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1.
Environ Pollut ; 350: 124044, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38677462

ABSTRACT

Phthalates may be associated with an increased risk of cardiometabolic diseases by interfering with glucose and lipid metabolism and by promoting adipogenesis. This study aimed to perform a systematic review and meta-analysis of the association between phthalate exposure and subclinical carotid atherosclerosis, using surrogate markers such as carotid intima-media thickness (IMT) and carotid plaques. The literature search was performed using four databases (Web of Science, Medline, PubMed, and Scopus), and this systematic review includes all available observational studies until July 6th, 2023. The Joanna Briggs Institute critical appraisal tool was used to assess the risk of bias. Meta-analyses were performed, and random effects models were used. Six high-quality cross-sectional studies and 2570 participants aged 12 to 70 were included. Six phthalate metabolites showed significant associations with subclinical carotid atherosclerosis. Exposure to MBzP, ΣDEHP, and MnBP was associated with increased carotid IMT. Exposure to MEP was associated with a higher prevalence of carotid plaques, and MiBP was associated with a lower prevalence. Mixed results were observed for MMP in older adults. The meta-analyses showed a high degree of heterogeneity, and the results are based on single studies. This study accurately describes the evidence of this association to date, suggesting that phthalates are associated with increased carotid IMT and a higher prevalence of carotid plaques. Further research is needed to elucidate this association, as phthalates are still used in the manufacture of everyday products, humans continue to be exposed to them, and atherosclerosis is a public health concern.


Subject(s)
Carotid Artery Diseases , Carotid Intima-Media Thickness , Environmental Exposure , Phthalic Acids , Humans , Carotid Artery Diseases/chemically induced , Environmental Exposure/statistics & numerical data , Environmental Pollutants , Adult , Aged , Middle Aged , Child , Adolescent , Young Adult , Cross-Sectional Studies
2.
Liver Int ; 44(5): 1075-1092, 2024 May.
Article in English | MEDLINE | ID: mdl-38385567

ABSTRACT

BACKGROUND AND AIMS: The beneficial effect of Hepatitis C virus (HCV) eradication by direct antiviral agents (DAAs) on liver fibrosis is well defined. Despite this, the impact of viral eradication in both hepatic and extra-hepatic metabolic features is underreached. This systematic review aimed to synthesize the evidence on the impact of HCV eradication by DAAs on liver steatosis, carotid atherosclerosis, glucidic impairment, dyslipidaemia, and weight gain. METHODS: A systematic search of the existing literature (up to December 2022) identified 97 original studies that fulfilled the inclusion criteria. RESULTS: Whereas total cholesterol and low-density lipoprotein (LDL) seem to increase after viral eradication, the cardiovascular damage expressed as carotid plaques and intima-media thickness seems to improve. Otherwise, the effect on liver steatosis, glucidic homeostasis, and weight seems to be strictly dependent on the presence of baseline metabolic disorders. CONCLUSION: Despite high heterogeneity and relatively short follow-up of included studies, we can conclude that the presence of metabolic risk factors should be strictly evaluated due to their impact on liver steatosis, glucidic and lipid homeostasis, and on weight gain to better identify patients at risk of liver disease progression despite the virus eradication.


Subject(s)
Carotid Artery Diseases , Fatty Liver , Hepatitis C, Chronic , Hepatitis C , Humans , Antiviral Agents/therapeutic use , Hepacivirus , Carotid Intima-Media Thickness , Hepatitis C, Chronic/drug therapy , Fatty Liver/chemically induced , Hepatitis C/drug therapy , Carotid Artery Diseases/chemically induced , Carotid Artery Diseases/drug therapy , Weight Gain
3.
Environ Res ; 244: 117900, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38092241

ABSTRACT

BACKGROUND: Lead exposure is associated with cardiovascular disease. Atherosclerosis has been hypothesized to be one of the underlying mechanisms behind this association. AIM: To investigate whether lead exposure is associated with an increased risk of atherosclerosis in the carotid arteries in a large Swedish population-based cohort. METHODS: We performed a cross-sectional study using data from the population-based Swedish CardioPulmonary bioImage Study (SCAPIS), including 5622 middle-aged men and women, enrolled 2013-2018. Blood lead (B-Pb), measured by inductively coupled plasma mass spectrometry, was used as exposure biomarker. The presence of atherosclerotic plaque in the carotid arteries (yes/no), total plaque area (mm2) and the presence of large plaques (>25 mm2) were determined by ultrasonography. Associations between B-Pb and the different outcomes were analysed using Poisson and linear regression models, adjusted for potential confounders. RESULTS: Atherosclerotic plaque was present in 57% of the individuals, for whom the median total plaque area was 16 mm2 (range: 0.2-222). The median B-Pb concentration was 14 µg/L (range: 0.75-203). After adjusting for potential confounders, individuals in the fourth quartile of B-Pb (Q4) had a prevalence ratio (PR) for plaque of 1.08 (95% CI: 1.01, 1.16) when compared with the first quartile (Q1). A 10 µg/L increase in B-Pb concentrations was associated with an increase of 0.92 mm2 (95% CI: 0.14, 1.71) in total plaque area. The PR for large plaque was 1.09 (95% CI: 0.84, 1.42 for Q4 vs Q1). CONCLUSIONS: This study shows an association between B-Pb and atherosclerosis in the carotid arteries providing some support for the hypothesis that atherosclerosis is one of the mechanisms underlying the association between lead exposure and cardiovascular disease.


Subject(s)
Atherosclerosis , Cardiovascular Diseases , Carotid Artery Diseases , Plaque, Atherosclerotic , Male , Middle Aged , Humans , Female , Plaque, Atherosclerotic/epidemiology , Carotid Artery Diseases/chemically induced , Carotid Artery Diseases/epidemiology , Sweden/epidemiology , Lead , Cross-Sectional Studies , Atherosclerosis/chemically induced , Atherosclerosis/epidemiology , Carotid Arteries/diagnostic imaging , Risk Factors
4.
Rev Clin Esp (Barc) ; 223(2): 77-83, 2023 02.
Article in English | MEDLINE | ID: mdl-36669741

ABSTRACT

INTRODUCTION AND OBJECTIVES: Retinal vein occlusion (RVO) and nonvalvular atrial fibrillation (NVAF) are associated with vascular risk factors (VRF) and aging. The aim of this study is to analyze differences in the prevalence of VRF, vascular events, glaucoma, and anticoagulant treatment in patients with NVAF and RVO compared to a control group of the general population from the same geographic area. METHODS: This is a prospective, single-center, case-control study. All patients diagnosed with RVO from December 2008 to March 2020 as well as a control group were included. Clinical, laboratory, electrocardiographic, and carotid ultrasound variables were analyzed. RESULTS: A total of 386 patients with RVO and 343 controls were studied. Patients with RVO and NVAF were older and more of them had hypertension, a history of vascular events, and carotid atheromatosis than subjects with RVO without NVAF. In patients with NVAF who were on anticoagulants, those who had RVO differed from the controls with NVAF in that they had a higher prevalence of glaucoma (32 vs. 5.3%; p<0.034), with no significant differences regarding age, VRF, vascular events, or type of anticoagulant therapy (acenocumarol or direct-acting oral anticoagulants). CONCLUSIONS: Patients with RVO and NVAF were older and had a higher prevalence of hypertension and carotid atheromatosis than subjects with RVO without NVAF. Patients with NVAF and RVO had higher prevalence of glaucoma than subjects with NVAF without RVO. In patients with NVAF, it is recommended to optimized VRF treatment and glaucoma control to prevent the development of RVO.


Subject(s)
Atrial Fibrillation , Carotid Artery Diseases , Glaucoma , Hypertension , Retinal Vein Occlusion , Humans , Atrial Fibrillation/complications , Atrial Fibrillation/epidemiology , Atrial Fibrillation/drug therapy , Case-Control Studies , Prospective Studies , Retinal Vein Occlusion/etiology , Retinal Vein Occlusion/complications , Anticoagulants/therapeutic use , Risk Factors , Hypertension/epidemiology , Carotid Artery Diseases/chemically induced , Carotid Artery Diseases/complications , Carotid Artery Diseases/drug therapy , Glaucoma/epidemiology , Glaucoma/chemically induced , Glaucoma/complications
5.
Phytomedicine ; 106: 154408, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36029646

ABSTRACT

BACKGROUND: Aspirin is an effective antiplatelet agent for the treatment of carotid atherosclerosis. However, the high risk of bleeding events associated with the drug makes it necessary to seek a safer alternative, with similar or more efficacy than aspirin. Dengzhan Shengmai (DZSM) capsules have been widely used to treat carotid atherosclerosis, and if proven to be non-inferior to aspirin, it may be preferable over the latter for carotid atherosclerosis treatment due to its numerous advantages. We conducted a randomised trial to test the non-inferiority of DZSM to aspirin for the treatment of carotid atherosclerotic plaques. METHODS: We performed a single-centre, prospective, open-label, randomised non-inferiority trial. Patients with carotid atherosclerotic plaques were enrolled and randomly assigned (1:1) to receive either DZSM capsules or aspirin. The follow-up period was 12 months. The primary outcome was the mean change in carotid intima-media thickness (IMT). Secondary outcomes included ischaemic events, rate of lumen stenosis, lipid levels, and plaque scores, length, counts, and vulnerability. Adverse events and laboratory test results were recorded as safety outcomes. The non-inferiority of DZSM was demonstrated when the lower limit of the one-sided 97.5% confidence interval (CI) of the difference in IMT between groups was more than -0.06 mm (margin of non-inferiority). This trial has been registered at ClinicalTrials.gov (CHiCTR1900021365). RESULTS: From 1 April 2019 to 30 September 2019, 150 patients were enrolled, and there was no statistical difference in demographics between the groups. Intention-to-treat analysis showed that the decrease in IMT(∆IMT) was 0.216 ± 0.160 and 0.225 ± 0.149 mm in the DZSM and aspirin groups, respectively. The one-sided 97.5% CI for the difference between ∆IMTs was (-0.0593, +∞). The non-inferiority of DZSM was demonstrated (Pnon-inferiority = 0.0234). There was no significant difference in the incidence of ischaemic events between the groups (P = 1.0). The DZSM group had significantly reduced plaque scores (P < 0.0001), length (P < 0.0001), and counts (P < 0.0001), and improved plaque vulnerability (P < 0.0001). The DZSM group also had reduced levels of low-density lipoprotein cholesterol (LDL-C) (P < 0.0001). Finally, the DZSM group had a lower incidence of total adverse events (14.7% vs. 28%, P = 0.046), especially gastrointestinal discomfort (5.3% vs. 16%, P = 0.034). Although there was no significant difference in bleeding events (0 vs. 5.3%, P = 0.120), the DZSM group tended to have a lower incidence. CONCLUSION: This trial demonstrated that DZSM was not inferior, in efficacy, to aspirin in treating carotid atherosclerotic plaques, and was found to be superior to aspirin in terms of safety. This study provides a new approach for treating carotid plaques, especially in aspirin-intolerant patients.


Subject(s)
Carotid Artery Diseases , Plaque, Atherosclerotic , Aspirin/therapeutic use , Carotid Artery Diseases/chemically induced , Carotid Artery Diseases/drug therapy , Carotid Intima-Media Thickness , Cholesterol, LDL , Drugs, Chinese Herbal , Humans , Plaque, Atherosclerotic/drug therapy , Platelet Aggregation Inhibitors , Prospective Studies , Treatment Outcome
6.
Environ Res ; 214(Pt 2): 113926, 2022 11.
Article in English | MEDLINE | ID: mdl-35868579

ABSTRACT

Long-term exposure to air pollution is associated with cardiovascular events. A main suggested mechanism is that air pollution accelerates the progression of atherosclerosis, yet current evidence is inconsistent regarding the association between air pollution and coronary artery and carotid artery atherosclerosis, which are well-established causes of myocardial infarction and stroke. We studied associations between low levels of long-term air pollution, coronary artery calcium (CAC) score, and the prevalence and area of carotid artery plaques, in a middle-aged population-based cohort. The Swedish CArdioPulmonary bioImage Study (SCAPIS) Gothenburg cohort was recruited during 2013-2017 and thoroughly examined for cardiovascular risk factors, including computed tomography of the heart and ultrasonography of the carotid arteries. In 5070 participants (age 50-64 years), yearly residential exposures to air pollution (PM2.5, PM10, PMcoarse, NOx, and exhaust-specific PM2.5 1990-2015) were estimated using high-resolution dispersion models. We used Poisson regression to examine associations between long-term (26 years' mean) exposure to air pollutants and CAC score, and prevalence of carotid artery plaques, adjusted for potential confounders. Among participants with carotid artery plaques, we also examined the association with plaque area using linear regression. Mean exposure to PM2.5 was low by international standards (8.5 µg/m3). There were no consistent associations between long-term total PM2.5 exposure and CAC score or presence of carotid artery plaques, but an association between total PM2.5 and larger plaque area in participants with carotid plaques. Associations with traffic-related air pollutants were consistently positive for both a high CAC score and bilateral carotid artery plaques. These associations were independent of road traffic noise. We found stronger associations among men and participants with cardiovascular risk factors. The results lend some support to atherosclerosis as a main modifiable pathway between low levels of traffic-related ambient air pollution and cardiovascular disease, especially in vulnerable individuals.


Subject(s)
Air Pollutants , Air Pollution , Atherosclerosis , Carotid Artery Diseases , Carotid Stenosis , Coronary Artery Disease , Myocardial Infarction , Air Pollutants/analysis , Air Pollutants/toxicity , Air Pollution/adverse effects , Air Pollution/analysis , Atherosclerosis/chemically induced , Carotid Artery Diseases/chemically induced , Carotid Artery Diseases/diagnostic imaging , Carotid Artery Diseases/epidemiology , Carotid Stenosis/chemically induced , Carotid Stenosis/epidemiology , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/epidemiology , Coronary Artery Disease/etiology , Environmental Exposure/adverse effects , Environmental Exposure/analysis , Humans , Male , Middle Aged , Myocardial Infarction/chemically induced , Particulate Matter/analysis , Particulate Matter/toxicity , Sweden/epidemiology , Vehicle Emissions
7.
Arterioscler Thromb Vasc Biol ; 42(1): 87-99, 2022 01.
Article in English | MEDLINE | ID: mdl-34879710

ABSTRACT

OBJECTIVE: Studies evaluating the association of metals with subclinical atherosclerosis are mostly limited to carotid arteries. We assessed individual and joint associations of nonessential metals exposure with subclinical atherosclerosis in 3 vascular territories. Approach and Results: One thousand eight hundred seventy-three Aragon Workers Health Study participants had urinary determinations of inorganic arsenic species, barium, cadmium, chromium, antimony, titanium, uranium, vanadium, and tungsten. Plaque presence in carotid and femoral arteries was determined by ultrasound. Coronary Agatston calcium score ≥1 was determined by computed tomography scan. Median arsenic, barium, cadmium, chromium, antimony, titanium, uranium, vanadium, and tungsten levels were 1.83, 1.98, 0.27, 1.18, 0.05, 9.8, 0.03, 0.66, and 0.23 µg/g creatinine, respectively. The adjusted odds ratio (95% CI) for subclinical atherosclerosis presence in at least one territory was 1.25 (1.03-1.51) for arsenic, 1.67 (1.22-2.29) for cadmium, and 1.26 (1.04-1.52) for titanium. These associations were driven by arsenic and cadmium in carotid, cadmium and titanium in femoral, and titanium in coronary territories and mostly remained after additional adjustment for the other relevant metals. Titanium, cadmium, and antimony also showed positive associations with alternative definitions of increased coronary calcium. Bayesian Kernel Machine Regression analysis simultaneously evaluating metal associations suggested an interaction between arsenic and the joint cadmium-titanium exposure. CONCLUSIONS: Our results support arsenic and cadmium and identify titanium and potentially antimony as atherosclerosis risk factors. Exposure reduction and mitigation interventions of these metals may decrease cardiovascular risk in individuals without clinical disease.


Subject(s)
Atherosclerosis/chemically induced , Carotid Artery Diseases/chemically induced , Coronary Artery Disease/chemically induced , Femoral Artery/drug effects , Metals/adverse effects , Occupational Exposure/adverse effects , Occupational Health , Adult , Antimony/adverse effects , Antimony/urine , Arsenic/adverse effects , Arsenic/urine , Asymptomatic Diseases , Atherosclerosis/diagnostic imaging , Atherosclerosis/epidemiology , Atherosclerosis/urine , Biomarkers/urine , Cadmium/adverse effects , Cadmium/urine , Carotid Artery Diseases/diagnostic imaging , Carotid Artery Diseases/epidemiology , Carotid Artery Diseases/urine , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/epidemiology , Coronary Artery Disease/urine , Cross-Sectional Studies , Female , Femoral Artery/diagnostic imaging , Humans , Male , Metals/urine , Middle Aged , Plaque, Atherosclerotic , Risk Assessment , Risk Factors , Spain/epidemiology , Titanium/adverse effects , Titanium/urine
8.
Biomolecules ; 11(12)2021 11 24.
Article in English | MEDLINE | ID: mdl-34944397

ABSTRACT

Successful imaging of atherosclerosis, one of the leading global causes of death, is crucial for diagnosis and intervention. Near-infrared fluorescence (NIRF) imaging has been widely adopted along with multimodal/hybrid imaging systems for plaque detection. We evaluate two macrophage-targeting fluorescent tracers for NIRF imaging (TLR4-ZW800-1C and Feraheme-Alexa Fluor 750) in an atherosclerotic murine cohort, where the left carotid artery (LCA) is ligated to cause stenosis, and the right carotid artery (RCA) is used as a control. Imaging performed on dissected tissues revealed that both tracers had high uptake in the diseased vessel compared to the control, which was readily visible even at short exposure times. In addition, ZW800-1C's renal clearance ability and Feraheme's FDA approval puts these two tracers in line with other NIRF tracers such as ICG. Continued investigation with these tracers using intravascular NIRF imaging and larger animal models is warranted for clinical translation.


Subject(s)
Carotid Artery Diseases/diagnostic imaging , Plaque, Atherosclerotic/diagnostic imaging , Quaternary Ammonium Compounds/administration & dosage , Succinimides/administration & dosage , Sulfonic Acids/administration & dosage , Animals , Carotid Artery Diseases/chemically induced , Carotid Artery Diseases/metabolism , Diet, High-Fat/adverse effects , Disease Models, Animal , Ferrosoferric Oxide/chemistry , Humans , Macrophages/metabolism , Male , Mice , Molecular Imaging , Optical Imaging , Plaque, Atherosclerotic/chemically induced , Plaque, Atherosclerotic/metabolism , Quaternary Ammonium Compounds/chemistry , Quaternary Ammonium Compounds/pharmacokinetics , Succinimides/chemistry , Succinimides/pharmacokinetics , Sulfonic Acids/chemistry , Sulfonic Acids/pharmacokinetics , Toll-Like Receptor 4/metabolism
9.
Bioengineered ; 12(1): 8135-8146, 2021 12.
Article in English | MEDLINE | ID: mdl-34592881

ABSTRACT

Atherosclerosis, a multifactorial vascular disease resulting from lipid metabolism disorders, features chronic inflammatory damage resulting from endothelial dysfunction, which usually affects multiple arteries. The carotid artery is a common site for clinical atherosclerosis evaluation. The aortic root is the standard site for quantifying atherosclerosis in mice. Due to the adverse reactions of first-line drugs, it is necessary to discover new drugs to prevent and treat atherosclerosis. Berberine (BBR) is one of the most promising natural products derived from herbal medicine Coptidis Rhizoma (Huanglian) that features significant anti-atherosclerosis properties. However, overall BBR mechanism against carotid atherosclerosis has not been clearly discovered. Our work aimed to investigate potential BBR mechanism in improving carotid atherosclerosis in ApoE knockout mice. Here, we proved that in ApoE -/- mice receiving high-fat diet for 12 weeks, BBR can reduce serum lipid levels, improve intimal hyperplasia, and antagonize carotid lipid accumulation, which may be achieved through regulating the PI3K/AKT/mTOR signaling pathway, regulating autophagy, promoting cell proliferation and inhibiting cell apoptosis. In summary, these data indicate that BBR can ameliorate carotid atherosclerosis. Therefore, it could be a promisingly therapeutic alternative for atherosclerosis.


Subject(s)
Berberine/administration & dosage , Carotid Artery Diseases/drug therapy , Diet, High-Fat/adverse effects , Signal Transduction/drug effects , Animals , Berberine/pharmacology , Carotid Artery Diseases/chemically induced , Carotid Artery Diseases/genetics , Carotid Artery Diseases/metabolism , Disease Models, Animal , Lipids/blood , Male , Mice , Mice, Knockout, ApoE , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , TOR Serine-Threonine Kinases/metabolism
10.
Int J Cardiol ; 342: 108-114, 2021 Nov 01.
Article in English | MEDLINE | ID: mdl-34339768

ABSTRACT

BACKGROUND: Air pollution is a well-described environmental factor with evidence suggesting a firm association with cardiovascular diseases. The purpose of this study was to determine the association of exposure to gaseous air pollutants on atherosclerosis burden. METHODS: 1955 inhabitants of the Corinthia region, aged 40 years or older, underwent clinical and biochemical assessment as well as carotid ultrasonography to evaluate carotid intima-media thickness (cIMT) and plaque burden. Analyzers recording time series concentration of CO, NO2, and SO2 were located at 4 different open sites (Regions 1, 2, 3 and 4) based on their proximity to industries, highways or shipyards. RESULTS: A higher concentration of CO, NO2, and SO2 was observed in Region 4 compared to the other regions. Mean cIMT (Region 1: 0.93 ± 0.24 mm; Region 2: 0.96 ± 0.40 mm; Region 3: 0.94 ± 0.39 mm; Region 4: 1.14 ± 0.55 mm, p < 0.001), maximum cIMT (p < 0.001) as well as carotid plaque burden (Region 1: 13.3%; Region 2: 18.8%; Region 3: 22.4%; Region 4: 38.6%, p < 0.001) were significantly higher in individuals of Region 4. Inhabitants of Region 4 had also higher levels of C reactive protein (Region 1: 4.56 ± 4.85 mg/l; Region 2: 3.49 ± 4.46 mg/l; Region 3: 4.03 ± 3.32 mg/l, Region 4: 5.16 ± 8.26 mg/l, p < 0.001). Propensity score analysis revealed higher inter-area differences in mean cIMT of individuals with coronary artery disease (CAD) (high vs low air pollution area: 1.56 ± 0.80 mm; vs. 1.18 ± 0.54 mm, p < 0.001) while there was no difference in cIMT of the matched population without CAD (p = 0.52). CONCLUSIONS: An increased carotid atherosclerotic and inflammatory burden is observed in inhabitants of areas with the highest concentration of air pollutants.


Subject(s)
Air Pollutants , Air Pollution , Carotid Artery Diseases , Air Pollutants/adverse effects , Air Pollutants/analysis , Air Pollution/adverse effects , Air Pollution/analysis , Carotid Arteries/diagnostic imaging , Carotid Artery Diseases/chemically induced , Carotid Artery Diseases/diagnostic imaging , Carotid Artery Diseases/epidemiology , Carotid Intima-Media Thickness , Humans , Inflammation/diagnosis , Inflammation/diagnostic imaging , Risk Factors
11.
Mol Cell Endocrinol ; 534: 111366, 2021 08 20.
Article in English | MEDLINE | ID: mdl-34126188

ABSTRACT

The phenotypic change of vascular smooth muscle cells (VSMCs) from a contractile to a synthetic form is a key player in atherogenic processes. Homeobox A5 (HOXA5), a transcription factor of the homeobox gene family, has been shown to regulate cell differentiation and morphogenesis. The present study was designed to clarify the involvement of HOXA5 in VSMC phenotypic transition in carotid atherosclerosis (CAS). Activated VSMCs in vitro and ApoE-/- mice in vivo were employed to determine HOXA5's function. Results showed that both the mRNA and protein expression levels of HOXA5 were decreased in platelet-derived growth factor-BB (PDGF-BB)-induced VSMCs. Overexpression of HOXA5 suppressed VSMC conversion from a contractile to a synthetic type in the presence of PDGF-BB, as evidenced by increased contractile markers (calponin, α-SMA and SM22α) along with decreased synthetic markers (vimentin, PCNA and thrombospondin). PDGF-BB-induced proliferation and migration of VSMCs were recovered by HOXA5. Knockdown of HOXA5 had the opposite effect on VSMCs. In vivo, a CAS model was established using ApoE-/- mice fed with a Western-type diet and placing a perivascular carotid collar. We observed a significant reduction in HOXA5 in the carotid arteries of CAS mice. Similar to the in vitro results, HOXA5 overexpression reduced neointimal hyperplasia and plaque formation and inhibited VSMC dedifferentiation and migration. Furthermore, PPARγ was also downregulated in vitro and in vivo, and its antagonist GW9662 reversed HOXA5-mediated inhibition of VSMC dedifferentiation and migration. In summary, we suggest that HOXA5 protects against CAS progression by inhibiting VSMC dedifferentiation through activation of PPARγ.


Subject(s)
Apolipoproteins E/genetics , Becaplermin/pharmacology , Carotid Artery Diseases/metabolism , Homeodomain Proteins/genetics , Homeodomain Proteins/metabolism , Muscle, Smooth, Vascular/cytology , Transcription Factors/genetics , Transcription Factors/metabolism , Animals , Carotid Artery Diseases/chemically induced , Carotid Artery Diseases/genetics , Cell Movement/drug effects , Cell Proliferation/drug effects , Cells, Cultured , Diet, Western , Disease Models, Animal , Down-Regulation , Gene Knockout Techniques , Humans , Mice , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/metabolism , Phenotype , Primary Cell Culture
12.
World Neurosurg ; 148: e242-e251, 2021 04.
Article in English | MEDLINE | ID: mdl-33412322

ABSTRACT

OBJECTIVE: Aneurysmal subarachnoid hemorrhage remains a devastating event with poorly understood pathophysiology. Previous studies have suggested that aneurysm wall inflammation may play a part in the development and potential rupture of aneurysms. The rabbit elastase aneurysm model is a well-established model, which produces aneurysms closely mimicking human cerebral aneurysms in flow dynamics and histopathology. The primary aim of this study was to correlate inflammatory changes after aneurysm formation using sequential vessel wall imaging with histopathologic analysis. A secondary aim was to evaluate the potential effect of gender and anti-inflammatory treatment with aspirin on this inflammatory response. METHODS: Twenty-seven New Zealand rabbits underwent surgery to create an aneurysm using elastase infusion at the right common carotid artery origin. Vessel wall imaging and histopathologic analysis was obtained at different time points after aneurysm creation. The rabbits were also randomized by gender and to treatment groups with or without aspirin. RESULTS: Histopathologic analysis revealed 3 distinct phases after aneurysm formation. These phases were an initial inflammatory phase, followed by a regeneration phase, and finally a connective tissue deposition phase. Vessel wall imaging demonstrated 2 distinct imaging patterns. No appreciable differences were seen in histology or imaging when comparing gender or treatment with aspirin. CONCLUSIONS: Inflammatory changes induced by the rabbit elastase aneurysm model can be correlated with histopathologic findings and observed on noninvasive vessel wall imaging. This may provide a method to study the inflammatory pathway as it pertains to aneurysmal development and subsequent rupture.


Subject(s)
Carotid Artery Diseases/chemically induced , Disease Models, Animal , Intracranial Aneurysm/complications , Magnetic Resonance Angiography , Pancreatic Elastase/toxicity , Rabbits/physiology , Animals , Aspirin/therapeutic use , Carotid Artery Diseases/diagnostic imaging , Carotid Artery Diseases/pathology , Carotid Artery, Common/diagnostic imaging , Carotid Artery, Common/drug effects , Carotid Artery, Common/pathology , Carotid Artery, Common/physiology , Disease Progression , Elastic Tissue/ultrastructure , Female , Hyperplasia , Infusions, Intra-Arterial , Intracranial Aneurysm/chemically induced , Intracranial Aneurysm/diagnostic imaging , Intracranial Aneurysm/drug therapy , Male , Myocytes, Smooth Muscle/pathology , Necrosis , Pancreatic Elastase/administration & dosage , Rabbits/immunology , Regeneration , Sex Characteristics , Single-Blind Method , Tunica Intima/pathology , Tunica Media/pathology , Vasculitis/drug therapy , Vasculitis/etiology , Vasculitis/pathology
13.
Catheter Cardiovasc Interv ; 96(4): E484-E492, 2020 10 01.
Article in English | MEDLINE | ID: mdl-32558228

ABSTRACT

OBJECTIVE: The present study evaluated the effect of endovascular administration of calcium chloride to the carotid artery of swines, to create a model of arterial calcification. METHODS: Fifteen Large White pigs were used for the study. Via endovascular treatment, carotid arteries were exposed during 9 min to either calcium chloride (experimental artery) or saline (control artery) with the use of the TAPAS catheter. Intravascular ultrasound (IVUS) imaging was obtained at baseline, postprocedure and at 30 days. Optical coherence tomography (OCT) imaging was obtained in vitro after carotids were harvested. Longitudinally cut parallel arterial segments were placed in a system of delicate clamps and underwent uniaxial strain test. All arteries underwent histopathological examination. RESULTS: Calcium chloride treated segments showed extensive circumferential parietal calcification evident on both IVUS and OCT. Reduction in minimal lumen area on IVUS was evident in experimental arteries both at 24 hr and 30 days postprocedure. Histopathologic assessment (Von Kossa stain) confirmed medial calcification with mild intimal thickening. Biomechanical testing showed treated segments to have smaller breaking strength and less elastic deformation than controls. CONCLUSION: We developed a nonexpensive, reproducible model of early carotid medial calcification in pigs. Our model has the potential to help the development of research to unravel mechanisms underlying arterial calcification, the use of current or new devices to treat calcified lesions as well as to serve as an option for training interventionalists on the use of such devices.


Subject(s)
Calcium Chloride , Carotid Artery Diseases/chemically induced , Carotid Artery, Common/pathology , Vascular Calcification/chemically induced , Animals , Biomechanical Phenomena , Carotid Artery Diseases/diagnostic imaging , Carotid Artery Diseases/pathology , Carotid Artery, Common/diagnostic imaging , Disease Models, Animal , Elasticity , Male , Neointima , Sus scrofa , Time Factors , Tomography, Optical Coherence , Ultrasonography, Interventional , Vascular Calcification/diagnostic imaging , Vascular Calcification/pathology
14.
Chem Biodivers ; 17(9): e2000431, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32583520

ABSTRACT

A series of aryloxyethylamine derivatives were designed, synthesized and evaluated for their biological activity. Their structures were confirmed by 1 H-NMR, 13 C-NMR, FT-IR and HR-ESI-MS. The preliminary screening of neuroprotection of compounds in vitro was detected by MTT, and the anti-ischemic activity in vivo was tested using bilateral common carotid artery occlusion in mice. Most of these compounds showed potential neuroprotective effects against the glutamate-induced cell death in differentiated rat pheochromocytoma cells (PC12 cells), especially for (4-fluorophenyl){1-[2-(4-methoxyphenoxy)ethyl]piperidin-4-yl}methanone, {1-[2-(4-methoxyphenoxy)ethyl]piperidin-4-yl}(4-methoxyphenyl)methanone, (4-bromophenyl){1-[2-(4-methoxyphenoxy)ethyl]piperidin-4-yl}methanone, {1-[2-(4-chlorophenoxy)ethyl]piperidin-4-yl}(4-chlorophenyl)methanone, (4-chlorophenyl)(1-{2-[(naphthalen-2-yl)oxy]ethyl}piperidin-4-yl)methanone, (4-chlorophenyl){1-[2-(4-methoxyphenoxy)ethyl]piperidin-4-yl}methanone and {1-[2-(4-bromophenoxy)ethyl]piperidin-4-yl}(4-chlorophenyl)methanone, which exhibited potent protection of PC12 cells at three doses (0.1, 1.0, 10 µM). Compounds (4-fluorophenyl){1-[2-(4-methoxyphenoxy)ethyl]piperidin-4-yl}methanone, (4-fluorophenyl){1-[2-(naphthalen-2-yloxy)ethyl]piperidin-4-yl}methanone, {1-[2-(4-methoxyphenoxy)ethyl]piperidin-4-yl}(4-methoxyphenyl)methanone and {1-[2-(4-chlorophenoxy)ethyl]piperidin-4-yl}(4-chlorophenyl)methanone possessed the significant prolongation of the survival time of mice subjected to acute cerebral ischemia and decreased the mortality rate at all five doses tested (200, 100, 50, 25, 12.5 mg/kg) and had significant neuroprotective activity. In addition, (4-fluorophenyl){1-[2-(4-methoxyphenoxy)ethyl]piperidin-4-yl}methanone, {1-[2-(4-methoxyphenoxy)ethyl]piperidin-4-yl}(4-methoxyphenyl)methanone and {1-[2-(4-chlorophenoxy)ethyl]piperidin-4-yl}(4-chlorophenyl)methanone possessed outstanding neuroprotection in vitro and in vivo. These compounds can be used as a promising neuroprotective agents for future development of new anti-ischemic stroke agents. Basic structure-activity relationships are also presented.


Subject(s)
Carotid Artery Diseases/prevention & control , Ethylamines/pharmacology , Ischemic Stroke/prevention & control , Neuroprotective Agents/pharmacology , Animals , Carotid Artery Diseases/chemically induced , Cell Survival/drug effects , Ethylamines/chemical synthesis , Ethylamines/chemistry , Female , Glutamates , Ischemic Stroke/chemically induced , Male , Mice , Mice, Inbred Strains , Neuroprotective Agents/chemical synthesis , Neuroprotective Agents/chemistry , PC12 Cells , Rats
15.
BMC Cardiovasc Disord ; 19(1): 289, 2019 12 12.
Article in English | MEDLINE | ID: mdl-31830904

ABSTRACT

BACKGROUND: The burden of cardiovascular disease (CVD) morbidity and mortality is higher among Indigenous persons, who also experience greater health disparities when compared to non-Indigenous Canadians, particularly in remote regions of Canada. Assessment of carotid intima-media thickness (cIMT), a noninvasive screening tool and can be used as biomarker to assess increased CVD risk. Few studies have examined environmental contaminant body burden and its association with cIMT. METHODS: Data from the Environment-and-Health Study in the Eeyou Istchee territory of northern Québec, Canada was used to assess complex body burden mixtures of POPs, metals and metalloids among (n = 535) Indigenous people between 15 and 87 years of age with cIMT. First, Principal Component Analysis (PCA) was used to reduce the complexity of the contaminant data. Second, based on the underlying PCA profiles from the biological data, we examined each of the prominent principal component (PC) axes on cIMT using multivariable linear regression models. Lastly, based on these PC axes, cIMT was also regressed on summed (Σ) organic compound concentrations, polychlorinated biphenyl, perfluorinated compounds, respectively, ∑10 OCs, ∑13 PCBs, ∑3PFCs, and nickel. RESULTS: Most organochlorines and PFCs loaded primarily on PC-1 (53% variation). Nickel, selenium, and cadmium were found to load on PC-5. Carotid-IMT was significantly associated with PC-1 ß = 0.004 (95 % CI 0.001, 0.007), and PC-5 ß = 0.013 (95 % CI 0.002, 0.023). However, the association appears to be greater for PC-5, accounting for 3% of the variation, and mostly represented by nickel. Results show that that both nickel, and ∑3PFCs were similarly associated with cIMT ß = 0.001 (95 % CI 0.0003, 0.003), and ß = 0.001 (95 % CI 0.0004, 0.002), respectively. But ∑10OCs was significantly associated with a slightly greater ß = 0.004 (95 % CI 0.001, 0.007) cIMT change, though with less precision. Lastly, ∑13PCBs also increased ß = 0.002 (95 % CI 0.0004, 0.003) cIMT after fully adjusting for covariates. CONCLUSION: Our results suggest that environmental contaminants are associated with cIMT. This is important for the Cree from the Eeyou Istchee territory who may experience higher body burdens of contaminants than non-Indigenous Canadians.


Subject(s)
Carotid Artery Diseases/chemically induced , Carotid Artery Diseases/diagnostic imaging , Carotid Intima-Media Thickness , Complex Mixtures/adverse effects , Environmental Exposure/adverse effects , Environmental Pollutants/adverse effects , Adolescent , Adult , Aged , Aged, 80 and over , Body Burden , Cardiotoxicity , Carotid Artery Diseases/ethnology , Female , Humans , Indians, North American , Indigenous Peoples , Male , Middle Aged , Predictive Value of Tests , Quebec/epidemiology , Risk Assessment , Risk Factors , Young Adult
16.
Environ Pollut ; 255(Pt 2): 113320, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31610505

ABSTRACT

Smoky coal burning is a predominant manner for heating and cooking in most rural areas, China. Air pollution is associated with the risk of atherosclerosis, however, the link between indoor air pollution induced by smoky coal burning and atherosclerosis is not very clear. Therefore, we designed a cross-sectional study to evaluate the association of long-term exposure to smoky coal burning pollutants with the risk of atherosclerosis. 426 and 326 participants were recruited from Nangong, China and assigned as the coal exposure and control group according to their heating and cooking way, respectively. The indoor air quality (PM2.5, CO, SO2) was monitored. The association between coal burning exposure and the prevalence of atherosclerosis was evaluated by unconditional logistic regression analysis, adjusted for confounding factors. The inflammatory cytokines mRNAs (IL-8, SAA1, TNF-α, CRP) expression in whole blood were examined by qPCR. People in the coal exposure group had a higher risk of carotid atherosclerosis compared with the control (risk ratio [RR], 1.434; 95% confidence interval [95%CI], 1.063 to 1.934; P = 0.018). The association was stronger in smokers, drinkers and younger (<45 years old) individuals. The elevation of IL-8 (0.24, 95%CI, 0.06-0.58; P < 0.05), CRP (0.37, 95%CI, 0.05-0.70; P < 0.05), TNF-α (0.41, 95%CI, 0.14-0.67; P < 0.01) mRNAs expression in whole blood were positively related to coal exposure. Our results suggested long-term exposure to smoky coal burning emissions could increase the risk of carotid atherosclerosis. The potential mechanism might relate that coal burning emissions exposure induced inflammatory cytokines elevation which had adverse effects on atherosclerotic plaque, and then promoted the development of atherosclerosis.


Subject(s)
Air Pollution, Indoor/analysis , Air Pollution/analysis , Atherosclerosis/epidemiology , Carotid Artery Diseases/epidemiology , Coal/analysis , Smoke/analysis , Atherosclerosis/chemically induced , Carotid Artery Diseases/chemically induced , China/epidemiology , Cooking/methods , Cross-Sectional Studies , Female , Heating/methods , Humans , Male , Middle Aged , Odds Ratio , Rural Population
17.
J Vasc Res ; 56(3): 139-151, 2019.
Article in English | MEDLINE | ID: mdl-31064000

ABSTRACT

BACKGROUND: It has been reported that smoking is one of the strongest positive risk factors for abdominal aortic aneurysms (AAAs). Although many studies have been directed to decipher the effect of smoking on AAA, its effect on macrophage activation has not yet been explored. OBJECTIVES: We have reported the importance of osteoclastogenesis (OCG) in aneurysm formation. Therefore, we examined the effect of cigarette smoking on OCG and arterial aneurysmal formation by using cigarette smoke extract (CSE) in this study. METHODS: Macrophage cell lines were stimulated with CSE, and their activation and differentiation were examined in vitro. Since macrophages activated through the OCG pathway are identified by tartrate-resistant acid phosphatase (TRAP) expression, these cells are referred to as TRAP-positive macrophages (TPMs) in this study. We also applied CSE-contained PBS in the calcium chloride-induced mouse carotid aneurysm model in vivo. RESULTS: Macrophages stimulated with CSE expressed significantly higher levels of nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), TRAP, cathepsin K, matrix metalloproteinase-9 and membrane-type metalloproteinase (MT1-MMP). CSE-treated mouse aneurysms showed increased aneurysm size with increased TPM infiltration and protease expression compared to non-CSE-treated mouse aneurysms. CONCLUSIONS: These results suggest that CSE intensifies OCG in macrophages and promotes arterial aneurysmal progression.


Subject(s)
Aneurysm/chemically induced , Carotid Artery Diseases/chemically induced , Macrophage Activation/drug effects , Macrophages/drug effects , Osteoclasts/drug effects , Osteogenesis/drug effects , Smoke/adverse effects , Tartrate-Resistant Acid Phosphatase/metabolism , Tobacco Products/adverse effects , Aneurysm/enzymology , Aneurysm/pathology , Animals , Calcium Chloride , Carotid Artery Diseases/enzymology , Carotid Artery Diseases/pathology , Cathepsin K/metabolism , Disease Models, Animal , Macrophages/enzymology , Macrophages/pathology , Male , Matrix Metalloproteinase 9/metabolism , Mice , Mice, Inbred C57BL , Osteoclasts/enzymology , Osteoclasts/pathology , RAW 264.7 Cells , Signal Transduction
18.
Circulation ; 139(17): 2003-2011, 2019 04 23.
Article in English | MEDLINE | ID: mdl-30759995

ABSTRACT

BACKGROUND: Ceramides have been implicated in the pathophysiology of HIV infection and cardiovascular disease. However, no study, to our knowledge, has evaluated circulating ceramide levels in association with subclinical cardiovascular disease risk among HIV-infected individuals. METHODS: Plasma levels of 4 ceramide species (C16:0, C22:0, C24:0, and C24:1) were measured among 398 women (73% HIV+) and 339 men (68% HIV+) without carotid artery plaques at baseline from the Women's Interagency HIV Study and the Multicenter AIDS Cohort Study. We examined associations between baseline plasma ceramides and risk of carotid artery plaque formation, assessed by repeated B-mode carotid artery ultrasound imaging over a median 7-year follow-up. RESULTS: Plasma levels of C16:0, C22:0, and C24:1 ceramides were significantly higher in HIV-infected individuals compared with those without HIV infection (all P<0.001), and further analysis indicated that elevated ceramide levels were associated with antiretroviral therapy use, particularly protease inhibitor use, in HIV-infected individuals (all P<0.001). All 4 ceramides were highly correlated with each other ( r=0.70-0.94; all P<0.001) and significantly correlated with total-cholesterol ( r=0.42-0.58; all P<0.001) and low-density lipoprotein cholesterol ( r=0.24-0.42; all P<0.001) levels. Of note, C16:0 and C24:1 ceramides, rather than C22:0 and C24:0 ceramides, were more closely correlated with specific monocyte activation and inflammation markers (eg, r=0.30 between C16:0 ceramide and soluble CD14; P<0.001) and surface markers of CD4+ T-cell activation. A total of 112 participants developed carotid artery plaques over 7 years, and higher levels of C16:0 and C24:1 ceramides were significantly associated with increased risk of carotid artery plaques (relative risk [95% CI]=1.55 [1.29, 1.86] and 1.51 [1.26, 1.82] per standard deviation increment, respectively; both P<0.001), after adjusting for demographic and behavioral factors. After further adjustment for cardiovascular disease risk factors and immune activation markers, these associations were attenuated but remained significant. The results were consistent between men and women and between HIV-infected and HIV-uninfected participants. CONCLUSIONS: In 2 HIV cohorts, elevated plasma levels of C16:0 and C24:1 ceramides, correlating with immune activation and inflammation, were associated with antiretroviral therapy use and progression of carotid artery atherosclerosis.


Subject(s)
Anti-Retroviral Agents/adverse effects , Carotid Artery Diseases/blood , Ceramides/blood , HIV Infections/drug therapy , Adult , Anti-Retroviral Agents/therapeutic use , Carotid Artery Diseases/chemically induced , Carotid Artery Diseases/diagnostic imaging , Carotid Artery Diseases/etiology , Comorbidity , Disease Progression , Female , Follow-Up Studies , HIV Infections/blood , HIV Infections/complications , HIV Protease Inhibitors/pharmacology , HIV Protease Inhibitors/therapeutic use , Humans , Inflammation/blood , Male , Middle Aged , Monocytes/metabolism , Multicenter Studies as Topic , Prospective Studies , Risk Factors , Socioeconomic Factors
19.
Korean J Intern Med ; 34(3): 579-587, 2019 May.
Article in English | MEDLINE | ID: mdl-28838227

ABSTRACT

BACKGROUND/AIMS: The aromatase inhibitors (AIs) are well known anti-hormonal therapy in endocrine-responsive breast cancer patients. It can lead to dyslipidemia and be the risk factor of cardiovascular disease due to low estrogen level. However, some recent studies comparing AIs with placebo have shown controversial results. The aim of this study was to investigate lipid profiles, measurement of carotid intima-media thickness (IMT) and the presence of plaque among endocrine-responsive breast cancer treated with AIs compared to ones that were not treated with AIs. METHODS: A total of 85 postmenopausal women, who underwent breast cancer surgery during the age of 50 to 64 without history of statin use were included. There were 42 patients who were treated with AIs over 1 year (group 1) and 43 patients without AIs use (group 2). Serum total cholesterol, high density lipoprotein cholesterol, triglycerides, fasting blood glucose, carotid IMT, and presence of plaque were assessed. RESULTS: The baseline characteristics were similar between two groups and there was no significant difference in carotid IMT irrespective of AIs administration. However, ultrasonographic evaluation of carotid artery revealed that the presence of plaque in AI users was significantly higher than in non-AI users (66.7% vs. 41.9%, p = 0.02; odds ratio, 4.21 in adjusted model; p = 0.01). History of diabetes was also the significant risk factor for the plaque formation. CONCLUSION: There was no significant difference in lipid profile itself between two groups, but more importantly the presence of the plaque was much higher indicating possible detrimental effect of AI on cardiovascular system.


Subject(s)
Aromatase Inhibitors/adverse effects , Breast Neoplasms/drug therapy , Carotid Artery Diseases/chemically induced , Carotid Intima-Media Thickness , Aged , Breast Neoplasms/blood , Carotid Artery Diseases/diagnostic imaging , Female , Humans , Lipids/blood , Middle Aged , Retrospective Studies , Risk Factors
20.
Arterioscler Thromb Vasc Biol ; 38(5): 1007-1019, 2018 05.
Article in English | MEDLINE | ID: mdl-29567680

ABSTRACT

OBJECTIVE: Cardiovascular diseases and depression are the leading causes of disability in Western countries. Clinical data on potential cardiovascular effects of serotonin reuptake inhibitors (SSRIs), the most commonly used antidepressant drugs, are controversial. In addition to blocking serotonin reuptake transporter in the brain, SSRIs deplete the major peripheral serotonin (5-hydroxytryptamine [5-HT]) storage by inhibiting serotonin reuptake transporter-mediated uptake in platelets. In this study, we aimed to investigate the effect of chronic SSRI intake on the development of atherosclerosis. APPROACH AND RESULTS: Treatment of apolipoprotein E-deficient mice with the SSRI fluoxetine for 2, 4, or 16 weeks increased atherosclerotic lesion formation, with most pronounced effect during early plaque development. Intravital microscopy of carotid arteries revealed enhanced myeloid cell adhesion on fluoxetine treatment. Mechanistically, we found that fluoxetine augmented vascular permeability and increased chemokine-induced integrin-binding activity of circulating leukocytes. In vitro stimulation of murine blood demonstrated that fluoxetine, but not 5-HT, could directly promote ß1 and ß2 integrin activation provided C-C motif chemokine ligand 5 was also present. Similar effects were observed with the SSRI escitalopram. Enhanced C-C motif chemokine ligand 5-induced integrin activation by fluoxetine was also confirmed in a human neutrophil-like cell line. In contrast to the proatherogenic properties of fluoxetine, pharmacological inhibition of the peripheral 5-HT synthesizing enzyme tryptophan hydroxylase 1 did not promote atherosclerosis, suggesting that the proatherogenic effect of fluoxetine occurs independent of peripheral 5-HT depletion. CONCLUSIONS: SSRI intake may promote atherosclerosis and therefore potentially increase the risk for acute cardiovascular events by a mechanism that is independent of 5-HT depletion.


Subject(s)
Aorta/drug effects , Aortic Diseases/chemically induced , Atherosclerosis/chemically induced , Carotid Arteries/drug effects , Carotid Artery Diseases/chemically induced , Fluoxetine/toxicity , Plaque, Atherosclerotic , Selective Serotonin Reuptake Inhibitors/toxicity , Animals , Aorta/metabolism , Aorta/pathology , Aortic Diseases/blood , Aortic Diseases/genetics , Aortic Diseases/pathology , Atherosclerosis/blood , Atherosclerosis/genetics , Atherosclerosis/pathology , Blood Platelets/drug effects , Blood Platelets/metabolism , CD18 Antigens/blood , Capillary Permeability/drug effects , Carotid Arteries/metabolism , Carotid Arteries/pathology , Carotid Artery Diseases/blood , Carotid Artery Diseases/genetics , Carotid Artery Diseases/pathology , Cell Adhesion/drug effects , Chemokine CCL5/blood , Disease Models, Animal , Disease Progression , Drug Administration Schedule , Fluoxetine/administration & dosage , HEK293 Cells , HL-60 Cells , Humans , Integrin beta1/blood , Male , Mice, Inbred C57BL , Mice, Knockout, ApoE , Myeloid Cells/drug effects , Myeloid Cells/metabolism , Serotonin/blood , Selective Serotonin Reuptake Inhibitors/administration & dosage , Signal Transduction , Time Factors
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