Carotid Atheroma Research Articles

Prevalence of Obstructive Sleep Apnoea and Its Association With Atherosclerotic Plaques in a Cohort of Subjects With Mild–Moderate Cardiovascular Risk

IntroductionClassic cardiovascular risk factors do not explain all the cardiovascular events. Obstructive sleep apnoea (OSA) has been proposed as a potential and prevalent cardiovascular risk factor. Our study aimed to describe the prevalence of OSA in a middle-aged cohort with mild–moderate cardiovascular risk and evaluate its association with atherosclerotic disease. MethodsThis is an observational cross-sectional ancillary study of the ILERVAS project which was aimed to study subclinical arterial disease in a cohort with mild–moderate cardiovascular risk. In a sample of consecutive subjects, we performed a sleep study and evaluate OSA prevalence and its association with carotid and femoral atheroma plaques and atherosclerotic burden. ResultsOverall, 966 subjects with a median age of 57 years (25–75th percentile; 52–62) and a body mass index (BMI) of 28.5kg/m2 (25.6–31.6) were included. Of these, 72.6% (69.7%–75.3%) had OSA (apnoea–hypopnoea index (AHI)≥5/h); 35.7% (32.8%–38.8%) had mild OSA (AHI 5–14.9/h) and 36.9% (33.9%–39.9%) had moderate/severe OSA (AHI≥15/h). Mean oxygen saturation and the percentage of time with oxygen saturation<90% (CT90) were associated with atherosclerotic burden (eβ (95%CI) 0.932 (0.892, 0.974); 1.005 (1.002, 1.009), respectively) and total plaque (OR (95%CI) 0.88 (0.797,0.971); 1.013 (1.004,1.021), respectively). No association with the AHI or oxygen desaturation index was found. ConclusionsThis study confirms a high prevalence of OSA in patients with mild–moderate cardiovascular risk and shows an association between atherosclerotic burden, total and femoral plaque with CT90 and mean oxygen saturation, suggesting the importance of OSA-related hypoxaemia in the induction of atherosclerotic disease.

Anticytomegalovirus CD4+ T Cells Are Associated With Subclinical Atherosclerosis in Persons With HIV.

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Carotid Atherosclerosis in Asymptomatic Patients with at Least One Cardiovascular Risk Factor: A Cross-Sectional Study in Yaounde, Cameroon

<i>Introduction</i>: Atherosclerosis is a leading cause of vascular disease worldwide. One of its main locations is in the carotid artery which is implicated in 20% of ischemic strokes. This study aimed to determine the frequency of carotid atherosclerosis in a group of asymptomatic patients with at least one cardiovascular risk factor. <i>Methodology</i>: This was a cross-sectional study from January to June 2021 (6 months). We included consenting adults followed up at the Yaoundé Central Hospital and the Yaoundé University Teaching Hospital, aged at least 50 years and having at least one cardiovascular risk factor such as hypertension, diabetes, dyslipidemia, smoking, or obesity. A Doppler ultrasound of the supra-aortic trunks was performed on each patient. Statistical analyses were performed using the chi-2 test for bivariate analysis and binary logistic regression for multivariate analyses. The threshold of significance was set at 0.05. <i>Results</i>: A total of 75 participants were included of which 26 were men and 49 women. The mean age (SD) was 62.96 (8.87) years. Hypertension was seen in 93.3% of the participants, dyslipidemia in 77.3%, obesity in 48%, type 2 diabetes in 34.7%, and 9.3% were smokers. High cardiovascular risk was seen in 22 (29.4%) participants. Twenty-seven participants (36%) had one or more carotid atheroma plaques, and 11 (14.7%) participants had a stenosis plaque. Hypercholesterolemia and high cardiovascular risk were associated with the presence of carotid atheroma plaque. <i>Conclusion</i>: The frequency of carotid atherosclerosis appears to be high in people over 50 years of age with at least one cardiovascular risk factor justifying the importance of control strategies against these factors.

Ateroma arteri karotis pada radiograf panoramik sebagai diagnosis awal aterosklerosis

Objectives: This review aimed to understand the radiographic features of carotid artery atheroma on panoramic radiographs as an early diagnosis of atherosclerosis. &#x0D; Literature Review: Carotid artery calcification is caused by a plaque known as an atheroma. Atheroma is a plaque composed of lipids and rich in calcium. If atheroma formation in the carotid arteries increases, it would cause stenosis of the blood vessels and increase the risk of stroke. On panoramic radiographs, carotid artery atheroma appears as a heterogeneous radiopaque image with an irregular shape and well-defined borders. Radiopaque image located inferior to the angle of the mandible, close to the cervical spine (C3-C5) and above the hyoid bone.&#x0D; Conclusion: Incidental findings on panoramic radiograph could be an initial reference for further examination and evaluation of atherosclerosis.

BIRC6 Is Associated with Vulnerability of Carotid Atherosclerotic Plaque.

Carotid atherosclerotic plaque rupture can lead to cerebrovascular accident (CVA). By comparing RNA-Seq data from vascular smooth muscle cells (VSMC) extracted from carotid atheroma surgically excised from a group of asymptomatic and symptomatic subjects, we identified more than 700 genomic variants associated with symptomatology (p < 0.05). From these, twelve single nucleotide polymorphisms (SNPs) were selected for further validation. Comparing genotypes of a hospital-based cohort of asymptomatic with symptomatic patients, an exonic SNP in the BIRC6 (BRUCE/Apollon) gene, rs35286811, emerged as significantly associated with CVA symptomatology (p = 0.002; OR = 2.24). Moreover, BIRC6 mRNA levels were significantly higher in symptomatic than asymptomatic subjects upon measurement by qPCR in excised carotid atherosclerotic tissue (p < 0.0001), and significantly higher in carriers of the rs35286811 risk allele (p < 0.0001). rs35286811 is a proxy of a GWAS SNP reported to be associated with red cell distribution width (RDW); RDW was increased in symptomatic patients (p < 0.03), but was not influenced by the rs35286811 genotype in our cohort. BIRC6 is a negative regulator of both apoptosis and autophagy. This work introduces BIRC6 as a novel genetic risk factor for stroke, and identifies autophagy as a genetically regulated mechanism of carotid plaque vulnerability.

Problem-based learning in dentistry: Diagnostic capability of dentists in the detection of calcified carotid artery atheroma on digital panoramic radiographs

Objective: The aim of this study was to evaluate the diagnostic capability of dentists in the identification of suggestive images of calcified carotid artery atheroma (CCAA) on panoramic radiographs (PRs) before and after using a problem-based learning method (PBL). Methodology: Five dentists (no specialists in oral and maxillofacial radiology) analyzed 102 digital PRs divided into: PRs with suggestive images of CCAA (n=51) and without suggestive images of CCAA (n=51). After the first analysis, the examiners attended an activity on soft tissue calcifications using the PBL method. Afterwards, they analyzed the 102 PRs again. The results of the analysis were calculated using the Cohen's Kappa Test and the Receptor Operational Characteristic Curves (ROC). Results and Discussion: Regarding examiners’ performance before and after the activity, the intra-examiner test showed reasonable Kappa coefficients (0-0.40). For inter-examiner agreement after the activity, the Kappa coefficient was almost perfect (&gt; 0.80). When comparing examiners’ performance after the activity with a template performed by an experienced radiologist, the Kappa Coefficient was &gt; 0.80 with significant agreement (p&lt;0.05). Conclusion: The precision and the probability of correctly detecting suggestive images of CCAA on PRs increased when the examiners participated in the active pedagogical method. The continuing education of the dentist and how it can make a difference in the systemic health of patients should be considered.

Inhibition of PFKFB3 Hampers the Progression of Atherosclerosis and Promotes Plaque Stability.

Aims6-phosphofructo-2-kinase/fructose-2,6-biphosphatase (PFKFB)3-mediated glycolysis is pivotal in driving macrophage- and endothelial cell activation and thereby inflammation. Once activated, these cells play a crucial role in the progression of atherosclerosis. Here, we analyzed the expression of PFKFB3 in human atherosclerotic lesions and investigated the therapeutic potential of pharmacological inhibition of PFKFB3 in experimental atherosclerosis by using the glycolytic inhibitor PFK158.Methods and ResultsPFKFB3 expression was higher in vulnerable human atheromatous carotid plaques when compared to stable fibrous plaques and predominantly expressed in plaque macrophages and endothelial cells. Analysis of advanced plaques of human coronary arteries revealed a positive correlation of PFKFB3 expression with necrotic core area. To further investigate the role of PFKFB3 in atherosclerotic disease progression, we treated 6–8 weeks old male Ldlr–/– mice. These mice were fed a high cholesterol diet for 13 weeks, of which they were treated for 5 weeks with the glycolytic inhibitor PFK158 to block PFKFB3 activity. The incidence of fibrous cap atheroma (advanced plaques) was reduced in PFK158-treated mice. Plaque phenotype altered markedly as both necrotic core area and intraplaque apoptosis decreased. This coincided with thickening of the fibrous cap and increased plaque stability after PFK158 treatment. Concomitantly, we observed a decrease in glycolysis in peripheral blood mononuclear cells compared to the untreated group, which alludes that changes in the intracellular metabolism of monocyte and macrophages is advantageous for plaque stabilization.ConclusionHigh PFKFB3 expression is associated with vulnerable atheromatous human carotid and coronary plaques. In mice, high PFKFB3 expression is also associated with a vulnerable plaque phenotype, whereas inhibition of PFKFB3 activity leads to plaque stabilization. This data implies that inhibition of inducible glycolysis may reduce inflammation, which has the ability to subsequently attenuate atherogenesis.

Relationship between carotid atheroma thickness and albuminuria in diabetic patients

&nbsp; Our aim in this study to assess the efficacy of albuminuria in type 2 diabetes mellitus to be as predictor and independent marker of atherosclerosis by measurement of carotid intimal-medial thickness (CIMT)&nbsp; by high frequency ultrasonography. One hundred twenty participants in this study, 45 as a control healthy person and the others 75 patients with type 2 diabetes mellitus were included in this study. We divided into three groups: group 1 which is the control group, and group 2 those patients who are the diabetic without albuminuria, and group 3 are the diabetic patients with albuminuria. The intimal-medial thickness (IMT) was measured by high frequency ultrasonography. Other laboratory investigations were measured like HbA1c, fasting blood sugar, lipid profile. The intimal-medial thickness (IMT) was found higher in group 3 than group 1 and group 2 (P value &lt; 0.05). In conclusion, there is a significant association between micro- albuminuria and IMT as a marker of atherosclerosis in type 2 diabetes mellitus.

In vivo imaging of reactive oxygen species (ROS)-producing pro-inflammatory macrophages in murine carotid atheromas using a CD44-targetable and ROS-responsive nanosensor

In this study, we report the in vivo imaging of reactive oxygen species (ROS)-overproducing pro-inflammatory macrophages in atherosclerotic plaques using a fluorescent ROS nanosensor. We designed the nanosensor by chemically conjugating hyaluronic acid (HA, a targeting ligand for CD44 receptor), chlorin e6 [Ce6; a near-infrared fluorescent (NIRF) dye], and a thioketal (TK) linker (ROS-degradable linker). The self-assembled nanosensor emitted weak NIRF signals in normal physiological conditions, whereas it emitted strong NIRF signals under ROS-abundant conditions. The cytocompatible nanosensor showed higher intracellular internalization via receptor-mediated endocytosis, which enabled the visualization of intracellular ROS in pro-inflammatory macrophages. Moreover, we demonstrated that the nanosensor enabled the successful targeting and imaging of CD44- and ROS-overproducing pro-inflammatory macrophages in atherosclerotic plaques, as validated by confocal microscopy and immunohistological analyses. These data suggest that our ROS nanosensor is suitable for ROS imaging in pro-inflammatory macrophages in vitro and in vivo and will be a promising approach for imaging atherosclerotic tissues and evaluating the effects of antioxidants.

Recent advances toward clinical applications of photoacoustic microscopy: a review.

Photoacoustic imaging (PAI) is an emerging technology that has been dramatically developed in the last decade. PAI, a combination of optical illumination and ultrasound detection, allows us to achieve fine resolution and obtain fruitful information of endogenous and exogenous chromophores. Among PAI imaging techniques, photoacoustic computed tomography (PACT) has been extensively used in human studies due to its deep tissue penetration (several centimeters). Alternatively, photoacoustic microscopy (PAM) offers higher resolution at the expense of penetration depth, which can also be advantageous in clinics. Recently, there has been increasing attention and studies on PAM of human tissues. In this paper, we will review principles of PAM and its applications to human tissues, including the breast tissue, carotid atheroma tissue, eye, gastrointestinal tissue, ovarian tissue and tooth ex vivo as well as the oral cavity and dermatological tissue in vivo. The paper is closed with the outlook regarding the potential applications of PAM in clinics.

Prevalence of soft tissue calcifications in cone beam computed tomography images in the region of head and neck

Objective: to evaluate the prevalence of calcifications in the soft tissues of the cervical-facial region using cone beam computed tomography (CBCT) images. Material and Methods: two hundred and ten CBCT exames was analyzed by 01 examiner previously trained, with fild of view (FOV) of 16 x 13 cm and voxel of 0.25 mm, in ICAT Vision software (Imaging Science International, Hatfield, PA, USA) in coronal, axial and sagittal sections. The following calcifications were evaluated: tonsiloliths, sialolites, calcification of the styloid complex, calcified carotid atheromas, calcifications in laryngeal cartilages, calcified lymph nodes and osteoma cutis. The findings were tabulated according to the total of the sample, related to the gender, age group of the individuals. Results: Calcification of the styloid complex was the most frequent in the sample studied in both genres (39.04%), followed by the presence of tonsiloliths (19.52%), and calcified lymph nodes (6,67%). Conclusion: calcifications are frequent radiographic findings in CBCT and important for the diagnosis of some possible pathologies that do not present clinical symptoms.KEYWORDSCone-beam computed tomography; Prevalence; Soft tissue calcification.

Relationship between the prevalence of soft tissue radiopacities on panoramic radiographs and medical conditions.

This study aimed to describe radiographic characteristics and the prevalence of selected anatomical structures and soft tissue radiopacities on panoramic radiographs and their relationship to medical conditions. A retrospective cross-sectional study was conducted with 814 consecutive patients aged 35-88 years and their panoramic radiographs. Soft tissue calcifications found in the mandibular angle area were recorded according to gender, age, and bilaterally. Patient medical records were reviewed for atherogenic risk factors including hypertension, diabetes, dyslipidemia, chronic renal disease, menopause, drug usage and any other systemic condition. Data were analyzed with the χ2 test and Fisher's Exact test; P<0.05 was considered statistically significant. Among the 814 patients, a total of 74 (9.1%) calcified carotid artery atheromas (CCAA) were identified, of which 34 (4.17%), 40 (3.19%), and 14 (1.7%) were right, left, and bilateral, respectively. Orthopantomographic examination revealed triticeous cartilage (7.3%) in the cervical bifurcation region, asymptomatic styloid process elongation 192 (23.5%), tonsilloliths 27 (3.3%), sialoliths 37 (4.5%), calcified lymph nodes 46 (5.7%), impacted roots 109 (13.4%), and foreign radiopaque materials 23 (%2.8). There was a significant age and gender difference between type II diabetes and CCAA. A positive correlation was found between styloid process elongation and temporomandibular joint disorders and antidepressant use. Soft tissue radiopacities can be a validated risk indicator of cardiovascular events or misdiagnosed pain. Dental practitioners must be aware of these atypical findings as they may be related to serious disease states and may require referral for further investigation.

Dual-Tracer Positron-Emission Tomography for Identification of Culprit Carotid Plaques and Pathophysiology In Vivo.

Inflammation and microcalcification are interrelated processes contributing to atherosclerotic plaque vulnerability. Positron-emission tomography can quantify these processes in vivo. This study investigates (1) 18F-fluorodeoxyglucose (FDG) and 18F-sodium fluoride (NaF) uptake in culprit versus nonculprit carotid atheroma, (2) spatial distributions of uptake, and (3) how macrocalcification affects this relationship. Individuals with acute ischemic stroke with ipsilateral carotid stenosis of ≥50% underwent FDG-positron-emission tomography and NaF-positron-emission tomography. Tracer uptake was quantified using maximum tissue-to-background ratios (TBRmax) and macrocalcification quantified using Agatston scoring. In 26 individuals, median most diseased segment TBRmax (interquartile range) was higher in culprit than in nonculprit atheroma for both FDG (2.08 [0.52] versus 1.89 [0.40]; P<0.001) and NaF (2.68 [0.63] versus 2.39 [1.02]; P<0.001). However, whole vessel TBRmax was higher in culprit arteries for FDG (1.92 [0.41] versus 1.71 [0.31]; P<0.001) but not NaF (1.85 [0.28] versus 1.79 [0.60]; P=0.10). NaF uptake was concentrated at carotid bifurcations, while FDG was distributed evenly throughout arteries. Correlations between FDG and NaF TBRmax differed between bifurcations with low macrocalcification (rs=0.38; P<0.001) versus high macrocalcification (rs=0.59; P<0.001). This is the first study to demonstrate increased uptake of both FDG and NaF in culprit carotid plaques, with discrete distributions of pathophysiology influencing vulnerability in vivo. These findings have implications for our understanding of the natural history of the disease and for the clinical assessment and management of carotid atherosclerosis.

Ferumoxytol-enhanced three-dimensional magnetic resonance imaging of carotid atheroma- a feasibility and temporal dependence study

Ferumoxytol is an ultrasmall super paramagnetic particles of iron oxide (USPIO) agent recently used for magnetic resonance (MR) vascular imaging. Other USPIOs have been previously used for assessing inflammation within atheroma. We aim to assess feasibility of ferumoxytol in imaging carotid atheroma (with histological assessment); and the optimum MR imaging time to detect maximum quantitative signal change post-ferumoxytol infusion. Ten patients with carotid artery disease underwent high-resolution MR imaging of their carotid arteries on a 1.5 T MR system. MR imaging was performed before and at 24, 48, 72 and 96 hrs post ferumoxytol infusion. Optimal ferumoxytol uptake time was evaluated by quantitative relaxometry maps indicating the difference in T2* (ΔT2*) and T2 (ΔT2) between baseline and post-Ferumoxytol MR imaging using 3D DANTE MEFGRE qT2*w and iMSDE black-blood qT2w sequences respectively. 20 patients in total (10 symptomatic and 10 with asymptomatic carotid artery disease) had ferumoxytol-enhanced MR imaging at the optimal imaging window. 69 carotid MR imaging studies were completed. Ferumoxytol uptake (determined by a decrease in ΔT2* and ΔT2) was identified in all carotid plaques (symptomatic and asymptomatic). Maximum quantitative decrease in ΔT2* (10.4 [3.5–16.2] ms, p < 0.001) and ΔT2 (13.4 [6.2–18.9] ms; p = 0.001) was found on carotid MR imaging at 48 hrs following the ferumoxytol infusion. Ferumoxytol uptake by carotid plaques was assessed by histopathological analysis of excised atheroma. Ferumoxytol-enhanced MR imaging using quantitative 3D MR pulse sequences allows assessment of inflammation within carotid atheroma in symptomatic and asymptomatic patients. The optimum MR imaging time for carotid atheroma is 48 hrs after its administration.

Differential expression of PHACTR1 in atheromatous versus normal carotid artery tissue

Variation in the phosphatase and actin regulator-1 (PHACTR1) gene, a downstream regulator of the endothelin-1 (EDN1) gene, has been implicated in the pathogenesis of several related vascular phenotypes including atherosclerotic coronary artery disease, non-atherosclerotic coronary artery dissection, and carotid artery dissection, though it has not been studied in carotid atherosclerosis. We analyzed differential expression of PHACTR1 and EDN1 between atheromatous and non-atheromatous carotid artery tissue within the same individual and found lower levels of PHACTR1 expression in the atheromatous carotid tissue.

Prevalence of Corotidenary Atheroma in Patients with Coronary Disease: Results of a Monocentric Transverse Study in the Algerian East

Introduction: Patients with ischemic heart disease often have many damages of another vascular territory sometimes without clinical translation, these associations are important to know. Carotid involvement is the most important in terms of morbidity and cardiovascular mortality. Objective: In our study we have studied the prevalence of carotid atheroma in coronary patients recruited in cardiology in the university hospital centers of the city of Constantine. Patients and Methods: Our study is descriptive, cross-sectional, monocentric performed in units of cardiovascular exploration of the Regional University Hospital of Constantine. Included subjects had at least one significant coronary lesion ≥50 on a main coronary artery, for each patient, a guided anamnesis and a cardiovascular clinical examination preceded the realization of the supra aortic trunk echodoppler by a vividE9 General Electric ultrasound system started in January 2014, using a linear scanning probe 12L, intended for peripheral vascular exploration, allowing for targeted screening and a precise lesion description. The TSA echodoppler is said to be pathological, if it was at least one atheromatous plaque and / or hemodynamic damage, on one of the carotid axes (common carotid, internal carotid, external carotid), or a carotid intima- media thickness IMT ≥ 1mm. The processing and exploitation of the data made use of SPSS22 software. The processing and exploitation of the data made use of SPSS22 software. Results: Three hundred coronary patients, middle aged of 61 with predominantly male net, were included. The average IMT of our population was higher among men than women; significant difference (P = 0.042). 51% of our global population had at least one atheromatous lesion on the left common carotid (LCC), dominated by atheromatous plaques (49.7%), hemodynamic lesions were observed in 1.3% of our coronary patients. The same finding was noted for the right common carotid (RCC), affected in 51.4% of our population whose predominant lesions were atheromatous plaques in 50.7%, followed by hemodynamic damages (0.7%).49.3% and 49% of our global population had at least one lesion on the left internal carotid (LIC), and the right internal carotid (RIC). Hemodynamic lesions were more frequent on RIC (5% vs 2%). 47% and 49% of our global population respectively had at least one attack on LEC and REC. Hemodynamic damages were observed in 1.7% on LEC and 1.3% on REC. Conclusion: Despite the development of vascular functional explorations, there is currently no argument about screening for extracardiac atherosclerotic lesions in populations of selected asymptomatic subjects, according to age criteria or risk factors. In practice, it is when a localization of atherosclerosis becomes symptomatic that the problem of a possible lesional association arises. Coronary artery disease is the most important in terms of morbidity and mortality, and it is often in the context of ischemic heart disease assessment that the modalities for evaluating the extension of atheromatous disease are discussed. These vascular lesions, however, have a significant prognostic importance, like the other comorbidities associated. The search for these lesions therefore seems important to adapt the therapeutic arsenal at the individual level.

Characterization of Carotid Atherosclerotic Plaques Using 3-Dimensional MERGE Magnetic Resonance Imaging and Correlation With Stroke Risk Factors.

Background and Purpose- High-resolution magnetic resonance imaging is capable of characterizing carotid atherosclerotic plaque morphology and composition. Most reported carotid plaque imaging techniques are 2-dimensional (2D) based with limited longitudinal coverage of ≈30 mm, which may be insufficient for complete visualization of extracranial carotid atheroma. A 3D black-blood imaging technique, motion-sensitized driven equilibrium prepared rapid gradient echo technique (3D-MERGE) can provide larger coverage. We sought to use 3D-MERGE to investigate carotid atherosclerosis plaque distribution and to analyze their correlation with clinical information and stroke risk factors. Methods- From 5 hospitals in China, 97 subjects suspected of recent stroke or transient ischemic attack were imaged with 3D-MERGE within 2 weeks of symptoms using 3T magnetic resonance imaging. Images were analyzed by 2 reviewers. Plaque length was calculated and categorized as plaques within, partially outside, or completely outside of typical 2D magnetic resonance imaging coverage. Associations between plaque features and clinical information, stroke risk factors were assessed. Results- Ninety-seven subjects with 194 carotid arteries (70 men and 27 women, mean age 60 years) were analyzed. Of the 136 plaques identified, 68 (50%) were within, 46 (33.8%) were partially outside, and 22 (16.2%) were completely outside of 2D magnetic resonance imaging coverage. Total plaque length was significantly positively associated with male sex (P<0.001), hypertension (P=0.011), and history of smoking (P<0.001). Hypertensive subjects were more likely to have at least one plaque completely outside the 2D magnetic resonance imaging coverage than nonhypertensive subjects (P=0.007). Conclusions- The 3D-MERGE allows for the identification of substantially more carotid plaques than 2D black-blood techniques. The extent and distribution of plaque, identified by the larger coverage afforded by 3D-MERGE, were found to correlate significantly with male sex and risk factors that are common among patients with stroke, including hypertension and history of cigarette smoking.

Analysis of Risk Factors for the Development of Carotid Artery Atheroma and the Role of Panoramic Radiography for Diagnosis: A Literature Review

Analysis of Risk Factors for the Development of Carotid Artery Atheroma and the Role of Panoramic Radiography for Diagnosis: A Literature Review

Prevalence and the Risk Factors for Asymptomatic Carotid Artery Stenosis Among Type II Diabetes Mellitus Patients

Prevalence and the Risk Factors for Asymptomatic Carotid Artery Stenosis Among Type II Diabetes Mellitus Patients

P.775 The impact of mental illness on compliance with therapy in patients with Parkinson's disease

Calcification is a hallmark of advanced atherosclerosis and an active process akin to bone remodeling. Heparanase (HPSE) is an endo-β-glucuronidase, which cleaves glycosaminoglycan chains of heparan sulfate proteoglycans. The role of HPSE is controversial in osteogenesis and bone remodeling while it is unexplored in vascular calcification. Previously, we reported upregulation of HPSE in human carotid endarterectomies from symptomatic patients and showed correlation of HPSE expression with markers of inflammation and increased thrombogenicity. The present aim is to investigate HPSE expression in relation to genes associated with osteogenesis and osteolysis and the effect of elevated HPSE expression on calcification and osteolysis in vitro.Transcriptomic and immunohistochemical analyses were performed using the Biobank of Karolinska Endarterectomies (BiKE). In vitro calcification and osteolysis were analysed in human carotid smooth muscle cells overexpressing HPSE and bone marrow-derived osteoclasts from HPSE-transgenic mice respectively.HPSE expression correlated primarily with genes coupled to osteoclast differentiation and function in human carotid atheromas. HPSE was expressed in osteoclast-like cells in atherosclerotic lesions, and HPSE-transgenic bone marrow-derived osteoclasts displayed a higher osteolytic activity compared to wild-type cells. Contrarily, human carotid SMCs with an elevated HPSE expression demonstrated markedly increased mineralization upon osteogenic differentiation.We suggest that HPSE may have dual functions in vascular calcification, depending on the stage of the disease and presence of inflammatory cells. While HPSE plausibly enhances mineralization and osteogenic differentiation of vascular smooth muscle cells, it is associated with inflammation-induced osteoclast differentiation and activity in advanced atherosclerotic plaques.