Progression Of Carotid Atherosclerotic Plaques Research Articles

Identification of metabolic components of carotid plaque in high-risk patients utilizing liquid chromatography-tandem mass spectrometry.

Carotid atherosclerosis is a chronic progressive vascular disease that can be complicated by stroke in severe cases. Prompt diagnosis and treatment of high-risk patients are quite difficult due to the lack of reliable clinical biomarkers. This study aimed to explore potential plaque metabolic markers of stroke-prone risk and relevant targets for pharmacological intervention. Carotid intima and plaque sample tissues were obtained from 20 patients with cerebrovascular symptoms of carotid origin. An untargeted metabolomics approach based on liquid chromatography-tandem mass spectrometry was utilized to characterize the metabolic profiles of the tissues. Multivariate and univariate analysis tools were used. A total of 154 metabolites were significantly altered in carotid plaque when compared with thickened intima. Of these, 62 metabolites were upregulated, whereas 92 metabolites were downregulated. Support vector machines identified the 15 most important metabolites, such as N-(cyclopropylmethyl)-N'-phenylurea, 9(S)-HOTrE, ACar 12:2, quinoxaline-2,3-dithiol, and l-thyroxine, as biomarkers for high-risk plaques. Metabolic pathway analysis showed that abnormal purine and nucleotide metabolism, amino acid metabolism, glutathione metabolism, and vitamin metabolism may contribute to the occurrence and progression of carotid atherosclerotic plaque. Our study identifies the biomarkers and related metabolic mechanisms of carotid plaque, which is stroke-prone, and provides insights and ideas for the precise prevention and targeted intervention of the disease.

Homocysteine Facilitates the Formation of Carotid Atherosclerotic Plaque Through Inflammatory and Noninflammatory Mechanisms.

Background: Elevated homocysteine (Hcy) was considered a significant risk factor in the development and progression of carotid atherosclerosis (CAS), which involves a combination of inflammatory and noninflammatory mechanisms. However, epidemiological surveys have presented conflicting results. In this study, we aim to offer an epidemiological viewpoint on how elevated Hcy impacts CAS and its potential mechanisms. Methods: Levels of high-sensitivity C-reactive protein (hsCRP) were measured to assess the inflammatory status. The estimation of CAS events was performed by assessing carotid intima-media thickness using Doppler ultrasonography. Univariate analysis was conducted to investigate the variations in biochemical parameters among three groups: normal, carotid atherosclerotic thickening (CAT), and carotid atherosclerotic plaque (CAP) formation. Logistic regression analysis was conducted to identify the risk factors associated with the progression of CAT and CAP. In addition, multivariate linear regression analysis was conducted to identify the independent factors that correlated with hsCRP levels. Results: The study encompassed 3897 participants, with 2992 (76.8%) being males and 905 (23.2%) being females. The incidence of CAT and CAP rose with higher Hcy levels, with an overall odds ratio (OR) of 2.04 [95% confidence intervals (CI) 1.69-2.40] for CAT and 2.68 (95% CI 2.32-3.05) for CAP. After adjusting for gender, age, and blood markers, the OR for CAT and CAP decreased, with an overall OR of 1.05 (95% CI 0.81-1.28) and OR of 1.24 (95% CI 1.02-1.46), respectively. CAP risk independently increased when Hcy level exceeded 19.7 μmol/L (P = 0.030), but not CAT risk (P = 0.299). The impact of hsCRP on CAS events is similar to that of Hcy, and a multiple linear analysis found a significant independent correlation between hsCRP and Hcy (P = 0.001). Conclusions: Elevated Hcy levels can facilitate the formation of CAP through both inflammatory and noninflammatory processes, but it does not independently influence CAT.

Comprehensive analysis identifies crucial genes associated with immune cells mediating progression of carotid atherosclerotic plaque.

Carotid atherosclerosis is prone to rupture and cause ischemic stroke in advanced stages of development. Our research aims to provide markers for the progression of atherosclerosis and potential targets for its treatment. We performed a thorough analysis using various techniques including DEGs, GO/KEGG, xCell, WGCNA, GSEA, and other methods. The gene expression omnibus datasets GSE28829 and GSE43292 were utilized for this comprehensive analysis. The validation datasets employed in this study consisted of GSE41571 and GSE120521 datasets. Finally, we validated PLEK by immunohistochemistry staining in clinical samples. Using the WGCNA technique, we discovered 636 differentially expressed genes (DEGs) and obtained 12 co-expression modules. Additionally, we discovered two modules that were specifically associated with atherosclerotic plaque. A total of 330 genes that were both present in DEGs and WGCNA results were used to create a protein-protein network in Cytoscape. We used four different algorithms to get the top 10 genes and finally got 6 overlapped genes (TYROBP, ITGB2, ITGAM, PLEK, LCP2, CD86), which are identified by GSE41571 and GSE120521 datasets. Interestingly, the area under curves (AUC) of PLEK is 0.833. Besides, we found PLEK is strongly positively correlated with most lymphocytes and myeloid cells, especially monocytes and macrophages, and negatively correlated with most stromal cells (e.g, neurons, myocytes, and fibroblasts). The expression of PLEK were consistent with the immunohistochemistry results. Six genes (TYROBP, ITGB2, ITGAM, PLEK, LCP2, CD86) were found to be connected with carotid atherosclerotic plaques and PLEK may be an important biomarker and a potential therapeutic target.

Association of carotid atherosclerotic plaque and intima-media thickness with the monocyte to high-density lipoprotein cholesterol ratio among low-income residents of rural China: a population-based cross-sectional study

BackgroundThe monocytes to high-density lipoprotein cholesterol ratio (MHR) has been identified as a potential biomarker for cardiovascular and cerebrovascular diseases. In this population-based cross-sectional study, we explored the relationships among carotid artery disease (CAD), including the presence of carotid atherosclerotic plaque (CAP) and carotid artery intima-media thickness (CIMT), the MHR, and related parameter changes.MethodsThis cross-sectional study, Conducted from April to June 2019 in a rural area of Tianjin, involved middle-aged and elderly participants. Based on carotid ultrasound examinations, participants were divided into CAP and non-CAP groups. Logistic regression and Receiver Operating Characteristic (ROC) curve analyses were utilized to assess MHR’s predictive value for CAP. Gender-specific analyses were also performed to examine predictive variations. The relationship between CIMT and MHR was evaluated using linear regression.ResultsOf the 2109 participants meeting the inclusion criteria, 51.6% were identified with CAP. Multivariate analysis revealed a significant association between MHR and CAP prevalence, (OR, 9.670; 95% CI, 2.359–39.631; P = 0.002), particularly in females (OR, 5.921; 95% CI, 1.823–19.231; P = 0.003), after adjusting for covariates. However, no significant correlation was found between CIMT and MHR when adjusted for other factors. The ROC analysis showed the area under the curve for MHR and CAP to be 0.569 (95% CI: 0.544–0.593; P < 0.001).ConclusionsThese findings suggested that it is crucial to enhance early screening and intervention for CAD, specifically focusing on the prevention and progression of CAP, to address the unique health challenges faced by low-income groups in rural settings. Emphasizing these preventive measures could significantly contribute to improving cardiovascular health outcomes in this vulnerable population.

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.

Bioinformatics analysis reveals the landscape of immune cell infiltration and immune-related pathways participating in the progression of carotid atherosclerotic plaques

Atherosclerosis is a systemic disease associated with inflammatory cell infiltration and activation of immune-related pathways. In our study, we aimed to uncover immune-related changes and explore novel immunological features in the development of carotid atherosclerotic plaques. First, we applied integrated bioinformatics methods, including CIBERSORT and gene set enrichment analysis (GSEA). The gene expression matrices GSE28829, GSE41571, and GSE43292 were obtained from the Gene Expression Omnibus (GEO) dataset. After a series of data pre-processing steps, the resulting combined expression matrices were analysed using the CIBERSORT, GSEA, and Cluster Profiler packages. After the comparison and analysis between the carotid atherosclerotic plaques in the early and advanced stages, we discovered that there is a higher percentage of activated memory CD4 T cells and a lower percentage of resting memory CD4 cells in advanced-stage plaques. Moreover, activation of memory CD4 T cells can promote the development of carotid atherosclerotic plaques. Additionally, FOXP3+ Treg cell maturation can also participate in the progression of carotid plaques.

Fucoidan Inhibits NLRP3 Inflammasome Activation by Enhancing p62/SQSTM1-Dependent Selective Autophagy to Alleviate Atherosclerosis.

NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation contributes to the progression of atherosclerosis, and autophagy inhibits inflammasome activation by targeting macrophages. We investigated whether fucoidan, a marine sulfated polysaccharide derived from brown seaweeds, could reduce NLRP3 inflammasome activation by enhancing sequestosome 1 (p62/SQSTM1)-dependent selective autophagy to alleviate atherosclerosis in high-fat-fed ApoE-/- mice with partial carotid ligation and differentiated THP-1 cells incubated with oxidized low-density lipoprotein (oxLDL). Fucoidan significantly ameliorated lipid accumulation, attenuated progression of carotid atherosclerotic plaques, deregulated the expression of NLRP3 inflammasome, autophagy receptor p62, and upregulated microtubule-associated protein light chain 3 (LC3)-II/I levels. Transmission electron microscopy and GFP-RFP-LC3 lentivirus transfection further demonstrated that fucoidan could activate autophagy. Mechanistically, fucoidan remarkably inhibited NLRP3 inflammasome activation, which was mostly dependent on autophagy. The inhibitory effects of fucoidan on NLRP3 inflammasome were enhanced by autophagy activator rapamycin (Rapa) and alleviated by autophagy inhibitor 3-methyladenine (3-MA). Fucoidan promoted the colocalization of NLRP3 and p62. Knockdown of p62 and ATG5 by small interfering RNA significantly reduced the inhibitory effects of fucoidan treatment on NLRP3 inflammasome. The data suggest that fucoidan can inhibit NLRP3 inflammasome activation by enhancing p62/SQSTM1-dependent selective autophagy to alleviate atherosclerosis.

Correlation between SHP-1 and carotid plaque vulnerability in humans

BackgroundAdvanced atherosclerotic plaques tend to indicate an increased risk of cerebral ischemic events. SH2 domain-containing protein tyrosine phosphatase 1 (SHP-1) is a class I classical nonreceptor protein tyrosine phosphatase associated with plaque stability, as shown by analysis of a Gene Expression Omnibus (GEO) dataset showing differences in mRNA levels. However, the correlation between SHP-1 and human carotid plaque stability at the protein level remains unclear. Methods and resultsThirty-nine carotid plaque tissue samples were acquired from 39 carotid artery stenosis patients after carotid endarterectomy. Hematoxylin and eosin, Masson trichrome, and CD68 staining was performed for pathological characterization, and immunohistochemical staining for SHP-1 was carried out. Within stable and unstable plaques, SHP-1 mainly accumulated in the necrotic area, plaque shoulder, and fibrous cap, similar to the distribution of CD68. A quantitative analysis of SHP-1 was carried out. The relative SHP-1-positive cell area was higher in the vulnerable group than in the stable group (P < .001). The number of symptomatic patients in the vulnerable group was no greater than that in the stable group (P = .098). Moreover, the integrated optical density (IOD)/area of SHP-1 was significantly higher in the vulnerable group than in the stable group (P < .001). Besides, SHP-1 colocalized with CD68 and vascular cell adhesion protein 1(VCAM-1). ConclusionsWe demonstrate that SHP-1 expression increases during carotid atherosclerotic plaque progression. The protein expression of SHP-1 was related to an increase in plaque instability in not only symptomatic but also asymptomatic patients with carotid artery stenosis. SHP-1 may play a role in atherosclerosis progression by macrophage polarization-mediated efferocytosis. Furthermore, SHP-1 may become a promising biomarker for plaque vulnerability in the future.

436 Prognostic value of calcium scoring in changes of echogenicity in carotid plaques

Abstract Background Atherosclerosis is a dynamic process, in which the characteristics of the plaques evaluated by imaging methods could represent the degree of inflamatory activity of the disease. Purpose Assess the value of the coronary calcium score in the changes of echogenicity of carotid plaques in a population with low-intermediate cardiovascular risk. Methods Patients with no cardiovascular history and low and intermediate Framingham risk score were evaluated. Patients attended at our institute for a preventive cardiovascular control between January 2012 and April 2013, and then a subsequent follow-up was made until January 2019. They were screened for coronary calcium scoring (CCS) and carotid plaque by ultrasound at first visit. Then the changes of carotid atherosclerotic disease were evaluated through new carotid ultrasound exam at follow up. A carotid artery plaque was defined as a localized protrusion of the vessel wall, which 1) extended into the lumen ≥ 1.5 mm, or 2) had a thickness exceeding the intima-media thickness (IMT) of the adjacent portion of the vessel wall by &amp;gt;50%. Plaque morphology was defined in terms of its echogenicity. Results 121 patients that have carotid atherosclerotic disease at first carotid ultrasound exam were included. The mean age was 61 ± 9 years, 72 (59%) male patients. Cardiovascular risk factors: hypertension: 68 (56%), dyslipidemia: 46 (38%), sedentary lifestyle: 24 (20%), overweight: 17 (14%), smoking: 29 (24%) and diabetes: 15 (12%). Median distribution of CCS was 192 (percentile distribution 25-75%: 8 – 224) Agatston units. Medium follow-up: 5 ± 1 year. At first ultrasonography study, 47 patients (39%) presented hypoechoic plaques, 61 patients (50%) isoechoic plaques and hyperechoic plaques in 13 patients (11%). After the follow-up, the distribution of the plates according to their sonographic characteristics was: hypoechoic plaques in 23 patients (19%), isoechoic plaques in 55 patients (45%) and hyperechoic plaques in 42 patients (36%). The incidence of the progression of sonographic changes of the carotid plaques varies according to CCS: 0-100:29%, 101-400: 54%, &amp;gt;401:53% (p &amp;lt; 0,001) Figure 1. The value of CCS was associated with the progression of carotid atherosclerotic plaque regardless of the use of statins and angiotensin-converting enzyme inhibitors or angiotensin 2 receptor blockers (Cox model p &amp;lt;0.001). Conclusions This study shows that there is an association between coronary calcium score and progression of carotid disease. Even in populations with low and intermediate cardiovascular risk, the higher the severity of the calcium score, the greater changes in the structure of the carotid plaque manifested in our work as changes in the echogenicity; regardless of the use of statins. These findings could be useful to assess the progression of atherosclerotic disease at a median follow up. Abstract 436 Figure. folow up

Gene expression profile analysis of the progression of carotid atherosclerotic plaques.

The present study aimed to examine the universal gene expression signature and the underlying molecular mechanisms involved in the progression of carotid atherosclerotic plaques. The gene expression dataset, GSE28829, containing 13 early and 16 advanced carotid atherosclerotic plaques was selected for analysis. The differentially expressed genes (DEGs) were identified and analyzed using bioinformatics analyses, including cluster analysis, Gene Ontology (GO) and pathway enrichment analyses. Finally, a protein-protein interaction (PPI) was constructed and analyzed. A total of 515 downregulated and 243 downregulated DEGs were identified. The cluster analysis revealed two separate two groups. In addition, the GO terms enriched by the upregulated DEGs were associated with immune response, and the downregulated DEGs were associated with cell adhesion. The upregulated DEGs were enriched in pathways associated with signaling in the immune system, and the downregulated DEGs were enriched in pathways associated with muscle contraction. In the PPI network analysis, ITGAM and ACTN2 had the highest decrees of connectivity in the upregulated and downregulated DEGs, respectively. These findings suggested that deregulation of the immune system and smooth muscle cell cytoskeleton accelerates the progression of carotid atherosclerotic plaques. The DEGs identified may offer potential in the prevention and treatment of atherosclerosis in the carotid artery.

Disease trends over time and CD4+CCR5+ T-cells expansion predict carotid atherosclerosis development in patients with systemic lupus erythematosus

Background and AimPatients with Systemic Lupus Erythematosus (SLE) present increased cardiovascular mortality compared to the general population. Few studies have assessed the long-term development and progression of carotid atherosclerotic plaque in SLE patients. Our aim was to investigate the association of clinical and laboratory markers of disease activity and classical cardiovascular risk factors (CVRF) with carotid atherosclerosis development in SLE patients in a prospective 5-year study. Methods and resultsClinical history and information on principal CVRFs were collected at baseline and after 5 years in 40 SLE patients (36 women, mean age 42 ± 9 years; 14.4 ± 7 years of mean disease duration) and 50 age-matched controls. Carotid Doppler ultrasonography was employed to quantify the atherosclerotic burden at baseline and at follow up. Clinimetrics were applied to assess SLE activity over time (SLEDAI). The association between basal circulating T cell subsets (including CD4+CCR5+; CD4+CXCR3+; CD4+HLADR+; CD4+CD45RA+RO−, CD4+CD45RO+RA− and their subsets) and atherosclerosis development was evaluated. During the 5-year follow up, 32% of SLE patients, developed carotid atherosclerosis compared to 4% of controls. Furthermore, considering SLEDAI changes over time, patients within the highest tertile were those with increased incidence of carotid atherosclerosis independently of CVRF. In addition, increased levels of CD4+CCR5+ T cells were independently associated with the development of carotid atherosclerosis in SLE patients. ConclusionSerial clinical evaluations over time, rather than a single point estimation of disease activity or CVRF burden, are required to define the risk of carotid atherosclerosis development in SLE patients. Specific T cell subsets are associated with long-term atherosclerotic progression and may further be of help in predicting vascular disease progression.

Short Telomeres, but Not Telomere Attrition Rates, Are Associated With Carotid Atherosclerosis.

Short telomeres are associated with atherosclerosis. However, the temporal relationship between atherosclerosis and telomere length is unclear. The objective of this work was to examine the temporal formation and progression of carotid atherosclerotic plaques in relation to telomere dynamics. In a longitudinal study, comprising 154 French men and women (aged 31-76 years at baseline), carotid plaques were quantified by echography, and telomere length on leucocytes was measured by Southern blots at baseline and follow-up examinations. Telomere attrition rates during the 9.5-year follow-up period were not different in individuals with plaques at both baseline and follow-up examinations (23.3±2.0 base pairs/y) than in individuals who developed plaques during the follow-up period (26.5±2.0 base pairs/y) and those without plaques at either baseline or follow-up examination (22.5±2.3 base pairs/y; P=0.79). At baseline, telomere length was associated with presence of carotid plaques (P=0.02) and with the number of regions with plaques (P=0.005). An interaction (P=0.03) between age and the presence of plaques was observed, such that the association between plaques and telomere length was more pronounced at a younger age. In conclusion, carotid atherosclerosis is not associated with increased telomere attrition during a 9.5-year follow-up period. Short telomere length is more strongly associated with early-onset than late-onset carotid atherosclerosis. Our results support the thesis that heightened telomere attrition during adult life might not explain the short telomeres observed in subjects with atherosclerotic disease. Rather, short telomeres antecedes the clinical manifestation of the disease.

Identification of Key Pathways and Genes in Advanced Coronary Atherosclerosis Using Bioinformatics Analysis.

Background Coronary artery atherosclerosis is a chronic inflammatory disease. This study aimed to identify the key changes of gene expression between early and advanced carotid atherosclerotic plaque in human. Methods Gene expression dataset GSE28829 was downloaded from Gene Expression Omnibus (GEO), including 16 advanced and 13 early stage atherosclerotic plaque samples from human carotid. Differentially expressed genes (DEGs) were analyzed. Results 42,450 genes were obtained from the dataset. Top 100 up- and downregulated DEGs were listed. Functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) identification were performed. The result of functional and pathway enrichment analysis indicted that the immune system process played a critical role in the progression of carotid atherosclerotic plaque. Protein-protein interaction (PPI) networks were performed either. Top 10 hub genes were identified from PPI network and top 6 modules were inferred. These genes were mainly involved in chemokine signaling pathway, cell cycle, B cell receptor signaling pathway, focal adhesion, and regulation of actin cytoskeleton. Conclusion The present study indicated that analysis of DEGs would make a deeper understanding of the molecular mechanisms of atherosclerosis development and they might be used as molecular targets and diagnostic biomarkers for the treatment of atherosclerosis.

P-Cresyl sulfate is associated with carotid arteriosclerosis in hemodialysis patients and promotes atherogenesis in apoE-/- mice.

p-Cresyl sulfate (PCS) is a risk factor of cardiovascular disease in patients with chronic kidney disease. Here we tested whether serum PCS levels were related to the rate and evolution of carotid atherosclerosis in hemodialysis patients and identified a potential mechanism. A total of 200 hemodialysis patients were categorized as with or without carotid atherosclerotic plaque and followed for 5 years. Serum PCS levels were found to be higher in patients with than without carotid atherosclerotic plaque and positively correlated with increased total plaque area during follow-up. Multiple logistic regression and mixed effects model analyses showed that serum PCS levels were independently associated with the incidence and progression of carotid atherosclerotic plaque. PCS induced inflammatory factor and adhesion molecule expression in endothelial cells and macrophages. In addition, PCS triggered monocyte-endothelial cell interaction in vitro and in vivo through increased production of reactive oxygen species. Compared with controls, increase of PCS levels produced by gavage promoted atherogenesis in 5/6-nephrectomized apoE-/- mice; a process attenuated by NADPH oxidase inhibitors. Thus, increased serum PCS levels are associated with the occurrence and progression of carotid atherosclerosis in hemodialysis patients and promote atherogenesis through increased reactive oxygen species production.

Beneficial clinical effects of grape seed proanthocyanidin extract on the progression of carotid atherosclerotic plaques.

BackgroundAtherosclerotic plaques indicate the occurrence of ischemia events and it is a difficult task for clinical physicians. Grape seed proanthocyanidin extract (GSPE) has been reported to exert an antiatherogenic effect by inducing regression of atherosclerotic plaques in animal experimental studies. In this study, the antiatherogenic effect of GSPE has been investigated in clinical use.MethodsConsecutive 287 patients diagnosed with asymptomatic carotid plaques or abnormal plaque free carotid intima-media thickness (CIMT) were randomly assigned to the GSPE group (n = 146) or control group (n = 141). The patients in the GSPE group received GSPE 200 mg per day orally, while patients in the control group were only enrolled in a lifestyle intervention program. Carotid ultrasound examination was performed at baseline and 6, 12, 24 months during follow-up. Mean maximum CIMT (MMCIMT), plaque score, echogenicity of plaques and ischemic vascular events were recorded.ResultsAs anticipated, after treatment, GSPE resulted in significant reduction in MMCIMT progression (4.2% decrease after six months, 4.9% decrease after 12 months and 5.8% decrease after 24 months) and plaque score (10.9% decrease after six months, 24.1% decrease after 12 months and 33.1% decrease after 24 months) for the primary outcome, while MMCIMT and plaque score were stable and even increased with the time going on in control group. The number of plaques and unstable plaques also decreased after treatment of GSPE. Furthermore, the carotid plaque can disappear after treatment with GSPE. The incidence rate for transitory ischemic attack (TIA), arterial revascularization procedure, and hospital readmission for unstable angina in GSPE group were statistically significant lower (P = 0.02, 0.08, 0.002, respectively) compared with the control group.ConclusionsGSPE inhibited the progression of MMCIMT and reduced carotid plaque size in GSPE treated patients, and with extended treatment, the superior efficacy on MMCIMT and carotid plaque occurred. Furthermore, the GSPE group showed lower rates of clinical vascular events.

Sustained Acceleration in Carotid Atherosclerotic Plaque Progression With Intraplaque Hemorrhage: A Long-Term Time Course Study

This study sought to determine the immediate and long-term effects of intraplaque hemorrhage (IPH) on plaque progression in the carotid artery. Previous studies have associated IPH in the carotid artery with more rapid plaque progression. However, the time course and long-term effect remain unknown. Carotid magnetic resonance imaging is a noninvasive imaging technique that has been validated with histology for the accurate in vivo detection of IPH and measurement of plaque burden. Asymptomatic subjects with 50% to 79% carotid stenosis underwent carotid magnetic resonance imaging at baseline and then serially every 18 months for a total of 54 months. Subjects with IPH present in at least 1 carotid artery at 54 months were selected. Subsequently, presence/absence of IPH and wall volume were determined independently in all time points for both sides. A piece-wise progression curve was fit by using a linear mixed model to compare progression rates described as annualized changes in wall volume between periods defined by their relationship to IPH development. From 14 subjects who exhibited IPH at 54 months, 12 arteries were found to have developed IPH during the study period. The progression rates were -20.5 ± 13.1, 20.5 ± 13.6, and 16.5 ± 10.8 mm(3)/year before, during, and after IPH development, respectively. The progression rate during IPH development tended to be higher than the period before (p = 0.080) but comparable to the period after (p = 0.845). The progression rate in the combined period during/after IPH development was 18.3 ± 6.5 mm(3)/year, which indicated significant progression (p = 0.008 compared with a slope of 0) and was higher than the period before IPH development (p = 0.018). No coincident ischemic events were noted for new IPH. The development of IPH posed an immediate and long-term promoting effect on plaque progression. IPH seems to alter the biology and natural history of carotid atherosclerosis. Early identification of patients with IPH may prove invaluable in optimizing management to minimize future sequelae.

A negative correlation between human carotid atherosclerotic plaque progression and plaque wall stress: In vivo MRI-based 2D/3D FSI models

It is well accepted that atherosclerosis initiation and progression correlate positively with low and oscillating flow wall shear stresses (FSS). However, this mechanism cannot explain why advanced plaques continue to grow under elevated FSS conditions. In vivo magnetic resonance imaging (MRI)-based 2D/3D multi-component models with fluid–structure interactions (FSI, 3D only) for human carotid atherosclerotic plaques were introduced to quantify correlations between plaque progression measured by wall thickness increase (WTI) and plaque wall (structure) stress (PWS) conditions. A histologically validated multi-contrast MRI protocol was used to acquire multi-year in vivo MRI images. Our results using 2D models (200–700 data points/patient) indicated that 18 out of 21 patients studied showed significant negative correlation between WTI and PWS at time 2 (T2). The 95% confidence interval for the Pearson correlation coefficient is ( - 0.443 ,- 0.246 ) , p < 0.0001 . Our 3D FSI model supported the 2D correlation results and further indicated that combining both plaque structure stress and flow shear stress gave better approximation results (PWS, T2: R 2 = 0.279 ; FSS, T1: R 2 = 0.276 ; combining both: R 2 = 0.637 ). These pilot studies suggest that both lower PWS and lower FSS may contribute to continued plaque progression and should be taken into consideration in future investigations of diseases related to atherosclerosis.

Presence of Intraplaque Hemorrhage Stimulates Progression of Carotid Atherosclerotic Plaques: A High-Resolution Magnetic Resonance Imaging Study

Presence of Intraplaque Hemorrhage Stimulates Progression of Carotid Atherosclerotic Plaques: A High-Resolution Magnetic Resonance Imaging Study

Predictors of carotid atherosclerotic plaque progression as measured by noninvasive magnetic resonance imaging

The purpose of this in vivo MRI study was to quantify changes in atherosclerotic plaque morphology prospectively and to identify factors that may alter the rate of progression in plaque burden. Sixty-eight asymptomatic subjects with ≥50% stenosis, underwent serial carotid MRI examinations over an 18-month period. Clinical risk factors for atherosclerosis, and medications were documented prospectively. The wall and total vessel areas, matched across time-points, were measured from cross-sectional images. The normalized wall index (NWI = wall area/total vessel area), as a marker of disease severity, was documented at baseline and at 18 months. Multiple regression analysis was used to correlate risk factors and morphological features of the plaque with the rate of progression/regression. On average, the wall area increased by 2.2% per year ( P = 0.001). Multiple regression analysis demonstrated that statin therapy ( P = 0.01) and a normalized wall index >0.64 ( P = 0.001) were associated with a significantly reduced rate of progression in mean wall area. All other documented risk factors were not significantly associated with changes in wall area. Findings from this study suggest that increased normalized wall index and the use of statin therapy are associated with reduced rates of plaque progression amongst individuals with advanced, asymptomatic carotid atherosclerosis.

Issue Highlights

HomeCirculationVol. 111, No. 21Issue Highlights Free AccessIn BriefPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessIn BriefPDF/EPUBIssue Highlights Originally published31 May 2005https://doi.org/10.1161/circ.111.21.2711Circulation. 2005;111:2711RHO-KINASE INHIBITOR IMPROVES INCREASED VASCULAR RESISTANCE AND IMPAIRED VASODILATION OF THE FOREARM IN PATIENTS WITH HEART FAILURE, by Kishi et al.Although increased vascular tone is a well-recognized feature in heart failure, the mechanisms responsible are incompletely understood. When activated by the small GTPase Rho, Rho-kinase inhibits the activity of myosin light chain phosphatase, thereby increasing vascular smooth muscle contraction. A Rho-kinase inhibitor, fasudil, was administered via the brachial artery to 26 patients with NYHA functional class II and III heart failure and to 26 control subjects, and forearm vascular resistance was determined by using plethesmography. Fasudil caused vasodilation and improved the vasodilation induced by reactive hyperemia in the patients with heart failure but not in the control subjects. By comparison, nitroprusside caused vasodilation in both groups. These observations suggest the involvement of Rho-kinase in mediating increased vascular tone in heart failure and raise the possibility of a new therapeutic approach. See p 2741.PRESENCE OF INTRAPLAQUE HEMORRHAGE STIMULATES PROGRESSION OF CAROTID ATHEROSCLEROTIC PLAQUES: A HIGH-RESOLUTION MAGNETIC RESONANCE IMAGING STUDY, by Takaya et al.Hemorrhage into atherosclerotic plaques has been recently reported in histopathologic studies, associated with larger plaque necrotic cores, as well as greater lipid content and macrophage infiltration. Whether intraplaque hemorrhage is simply associated with larger or more complex plaques or indeed stimulates plaque progression has not been clarified. In this issue, Takaya and colleagues use serial cardiovascular magnetic resonance imaging studies of the carotid arteries over 18 months in patients with carotid atherosclerosis to demonstrate that the presence of intraplaque hemorrhage on the initial examination was associated with greater progression of plaque atherosclerosis. Those with hemorrhage at baseline had greater progression of lipid-rich necrotic core volume as well as wall volume, independent of the volume of hemorrhage components, and were also more likely to have recurrent plaque hemorrhage. These important data suggest that intraplaque hemorrhage contributes significantly to the acceleration of atherosclerosis in this vascular bed. See p 2768.EXPRESSION OF HUMAN MYELOPEROXIDASE BY MACROPHAGES PROMOTES ATHEROSCLEROSIS IN MICE, by McMillen et al.The relation between oxidative stress and atherosclerosis is complex. Recent developments suggest that myeloperoxidase, a neutrophil enzyme, may mediate oxidative events important to atherosclerosis. Early studies examining how this enzyme may promote atherosclerosis were hampered by the lack of an appropriate animal model. This hurdle to studying myeloperoxidase has now been overcome by the development of a mouse expressing the human myeloperoxidase gene. McMillen and colleagues report this new finding and demonstrate how bone marrow-derived human myeloperoxidase can accelerate atherosclerosis. See p 2798.Visit http://www.circ.ahajournals.org:Cardiology Patient PageTreatment of Elevated Cholesterol. See p e360.Images in Cardiovascular MedicineA Case of Transient Constrictive Pericarditis. See p e364.Constrictive Epicarditis as an Unusual Cause of Constrictive Physiology: Typical Presentation With Unusual Pathology. See p e365. Download figureDownload PowerPointTwo-Dimensional and Real-Time Three-Dimensional Echocardiographic Fetal Diagnosis of Aorto-Ventricular Tunnel. See p e367.CorrespondenceSee p e369. Previous Back to top Next FiguresReferencesRelatedDetails May 31, 2005Vol 111, Issue 21 Advertisement Article InformationMetrics https://doi.org/10.1161/circ.111.21.2711 Originally publishedMay 31, 2005 PDF download Advertisement