osteoprotegerin and Carotid-Stenosis

Atherosclerotic plaque stabilization is a promising strategy to prevent cerebrovascular events in patients with carotid atherosclerosis. Vascular calcification inhibitors, known osteopontin (OPN) and osteoprotegerin (OPG), have emerged as novel cardiovascular biomarkers. This open-label, prospective study aimed to examine whether aggressive lipid-lowering therapy with atorvastatin is more effective than moderate lipid-lowering in increasing carotid plaque echogenicity, assessed by Gray-Scale Median (GSM) score and suppressing serum OPN and OPG levels in patients with moderate carotid stenosis.. One hundred forty patients (64 males, 76 females), aged 50 to 75 years, with carotid stenosis (North American Symptomatic Carotid Endarterectomy Trial [NASCET]: 30%-60% for symptomatic and 30%-70% for asymptomatic), but without indications for surgical intervention, were enrolled. Patients with coronary heart disease, renal failure, hypothyroidism, osteoporosis, and ongoing use of statins were excluded. Patients were randomly assigned to: Group A (N = 70): Moderate lipid-lowering therapy with low-dose of atorvastatin (10 mg-20 mg) to target LDL-C <100 mg/dL. Group B (N = 70): Aggressive lipid-lowering therapy with high-dose of atorvastatin (80 mg) to target LDL-C <70 mg/dL. Blood pressure, lipid and glycemic indexes, hsCRP, serum OPN, and OPG were measured at baseline and after 12 months as well as the GSM score. Independent samples t test, paired samples t test, Pearson correlation, and multiple regression analysis were used (P < .05).. There were no significant differences between groups at baseline. Three patients in group A experienced either cerebrovascular or cardiac ischemic attacks, while two patients in group B underwent coronary angioplasty during follow-up. Group B showed a more pronounced improvement in total cholesterol and LDL-cholesterol compared with group A (P < .05). Moreover, atorvastatin treatment suppressed serum hsCRP, OPN, and OPG levels from baseline in both groups (P < .001). Notably, aggressive treatment decreased OPN (P = .012) and OPG (P = .025) levels to a greater degree compared with moderate treatment. Similarly, GSM score was remarkably increased in both groups, but that augmentation was greater in group B (from 66.39 +/- 23.66 to 100.4 +/- 25.31) than in group A (from 64.4 +/- 23.62 to 85.39 +/- 20.21) (P = .024). No change in the degree of carotid stenosis was noted in both treatment arms. Importantly, the aforementioned reduction in OPN (r = -0.517, P = .024) and OPG (r = -0.312, P = .008) levels was inversely associated with GSM score changes in univariate and standard multiple regression analysis (R(2) = 0.411, P = .021).. Among patients with moderate carotid stenosis, an aggressive atorvastatin regimen enhanced carotid plaque echogenicity and reduced serum OPN and OPG levels to a greater extent than respective moderate atorvastatin therapy. Most importantly, those atorvastatin-induced effects were associated with OPN and OPG suppression in a dose-dependent manner.

Topics: Aged; Atorvastatin; Biomarkers; C-Reactive Protein; Carotid Stenosis; Cerebrovascular Disorders; Cholesterol, LDL; Dose-Response Relationship, Drug; Female; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Myocardial Ischemia; Osteopontin; Osteoprotegerin; Prospective Studies; Pyrroles; Severity of Illness Index; Time Factors; Treatment Outcome; Ultrasonography, Doppler

Carotid plaque echogenicity quantified by the Gray-Scale Median (GSM) score has been associated with plaque vulnerability. The aim of this study was to assess whether intensive lipid-lowering treatment with atorvastatin in patients with carotid artery stenosis ameliorates novel vascular calcification inhibitors, such as osteopontin (OPN) and osteoprotegerin (OPG), and improves GSM score.. Ninety-seven patients with carotid stenosis (>40%), but without indication for intervention, were treated for 6 months with atorvastatin (10mg-80mg) to target LDL<100mg/dl. Fifty-two age-and sex-matched healthy individuals served as the control group. Blood samples and GSM were obtained at the beginning and after 6 months.. Systolic blood pressure, hsCRP, fibrinogen, OPN and OPG levels differed significantly between patients with carotid stenosis and healthy controls at baseline (p<0.05). Atorvastatin treatment improved lipid profile and significantly reduced hsCRP (p=0.002), WBC count (p=0.041), OPN (p<0.001) and OPG levels (p<0.001). GSM score increased considerably after atorvastatin therapy (from 58.33+/-24.38 to 79.33+/-22.3; p<0.001) and that effect appeared related to OPN (p=0.001), OPG (p=0.013) and LDL (p=0.01) reduction.. In patients with carotid stenosis, intensive lipid-lowering therapy with statins attenuates serum OPN and OPG levels and enhances carotid plaque echogenicity, outlining their beneficial effects on plaque stability.

Topics: Aged; Atorvastatin; Biomarkers; Blood Pressure; C-Reactive Protein; Calcinosis; Carotid Stenosis; Female; Fibrinogen; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Leukocyte Count; Male; Middle Aged; Osteopontin; Osteoprotegerin; Prospective Studies; Pyrroles; Severity of Illness Index; Treatment Outcome; Ultrasonography

Carotid atherosclerosis represents one of the complications of diabetes mellitus. In particular, plaque instability contributes to disease progression and stroke incidence. High mobility group box-1 (HMGB1) is a nuclear protein involved in promotion and progression of atherosclerosis and cardiovascular diseases. The aim of this study was to analyze the relationship between HMGB1 serum levels, main inflammatory cytokines, the presence of internal carotid stenosis and unstable plaque in a diabetic population.. We studied 873 diabetic patients, including 347 patients with internal carotid artery stenosis (ICAS) who underwent carotid endarterectomy and 526 diabetic patients without internal carotid artery stenosis (WICAS). At baseline, HMGB1 and the main inflammatory cytokines serum levels were evaluated. For ICAS patients, the histological features of carotid plaque were also collected to differentiate them in patients with stable or unstable atherosclerotic lesions.. We found that HMGB1 serum levels, osteoprotegerin, high-sensitivity C-reactive protein, tumor necrosis factor-alpha and interleukin-6, were significantly higher in diabetic ICAS patients compared to diabetic WICAS patients. Among ICAS patients, individuals with unstable plaque had higher levels of these cytokines, compared to patients with stable plaque. A multivariable stepwise logistic regression analysis showed that HMGB1 and osteoprotegerin remained independently associated with unstable plaque in ICAS patients.. The present study demonstrated that HMGB1 is an independent risk factor for carotid plaque vulnerability in an Italian population with diabetes mellitus, representing a promising biomarker of carotid plaque instability and a possible molecular target to treat unstable carotid plaques and to prevent stroke.

Topics: Aged; Biomarkers; C-Reactive Protein; Carotid Stenosis; Case-Control Studies; Diabetes Mellitus, Type 2; Female; HMGB1 Protein; Humans; Inflammation Mediators; Interleukin-6; Italy; Male; Osteoprotegerin; Plaque, Atherosclerotic; Prognosis; Risk Assessment; Risk Factors; Rupture, Spontaneous; Tumor Necrosis Factor-alpha

Osteoprotegerin (OPG) is a member of the tumor necrosis factor receptor superfamily and is involved in the progress of atherosclerosis. We chose a gene polymorphism locus, OPG rs3102735, to explore how OPG gene polymorphisms relate to the occurrence of ischemic stroke and microembolic signals and to evaluate their relationship with the severity of neurologic deficits at admission and the degree of vascular stenosis.. We studied 251 patients diagnosed with large artery atherosclerosis (LAA) stroke and 121 controls. The LAA stroke patients were divided into clinical subgroups according to the presence of microembolic signals, severity of neurologic deficits at admission, and the degree of vascular stenosis. The OPG rs3102735 gene polymorphism was examined by polymerase chain reaction and restriction fragment length polymorphism. The microembolic signals (MES) were monitored by transcranial Doppler (TCD) for 60min within 72h of stroke onset. The severity of neurologic deficits at admission was evaluated by the National Institutes of Health Stroke Scale (NIHSS).. The CC+CT genotypes and allele C frequencies of the rs3102735 gene polymorphism were significantly higher in the LAA group than in the control group (39% vs. 25.6%, P=0.026; 21.7% vs.13.2%, P=0.006), higher in MES-positive compared to MES-negative patients (58.7% vs. 32.4%, P<0.01; 34.1% vs.17.6%, P<0.01), and higher in patients with an NIHSS Score (≥6) than in those with an NIHSS Score (<6) (46.9% vs.33.3%, P=0.031; 43.4% vs.18.3%, P=0.04). However, the genotypes and allele frequencies of SNPs in rs3102735 did not show significant differences in the degree of vascular stenosis (P>0.05).. Our findings suggest that the OPG rs3102735 gene polymorphism might be related to the occurrence of LAA ischemic stroke, microembolic signals and stroke severity and not the degree of vascular stenosis.

Topics: Acute Disease; Aged; Brain Ischemia; Carotid Stenosis; Female; Humans; Male; Middle Aged; Osteoprotegerin; Polymorphism, Single Nucleotide; Stroke

Osteoprotegerin (OPG) is a kind of tumor necrosis factor, which is related to bone metabolism and vascular calcification. The increase of Osteoprotegerin concentration in serum is related to cardiovascular diseases in humans. The purpose of this study was to figure out the relevance between osteoprotegerin in serum and carotid calcification. Serum OPG concentrations were compared in 145 patients who underwent carotid sonography (average age: 68 ± 9 years old, male: female = 81:64). A calcified plaque (CP) (37 people [27%]), a noncalcified plaque (NCP) (54 people [37%]), and a nonplaque (NP) (54 people [37%]) were classified for this study. No significant differences among 3 groups were demonstrated in the distribution of age, diabetes, high blood pressure, and hyperlipidemia. Serum osteoprotegerin concentrations were significantly increased in CP group rather than NCP group or NP group; (median [interquartile range], 4016 [1410] vs 3210 [1802] pg/mL, P < 0.05 and 4016 [1410] vs 3204 [1754] pg/mL, P < 0.05). Serum osteoprotegerin concentrations did not indicate a significant difference between NCP Group or NP Group. This study had proved that patient group accompanied with carotid calcification in carotid artery disease had an increased serum OPG concentration, so it could consider that OPG plays an important function on calcification related to arteriosclerosis.

Topics: Age Factors; Aged; Biomarkers; Calcinosis; Carotid Intima-Media Thickness; Carotid Stenosis; Electrocardiography; Female; Humans; Male; Middle Aged; Osteoprotegerin; Retrospective Studies; Risk Factors; Sex Factors; Tomography, X-Ray Computed

Endothelial microparticles (EMPs) are released from dysfunctional endothelial cells. We hypothesised that patients with unstable carotid plaque have higher levels of circulating microparticles compared to patients with stable plaques, and may correlate with serum markers of plaque instability and inflammation. Circulating EMPs, platelet MPs (PMPs) and inflammatory markers were measured in healthy controls and patients undergoing carotid endarterectomy. EMP/PMPs were quantified using flow cytometry. Bioplex assays profiled systemic inflammatory and bone-related proteins. Immunohistological analysis detailed the contribution of differentially-regulated systemic markers to plaque pathology. Alizarin red staining showed calcification. EMPs and PMPs were significantly higher in patients with carotid stenosis (≥ 70%) compared to controls, with no differences between asymptomatic vs symptomatic patients. Asymptomatic patients with unstable plaques exhibited higher levels of EMPs, CXCL9 and SCGF-β compared to those with stable plaques. CXCL9, and SCGF-β were detected within all plaques, suggesting a contribution to both localised and systemic inflammation. Osteopontin and osteoprotegerin were significantly elevated in the symptomatic vs asymptomatic group, while osteocalcin was higher in asymptomatic patients with stable plaque. All plaques exhibited calcification, which was significantly greater in asymptomatic patients. This may impact on plaque stability. These data could be important in identifying patients at most benefit from intervention.

Topics: Aged; Aged, 80 and over; Carotid Stenosis; Cell-Derived Microparticles; Chemokine CXCL9; Cytokines; Endarterectomy, Carotid; Endothelial Cells; Female; Hematopoietic Cell Growth Factors; Humans; Inflammation Mediators; Lectins, C-Type; Male; Middle Aged; Osteocalcin; Osteopontin; Osteoprotegerin

Systemic and intraplaque biomarkers have been widely investigated in clinical cohorts as promising surrogate parameters of cardiovascular vulnerability. In this pilot study, we investigated if systemic and intraplaque levels of calcification biomarkers were affected by treatment with a statin in a cohort of patients with severe carotid stenosis and being asymptomatic for ischemic stroke. Patients on statin therapy had reduced serum osteopontin (OPN), RANKL/osteoprotegerin (OPG) ratio, and MMP-9/pro-MMP-9 activity as compared to untreated patients. Statin-treated patients exhibited increased levels of collagen and reduced neutrophil infiltration in downstream portions of carotid plaques as compared to untreated controls. In upstream plaque portions, OPG content was increased in statin-treated patients as compared to controls. Other histological parameters (such as lipid, macrophage, smooth muscle cell, and MMP-9 content) as well as RANKL, RANK, and OPG mRNA levels did not differ between the two patient groups. Serum RANKL/OPG ratio positively correlated with serum levels of neutrophilic products, intraplaque neutrophil, and MMP-9 content within downstream portions of carotid plaques. In conclusion, statin treatment was associated with improvement in serum RANKL levels and reduced neutrophil activity both systemically and in atherosclerotic plaques.

Topics: Aged; Atherosclerosis; Atorvastatin; Carotid Stenosis; Cohort Studies; Female; Fluorobenzenes; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Matrix Metalloproteinase 9; Middle Aged; Neutrophil Activation; Neutrophils; NF-kappa B; Osteopontin; Osteoprotegerin; Pyrimidines; Pyrroles; RANK Ligand; Risk Factors; RNA, Messenger; Rosuvastatin Calcium; Simvastatin; Sulfonamides

Vascular calcification, recapitulating bone formation, has a profound impact on plaque stability. The aim of the present study was to determine the influence of bone-like vascular calcification (named osteoid metaplasia = OM) and of osteoprotegerin on plaque stability.. Tissue from carotid endarterectomies were analysed for the presence of calcification and signs of vulnerability according to AHA grading system. Osteoprotegerin (OPG), pericytes and endothelial cells were sought using immuno-histochemistry. Symptoms and preoperative imaging findings (CT-scan, MRI and Doppler-scan) were analyzed. Human pericytes were cultured to evaluate their ability to secrete OPG and to influence mineralization in the plaque.. Seventy-three carotid plaques (49 asymptomatic and 24 symptomatic) were harvested. A significantly higher presence of OM (18.4% vs 0%, p<0.01), OPG (10.2% of ROI vs 3.4% of ROI, p<0.05) and pericytes (19% of ROI vs 3.8% of ROI, p<0.05) were noted in asymptomatic compared to symptomatic plaques. Consistently, circulating OPG levels were higher in the plasma of asymptomatic patients (3.2 ng/mL vs 2.5 ng/mL, p = 0.05). In vitro, human vascular pericytes secreted considerable amounts of OPG and underwent osteoblastic differentiation. Pericytes also inhibited the osteoclastic differentiation of CD14+ cells through their secretion of OPG.. OPG (intraplaque an plasmatic) and OM are associated with carotid plaque stability. Pericytes may be involved in the secretion of intraplaque OPG and in the formation of OM.

Topics: Carotid Stenosis; CD146 Antigen; Cell Differentiation; Humans; Metaplasia; Osteoblasts; Osteoprotegerin; Pericytes; Plaque, Atherosclerotic; RANK Ligand; Vascular Calcification

Osteoprotegerin (OPG) is a secretory glycoprotein which belongs to the tumor necrosis factor receptor family. Various mechanisms have been suggested by which calcification might alter atherosclerotic plaque stability, but the significance of this intimal calcification is controversial. High concentrations of OPG have been associated with the presence of vascular and cardiovascular diseases. This study was designed to assess the association between gene polymorphisms of the OPG gene (TNFRSF11B), the serum OPG level, and plaque stability in patients with carotid atherosclerosis.. We studied 177 patients with internal carotid artery stenosis who underwent carotid endarterectomy and also 303 controls. Carotid endarterectomy samples removed from patients were assessed by immunohistochemistry. Concentrations of OPG were measured and gene polymorphisms were examined by polymerase chain reaction and restriction enzyme analysis and were compared, initially between patients with carotid atherosclerosis and controls, and subsequently between stable and unstable carotid plaques.. We found that the GG genotype of the T245G polymorphism, the CC genotype of the T950C polymorphism, and the CC genotype of the G1181C polymorphism were significantly higher in patients with carotid plaque than in controls (21.5% versus 10.9% , P<0.01; 15.8% versus 7.6%, P<0.01; and 20.3% versus 10.9%, P<0.01, respectively) and that these polymorphisms were associated with high serum OPG levels (4.02 [3.07] versus 2.94 [1.81] pmol/L; P<0.01), which were significantly higher in patients with unstable atherosclerotic plaques (5.86 [4.02] versus 3.53 [1.87] pmol/L; P<0.01).. The TNFRSF11B gene polymorphisms studied are associated with high serum OPG levels and might be potential markers for plaque instability.

Topics: Aged; Aged, 80 and over; Biomarkers; Carotid Stenosis; Female; Genetic Predisposition to Disease; Genetic Variation; Humans; Male; Middle Aged; Osteoprotegerin; Plaque, Atherosclerotic; Polymorphism, Genetic

In symptomatic patients treated with ipsilateral carotid artery stenting (CAS) plus intensive lipid lowering, we assessed the changes of osteopontin (OPN), osteoprotegerin (OPG) and the Gray-Scale Median (GSM) score contralateral to symptomatic carotid stenosis.. Forty-six symptomatic patients (group A) with significant carotid stenosis (North American Symptomatic Carotid Endarterectomy Trial (NASCET): >70%) underwent ipsilateral CAS. Those patients had simultaneously contralateral low-grade carotid stenosis (NASCET: 30-69%). Group B included 67 symptomatic patients with low-grade bilateral carotid stenosis (NASCET: 30-69%), but without indications for revascularisation. All patients were treated with atorvastatin (10-80mg) to target low-density lipoprotein (LDL)<100mgdl(-1). Blood samples and plaques' GSM score contralateral to brain infarct were assayed at baseline and after 6 months.. At baseline, there were no significant differences between groups (p>0.05). Six-month atorvastatin treatment equivalently improved lipid profile in both groups (p<0.05). The parameters hsCRP, OPN and OPG were significantly down-regulated within both groups, but to a greater extent in group A (p<0.05). Besides this, contralateral GSM score was significantly improved from baseline in both groups (p<0.01), but that increment was more pronounced in group A (vs. group B; p=0.041). These changes were inversely correlated with changes in OPN (p=0.014), OPG (p=0.011) and LDL (p=0.041).. Ipsilateral CAS plus intensive lipid-lowering therapy was associated with enhanced contralateral carotid plaque stability and attenuated inflammatory burden and calcification inhibitors to a greater extent than atorvastatin therapy alone in patients with bilateral carotid stenosis.

Topics: Aged; Angioplasty; Atorvastatin; Biomarkers; C-Reactive Protein; Calcinosis; Carotid Stenosis; Combined Modality Therapy; Down-Regulation; Female; Greece; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Osteopontin; Osteoprotegerin; Prospective Studies; Pyrroles; Severity of Illness Index; Stents; Time Factors; Treatment Outcome; Ultrasonography, Doppler

Osteopontin (OPN) and osteoprotegerin (OPG) are well-known vascular calcification inhibitors, which have been recently demonstrated to correlate with inflammation and cardiovascular events incidence. The aim of this cross-sectional study is to survey whether OPN and OPG are involved in carotid plaque vulnerability. For this reason, we assessed serum OPN and OPG levels in patients with carotid stenosis, and we explored their relationship with carotid plaque echogenicity and subsequent cerebrovascular ischemic events.. A total of 164 Whites were selected from a large cohort of 297 subjects to participate. In particular, 114 patients (61 men, 53 women), aged 55 to 80, had recently-diagnosed ICA stenosis higher than 50%. A group of 50 age-, sex-, and body mass index (BMI)-matched healthy individuals served as healthy controls. Patients with renal failure, hypothyroidism, osteoporosis, and lipid-lowering therapy were excluded. Images of both carotids were obtained from all participants using a high-resolution color duplex ultrasound and the gray-scale median (GSM) score was calculated. Brain computed tomography (CT), and magnetic resonance imaging (MRI) scans when CT was questionable, were performed on all patients with carotid stenosis. Clinical parameters, lipid and glycemic indexes, hsCRP, fibrinogen, white blood cells (WBC) count, OPN, and OPG were measured. Independent t test, one-way ANOVA, Pearson correlation, and multiple regression analysis were used for statistical analysis.. Among patients with carotid stenosis, 60 had history of ipsilateral stroke or TIA and positive CT or MRI findings (group A), while 54 had no neurological symptoms and negative CT and MRI scan (group B). Overall, patients with carotid stenosis showed worse lipid profile and increased waist circumference, blood pressure, hsCRP, fibrinogen, WBC count, OPN, and OPG levels compared with healthy subjects (group C) (P <.05). Statistical analysis revealed that group A had significantly lower levels of GSM than group B (57.41 +/- 38.19 vs 76.32 +/- 36.72; P = .008) and higher levels of hsCRP, OPN, and OPG than groups B and C (P < .05). Concerning the latter, biochemical markers group B showed only elevated OPG levels compared with group C (P = .038). Notably, GSM was considerably associated with serum OPN and OPG and waist circumference in patients with carotid atherosclerosis in univariate (r = -0.333; P = .032, r = -0.575; P < .001, r = -0.590; P =.006, respectively) and multiple regression analysis (R(2) = 0.445; P =.006).. The present study demonstrated elevated serum OPN and OPG levels in patients with carotid stenosis and documented an independent association between these biochemical markers, GSM and carotid-induced symptomatology. Therefore bone-matrix proteins combined with GSM could be potential markers for vulnerable carotid plaques.

Topics: Aged; Biomarkers; Blood Pressure; Body Size; C-Reactive Protein; Carotid Stenosis; Case-Control Studies; Cross-Sectional Studies; Female; Fibrinogen; Greece; Humans; Ischemic Attack, Transient; Leukocyte Count; Lipids; Logistic Models; Magnetic Resonance Angiography; Male; Middle Aged; Osteopontin; Osteoprotegerin; Stroke; Tomography, X-Ray Computed; Ultrasonography, Doppler, Color; Up-Regulation

Osteoprotegerin (OPG) is a member of the tumour necrosis factor superfamily involved in the regulation of bone metabolism and vascular calcification. High serum values of OPG are associated with cardiovascular disease in humans. The purpose was to investigate serum OPG levels in subclinical carotid atherosclerosis and the relation between OPG levels and plaque morphology. OPG levels were compared in 29 persons with echogenic carotid plaques, 30 persons with echolucent plaques and 41 persons without carotid plaques, all recruited from a population health study. Computerized assessment of plaque echogenicity was done by use of the gray scale median (GSM). Participants with echogenic carotid plaques had lower serum OPG level (1.23 ng/ml; 1.02-1.48) (geometric mean; 95% CI) than persons with echolucent plaques (1.76 ng/ml; 1.46-2.14) and those without plaques (1.89 ng/ml; 1.60-2.21). OPG and PTH were independently related to GSM. A significant trend for decrease in GSM across quartiles of OPG was found (p=0.003) which remained significant even after adjustment for PTH and smoking. The present study demonstrates lower serum OPG levels in persons with subclinical echogenic carotid plaques and identified an inverse relation between serum OPG and plaque echogenicity. The findings support the concept that OPG may play an important role in arterial calcification.

Topics: Aged; Carotid Artery, Internal; Carotid Stenosis; Female; Humans; Image Processing, Computer-Assisted; Lipids; Male; Osteoprotegerin; Ultrasonography

The aim of this study was to compare the concentration of osteoprotegerin (OPG), receptor activator of nuclear factor kappaB ligand (RANKL), and osteopontin (OPN) in stable (asymptomatic) and unstable (symptomatic) carotid atherosclerosis. In addition, we were interested in the effect of angiotensin II blockade on the secretion of these proteins by unstable atherosclerosis.. Endarterectomy samples removed from patients with recent (within 6 weeks) or no previous focal neurological symptoms were assessed by immunohistochemistry, Western analysis, and explant culture. Concentrations of OPG, RANKL, and OPN were measured by mean optical density (MOD), densitometry of protein bands, and enzyme-linked immunosorbent assay of supernatants from explant culture, and compared between symptomatic and asymptomatic patients.. The concentration of OPG and OPN within the proximal internal carotid (PIC) part of the endarterectomy specimen removed from symptomatic patients was elevated 2- and 4-fold, respectively. Although the concentration of RANKL did not differ according to patients' symptoms, the quantity of OPG secreted by explants of the PIC was greater in explants from symptomatic patients and could be significantly reduced within 48 hours of incubation with the angiotensin II blocker irbesartan.. OPG and OPN are upregulated in symptomatic human carotid atherosclerosis with possible implications for plaque stability. Angiotensin II blockade is able to downregulate OPG secretion in vitro.

Topics: Aged; Angiotensin II; Arteriosclerosis; Biphenyl Compounds; Blotting, Western; Carotid Stenosis; Carrier Proteins; Culture Techniques; Female; Glycoproteins; Humans; Immunohistochemistry; Irbesartan; Male; Membrane Glycoproteins; Middle Aged; Osteopontin; Osteoprotegerin; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Sialoglycoproteins; Tetrazoles; Up-Regulation