Journal of atherosclerosis and thrombosis (J Atherosclerosis Thromb)

Publisher: Nihon Dōmyaku Kōka Gakkai

Journal description

Current impact factor: 2.77

Impact Factor Rankings

2015 Impact Factor Available summer 2015
2013 / 2014 Impact Factor 2.77
2012 Impact Factor 2.933
2011 Impact Factor 2.692
2010 Impact Factor 2.293
2009 Impact Factor 3.048
2008 Impact Factor 2.625
2007 Impact Factor 2.835

Impact factor over time

Impact factor

Additional details

5-year impact 2.99
Cited half-life 3.60
Immediacy index 0.41
Eigenfactor 0.01
Article influence 0.77
Website Journal of Atherosclerosis and Thrombosis website
Other titles Journal of atherosclerosis and thrombosis (Online)
ISSN 1340-3478
OCLC 53835682
Material type Document, Internet resource
Document type Internet Resource, Computer File, Journal / Magazine / Newspaper

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: In the recent issue of the Journal of Atherosclerosis and Thrombosis, Wang et al. assessed the relationship between the red cell distribution width (RDW) and acute myocardial infarction (AMI). However, assessing all parameters affecting the RDW, determining the optimum RDW cut-off value for predicting the prognosis of coronary artery disease (CAD), excluding metabolic comorbidities affecting the RDW values and identifying the specific range for the WBC count within the exclusion criteria would provide more reliable results and improve the credibility of the entire article in this study population.
    Journal of atherosclerosis and thrombosis 02/2015; 22(2). DOI:10.5551/jat.27573
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    ABSTRACT: Aim: The carotid intima-media thickness (CIMT) is now validated as a sensitive marker of atherosclerosis and is directly associated with an increased risk of cardiovascular disease. Considering that the independent association between the serum uric acid level and CIMT remains controversial due to the complex interrelationship with other known cardiovascular risk factors, further studies are needed. The aim of the present study is to explore the association between the serum uric acid level and CIMT in a general Chinese population and determine whether the association differs according to varied metabolic status. Methods: The present study was cross-sectional in design. A total of 10,281 community-based participants 40 years of age or older from Shanghai, China were included in the current analysis. All participants underwent a detailed questionnaire interview, anthropometric measurements and ultrasonography to assess the CIMT. Blood and urine samples were collected for the biochemical measurements. Results: The serum uric acid levels were positively associated with obesity- and diabetes-related parameters and the CIMT. In a logistic regression model controlling for potential confounders, compared with the participants in the first quartile of the uric acid level, those in the fourth quartile had a higher odds of an elevated CIMT in both men (odds ratio [OR]=1.37; 95% confidence interval [CI]=1.07-1.75) and women (OR=1.48; 95% CI=1.12-1.94). The subgroup analyses revealed that an association between an elevated CIMT and the serum uric acid level persisted regardless of diuretic use and the hypertension, diabetes mellitus and chronic kidney disease status. However, the association disappeared in the patients who consumed alcohol and in premenopausal women. Conclusions: The serum uric acid level is positively associated with an elevated CIMT in middle-aged and elderly Chinese subjects, independent of known risk determinants of cardiovascular disease.
    Journal of atherosclerosis and thrombosis 02/2015; DOI:10.5551/jat.26260
  • Journal of atherosclerosis and thrombosis 02/2015; DOI:10.5551/jat.ED004
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    ABSTRACT: Aim: The current study investigated how prevalent the absence of a prior history of intermittent claudication would be in patients with critical limb ischemia (CLI) and examined the associated clinical features.Methods: We used a database of 559 Japanese CLI patients participating in a multicenter prospective study. A history of intermittent claudication prior to CLI onset was surveyed at registration. The 95% confidence interval (CI) of its prevalence was calculated using the Clopper-Pearson method. Logistic regression analysis was performed to assess the association between the clinical features and the absence of preceding intermittent claudication.Results: The study subjects were 73±10 years old and 67% were male. Tissue loss occurred in 82% of this population. The prevalence of the absence of prior intermittent claudication was 50% [95% CI: 46-55%]. In multivariate logistic regression analysis, a non-ambulatory status, diabetes mellitus, and regular dialysis were significantly and independently associated with the lack of a prior history of intermittent claudication (all p<0.05). Indeed, the presence of these features was associated with a higher prevalence of the lack of the history. Regular dialysis, but not non-ambulatory status or diabetes mellitus, lost its statistical significance after further adjustment for the presence of isolated infrapopliteal lesions, whereas the presence of isolated infrapopliteal lesions itself was significantly associated with a lack of prior intermittent claudication.Conclusions: The absence of a prior history of intermittent claudication was prevalent in CLI patients. Patients with a non-ambulatory status, diabetes mellitus, and regular dialysis were more likely to lack a prior history of intermittent claudication.
    Journal of atherosclerosis and thrombosis 02/2015; DOI:10.5551/jat.28217
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    ABSTRACT: Aim: The aim of this study was to identify the age and sex-specific reference ranges for the non-high-density lipoprotein cholesterol (non-HDLC) levels in Japanese children.Methods: The subjects included 441,431 schoolchildren (207,015 boys, 234,416 girls) 9-16 years of age who participated in a screening and care program for lifestyle-related diseases from 2006 to 2011. The serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) levels were measured, and the non-HDL-C levels were calculated. The serum lipid levels were analyzed according to age and sex.Results: The overall mean non-HDL-C level was 105.7±24.0 mg/dL, with a sex difference: boys=103.0±24.0 mg/dL and girls=108.2±23.8 mg/dL. In boys, the median non-HDL-C level decreased gradually from 104 mg/dL in the 9-year-old age group to 96 mg/dL in the 15-year-old age group. The 75th percentile level was approximately 120 mg/dL in the 9- to 11-year-old groups and decreased at approximately 113 mg/dL in the 12- to 15-year-old groups, whereas the 95th percentile level was approximately 150 mg/dL in the 9- to 11-year-old groups and decreased at approximately 140 mg/dL in the 13- to 15-year-old groups. In girls, the median non-HDL-C level remained unchanged at approximately 105 mg/dL, with 75th and 95th percentile levels of approximately 122 and 150 mg/dL, respectively.Conclusions: The non-HDL-C levels vary by age and sex. The age- and sex-specific reference ranges for the non-HDL-C levels may be a valuable tool for management with respect to preventing the development of atherosclerosis in childhood.
    Journal of atherosclerosis and thrombosis 02/2015; DOI:10.5551/jat.28100
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    ABSTRACT: Aim: The immune system may play an important role in the pathogenesis of cardiovascular disease. T cell-driven inflammation in human hypertension and atherosclerosis has recently been revealed. In the present study, we evaluated the association between serum levels of the C-X-C chemokine receptor type 3 chemokines and the carotid intima media thickness (IMT) in humans.Methods: One hundred sixty-four consecutive patients undergoing baseline and 2-year follow-up carotid IMT (110 men, 62.4±10.0 years) were enrolled. The maximum carotid IMT (max-IMT) and the mean carotid IMT (mean-IMT) were measured at baseline and after 24 months. Clinical and laboratory variables, including serum levels of the monokine induced by gamma interferon (MIG) and interferon gamma-induced protein 10 (IP-10), were analyzed at the time of initial enrollment.Results: The baseline max- and mean-IMT were 0.992±0.235 and 0.793±0.191 mm, respectively. The serum levels of MIG and IP-10 significantly correlated with the carotid IMT. However, there was no significant correlation between the serum levels of MIG or IP-10 and IMT changes. A multivariate regression analysis revealed the serum MIG to be independently associated with the carotid IMT (max-IMT: β=0.194, p=0.010; mean-IMT: β=0.184, p=0.016) when controlled for age, sex, diabetes mellitus history, smoking history, body mass index, blood pressure, total cholesterol, high-density lipoprotein cholesterol, high-sensitivity C-reactive protein, and aspirin and statin medication.Conclusions: Circulating MIG levels are independently associated with the carotid IMT, after adjusting for confounding factors and medications. These findings indicate the potential clinical implication of MIG with respect to early atherosclerosis in humans.
    Journal of atherosclerosis and thrombosis 01/2015; DOI:10.5551/jat.28886
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    ABSTRACT: Aims: High mobility group box 1 (HMGB1) is a DNA-binding protein secreted into the extracellular space from necrotic cells that acts as a cytokine. We examined the role of HMGB1 in angiogenesis from bone marrow-derived cells in the heart using transgenic mice exhibiting the cardiac-specific overexpression of HMGB1 (HMGB1-TG). Methods: HMGB1-TG mice and wild-type littermate (WT) mice were lethally irradiated and injected with bone marrow cells from green fluorescent protein mice through the tail vein. After bone marrow transplantation, the left anterior descending artery was ligated to induce myocardial infarction (MI). Results: Flow cytometry revealed that the levels of circulating endothelial progenitor cells (EPCs) mobilized from the bone marrow increased after MI in the HMGB-TG mice versus the WT mice. In addition, the size of MI was smaller in the HMGB1-TG mice than in the WT mice, and immunofluorescence staining demonstrated that the number of engrafted vascular endothelial cells derived from bone marrow in the border zones of the MI areas was increased in the HMGB1-TG mice compared to that observed in the WT mice. Moreover, the levels of cardiac vascular endothelial growth factor after MI were higher in the HMGB1-TG mice than in the WT mice. Conclusions: The present study demonstrated that HMGB1 promotes angiogenesis and reduces the MI size by enhancing the mobilization and differentiation of bone marrow cells to EPCs as well as their migration to the border zones of the MI areas and engraftment as vascular endothelial cells in new capillaries or arterioles in the infarcted heart.
    Journal of atherosclerosis and thrombosis 01/2015; DOI:10.5551/jat.27235
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    ABSTRACT: Aim: 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are cholesterol-lowering drugs with a variety of pleiotropic effects including antithrombotic properties. Tissue factor pathway inhibitor (TFPI), which is produced predominantly in endothelial cells and platelets, inhibits the initiating phase of clot formation. We investigated the effect of fluvastatin on TFPI expression in cultured endothelial cells.Methods: Human umbilical vein endothelial cells (HUVECs) were treated with fluvastatin (0-10μM). The expression of TFPI mRNA and antigen were detected by RT-PCR and western blotting, respectively. The effects of mevalonate intermediates, small GTP-binding inhibitors, and signal transduction inhibitors were also evaluated to identify which pathway was involved. A luciferase reporter assay was performed to evaluate the effect of fluvastatin on TFPI transcription. The stability of TFPI mRNA was estimated by quantitating its levels after actinomycin D treatment.Results: Fluvastatin increased TFPI mRNA expression and antigen in HUVECs. Fluvastatin-induced TFPI expression was reversed by co-treatment with mevalonate or geranylgeranylpyrophosphate (GGPP). NSC23766 and Y-27632 had no effect on TFPI expression. SB203580, GF109203, and LY294002 reduced fluvastatin-induced TFPI upregulation. Moreover, fluvastatin did not significantly affect TFPI promoter activity. TFPI mRNA degradation in the presence of actinomycin D was delayed by fluvastatin treatment.Conclusions: Fluvastatin increases endothelial TFPI expression through inhibition of mevalonate-, GGPP-, and Cdc42-dependent signaling pathways, and activation of the p38 MAPK, PI3K, and PKC pathways. This study revealed unknown mechanisms of the anticoagulant effect of statins and gave a new insight to its therapeutic potential for the prevention of thrombotic diseases.
    Journal of atherosclerosis and thrombosis 01/2015; DOI:10.5551/jat.28175
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    ABSTRACT: Aim: Paraoxonase-1 (PON1) is an antiatherosclerotic enzyme located on high-density lipoprotein (HDL). The effects of anaerobic exercise on PON1 activity are unknown. Here we investigated the effects of anaerobic judo training on three different activities of same PON1 enzyme (TDPON1), including basal PON1, salt-stimulated PON1 (SPON1), and arylesterase (AE) activities, of serum, HDL, and HDL subgroups (HDLs; HDL and its subgroups) and its relationship with PON1-Q192R phenotype (PON1P).Methods: Our study included 18 Turkish national female judoists (mean age: 17.9±0.8 years). Before and after 5 months of anaerobic training, critical speed (CS), TDPON1 activities, cholesterol levels in the serum and supernatants of HDLs obtained by polyethylene glycol, and other major blood lipids and lipoproteins (BLLPs) including triglycerides were determined using blood samples taken after overnight fasting. PON1P groups (PGs) were categorized as QQ (QG; persons with low activity) and R carriers (QR+RR) (RG; persons with high activity) according to SPON1/AE activity ratios. The results were considered statistically significant at P≤0.05.Results: Anaerobic training resulted in significantly increased the cholesterol levels of HDLs (except HDL2-C) in all subjects, but not HDLs-C in PGs. Anaerobic training resulted in significant increases in most TDPON1 activities of serum and HDLs in all subjects and (except AE) in PGs, whereas SPON1 and HDL2 AE activities increased only in the RG, which was related to PON1P. However, PON1P was not related to other measured markers, including basal BLLP profiles.Conclusions: Anaerobic training improved most TDPON1 activities of serum and HDLs and HDLs -C levels (except HDL2-C) in all subjects, but not HDLs-C in PGs. The beneficial effects of anaerobic training on SPON1 and HDL2 AE activities were depend on PON1P. The lack of response of HDL2-C to anaerobic exercise will require further research.
    Journal of atherosclerosis and thrombosis 01/2015; DOI:10.5551/jat.25809
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    ABSTRACT: Aim: Macrophage-derived chemokine (CCL22) is a member of the CC-family of chemokines synthesized by monocyte-derived macrophages. Previous studies have reported a relationship between CCL22 and atherosclerosis and the role of histamine in this pathway. Histamine ncreases the CCL22 expression in human monocytes via the H2 receptor. In this study, we investigated the effects of CCL22 and the role of histamine in mouse monocytes with respect to atherosclerosis.Methods and Results: The expression of CCL22 was investigated in apolipoprotein E (apoE)-deficient mice. The mice had high serum concentrations of CCL22 and their atherosclerotic lesions contained abundant levels of CCL22. In addition, when the mouse monocyte cell line (J774A.1 cells) differentiated into macrophage-like cells, the cells showed a similar expression of CCL22 and reduced expression of H2 receptors. Histamine is synthesized from l-histidine by histidine decarboxylase (HDC) in a single enzymatic step. HDC knockout mice were compared with apoE/HDC double knockout mice. The findings indicated that the expression of CCL22 in atherosclerosis models is under the influence of histamine. In addition, in vitro studies using J774A.1 cells and an in vivo study using histamine receptor knockout mice showed that histamine stimulates the CCL22 expression via the histamine H2 receptor.Conclusions: The current results support our previous CCL22 studies in the setting of human atherosclerosis and suggest that this molecule is involved in the atherogenic processes in a mouse model of atherosclerosis.
    Journal of atherosclerosis and thrombosis 12/2014; DOI:10.5551/jat.27417
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    ABSTRACT: Aim: Whether there are differences among statins in their effect on the kidney function in diabetic patients remains controversial. In this report, we aimed to examine the comparative effects of statins on the kidney function in a long-term follow-up study.Methods: This was a single-center longitudinal observational historical cohort study. We enrolled 326 Japanese adult ambulatory patients with type 2 diabetes who were newly prescribed one of four statins (pravastatin, rosuvastatin, atorvastatin and pitavastatin) and who had an estimated glomerular filtration rate (eGFR) of ≥30 mL/min/1.73m(2). The outcome measurement was the annual rate of change in eGFR. We used the standardized inverse probability of treatment weighted (IPTW) method based on the propensity score to adjust for the effects of confounding factors. Furthermore, in order to take into account the variety in the number and spacing of eGFR measurements and the duration of the follow-up period for each individual, we conducted a linear mixed-effects model regression analysis.Results: The median follow-up period was 4.3years (range, 3.0-7.1years). In an analysis using the IPTW method, the mean (±standard error) annual rate of change in eGFR among the patients treated with pravastatin (-0.86±0.28 mL/min/1.73m(2)/year) was significantly lower than that observed among the patients treated with rosuvastatin (-1.80±0.27, p=0.02), atorvastatin (-1.99± 0.28, p=0.004) and pitavastatin (-2.23±0.49, p=0.02). Similar results were obtained in the linear mixed-effects model regression analysis.Conclusions: Pravastatin may be superior to rosuvastatin, atorvastatin and pitavastatin in preserving the kidney function in patients with type 2 diabetes.
    Journal of atherosclerosis and thrombosis 12/2014; DOI:10.5551/jat.26823
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    ABSTRACT: Aim: In addition to type 2 diabetes, an elevated Lp(a) level is known to be a surrogate biomarker of cardiovascular disease. However, recent studies have demonstrated that the Lp(a) levels are lower in type 2 diabetic patients than in non-diabetic subjects. Therefore, we sought to evaluate the prognostic value of elevated lipoprotein(a) [Lp(a)] in type 2 diabetic patients with symptomatic coronary artery disease (CAD).Methods: A total of 1494 diabetic patients with CAD (62.3% men, mean age: 63.5±10.3 years) were enrolled. CAD was diagnosed using invasive coronary angiography, and laboratory values for lipid parameters, including Lp(a), were obtained on the day of coronary angiography. The patients were divided into tertile groups according to the individual Lp(a) level. The baseline characteristics, coronary angiographic findings, duration of follow-up and major adverse cardiovascular events (MACEs) were recorded.Results: Over a mean follow-up period of 4.4±2.6 years, there were 59 MACEs (35 cardiac deaths and 24 cases of non-fatal myocardial infarction), for an event rate of 3.9%. A survival probability plot according to the Lp(a) tertile revealed that an elevated Lp(a) level was associated with a worse prognosis (p=0.008), after adjusting for age, gender, hypertension, hyperlipidemia, smoking and the extent of CAD. Furthermore, the addition of an elevated Lp(a) level to the reference model improved the integrated discrimination improvement (0.0216, p<0.001), continuous net reclassification improvement (NRI) (0.5721, p=0.012) and NRI (0.1549, p=0.004) values.Conclusions: In terms of the prognosis, elevated Lp(a) is associated with worse outcomes in type 2 diabetic patients with symptomatic CAD. Furthermore, an elevated Lp(a) level has incremental prognostic value in type 2 diabetic patients with symptomatic CAD.
    Journal of atherosclerosis and thrombosis 11/2014; DOI:10.5551/jat.25551
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    ABSTRACT: Aim: It has been reported that beta-blockers (BB) reduce cardiovascular events in patients with atherosclerotic disease. However, little is known about the efficacy of these drugs in patients with critical limb ischemia (CLI). We investigated whether beta-blocker therapy affects the clinical outcomes of CLI patients.Methods: Between March 2004 and December 2011, 1,873 consecutive CLI patients who received endovascular therapy (EVT) (394 BB-treated patients and 1,479 non-BB-treated patients) for de novo infrainguinal lesions were identified retrospectively. A propensity score analysis was used for risk adjustment in a multivariable analysis and one-to-one matching (BB: 305, non-BB 305). The primary endpoint was amputation-free survival (AFS), and the secondary endpoints were overall survival and the rates of limb salvage and freedom from major adverse limb events (MALE; including repeat reintervention, surgical conversion and major amputation). The mean follow-up period was 22±15 months.Results: In the propensity score-matched pair analysis, there were no significant differences in AFS between the patients treated with and without beta-blockers (58.8% vs. 58.5% at three years, log-rank p=0.76). There were also no significant differences in the limb salvage rate (88.3% vs. 88.8 at three years, log-rank P=0.41), overall survival (63.0% vs. 62.4% at three years, log-rank P=0.70) and freedom from MALE (43.6% vs. 44.9% at three years, log-rank P=0.58) between the patients treated with and without beta-blockers.Conclusions: The present results suggest that beta-blocker therapy does not worsen the clinical outcomes after EVT in CLI patients.
    Journal of atherosclerosis and thrombosis 11/2014; DOI:10.5551/jat.27359
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    ABSTRACT: Aim: Lysophospholipids, particularly sphingosine 1-phosphate and lysophosphatidic acid, are known to be involved in the pathogenesis of atherosclerosis; however, the role of lysophosphatidylserine (LysoPS) in the onset of atherosclerotic diseases remains uncertain.Methods: We investigated the effects of LysoPS on the uptake of oxidized low-density lipoprotein (oxLDL) and the modulation of inflammatory mediators and ER stress utilizing RAW264.7 cells and mouse peritoneal macrophages (MPMs).Results: We found that LysoPS augmented cholesterol accumulation in both models. Consistent with these findings, LysoPS increased the expression of scavenger receptors (CD36, MSR1, LOX1 and TLR4). Regarding the involvement of these lipids in inflammation, LysoPS significantly decreased the expression of inflammatory mediators in lipopolysaccharide (LPS)-treated RAW264.7 cells and MPMs. LysoPS also attenuated ER stress in LPS-untreated RAW264.7 cells. The expression patterns of LysoPS receptors differed considerably among the LPS-untreated RAW264.7 cells, LPS-treated RAW264.7 cells and MPMs.Conclusions: LysoPS may have proatherosclerotic properties in the setting of foam cell formation as well as antiatherosclerotic effects on inflammation in macrophages.
    Journal of atherosclerosis and thrombosis 11/2014; DOI:10.5551/jat.25650
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    ABSTRACT: Aim: To examine whether the inflammatory markers C-reactive protein (CRP) and fibrinogen are associated with biomarkers of atherosclerosis [carotid intima-media thickness (IMT) and coronary artery calcification (CAC)] in the general male population, including Asians.Methods: Population-based samples of 310 Japanese, 293 Japanese-American and 297 white men 40-49 years of age without clinical cardiovascular disease underwent measurement of IMT, CAC and the CRP and fibrinogen levels as well as other conventional risk factors using standardized methods. Statistical associations between the variables were evaluated using multiple linear or logistic regression models.Results: The Japanese group had significantly lower levels of inflammatory markers and subclinical atherosclerosis than the Japanese-American and white groups (P-values all <0.001). The mean level of CRP was 0.66 vs. 1.11 and 1.47 mg/L, while that of fibrinogen was 255.0 vs. 313.0 and 291.5 mg/dl, respectively. In addition, the mean carotid IMT was 0.61 vs. 0.73 and 0.68 mm, while the mean prevalence of CAC was 11.6% vs. 32.1% and 26.3%, respectively. Body mass index (BMI) showed significant positive associations with both the CRP and fibrinogen levels. Although CRP showed a significant positive association with IMT in the Japanese men, this association became non-significant following adjustment for traditional risk factors or BMI. In all three populations, CRP was not found to be significantly associated with the prevalence of CAC. Similarly, fibrinogen did not exhibit a significant association with either IMT or the prevalence of CAC.Conclusions: The associations between inflammatory markers and subclinical atherosclerosis may merely reflect the strong associations between BMI and the levels of inflammatory markers and incidence of subclinical atherosclerosis in both Eastern and Western populations.
    Journal of atherosclerosis and thrombosis 11/2014; DOI:10.5551/jat.23580
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    ABSTRACT: Aim: RhoA is a critical factor in regulating the proliferation and migration of arterial smooth muscle cells (ASMCs) in patients with arteriosclerosis obliterans (ASO). RhoA is modulated by microRNA-133a (miR-133a) in cardiac myocytes and bronchial smooth muscle cells. However, the relationship between miR-133a and RhoA with respect to the onset of ASO in the lower extremities is uncertain.Methods: We employed in situ hybridization (ISH) and immunohistochemistry (IHC) to detect the location of miR-133a and RhoA in ASO clinical samples, respectively. 5-ethynyl-2'-deoxyuridine (EdU), cell counting kit-8 (CCK-8), Transwell and wound closure assays were utilized to determine the features of human ASMC (HASMC) proliferation and migration. The expression of miR-133a in the HASMCs was assessed using quantitative real-time PCR (qRT-PCR), while that of RhoA was examined via qRT-PCR and Western blotting.Results: We found miR-133a and RhoA to be primarily located in the ASMCs of ASO. miR-133a was significantly downregulated in the ASO tissues and proliferating HASMCs. In contrast, RhoA was upregulated in the ASO samples. The proliferation and migration of HASMCs was markedly promoted by the downregulation of miR-133a and inhibited by the upregulation of miR-133a. The Luciferase assay confirmed that RhoA was a direct target of miR-133a. The upregulation of miR-133a in the HASMCs decreased the RhoA expression at the protein level. Inversely, the downregulation of miR-133a increased the RhoA protein expression. Of note, the overexpression of RhoA in the HASMCs attenuated the anti-proliferative and anti-migratory effects of miR-133a.Conclusions: Our data indicate that miR-133a regulates the functions of HASMCs by targeting RhoA and may be involved in the pathogenesis of ASO. These findings may lead to the development of potential therapeutic targets for ASO of the lower extremities.
    Journal of atherosclerosis and thrombosis 11/2014; DOI:10.5551/jat.27839
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    ABSTRACT: Aim: It is challenging to identify causal (or target) genes at individual loci detected using genome-wide association studies (GWAS). In order to follow up GWAS loci, we investigated functional genes at homologous loci identified using human lipid GWAS that responded to a high-fat, high-cholesterol diet (HFD) intervention in an animal model.Methods: The HFD intervention was carried out for four weeks in male rats of the spontaneously hypertensive rat strain. The liver and adipose tissues were subsequently excised for analyses of changes in the gene expression as compared to that observed in rats fed normal rat chow (n=8 per group). From 98 lipid-associated loci reported in previous GWAS, 280 genes with rat orthologs were initially selected as targets for the two-staged analysis involving screening with DNA microarray and validation with quantitative PCR (qPCR). Consequently, genes showing a differential expression due to HFD were examined for changes in the expression induced by atorvastatin, which was independently administered to the rats.Results: Using the HFD intervention in the rats, seven known (Abca1, Abcg5, Abcg8, Lpl, Nr1h3, Pcsk9 and Pltp) and three novel (Madd, Stac3 and Timd4) genes were identified as potential significant targets, with an additional list of 23 suggestive genes. Among these 33 genes, Stac3, Fads1 and six known genes exhibited nominally significant expression changes following treatment with atorvastatin. Six (of 33) genes overlapped with those previously detected in the expression QTL studies.Conclusions: Our experimental in vivo approach increases the ability to identify target gene(s), when combined with other functional studies, thus improving understanding of the mechanisms by which GWAS variants act.
    Journal of atherosclerosis and thrombosis 11/2014; DOI:10.5551/jat.27706
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    ABSTRACT: Ischemic heart disease is the single leading cause of death and a significant cause of morbidity among women in industrialized countries. Current guidelines recommend antiplatelet therapy as the main cornerstone for the prevention and treatment of cardiovascular disease. Unfortunately, evidence is emerging that the response to antiplatelet drugs differs according to sex, although the biological basis for this gender disparity is unknown. In order to explain the epidemiological data showing a more severe clinical expression of cardiovascular disease in addition to adverse outcomes despite optimal pharmacological and interventional approaches in women compared to men, differences in platelet reactivity related to sex and gender are currently under investigation. In this report, we review available data from clinical trials of antiplatelet drugs administered for primary and secondary prevention, focusing on the underenrollment of female subjects in interventional randomized studies and weak community awareness of the impact of cardiovascular disease on life expectancy in women. Based on our findings, the development of real gender-oriented evidence-based guidelines for antiplatelet use in the setting of cardiovascular disease is urgently required.
    Journal of atherosclerosis and thrombosis 11/2014; DOI:10.5551/jat.24935
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    ABSTRACT: Aim: Deep pontine lacunar infarction (DPLI) not involving the basal pial surface of the medial part of the pons, is known to be a small vessel disease in the territory of the basilar artery (BA). In the present study, we examined whether morphological features of the BA differ in individuals with an advanced age and may be associated with DPLI.Methods: This study included 338 healthy subjects and 78 patients with DPLI treated at the stroke centers of three university hospitals in Korea. Time-Of-Flight magnetic resonance angiographic images were transported to a central lab and analyzed blind to obtain the clinical data. For the quantitative analysis, the BA was projected two-dimensionally in the anteroposterior and lateral views and perceived as triangles of the vertebrobasilar junction, angulation point and BA division. The angles and triangular areas were summated into angulation indexes and used to quantify the degree of BA tortuosity.Results: The BA showed a more acute angle at the angulation point in the elderly patients than in the healthy subjects. Compared to the healthy subjects, the DPLI patients exhibited significantly larger angles at the vertebrobasilar junction, in addition to the acute angles noted at the angulation point. A unit increase in the BA angle indexes at the vertebrobasilar junction and angulation points for DPLI was found to have an odds ratio of 1.15 (95% confidence interval, 1.05-1.26) and 0.95 (95% CI, 0.91-0.99), respectively, even after adjusting for potential confounders.Conclusions: The angulation point of the BA becomes more acute in elderly individuals. In this study, the vertebrobasilar junction showed a larger angle in the patients with DPLI than in the healthy controls.
    Journal of atherosclerosis and thrombosis 11/2014; DOI:10.5551/jat.26245
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    ABSTRACT: Coronary artery disease (CAD) due to obstructive atherosclerosis is a leading cause of death and has been recognized as a worldwide health threat. Measures to decrease low-density lipoprotein cholesterol (LDL-C) levels are the cornerstone in the management of patients with atherosclerotic cardiovascular disease, particularly those with CAD, for over two decades. Proprotein convertase subtilisin/kexin type 9 (PCSK9), a newly recognized protein, plays a key role in cholesterol homeostasis by enhancing degradation of hepatic LDL receptor (LDLR). Interestingly, PCSK9 is also involved in the inflammatory process. Plasma PCSK9 and lipid or nonlipid cardiovascular risk factors are correlated, and the associations between PCSK9 with cardiovascular health and disease make this protein worthy of attention for the treatment of hyperlipidemia and atherosclerosis. Here, we provide an overview of the physiological role of PCSK9, which contributes to atherosclerosis, and provide data on PCSK9 as a novel pharmacological target. Clinical evidence shows that PCSK9 inhibition is as promising as statins as a target to treat CAD. The efficacy of these drugs may potentially enable effective CAD prophylaxis for more patients.
    Journal of atherosclerosis and thrombosis 11/2014; DOI:10.5551/jat.27615