Artery Atherosclerotic Plaques Research Articles

Progressive changes of elastic moduli of arterial wall and atherosclerotic plaque components during plaque development in human coronary arteries.

Stiffness of the arterial wall and atherosclerotic plaque components is a determinant of the stress field within plaques, which has been suggested to be an indicator of plaque vulnerability. The diversity and inhomogeneous structure of atherosclerotic lesions complicate the characterization of plaque components. In the present study, stiffness of the arterial wall and atherosclerotic plaque components in human coronary arteries was examined in early and developed atherosclerotic lesions. The force-spectroscopy mode of the atomic force microscope and histological examination were used for determination of elastic moduli at specified locations within samples. Fibrous cap (E = 14.1 ± 3.8kPa) showed lower stiffness than the fibrous tissue beneath the lipid pool (E = 17.6 ± 3.2kPa). Calcification zones (E = 96.1 ± 18.8kPa) and lipid pools (E = 2.7 ± 1.8kPa) were the stiffest and softest components of atherosclerotic lesions, respectively. The increase of media stiffness (%44.8) and reduction of the elastic modulus of the internal elastic lamina (%28.9) was observed in coronary arteries. Moreover, significant differences were observed between the stiffness of medial layer in diseased parts and free-plaque segments in incomplete plaques of coronary arteries. Our results can be used for better understanding of remodeling mechanisms of the arterial wall with plaque development. Graphical abstract Stiffness alteration of the arterial wall and atherosclerotic plaque components with plaque development in coronary arteries.

Associations of sclerostin with carotid artery atherosclerosis and all-cause mortality in Chinese patients undergoing maintenance hemodialysis

BackgroundPrevious clinical studies found inconsistent relationship between circulating sclerostin levels and treatment outcome in patients undergoing maintenance hemodialysis (MHD). Therefore, this study aimed to assess the associations of sclerostin with carotid artery atherosclerosis and all-cause mortality in Chinese patients undergoing MHD.MethodsThis retrospective study assessed 84 patients undergoing MHD at the Nephrology Department of Beijing Hospital from January to April 2012, with a median follow-up of 61.2 months (range: 11.5 to 63 months). Carotid artery intima-media thicknesses (CIMTs) and atherosclerotic plaques were measured by B-mode Doppler ultrasound at baseline. Blood samples were collected for measuring serum sclerostin and soluble klotho (s-klotho) levels. The associations of sclerostin levels with carotid artery atherosclerosis was evaluated by correlation methods. Predictive factors of mortality were assessed by multivariate COX regression.ResultsBaseline serum sclerostin averaged 162.01 pmol/L, with an interquartile range of 121.69 to 225.22 pmol/L, while CIMT values were 1.35 ± 0.39 mm. Carotid artery atherosclerotic plaques were detected in 68 subjects (81%). Subjects with sclerostin levels above the median value had higher CIMT (p = 0.038) and higher prevalence of atherosclerotic plaque (p = 0.025). During follow-up, 27 patients died; Kaplan-Meier curves indicated that subjects with high sclerostin levels (above the median value at baseline) had shorter survival (log rank p = 0.011). In multivariate COX regression analysis, serum sclerostin (HR, 1.095; 95% confidence interval [CI] 1.022–1.174, p = 0.010) and albumin (HR, 0.742; 95%CI 0.612–0.900, p = 0.002) levels were independent predictors of all-cause mortality.ConclusionsSclerostin is positively associated with CIMT. In addition, patients with low baseline serum sclerostin undergoing MHD show better survival.

Antithrombotic treatment is associated with intraplaque haemorrhage in the atherosclerotic carotid artery: a cross-sectional analysis of The Rotterdam Study.

AimsAntithrombotic treatment plays a key role in stroke prevention, but their direct effects on the composition of carotid artery atherosclerotic plaques are unknown. To investigate the association of antithrombotic treatment with carotid artery plaque composition, with a specific focus on an intraplaque haemorrhage (IPH).Methods and resultsFrom the population-based Rotterdam Study, 1740 participants with carotid atherosclerosis on ultrasound (mean age 72.9 years, 46.0 women) underwent magnetic resonance imaging of the carotid arteries to assess plaque composition. Information on the use of oral anticoagulants [vitamin K antagonists (VKA)] and antiplatelet agents (salicylates), including duration of use and dosage, was obtained from pharmacy records for all participants. We used logistic regression models to assess the association between the use of anticoagulants and antiplatelet agents, and the different plaque components adjusting for confounders. Current and past use of VKA [adjusted odds ratio (OR): 1.88, 95% confidence interval (CI): 0.74–4.75 and OR 1.89, 95% CI: 0.91–3.93] and antiplatelet agents (OR: 1.22, 95% CI: 0.91–1.62), and (OR: 1.23, 95% CI: 0.86–1.75) showed positive trend with a higher presence of IPH. Also, a longer duration of use was associated with a higher frequency of IPH (OR: 3.15, 95% CI: 1.23–8.05) for the use of VKA, and longer duration of the use for antiplatelet agents showed a positive trend (OR: 1.21, 95% CI: 0.88–1.67). We also found that higher levels of international normalized ratio above 2.97 for VKA (OR: 1.48, 95% CI: 1.03–2.15) and higher daily defined dosage than 1.0 for antiplatelet agents (OR: 1.50, 95% CI: 1.21–1.87) were related to a higher frequency of IPH. We found no association with lipid core or calcification.ConclusionsThe use of antithrombotic treatment relates to a higher frequency of IPH in carotid atherosclerotic plaques.

MicroRNA-221/222 expression in atherosclerotic coronary artery plaque versus internal mammarian artery and in peripheral blood samples

Background: Atherosclerosis is a disease of the arterial wall with predilection to some sites on others. MicroRNAs (miRNAs) are a class of the non-coding RNAs regulating the target gene expression at post-transcriptional level. Different miRNAs were found at distinct stages of plaque development and expression of miRNAs’ might play an important role in the local behaviour of atherosclerotic plaques.Objective: We aimed to investigate and compare mirR-221/222 expression levels in tissues and in circulation in patients with and without overt atherosclerosis.Methods: RNA was isolated from 40 tissues as 20 tissue samples from coronary artery atherosclerotic plaques (CAAP) and internal mammary arteries (IMA), obtained from same individual) and 80 blood (44 patients with atherosclerosis and 36 healthy subjects) samples. MiR-221/222 expression levels were measured using real time PCR.Results: Expression levels of miR-221 was significantly increased in CAAP compared with completely atherosclerosis-free IMA tissues with a 8.94 times fold-change (p = 0.015). The miR-221 expression in tissue samples was significantly different in patients with hypercholesterolemia (p = 0.010), hypertension (p = 0.018) and family history of CAD (p = 0.033) versus not. Expression of miR-222 was not statistically significant between the two tissue samples overall.Conclusions: MiR-221 may be a potential biomarker for local atherosclerotic behavior

Loss of Insulin Actions on Arterial Smooth Muscle Cells May Enhance Unstable Atherosclerotic Plaque Formation

Formation of unstable atherosclerotic plaque, a major cause of cardiovascular mortality, is accelerated in insulin resistance and diabetes. Previous studies have suggested that endothelial dysfunction and systemic hyperlipidemia due to loss of insulin actions can accelerated its formation. However, the mechanism for insulin resistance to accelerate the various pathologies of unstable plaque, such as decreases in VSMC and extra cellular matrix (ECM) and increased inflammatory cells, have not been defined. Since insulin actions on the vascular wall are diminished in insulin resistant states, we assessed the loss of insulin action in VSMC and its effect on the formation of atherosclerotic plaque. Insulin receptor (IR) was specifically deleted from VSMC by breeding SM22 a promoter Cre and IR Flox mice to produce SMIRKO mice which were mated with ApoE-/- mice to generate SMIRKO/ ApoE-/- mice. Cultured VSMC from SMIRKO/ApoE-/- mice showed decreased insulin signaling and stimulated proliferation by >50%, but not to PDGF. Weight, blood pressure, glucose, and systemic insulin tolerance were comparable between ApoE-/- and SMIRKO/ApoE-/- mice; which were fed with normal chow to mimic pathophysiological hyperlipidemia encountered clinically. Surprisingly, SMIRKO/ ApoE-/- mice developed significantly more atherosclerotic aortic plaques (Sudan IV staining for lipid content) compared to ApoE-/- mice with parallel increases of macrophage content and inflammatory cytokines such as IL18 and ICAM1. In contrast, SMC as measured by SM22α staining was decreased with elevation of necrotic plaques (p<0.05). Further, proliferative index of VSMC as measured by Ki67 staining and expression of hyaluronan synthase-2 were decreased. Thus, surprisingly, the loss of insulin’s specific actions on VSMC to increase proliferation increased inflammatory cell influx as observed in insulin resistance, may accelerated formation of unstable plaques in diabetes. Disclosure Q. Li: None. J. Fu: None. K. Park: None. C. Rask-Madsen: Research Support; Self; Novo Nordisk A/S. G.L. King: Research Support; Self; Sanofi-Aventis.

Population distribution of traditional and the emerging cardiovascular risk factors carotid plaque and IMT: the REFINE-Reykjavik study with comparison with the Tromsø study

ObjectivesPopulation statistics for carotid plaque and cardiovascular risk factors reported in scientific journals are usually presented as averages for the population or age and sex adjusted, rather than sex and...

P-79 - Effects of a novel selenosugar on primary human vascular cells, mouse aortic rings and atherosclerosis in apoE-/- mice

Atherosclerosis is characterized by chronic low-grade inflammation, large numbers of activated leukocytes, and the deposition of cholesterol and lipids in the artery wall. This project has investigated a novel seleno-sugar (1,4-anhydro-4-seleno-D-talitol, SeTal) as a potential regulator of oxidative stress, inflammation and atherosclerosis. SeTal did not affect the viability of human coronary artery endothelial and smooth muscle cells at low mM concentrations, or modulate thioredoxin reductase 1 or glutathione peroxidase 1 activity or levels. Concurrent or pre-treatment of cells with SeTal protected against toxicity induced by H2O2 or HOCl. Studies on murine aortic rings showed that high concentrations of SeTal alone induced aortic relaxation on long-term treatment, and preserved endothelial cell-dependent relaxation on exposure to 50 µM HOCl. Oral dosing with SeTal (via drinking water) of apoE-/- mice did not affect weight gain, water consumption, or animal welfare. Intact SeTal was detected in plasma, liver and kidneys at micromolar levels. Plasma total cholesterol, triglycerides, and the inflammatory markers MCP-1, IL-6 and SAA were unaffected. The effects of SeTal on arterial atherosclerotic plaque size and composition will be presented.

Identification of high-risk plaque features in intracranial atherosclerosis: initial experience using a radiomic approach

ObjectivesTo evaluate a quantitative radiomic approach based on high-resolution magnetic resonance imaging (HR-MRI) to differentiate acute/sub-acute symptomatic basilar artery plaque from asymptomatic plaque.MethodsNinety-six patients with basilar artery stenosis underwent HR-MRI between January 2014 and December 2016. Patients were scanned with T1- and T2-weighted imaging, as well as T1 imaging following gadolinium-contrast injection (CE-T1). The stenosis value, plaque area/burden, lumen area, minimal luminal area (MLA), intraplaque haemorrhage (IPH), contrast enhancement ratio and 94 quantitative radiomic features were extracted and compared between acute/sub-acute and asymptomatic patients. Multi-variate logistic analysis and a random forest model were used to evaluate the diagnostic performance.ResultsIPH, MLA and enhancement ratio were independently associated with acute/subacute symptoms. Radiomic features in T1 and CE-T1 images were associated with acute/subacute symptoms, but the features from T2 images were not. The combined IPH, MLA and enhancement ratio had an area under the curve (AUC) of 0.833 for identifying acute/sub-acute symptomatic plaques, and the combined T1 and CE-T1 radiomic approach had a significantly higher AUC of 0.936 (p = 0.01). Combining all features achieved an AUC of 0.974 and accuracy of 90.5%.ConclusionsRadiomic analysis of plaque texture on HR-MRI accurately distinguished between acutely symptomatic and asymptomatic basilar plaques.Key Points• High-resolution magnetic resonance imaging can assess basilar artery atherosclerotic plaque.• Radiomic features in T1 and CE-T1 images are associated with acute symptoms.• Radiomic analysis can accurately distinguish between acute symptomatic and asymptomatic plaque.• The highest accuracy may be achieved by combining radiomic and conventional features.

Minocycline Inhibits PDGF‐BB‐induced Human Aortic Smooth Muscle Cell Proliferation and Migration via Induction of RECK

Minocycline is an FDA‐approved tetracycline antibiotic that exerts anti‐inflammatory and anti‐apoptotic effects independent of its bactericidal activity. For example, it attenuates neointima formation after arterial injury and atherosclerotic plaque development in an animal model of diet‐induced atherosclerosis via inhibition of smooth muscle cell (SMC) proliferation and migration; however, the molecular mechanisms underlying this inhibition are not completely known. Here we investigated whether minocycline inhibits PDGF‐BB‐induced primary human aortic SMC (HASMC) proliferation and migration in vitro. Our results show that PDGF‐BB stimulates proliferation (~2.92‐fold, P<0.05) and migration (~1.8‐fold, P<0.05) of HASMC via a redox‐sensitive mechanism involving NOX2 (inhibited by gp91dstat) and NOX4 (inhibited by GKT137831). Reversion‐Inducing‐Cysteine‐Rich Protein with Kazal Motifs (RECK) is a cell surface expressed, membrane anchored matrix metalloproteinase inhibitor. For the first time, our results show that PDGF‐BB downregulates RECK expression in a time‐dependent manner (by ~80% at 6 h, n=3, P<0.01), but induces miR‐221 and miR‐222 expression (~1.8‐fold and ~2.23‐fold, respectively). The reporter assays revealed that both miRs bind the 3′UTR of RECK mRNA, inhibiting its expression by ~50% (P<0.01). Supporting these observations, transduction of miR‐221 or miR‐222 mimics suppress RECK expression, but their antagomirs reverse PDGF‐BB‐induced inhibition of HASMC proliferation and migration. Further investigations revealed that PDGF‐BB activates the redox‐sensitive nuclear transcription factors NF‐kB and AP‐1 in HASMC, and shRNA directed against the AP‐1 subunit c‐Jun and the p65 subunit of NF‐kB each inhibit PDGF‐BB‐induced miR‐221 or miR‐222 expression, suggesting that PDGF‐BB suppresses RECK expression in HASMC in part via AP‐1‐ and NF‐kB‐dependent miR‐221 and miR‐222 induction. Notably, minocycline increases RECK expression dose‐dependently within the therapeutic dose of 1–100 μM, and inhibits PDGF‐BB‐induced HASMC proliferation and migration. Intriguingly, silencing RECK reverses the inhibitory effects of minocycline on PDGF‐BB‐induced migration and proliferation. Together, these results demonstrate that PDGF‐BB downregulates RECK expression in HASMC via AP‐1‐ and NF‐kB‐dependent miR‐221 and miR‐222 induction, and minocycline reverses PDGF‐BB‐induced ROS generation, miR‐221 and miR‐222 induction, and RECK suppression. These findings suggest that the induction of RECK is one of the mechanisms by which minocycline exerts vasculoprotective effects.Support or Funding InformationNIH R01‐HL‐070241 (PD)VA Merit Award I01‐BX002255 (BC)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Association of monocyte to high-density lipoprotein cholesterol ratio with carotid artery intima-media thickness in patients with systemic lupus erythematosus.

The purpose of this study was to evaluate the relationship between monocyte to high-density lipoprotein cholesterol ratio (MHR) and carotid atherosclerostic plaque in patients with systemic lupus erythematosus (SLE). A total of214 SLE patients were divided into two groups according to the results of ultrasonic examination: carotid arterial atherosclerotic plaque groups and noncarotid arterial atherosclerosis groups. The values of monocyte to high-density lipoprotein-cholesterol ratio (MHR) increase in carotid arterial atherosclerotic plaque groups compared with noncarotid arterial atherosclerosis groups (0.32±0.18 vs0.26±0.15; p=0.015). There was a significant correlation between MHR and carotid artery intima-media thickness (r=0.228; p=0.001) in patients with SLE. Our study suggests that the values of MHR could be a marker to assess carotid artery intima-media thickness in patients with SLE.

Imaging of neoangiogenesis of internal carotid artery's atherosclerotic plaque by contrast-enhanced sonography and histological examination

Previously, atherosclerosis was considered a disease accompanied exclusively by lipids accumulation. At present time success of fundamental and experimental science confirmed that atherosclerotic process is also associated with neovascularization and prolonged inflammatory response at all stages of atherogenesis from initial manifestations to thrombotic complications. The cause of atherosclerotic plaque instability is neovascularization, which is accompanied by intra-plaque hemorrhage and damage. Complications of carotid arteries atherosclerosis are strokes and transient ischemic attacks. The use of a wide range of diagnostic and pathohistological techniques is required for assessing this pathology. The most promising diagnostic technique is Contrast Enhanced Ultrasonography (CEUS) which allows to assess neovascularization degree in atherosclerotic plaque through the injection of a contrast agents.

Circulating α-Klotho Levels in Hemodialysis Patients and Their Relationship to Atherosclerosis

Background/Aims: Serum soluble Klotho (sKlotho) plays a role in cardiovascular disease in some populations. However, information regarding the effect of serum sKlotho on atherosclerosis in patients on maintenance hemodialysis (MHD) is limited. Therefore, we tested the level of serum sKlotho in MHD patients to investigate atherosclerosis disease and determine the relationship between sKlotho and atherosclerosis. Methods: Using cross-sectional research, anthropometric and laboratory data were collected for 330 MHD patients. The levels of serum sKlotho before dialysis were tested by enzyme-linked immunosorbent assay. Carotid intima-middle thickness (cIMT) and the number of carotid artery atherosclerotic plaques were measured by color Doppler ultrasonography. The risk factors of atherosclerosis were explored by multivariate logistic regression analysis. Results: Among 330 MHD patients, the average serum sKlotho was (379.93±143.66) pg/ml. The level of serum sKlotho was positively related to hemoglobin (P< 0.05). It was negatively correlated with systolic pressure, pulse pressure, ultrafiltration volume, serum phosphorus, corrected serum calcium×phosphorus, high-sensitivity C-reactive protein (Hs-CRP), cIMT and carotid atherosclerotic plaque quantity and atherosclerosis (P< 0.05). Multivariate logistic regression analysis showed that age (OR = 1.108, 95% CI = 1.067 ∼ 1.151, P = 0.000), dry weight (OR = 1.050, 95% CI = 1.014 ∼ 1.088, P = 0.007), Hs-CRP (OR = 1.126, 95% CI = 1.005 ∼ 1.261, P = 0.041), and serum sKlotho (OR = 0.997, 95% CI = 0.995 ∼ 1.000, P = 0.032) were risk factors for atherosclerosis in MHD patients. Conclusion: Serum sKlotho was related to systolic pressure, pulse pressure, ultrafiltration volume, hemoglobin, serum phosphorus, corrected serum calcium×phosphorus, Hs-CRP, increased cIMT, carotid atherosclerotic plaque quantity and atherosclerosis. Age, dry weight, Hs-CRP, and serum sKlotho were risk factors for atherosclerosis in MHD patients. Serum sKlotho may be a novel risk factor for atherosclerosis in MHD patients.

Relationship of femoral artery ultrasound measures of atherosclerosis with chronic kidney disease

BackgroundChronic kidney disease (CKD) is strongly associated with peripheral artery disease (PAD). Detection of subclinical PAD may allow early interventions for or prevention of PAD in persons with CKD. Whether the presence of atherosclerotic plaque and femoral intima-media thickness (IMT) are associated with kidney function is unknown. MethodsWe performed a cross-sectional observational study of 1029 community-living adults. We measured superficial and common femoral artery IMT and atherosclerotic plaque presence by ultrasound. Estimated glomerular filtration rate (eGFR; continuous) and eGFR <60 mL/min/1.73 m2 (binary) were evaluated as outcomes. ResultsMean age was 70 ± 10 years, mean eGFR was 78 ± 17 mL/min/1.73 m2, and 156 (15%) individuals had eGFR <60 mL/min/1.73 m2; 260 (25%) had femoral artery plaque. In models adjusted for demographics and cardiovascular risk factors, individuals with femoral artery plaque had mean eGFR approximately 3.0 (95% confidence interval, −5.3 to −0.8) mL/min/1.73 m2 lower than those without plaque (P < .01). The presence of plaque was also associated with a 1.7-fold higher odds of eGFR <60 mL/min/1.73 m2 (95% confidence interval, 1.1-2.8; P < .02). Associations were similar in persons with normal ankle-brachial index. The directions of associations were similar for femoral IMT measures with eGFR and CKD but were rendered no longer statistically significant with adjustment for demographic variables and cardiovascular disease risk factors. ConclusionsFemoral artery plaque is significantly associated with CKD prevalence in community-living individuals, even among those with normal ankle-brachial index. Femoral artery ultrasound may allow evaluation of relationships and risk factors linking PAD and kidney disease earlier in its course.

Non-invasive characterization of coronary artery atherosclerotic plaque using dual energy CT: Explanation in ex-vivo samples

PurposeIn this study non-calcified plaque composition is evaluated by Dual Energy CT (DECT). Energy Dispersive X-ray Spectroscopy (EDS) has been used to study the Plaque composition. An attempt has been made to explain the DECT results with EDS analysis. MethodsThirty-two ex-vivo human cadaver coronary artery samples were scanned by DECT and data was evaluated to calculate their effective atomic number and electron density (Zeff & ρe) by inversion method. Result of DECT was compared with pathology to assess their differentiating capability. The EDS study was used to explain DECT outcome. ResultsDECT study was able to differentiate vulnerable plaque from stable with 87% accuracy (area under the curve (AUC):0.85 [95% confidence interval {CI}:0.73–0.98}] and Kappa Coefficient (KC):0.75 with respect to pathology. EDS revealed significant compositional difference in vulnerable and stable plaque at p < .05. The weight percentage of higher atomic number elements like F, Na, Mg, S, Si, P, Cl, K and Ca was found to be slightly more in vulnerable plaques as compared to a stable plaque. EDS also revealed a significantly increased weight percentage of nitrogen in stable plaques. ConclusionsThe EDS results were able to explain the outcomes of DECT study. This study conclusively explains the physics of DECT as a tool to assess the nature of non-calcified plaques as vulnerable and stable. The method proposed in this study allows for differentiation between vulnerable and stable plaque using DECT.

Etiology of isolated pontine infarctions: a study based on high-resolution MRI and brain small vessel disease scores

BackgroundIn this retrospective study, we investigated the main pathogenesis of the two types of isolated pontine infarction: paramedian pontine infarcts (PPIs) and small deep pontine infarcts (SDPIs).MethodsAcute ischemic stroke patients, comprising 117 PPI patients and 40 SDPI patients, were enrolled. High-resolution magnetic resonance imaging (HR-MRI) and routine MRI sequences were performed for each patient, and clinical data were collected. The following brain small vessel disease (SVD) features of the MRI scans were each rated (0 or 1) separately: asymptomatic lacunar infarcts, white matter lesions (WMLs), deep and infratentorial cerebral microbleeds (CMBs), and enlarged perivascular spaces in the basal ganglia. The ratings were also summed in an ordinal “SVD score” (range: 0–4). The difference in the SVD score between the PPI and SDPI groups was determined. The presence and location of basilar artery (BA) atherosclerotic plaques (based on HR-MRI) in the two groups was evaluated.ResultsThere was a significant difference in the total SVD score and three of the four independent SVD features (asymptomatic lacunar infarcts, WMLs, and deep and infratentorial CMBs) between the two groups. The prevalence of BA plaques relevant to the infarcts in the PPI group was significantly higher than that in the SDPI group, whereas the prevalence of plaques irrelevant to the infarcts was similar between the two groups. The degree of BA stenosis was slightly higher in the PPI group than in the SDPI group. Diabetes mellitus was much more prevalent in the PPI group. The National Institute of Health Stroke Scale score was higher in the PPI group, which is in accordance with the larger infarct size in the PPI group.ConclusionBA atherosclerosis may be the major cause of PPI, while SVD may be the main mechanism underlying SDPI. HR-MRI combined with the total SVD score should be helpful to explore the pathogenesis underlying isolated pontine infarctions, especially in cases involving low-grade BA stenosis.

Percutaneous Sampling of Local Biomolecule Gradients Across Coronary Artery Atherosclerotic Plaques

A percutaneous catheter device, the Liquid Biopsy System, was developed to sample the unstirred boundarylayer of blood upstream and downstream of intact and disrupted human coronary atherosclerotic plaques. Using multiplexed proximity extension assays, release of 20 biomolecules was simultaneously detected in samples taken across plaques before balloon angioplasty, including the soluble form of the endothelial lectin-like oxidized LDL receptor. Additional biomolecules, including matrix metalloproteinase-12, were released after plaque disruption with angioplasty. These experiments demonstrate the power of the LiquidBiopsy System to yield new scientific insights and its ultimate potential to generate new biomarkers and surrogate endpoints for clinical trials.

Atherosclerotic plaque features and distribution in bilateral carotid arteries of asymptomatic elderly population: A 3D multicontrast MR vessel wall imaging study

PurposeThis study sought to investigate the characteristics of morphology, compositions and distribution of carotid atherosclerotic plaques in asymptomatic elderly population using three dimensional (3D) multicontrast magnetic resonance vessel wall imaging. Materials and methods146 asymptomatic elderly subjects (≥60years) were recruited and underwent 3D multicontrast MR vessel wall imaging for bilateral carotid arteries on a 3.0T MR scanner. The presence of carotid atherosclerotic plaque was determined and the stenosis was measured. The characteristics of plaque morphology and compositions were evaluated and compared among distal internal carotid artery (D-ICA), proximal-ICA (P-ICA), carotid bulb (CB), distal common carotid artery (D-CCA) and proximal-CCA (P-CCA). ResultsOf all recruited 140 subjects (72.1±5.7years, 63 males), 87 (62.1%) had carotid plaques, 17 (12.1%) had high-risk plaques and 51 (36.4%) had multiple plaques. Of all 280 carotid arteries, only 16 (5.7%) had luminal stenosis (21.1%±11.4%). Among carotid arteries without luminal stenosis, the prevalence of plaque and high-risk plaques was 43.2% and 8.3%, respectively. Carotid plaques were mostly found in CB segment (33.9%), followed by P-ICA (13.6%), P-CCA (11.1%), D-CCA (4.6%) and D-ICA (3.6%). Age was independently associated with presence of multiple carotid plaques (odds ratio, 1.835; 95% confidence interval, 1.196–2.815; P=0.005). ConclusionCarotid artery atherosclerotic plaques are prevalent and a substantial number of high-risk plaques can be found in the asymptomatic elderly subjects. Longitudinal studies are warranted to investigate the risk of having ischemic stroke for asymptomatic elderly individuals with carotid artery high risk plaques.

Time-dependent trends in cardiovascular adverse events during follow-up after carotid or iliofemoral endarterectomy.

Recent observations have suggested a decline in vulnerable carotid artery and iliofemoral atherosclerotic plaque characteristics over the past decade. The aim of this study was to determine whether, in the presence of clinically manifest carotid or peripheral artery disease, secondary adverse cardiovascular events decreased over this period. Patients included in the Athero-Express biobank between 2003 and 2012 were analysed. During 3-year follow-up, composite cardiovascular endpoints were documented yearly, including: myocardial infarction, coronary interventions, stroke, peripheral interventions and cardiovascular death. The major cardiovascular endpoint consisted of myocardial infarction, stroke and cardiovascular death. Some 1684 patients who underwent carotid endarterectomy (CEA) and another 530 who had iliofemoral endarterectomy (IFE) were analysed. In total, 405 (25·2 per cent) and 236 (45·9 per cent) patients had a composite cardiovascular endpoint within 3 years after CEA and IFE respectively. Corrected for possible confounders, the percentage of patients with a secondary cardiovascular event after CEA did not change over time (hazard ratio (HR) 0·91, 95 per cent c.i. 0·65 to 1·28; P = 0·590, for 2011-2012 versus 2003-2004). In patients who had IFE, the incidence of secondary cardiovascular events significantly decreased only in the last 2 years (HR 0·62, 0·41 to 0·94; P = 0·024), owing to a decrease in peripheral (re)interventions in 2011-2012 (HR 0·59, 0·37 to 0·94; P = 0·028). No decrease in major cardiovascular events was observed in either group. In patients who had undergone either CEA or IFE there was no evidence of a decrease in all secondary cardiovascular events. There were no differences in major cardiovascular events.

The correlation of carotid artery structure characteristics and residual stenosis after stenting

Objective To analyze the correlation of characteristics of carotid artery structure and the incidence of residual stenosis after carotid artery stent (CAS) placement and its influencing factors using color Doppler flow imaging (CDFI). Methods Five hundred and ninety-six cases from January 2013 to December 2015 who underwent CAS (600 pieces of stent) were included in this study. All patients were examined by CDFI within 1 month before and 1 week after carotid artery stenting. The incidence of residual stenosis was analysed. The correlation of residual stenosis and the characteristics of carotid artery lesions and atherosclerotic plaque before stenting were analyzed respectively. Results There was positive correlation between the incidence rates of residual stenosis and irregularly shaped plaque (odd ratios, 9.02; 95% confidence interval, 5.21-15.59, P<0.05), the plaques with calcification in the surface(odd ratios, 2.55; 95% confidence interval, 1.45-4.49, P<0.05), the residual diameter of carotid stenosis less than 1.0 mm(odd ratios, 1.61; 95% confidence interval, 1.06-2.45, P<0.05), which were the independent risk factors for influencing residual stenosis after CAS. Conclusions Choosing a more adaptable stent based on the characteristics of carotid artery lesions and atherosclerotic plaque by CDFI before stenting may be useful for the patients to get best result of revascularization. The rate of residual stenosis may be decreased. Key words: Ultrasonography, Doppler, color; Carotid stenosis; Residual stenosis; Rish factors

Expression levels of atherosclerosis-associated miR-143 and miR-145 in the plasma of patients with hyperhomocysteinaemia

BackgroundAn elevated level of homocysteine (Hcy) in the blood is designated hyperhomocysteinaemia (Hhcy) and is regarded as a strong risk factor for the development of atherosclerosis (ATH), although the association remains controversial. Considered to be essential gene expression regulators, micro-RNAs (miRNAs) modulate cardiovascular disease development and thus can be regarded as potential biomarkers and therapeutic targets in atherosclerosis. The aim of the current study is to investigate the expression levels of atherosclerosis-associated miR-143 and miR-145 in Hhcy patients and predict the progress of atherosclerosis in Hhcy patients.MethodsA total of 100 participants were enrolled and included normal control subjects (NC = 20), hyperhomocysteinaemia alone subjects (Hhcy = 25), hyperhomocysteinaemia and carotid artery atherosclerosis combined subjects (Hhcy + ATH = 30) and patients with standalone carotid artery atherosclerosis (ATH = 25). Plasma Hcy, supplementary biochemical parameters and carotid artery ultrasonography (USG) were measured in all participants. MicroRNA expression levels in the peripheral blood were calculated by real-time reverse transcription-polymerase chain reaction (qRT-PCR). The correlations of miR-143 and miR-145 with Hcy, blood lipid parameters and carotid artery atherosclerotic plaques were evaluated using Pearson’s correlation coefficients. Receiver operating characteristic (ROC) curve analyses were performed to evaluate the capacities of miR-143 and miR-145 for the detection of Hhcy and atherosclerosis patients.ResultsMiR-143 and miR-145 exhibited trends towards significance with stepwise decreases from the NC to Hhcy groups and then to the Hhcy + ATH and ATH groups. Similar results were observed in the carotid artery plaque group (Hhcy + ATH and ATH grups) compared with the no-plaque group (NC and Hhcy groups). The miR-143 expression level exhibited significant negative correlations with Hcy, total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c). The miR-145 expression level exhibited significant negative correlations with Hcy, TC, triglyceride (TG) and LDL-c. MiR-143 and miR-145 exhibited the greatest area under the curves (AUCs) (0.775 and 0.681, respectively) for the detection of every Hhcy patient, including those in the Hhcy and Hhcy + ATH groups, from among all subjects.ConclusionThe results indicated that the levels of atherosclerosis-associated circulating miR-143 and miR-145 are linked to Hhcy. MiR-143 may be used as a potential non-invasive biomarkers of Hhcy and thus may be helpful in predicting the progress of atherosclerosis in Hhcy patients.