDL and hs CRP but did not created with clinical manifestation and disease duration. Carotid atherosclerotic plaques were found in 5 pts with BD - mean age 40,0+-8,1, who had traditional cardiovascular risk factors (high body masse index, hypertension) and received long time therapy with glucocorticoids.CONCLUSIONS: The thickness IMT in BD pts was lower than what we expected. The thinning IMT may be one of the risk factors for aneurysm formation in pts with BD.CLINICAL IMPLICATIONS: The thinning IMT may be one of the risk factors for aneurysm formation in pts with BD.DISCLOSURES: No relevant relationships by Zemfira AlekberovaNo relevant relationships by Lidia AnanyevaNo relevant relationships by Regina Goloeva SESSION TITLE: Chest Infections and Disorders of the Pleura Abstract Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/18/2022 01:30 pm - 02:30 pm PURPOSE: Behcet's disease (BD) is systemic vasculitis, which affects all types and sizes of vessels. Increased carotid intima-media thickness (IMT) is parameter associated with subclinical atherosclerosis.To evaluate the IMT of carotid artery in patients with BD METHODS: The study includes 95 patient with BD 45 healthy controls matched for age and gender. IMT were assessed by using high-resolution B-mode ultrasonography. High-sensitivity C-reactive protein (Hs CRP) concentration in the serum samples were measured by immunonephelometric assay (BN-100 Analyzer; Dade Behring). RESULTS: The male-to-female ratio was 3,7:1, the mean age of pts was 29.7 (23-35) yrs, the mean age at the disease onset - 19,9 (14-25) yrs, the mean disease duration - 9,6 (4-15) yrs. Arterial hypertension, smoked, diabetes mellitus, lipid profile, mean IMT carotid artery, IMT > 0,5-0,89 mm, IMT - 0,9 - 1,2 mm, IMT > 1,2 mm (plaques) were similar in BD pts compared with controls. In pts thinning IMT and concentration of hs CRP were significantly higher compared with controls (IMT <0,5 mm - 31,6% vs. 6,6%, p<0,05), (hs CRP 2,42 +-21,0 vs. 0,3 +-0,63, p <0,05). IMT correlate with age of pts, concentration of total cholesterol, LDL and hs CRP but did not created with clinical manifestation and disease duration. Carotid atherosclerotic plaques were found in 5 pts with BD - mean age 40,0+-8,1, who had traditional cardiovascular risk factors (high body masse index, hypertension) and received long time therapy with glucocorticoids. CONCLUSIONS: The thickness IMT in BD pts was lower than what we expected. The thinning IMT may be one of the risk factors for aneurysm formation in pts with BD. CLINICAL IMPLICATIONS: The thinning IMT may be one of the risk factors for aneurysm formation in pts with BD. DISCLOSURES: No relevant relationships by Zemfira Alekberova No relevant relationships by Lidia Ananyeva No relevant relationships by Regina Goloeva

The roles and mechanisms of miR-26 derived from exosomes of adipose-derived stem cells in the formation of carotid atherosclerotic plaque.

This study explored the serum concentrations of miR-26 in patients with carotid atherosclerosis (CAS) and defined the roles and mechanisms of miR-26 derived from the exosomes of adipose-derived stem cells (ADSC-exos). The carotid artery width was diagnosed by ultrasound examination in patients with different degrees of CAS. The serum levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) in patients were detected by biochemistry. The serum levels of miR-26 were determined by quantitative polymerase chain reaction (qPCR). A model of CAS in ApoE-/- mice fed with a rich-fat diet was established to analyze the regulatory effects of serum miR-26 on blood lipids in mice. Adipose mesenchymal stem cell lines transfected with miR-26 were established. The regulatory relationship between the expression levels of inflammatory factors, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-1β, and the expression levels of miR-26 in the supernatant of each group of cells was determined by qPCR. The ADSC-exos were extracted from ADSCs and injected into model mice through the tail vein. The therapeutic effect of ADSCs expressing miR-26 on model mice was evaluated by detecting the levels of inflammatory factors and blood lipids in the serum of the mice. The degree of atherosclerosis (AS) was positively associated with the intima-media thickness (IMT) of the carotid artery. The serum levels of miR-26 in patients were inversely correlated with the levels of blood lipids (TC, TG, and LDL-C), and positively correlated with HDL-C levels. Similarly, in the CAS mouse model, the serum levels of miR-26 were inversely correlated with the levels of blood lipids (TC, TG, and LDL-C), and positively correlated with HDL-C level. In ADSCs transfected with miR-26, the miR-26 expression in the cell supernatant was negatively regulated by the expression of inflammatory factors, TNF-α, IL-6, and IL-1β, in the cell supernatant. ADSC-exos expressing miR-26 has positive effects on correcting blood lipids and inflammatory factors in the mouse model of CAS. miR-26 has an active role in CAS and may be a novel target for the treatment of CAS in the future.

Exploring the risk factors for ischemic cerebrovascular disease in systemic lupus erythematosus: A single-center case-control study.

ObjectivesIschemic cerebrovascular disease (ICVD) is one of the most common and severe complications in systemic lupus erythematosus (SLE). We aim to explore the risk factors for ICVD in SLE and to assess their associated clinical characteristics.MethodsIn this study, 44 lupus patients with ICVD (ICVD-SLE) and 80 age- and sex-matched lupus patients without ICVD (non-ICVD-SLE) who were hospitalized in our center between 2014 and 2021 were enrolled. A comprehensive set of clinical and socio-demographic data was recorded. In the ICVD-SLE group, the modified Rankin score (mRS) at 90 days after the occurrence of ICVD, the brain MRI, and arterial ultrasonography findings were collected. Group comparisons were made with continuous variables using an independent t-test or the Mann–Whitney test, and with categorical variables using the chi-square test or Fisher exact test. Multivariate logistic regression analysis was performed to identify the risk factors for ICVD in SLE. Patients with ICVD-SLE were divided into three subgroups according to the gradations of intracranial arterial stenosis (ICAS). The subgroup comparisons were performed by one-way ANOVA test or Kruskal–Wallis test.ResultsOf the 44 patients with ICVD, 45% had a large-vessel ischemic stroke, 50% had a symptomatic lacunar stroke, and 9% had a transient ischemic attack. 2 (4.5%) had both large-vessel ischemic stroke and symptomatic lacunar stroke. Multivariate logistic regression analysis showed that cutaneous vasculitis (OR=7.36, 95% CI=2.11–25.65), anticardiolipin antibody (aCL) (OR=4.38, 95% CI=1.435–13.350), and lupus anticoagulant (LA) (OR=7.543,95% CI=1.789–31.808) were the risk factors, and hydroxychloroquine (HCQ) therapy (OR=0.198, 95% CI=0.078–0.502) was the protective factor, after controlling for confounders. During the analysis of the subgroups, no significant difference was observed between the patients in the group without internal carotid arterial occlusion (ICAS) and those with severe ICAS except for diagnostic delay. However, patients in the moderate ICAS group were older when SLE occurred (P<0.01), had a longer diagnostic delay (P<0.01), a lower percentage of hypocomplementemia (P=0.05) and steroids and HCQ therapy (P=0.01, P=0.05, respectively), a trend toward lower mRS score, but a higher incidence of carotid atherosclerotic plaque (P<0.01), when compared with the other two subgroups.ConclusionCutaneous vasculitis and antiphospholipid antibodies (aPLs) are associated with an increased risk of ICVD, while HCQ therapy may provide protection against ICVD in SLE. The ICVD in younger lupus patients is associated with complement-mediated inflammation and poorer outcome, and require immunosuppressive therapy, whereas the ICVD in elderly patients are characterized by moderate ICAS and carotid atherosclerotic plaques.

Identification of immune cell infiltration and diagnostic biomarkers in unstable atherosclerotic plaques by integrated bioinformatics analysis and machine learning.

ObjectiveThe decreased stability of atherosclerotic plaques increases the risk of ischemic stroke. However, the specific characteristics of dysregulated immune cells and effective diagnostic biomarkers associated with stability in atherosclerotic plaques are poorly characterized. This research aims to investigate the role of immune cells and explore diagnostic biomarkers in the formation of unstable plaques for the sake of gaining new insights into the underlying molecular mechanisms and providing new perspectives for disease detection and therapy.MethodUsing the CIBERSORT method, 22 types of immune cells between stable and unstable carotid atherosclerotic plaques from RNA-sequencing and microarray data in the public GEO database were quantitated. Differentially expressed genes (DEGs) were further calculated and were analyzed for enrichment of GO Biological Process and KEGG pathways. Important cell types and hub genes were screened using machine learning methods including least absolute shrinkage and selection operator (LASSO) regression and random forest. Single-cell RNA sequencing and clinical samples were further used to validate critical cell types and hub genes. Finally, the DGIdb database of gene–drug interaction data was utilized to find possible therapeutic medicines and show how pharmaceuticals, genes, and immune cells interacted.ResultsA significant difference in immune cell infiltration was observed between unstable and stable plaques. The proportions of M0, M1, and M2 macrophages were significantly higher and that of CD8+ T cells and NK cells were significantly lower in unstable plaques than that in stable plaques. With respect to DEGs, antigen presentation genes (CD74, B2M, and HLA-DRA), inflammation-related genes (MMP9, CTSL, and IFI30), and fatty acid-binding proteins (CD36 and APOE) were elevated in unstable plaques, while the expression of smooth muscle contraction genes (TAGLN, ACAT2, MYH10, and MYH11) was decreased in unstable plaques. M1 macrophages had the highest instability score and contributed to atherosclerotic plaque instability. CD68, PAM, and IGFBP6 genes were identified as the effective diagnostic markers of unstable plaques, which were validated by validation datasets and clinical samples. In addition, insulin, nivolumab, indomethacin, and α-mangostin were predicted to be potential therapeutic agents for unstable plaques.ConclusionM1 macrophages is an important cause of unstable plaque formation, and CD68, PAM, and IGFBP6 could be used as diagnostic markers to identify unstable plaques effectively.

Anti-Phosphatidylethanolamine and Anti-Phosphatidylserine Antibodies-Association with Renal Involvement, Atherosclerosis, Cardiovascular Manifestations, Raynaud Phenomenon and Disease Activity in Polish Patients with Systemic Lupus Erythematosus.

Objective. To evaluate the association between anti-phosphatidylethanolamine (aPE) and anti-phosphatidylserine (aPS) antibodies and cardiovascular risk, organ involvement and disease activity in systemic lupus erythematosus (SLE) patients. Methods. We studied 93 SLE patients and 30 controls. We analyzed levels of anti-phospholipid antibodies, including aPS and aPE, the profiles of antinuclear, anti-neutrophil cytoplasmic (ANCA) and anti-endothelial antibodies, carotid intima-media thickness (cITM) and atherosclerotic plaque presence, ankle-brachial and high resistance indices, atherosclerotic risk factors, organ manifestations and treatment. Results. Levels of aPS and aPE were significantly higher in SLE patients in comparison with the controls (p = 0.038 and p = 0.044, respectively). aPS was associated with the risk of Raynaud’s phenomenon (p = 0.021) development. aPE increased the risk of renal involvement (p = 0.049), cerebral stroke (p = 0.050), high vlues of cIMT (p = 0.041) development as well as occurrence of selected serological markers associated with activity of the disease such as anti-double stranded DNA (p = 0.021). The long duration of regular smoking (p = 0.021) and the high number of cigarettes/day (p = 0.015) were significantly associated with the risk of aPE occurrence. Conclusions. Patients with aPS and aPE are at risk of vascular involvement. Especially the presence of aPE may significantly increase the risk of thrombotic complications development in SLE patients without classical serological markers of APS. Finally, aPE might be used as a marker of disease activity and risk of renal injury development in this patient group. The classical atherosclerotic markers including lipid indices play an important role in complex analysis of cardiovascular risk in lupus patients and enable to identify patients at the highest risk and implement effective preventive, diagnostic and therapeutic procedures.

3D-Arterial analysis software and CEUS in the assessment of severity and vulnerability of carotid atherosclerotic plaque: a comparison with CTA and histopathology

PurposeOur purpose is to assess Multiparametric Ultrasound (MPUS) efficacy for evaluation of carotid plaque vulnerability and carotid stenosis degree in comparison with Computed Tomography angiography (CTA) and histology.Material and methods3D-Arterial Analysis is a 3D ultrasound software that automatically provides the degree of carotid stenosis and a colorimetric map of carotid plaque vulnerability.We enrolled 106 patients who were candidates for carotid endarterectomy. Prior to undergoing surgery, all carotid artery plaques were evaluated with Color-Doppler-US (CDUS), Contrast-Enhanced Ultrasound (CEUS), and 3D Arterial analysis (3DAA) US along with Computerized Tomographic Angiography (CTA) to assess the carotid artery stenosis degree. Post-surgery, the carotid specimens were fixed with 10% neutral buffered formalin solution, embedded in paraffin and used for light microscopic examination to assess plaque vulnerability morphological features.ResultsThe results of the CTA examinations revealed 91 patients with severe carotid stenoses with a resultant diagnostic accuracy of 82.3% for CDUS, 94.5% for CEUS, 98.4% for 3DAA, respectively. The histopathological examination showed 71 vulnerable plaques with diagnostic accuracy values of 85.8% for CDUS, 93.4% for CEUS, 90.3% for 3DAA, 92% for CTA, respectively.ConclusionsThe combination of CEUS and 3D Arterial Analysis may provide a powerful new clinical tool to identify and stratify “at-risk” patients with atherosclerotic carotid artery disease, identifying vulnerable plaques. These applications may also help in the postoperative assessment of treatment options to manage cardiovascular risks.

Identification of potential biomarkers and pathways associated with carotid atherosclerotic plaques in type 2 diabetes mellitus: A transcriptomics study.

Type 2 diabetes mellitus (T2DM) affects the formation of carotid atherosclerotic plaques (CAPs) and patients are prone to plaque instability. It is crucial to clarify transcriptomics profiles and identify biomarkers related to the progression of T2DM complicated by CAPs. Ten human CAP samples were obtained, and whole transcriptome sequencing (RNA-seq) was performed. Samples were divided into two groups: diabetes mellitus (DM) versus non-DM groups and unstable versus stable groups. The Limma package in R was used to identify lncRNAs, circRNAs, and mRNAs. Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, protein-protein interaction (PPI) network creation, and module generation were performed for differentially expressed mRNAs. Cytoscape was used to create a transcription factor (TF)-mRNA regulatory network, lncRNA/circRNA-mRNA co-expression network, and a competitive endogenous RNA (ceRNA) network. The GSE118481 dataset and RT-qPCR were used to verify potential mRNAs.The regulatory network was constructed based on the verified core genes and the relationships were extracted from the above network. In total, 180 differentially expressed lncRNAs, 343 circRNAs, and 1092 mRNAs were identified in the DM versus non-DM group; 240 differentially expressed lncRNAs, 390 circRNAs, and 677 mRNAs were identified in the unstable versus stable group. Five circRNAs, 14 lncRNAs, and 171 mRNAs that were common among all four groups changed in the same direction. GO/KEGG functional enrichment analysis showed that 171 mRNAs were mainly related to biological processes, such as immune responses, inflammatory responses, and cell adhesion. Five circRNAs, 14 lncRNAs, 46 miRNAs, and 54 mRNAs in the ceRNA network formed a regulatory relationship. C22orf34—hsa-miR-6785-5p—RAB37, hsacirc_013887—hsa-miR-6785-5p/hsa-miR-4763-5p/hsa-miR-30b-3p—RAB37, MIR4435-1HG—hsa-miR-30b-3p—RAB37, and GAS5—hsa-miR-30b-3p—RAB37 may be potential RNA regulatory pathways. Seven upregulated mRNAs were verified using the GSE118481 dataset and RT-qPCR. The regulatory network included seven mRNAs, five circRNAs, six lncRNAs, and 14 TFs. We propose five circRNAs (hsacirc_028744, hsacirc_037219, hsacirc_006308, hsacirc_013887, and hsacirc_045622), six lncRNAs (EPB41L4A-AS1, LINC00969, GAS5, MIR4435-1HG, MIR503HG, and SNHG16), and seven mRNAs (RAB37, CCR7, CD3D, TRAT1, VWF, ICAM2, and TMEM244) as potential biomarkers related to the progression of T2DM complicated with CAP. The constructed ceRNA network has important implications for potential RNA regulatory pathways.

Detecting vulnerable carotid plaque and its component characteristics: Progress in related imaging techniques.

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.