Plasma Osteopontin Levels Research Articles

The rs1126616 Single Nucleotide Polymorphism of the Osteopontin Gene Is Independently Associated with Cardiovascular Events in a Chronic Kidney Disease Cohort.

Chronic kidney disease (CKD) is associated with a higher risk of cardiovascular events (CVE), partly due to the higher burden of atherosclerosis. Circulating Osteopontin (OPN) levels have been also shown to have a potential role in the development of atherosclerosis. Indeed, CKD patients show an increase in circulating OPN levels, but their effect of CKD-related atherosclerosis is not clear. Polymorphisms in the OPN gene (SPP1) have been studied in atheromatous disease, but reported results show conflictive findings. Thus, the main aim of the present study is to analyze the influence of SPP1 polymorphisms in CVE in CKD patients, taking into account circulating OPN levels. We followed 559 healthy controls and 2445 CKD patients without previous CVE from the National Observatory of Atherosclerosis in Nephrology study (NEFRONA study). After 48 months of follow-up 206 CVE were recorded. Genotyping for rs9138, rs1126616, rs1126772, rs11730582 and rs28357094 polymorphisms of the SPP1 gene was performed along with the measurements of plasma OPN levels. The group of patients with CVE showed higher incidence of atherosclerotic plaque (90.3% vs 64.5%; p < 0.001) and higher OPN levels (p < 0.001) at baseline. Patients with the heterozygous genotype of the rs1126616 polymorphism showed a higher hazard ratio of having a CVE, even after adjustment for multiple potential confounders. After adjustment, OPN levels were no longer associated with the incidence of CVE. We found that the rs1126616 single nucleotide polymorphism (SNP) of the SPP1 gene is independently associated with a higher incidence of CVE in a cohort of CKD patients and that it could be used to predict CVE risk.

Plasma osteopontin may predict neuroinflammation and the severity of pediatric traumatic brain injury

Traumatic brain injury (TBI) is the leading cause of death in children and adolescents in developed countries, but there are no blood-based biomarkers to support the diagnosis or prognosis of pediatric TBI to-date. Here we report that the plasma levels of osteopontin (OPN), a phosphoprotein chiefly secreted by macrophages and/or activated microglia, may contribute to this goal. In animal models of TBI, while OPN, fibrillary acidic protein (GFAP), and matrix metalloproteinase 9 (MMP-9) were all readily induced by controlled cortical impact in the brains of one-month-old mice, only OPN and GFAP ascended in the blood in correlation with high neurological severity scores (NSS). In children with TBI (three to nine years of age, n = 66), the plasma levels of OPN, but not GFAP, correlated with severe TBI (Glasgow Coma Score ≤ 8) and intracranial lesions at emergency department. In addition, the plasma OPN levels in severe pediatric TBI patients continued to ascend for 72 h and correlated with mortality and the days requiring ventilator or intensive care unit support, whereas the plasma GFAP levels lacked these properties. Together, these results suggest that plasma OPN outperforms GFAP and may be a neuroinflammation-based diagnostic and prognostic biomarker in pediatric TBI.

Calcitriol Analogues Decrease Lung Metastasis but Impair Bone Metabolism in Aged Ovariectomized Mice Bearing 4T1 Mammary Gland Tumours.

Calcitriol and its analogues are considered drugs supporting the anticancer treatment of breast cancer and preventing the osteoporosis that results from the development of cancer or from chemotherapy or hormone therapy. Following the orthotopic implantation of 4T1 mammary carcinoma cells into aged ovariectomized (OVX) mice, we evaluated the effects of calcitriol and its two analogues, PRI-2191 and PRI-2205, on metastatic spread and bone homeostasis. Calcitriol and its analogues temporarily inhibited the formation of metastases in the lungs. Unexpectedly, only mice treated with calcitriol analogues showed a deterioration of bone-related parameters, such as bone column density, marrow column density and the CaPO4 coefficient. These findings correlated with an increased number of active osteoclasts differentiated from bone marrow-derived macrophages in mice treated with the analogues. Interestingly, in the tumours from mice treated with PRI-2191 and PRI-2205, the expression of Tnfsf11 (RANKL) was increased. On the other hand, osteopontin (OPN) levels in plasma and tumour tissue, as well as TRAC5b levels in tumours, were diminished by calcitriol and its analogues. Despite a similar action of both analogues towards bone metabolism, their impact on vitamin D metabolism differed. In particular, PRI-2191 and calcitriol, not PRI-2205 treatment significantly diminished the levels of both 25(OH)D3 and 24,25(OH)2D3. In conclusion, though there is evident antimetastatic activity in old OVX mice, signs of increased bone metabolism and deterioration of bone mineralization during therapy with calcitriol analogues were observed.

Identification of osteopontin as a biomarker of human exposure to fine particulate matter

Ambient particulate matter (PM) exposure is associated with pulmonary and cardiovascular diseases; however, there is scant research linking data on animal and human cells. The objective of this study was to investigate these associations. Vascular remodeling plays a crucial role in both pulmonary and cardiovascular diseases. Therefore, we conducted a transcriptomic analysis using vascular smooth muscle cells (VSMCs) to identify potential regulators or markers of PM exposure. We demonstrated that fine and coarse PM increased VSMC proliferation in mice. We conducted a genome-wide cDNA microarray analysis, followed by a pathway analysis of VSMCs treated with coarse PM for durations of 24, 48, and 72 h. Sixteen genes were discovered to be time-dependently upregulated and involved in VSMC proliferation. Osteopontin (OPN) is indicated as one of the regulators of these upregulated genes. Both fine and coarse PM from industrial and urban areas significantly increased OPN expression in VSMCs and macrophages. Moreover, oropharyngeal instillation of fine and coarse PM for 8 weeks increased the VSMCs in the pulmonary arteries of mice. OPN level was consistently increased in the lung tissues, bronchoalveolar lavage fluid, and serum of mice. Moreover, we analyzed the plasma OPN levels of 72 healthy participants recruited from the studied metropolitan area. Each participant wore a personal PM2.5 sampler to assess their PM2.5 exposure over a 24 h period. Our results indicate that personal exposure to fine PM is positively correlated with plasma OPN level in young adults. The data obtained in this study suggest that exposure to fine and coarse PM may cause pulmonary vascular lesions in humans and that OPN level may be a biomarker of PM exposure in humans.

Visceral Adipose Tissue Drives Cardiac Aging Through Modulation of Fibroblast Senescence by Osteopontin Production.

Aging induces cardiac structural and functional changes linked to the increased deposition of extracellular matrix proteins, including OPN (osteopontin), conducing to progressive interstitial fibrosis. Although OPN is involved in various pathological conditions, its role in myocardial aging remains unknown. OPN deficient mice (OPN-/-) with their wild-type (WT) littermates were evaluated at 2 and 14 months of age in terms of cardiac structure, function, histology and key molecular markers. OPN expression was determined by reverse-transcription polymerase chain reaction, immunoblot and immunofluorescence. Luminex assays were performed to screen plasma samples for various cytokines/adipokines in addition to OPN. Similar explorations were conducted in aged WT mice after surgical removal of visceral adipose tissue (VAT) or treatment with a small-molecule OPN inhibitor agelastatin A. Primary WT fibroblasts were incubated with plasma from aged WT and OPN-/- mice, and evaluated for senescence (senescence-associated β-galactosidase and p16), as well as fibroblast activation markers (Acta2 and Fn1). Plasma OPN levels increased in WT mice during aging, with VAT showing the strongest OPN induction contrasting with myocardium that did not express OPN. VAT removal in aged WT mice restored cardiac function and decreased myocardial fibrosis in addition to a substantial reduction of circulating OPN and transforming growth factor β levels. OPN deficiency provided a comparable protection against age-related cardiac fibrosis and dysfunction. Intriguingly, a strong induction of senescence in cardiac fibroblasts was observed in both VAT removal and OPN-/- mice. The addition of plasma from aged OPN-/- mice to cultures of primary cardiac fibroblasts induced senescence and reduced their activation (compared to aged WT plasma). Finally, Agelastatin A treatment of aged WT mice fully reversed age-related myocardial fibrosis and dysfunction. During aging, VAT represents the main source of OPN and alters heart structure and function via its profibrotic secretome. As a proof-of-concept, interventions targeting OPN, such as VAT removal and OPN deficiency, rescued the heart and induced a selective modulation of fibroblast senescence. Our work uncovers OPN's role in the context of myocardial aging and proposes OPN as a potential new therapeutic target for a healthy cardiac aging.

Chemotherapy-generated cell debris stimulates colon carcinoma tumor growth via osteopontin.

Colon cancer recurrence after therapy, such as 5-fluorouracil (5-FU), remains a challenge in the clinical setting. Chemotherapy reduces tumor burden by inducing cell death; however, the resulting dead tumor cells, or debris, may paradoxically stimulate angiogenesis, inflammation, and tumor growth. Here, we demonstrate that 5-FU–generated colon carcinoma debris stimulates the growth of a subthreshold inoculum of living tumor cells in subcutaneous and orthotopic models. Debris triggered the release of osteopontin (OPN) by tumor cells and host macrophages. Both coinjection of debris and systemic treatment with 5-FU increased plasma OPN levels in tumor-bearing mice. RNA expression levels of secreted phosphoprotein 1, the gene that encodes OPN, correlate with poor prognosis in patients with colorectal cancer and are elevated in chemotherapy-treated patients who experience tumor recurrence vs. no recurrence. Pharmacologic and genetic ablation of OPN inhibited debris-stimulated tumor growth. Systemic treatment with a combination of a neutralizing OPN antibody and 5-FU dramatically inhibited tumor growth. These results demonstrate a novel mechanism of tumor progression mediated by OPN released in response to chemotherapy-generated tumor cell debris. Neutralization of debris-stimulated OPN represents a potential therapeutic strategy to overcome the inherent limitation of cytotoxic therapies as a result of the generation of cell debris.—Chang, J., Bhasin, S. S., Bielenberg, D. R., Sukhatme, V. P., Bhasin, M., Huang, S., Kieran, M. W., Panigrahy, D. Chemotherapy-generated cell debris stimulates colon carcinoma tumor growth via osteopontin.

Renal effects of glucagon-like peptide receptor agonists in patients with type 1 diabetes mellitus.

The purpose of our study is to assess the effects of glucagon-like peptide-1 receptor agonists (GLP-1R agonists) on early markers of kidney damage in patients with type 1 diabetes mellitus (DM). The study included 27 patients with type 1 diabetes with normo- (n=16) and microalbuminuria (n=11) on intensive insulin injection regimen with insulin analogs. Patients were divided into two groups: 15 patients continued insulin therapy throughout the follow-up period, 12 patients were given 1.2 mg GLP-1R agonist (Liraglutide) once a day in addition to the insulin therapy for 6 months. HbA1c, lipid profile, classic markers of kidney damage (albuminuria, creatinine, glomerular filtration rate); plazma (neutrophilic gelatinase-associated lipoxalin - NGAL, molecule renal damage of type 1 - KIM-1, cystatin C, osteopontin) and urinary kidney biomarkers (nephrin, podocyne, uromodulin, NGAL, KIM-1, collagen type IV, cystatin C) were evaluated prior and in dynamics at 6 months. Kidney biomarkers levels were assessed by the enzyme-linked immunosorbent assay (ELISA). We observed a significant decrease in the urinary excretion of type IV collagen, cystatin C, increased uromodulin excretion and decrease in the plasma levels of osteopontin, NGAL and cystatin C in the group of combined insulin and GLP-1R agonist therapy. Changes in the level of sensitive kidney biomarkers indicate a possible renoprotective effect of GLP-1R agonist therapy in patients with type 1 diabetes at an early stages of kidney damage.

Osteopontin levels in plasma, muscles, and bone in patient with non-healing diabetic foot ulcers: A new player in wound healing process?

BackgroundThe present study was designed to investigate the impact of osteopontin (OPN) in different tissue (e.g., plasma, muscles and bone) on amputation rate (in-hospital and during one year follow-up) for non-healing diabetic foot ulcers (DFUs). MethodsThis pilot study consisted of 30 diabetic patients, hospitalized due to non-healing DFUs. Patients were divided into two groups: Group 1 included 14 patients who underwent limb-preserved debridement procedure without amputation; Group 2 included 16 subjects who underwent amputation. Additionally, recurrent amputation rate during 1 year follow-up was investigated. ResultsPlasma OPN was higher and bone OPN was lower in Group 2 compared to Group 1 (p = 0.016 and p = 0.004, respectively). In the logistic regression analysis, bone OPN emerged as a significant independent predictor of amputation (OR = 0.042, 95% CI 0.003–0.699, p = 0.027). Plasma OPN was also associated with amputation such that each unit increase in plasma OPN was associated with an increase in odds of amputation of 17.7% (95% CI 0.997–1.388, p = 0.045). During 1 year follow-up 11 patients underwent recurrent amputation. Plasma OPN were higher and bone osteopontin was lower in patients who underwent amputation compared to patients who did not need amputation at one year follow-up. However, in GLM analysis bone OPN was only marginally associated with one year amputation (OR 0.001, 95% CI 0.000–2.0, p = 0.076). ConclusionsDecreased levels of OPN in bone and increased plasma OPN are independently associated with in-hospital amputation. Consequently, plasma OPN may be relevant in the routine assessment of amputation risk in this patient population.

Post-surgical resection prognostic value of combined OPN, MMP7, and PSG9 plasma biomarkers in hepatocellular carcinoma

Biomarkers for hepatocellular carcinoma (HCC) following curative resection are not currently sufficient for prognostic indication of overall survival (OS) and disease-free survival (DFS). The aim of this study was to investigate the prognostic performance of osteopontin (OPN), matrix metalloproteinase 7 (MMP7), and pregnancy specific glycoprotein 9 (PSG9) in patients with HCC. A total of 179 prospective patients with HCC provided plasma before hepatectomy. Plasma OPN, MMP7, and PSG9 levels were determined by enzyme-linked immunosorbent assay. Correlations between plasma levels, clinical parameters, and outcomes (OS and DFS) were overall analyzed. High OPN ( ⩾ 149.97 ng/mL), MMP7 ( ⩾ 2.28 ng/mL), and PSG9 ( ⩾ 45.59 ng/mL) were prognostic indicators of reduced OS (P < 0.001, P < 0.001, and P = 0.007, respectively). Plasma PSG9 protein level was an independent factor in predicting OS (P = 0.008) and DFS (P = 0.038). Plasma OPN + MMP7 + PSG9 elevation in combination was a prognostic factor for OS (P < 0.001). OPN was demonstrated to be a risk factorassociated OS in stage I patients with HCC and patients with low α-fetoprotein levels ( < 20 ng/mL). These findings suggested that OPN, MMP7, PSG9 and their combined panels may be useful for aiding in tumor recurrence and mortality risk prediction of patients with HCC, particularly in the early stage of HCC carcinogenesis.

Osteopontin levels in plasma, muscles and bone in patient with non-healing diabetic foot ulcers: a new player in wound healing process?

Osteopontin levels in plasma, muscles and bone in patient with non-healing diabetic foot ulcers: a new player in wound healing process?

Correlation of hypoxia status with radiosensitizing effects of sodium glycididazole: A preclinical study.

The correlation of pretreatment hypoxia status with the radiosensitization effect of sodium glycididazole (CMNa) was not previously defined. The purpose of the present study was to evaluate the tumor hypoxia status in various cancer xenografts and to investigate the correlation between tumor hypoxia status and radiosensitizing effects of CMNa based on the pharmacokinetic and pharmacodynamic parameters. Human esophageal cancer (EC109), head and neck cancer (FaDu) and lung cancer (A549) nude mice xenografts were used. The concentrations of CMNa and its metabolites in the tumors and normal tissues were determined by high-performance liquid chromatography following intravenous injection of 171.9, 57.3 or 19.1 mg/kg CMNa. The tumors were irradiated with 30 Gy in 6 fractions with CMNa administration prior to each irradiation. The tumor growth delay values were calculated for each treatment group and compared with groups treated with radiation alone. Tumor hypoxia status was verified by immunohistostaining of tissues for hypoxia inducible factor 1α (HIF-1α) staining, and the concentration of plasma osteopontin (OPN) was determined using ELISA. The correlation between OPN concentration and tumor growth delay was subsequently analyzed. It was observed that the drug concentration in the tumor was 1.6-2.8 times higher compared with adjacent muscle, particularly at high and medium doses. CMNa was able to sensitize tumors to irradiation, particularly for EC109 and FaDu xenografts at high dose (P<0.05). Furthermore, there was markedly increased expression of HIF-1α and plasma OPN levels in FaDu and EC109 xenografts compared with A549. Additionally, it was indicated that pretreatment hypoxia status might be correlated with the radiosensitizing effects of CMNa. The present data demonstrated that tumor hypoxia status might be correlated with the radiosensitizing effects of CMNa in different tumor models.

Natalizumab reduces serum pro-angiogenic activity in MS patients.

Angiogenesis has been implicated in the pathobiology of multiple sclerosis (MS). Osteopontin exerts a pro-angiogenetic effect and is increased in body fluid of MS patients. To evaluate the effect of 1year natalizumab treatment on serum pro-angiogenic activity and on plasma osteopontin levels in relapsing (RR) MS patients. Ten RRMS patients scheduled for natalizumab treatment were enrolled and evaluated at baseline and after 1-year natalizumab treatment. Pro-angiogenic activity was assessed by a chick embryo chorioallantoic membrane assay (CAM), osteopontin levels were evaluated by an enzyme-linked immunosorbent assay. Plasma and serum samples of 10 treatment-naïve RRMS and 10 healthy controls (HCs) were used as controls of baseline evaluations. Both treatment-naïve and natalizumab scheduled RRMS patients had higher baseline vessel density (22.0 ± 3.9 and 22.5 ± 2.6, p < 0.0001) and higher osteopontin levels (65.7 ± 24.3ng/ml and 65.9 ± 16.6ng/ml, p = 0.019 and p = 0.029, respectively) than HCs (9.0 ± 2.2; 48.5 ± 7.8ng/ml, respectively). Baseline osteopontin levels and vessel density were significantly correlated (rs = 0.373, p = 0.043). After 1year of treatment, the number of vessels and the osteopontin levels, were significantly reduced (11.9 ± 2.1, p < 0.005; 49.3 ± 20.0ng/ml, p = 0.028). Our results suggest that natalizumab could exert its anti-inflammatory properties also by inhibiting the angiogenetic mechanisms in RRMS patients.

Plasma osteopontin level as a diagnostic marker of hepatocellular carcinoma in patients with radiological evidence of focal hepatic lesions.

Hepatocellular carcinoma is one of the most aggressive malignant tumors and has limited treatment options. Needle-guided biopsies have been utilized as a tool to diagnose malignant focal hepatic lesions. These techniques are discouraged because of their complications. Nowadays, alpha fetoprotein is the most widely used tumor marker for screening and diagnosis of hepatocellular carcinoma. Nevertheless, this marker has limitations. The diagnostic role of plasma osteopontin as an adjuvant or alternative marker to alpha fetoprotein to detect hepatocellular carcinoma in Egyptian patients with focal hepatic lesions was evaluated in this study. Eighty participants were recruited from the Egyptian National Liver Institute and were self-assigned to three groups, namely, focal hepatic lesions (n = 40), liver cirrhosis (n = 20), and controls (n = 20). Participants' plasma osteopontin and serum alpha fetoprotein levels were determined and were compared across the three groups. The discriminatory ability of plasma osteopontin for hepatocellular carcinoma was lower than that of alpha fetoprotein. Osteopontin and alpha fetoprotein were not correlated with each other. Neither the gender nor the age of the patients showed a significant association with plasma osteopontin level. Measuring plasma osteopontin level alone has no advantage over serum alpha fetoprotein in patients with focal hepatic lesions due to chronic liver disease.

Acute-Phase Plasma Osteopontin as an Independent Predictor for Poor Outcome After Aneurysmal Subarachnoid Hemorrhage.

Experimental studies reported that osteopontin (OPN), a matricellular protein, is induced in brain after subarachnoid hemorrhage (SAH). The aim of this study was to investigate the relationships between plasma OPN levels and outcome after aneurysmal SAH in a clinical setting. This is a prospective study consisting of 109 aneurysmal SAH patients who underwent aneurysmal obliteration within 48h of SAH. Plasma OPN concentrations were serially determined at days 1-3, 4-6, 7-9, and 10-12 after onset. Various clinical factors as well as OPN values were compared between patients with 90-day good and poor outcomes. Plasma OPN levels were significantly higher in SAH patients compared with control patients and peaked at days 4-6. Poor-outcome patients had significantly higher plasma OPN levels through all sampling points. Receiver-operating characteristic curves demonstrated that OPN levels at days 10-12 were the most useful predictor of poor outcome at cutoff values of 915.9pmol/L (sensitivity, 0.694; specificity, 0.845). Multivariate analyses using the significant variables identified by day 3 showed that plasma OPN ≥ 955.1pmol/L at days 1-3 (odds ratio, 10.336; 95% confidence interval, 2.563-56.077; p < 0.001) was an independent predictor of poor outcome, in addition to increasing age, preoperative World Federation of Neurological Surgeons grades IV-V, and modified Fisher grade 4. Post hoc analyses revealed no correlation between OPN levels and serum levels of C-reactive protein, a non-specific inflammatory parameter, at days 1-3. Acute-phase plasma OPN could be used as a useful prognostic biomarker in SAH.

Prognostic implications of the co-detection of the urokinase plasminogen activator system and osteopontin in patients with non-small-cell lung cancer undergoing radiotherapy and correlation with gross tumor volume.

The urokinase plasminogen activator system (uPA, uPAR, PAI‑1) is upregulated in cancer and high plasma levels are associated with poor prognosis. Their interaction with hypoxia-related osteopontin (OPN) which is also overexpressed in malignant tumors suggests potential clinical relevance. However, the prognostic role of the uPA system in the radiotherapy (RT) of non-small-cell lung cancer (NSCLC), particularly in combination with OPN, has not been investigated so far. uPA, uPAR, PAI‑1 and OPN plasma levels of 81patients with locally advanced or metastasized NSCLC were prospectively analyzed by ELISA before RT and were correlated to clinical patient/tumor data and prognosis after RT. uPAR plasma levels were higher in M1; uPA and PAI‑1 levels were higher in M0 NSCLC patients. uPAR correlated with uPA (p < 0.001) which also correlated with PAI‑1 (p < 0.001). The prognostic impact of OPN plasma levels in the RT of NSCLC was previously reported by our group. PAI‑I plasma levels significantly impacted overall (OS) and progression-free survival (PFS). Low PAI‑1 levels were associated with a significantly reduced OS and PFS with a nearly 2‑fold increased risk of death (p = 0.029) and tumor progression (p = 0.029). In multivariate analysis, PAI‑1 levels remained an independent prognostic factor for OS and PFS with a 3‑fold increased risk of death (p = 0.001). If PAI‑1 plasma levels were combined with OPN or tumor volume, we found an additive prognostic impact on OS and PFS with a 2.5- to 3‑fold increased risk of death (p = 0.01). Our results suggest that PAI-1 but not uPA and uPAR might add prognostic information in patients with advanced NSCLC undergoing RT. High pretreatment PAI-1 plasma levels were found predominantly in M0-stage patients and indicate a favorable prognosis as opposed to OPN where high plasma levels are associated with poor survival and metastasis. In combination, PAI-1 and OPN levels successfully predicted outcome and additively correlated with prognosis. These findings support the notion of an antidromic prognostic impact of OPN and PAI-1 plasma levels in the RT of advanced NSCLC.

Role of Osteopontin in Systemic Lupus Erythematosus

Background: Systemic lupus erythematosus (SLE) is a multisystemic disease, caused by a variety of factors, which lead to immunological abnormalities. Osteopontin (OPN) is a pleiotropic protein, important in bone remodeling and immune system signaling. It produced by various cells, including immune cells, and played a key role in regulating T-helper 1/T-helper 2 balances, stimulating B lymphocytes to produce antibodies, regulating macrophages, neutrophils and inducing dendritic cells. Over expression of OPN has been associated with the pathogenesis of immune-mediated diseases. Objectives: To investigate the role of osteopontin in SLE and to assess its relation to disease activity and subclinical atherosclerosis. Subjects and Methods: This cross sectional case control study was conducted on 30 SLE patients fulfilling SLICCA /ACR criteria for SLE classification and 30 subjects sex- and age-matched apparently healthy as control group. All patients were assessed for SLE disease activity by the systemic lupus activity Index (SLEDAI). Serum OSP and Doppler ultrasound for carotid artery media thickness (CIMT) were measured in all patients and control. Results: Plasma OPN levels were significantly higher in SLE patients than in control group (P<0.001) and had significant positive correlation with disease activity (r 0,595, P<0.05) and CIMT (r = 0.400, P <0.001), but there was no significant correlation between CIMT and disease activity. Conclusion: serum level of OPN was higher in SLE patients and correlated with disease activity and CIMT, and can be used as a marker of subclinical atherosclerosis.

Association between decreased osteopontin and acute mountain sickness upon rapid ascent to 3500 m among young Chinese men.

Hypoxia causes oxidative stress and a decrease in osteopontin (OPN) in rats; however, little is known about the change in OPN in lowlander humans during hypobaric hypoxia. We explore the role of the predicted decrease in plasma OPN levels in humans upon high-altitude exposure and its relationship with acute mountain sickness (AMS), as well as superoxide dismutase (SOD) and malondialdehyde (MDA). Before and during acute altitude exposure, 261 men's plasma OPN, SOD, MDA, heart rate and pulse oximeter saturation (SpO2) were measured. AMS as assessed using the Lake Louise score (LLS) was defined as headache with a total LLS ≥3. Subjects were divided into AMS-0 (non-AMS subjects), mild AMS (headache with total LLS = 3 or 4) and severe AMS groups (headache with total LLS ≥5). At 600 m, no difference in plasma OPN, SOD and MDA was observed between groups. At 3500 m, plasma OPN in severe AMS group was significantly decreased as compared with 600 m. Plasma SOD showed a tendency to decrease during altitude exposure. The opposite trend was observed for plasma MDA. Correlation analysis showed that total LLS was significantly correlated with OPN (ρ = -0.247, P < 0.001) and SOD (ρ = -0.224, P < 0.001). OPN showed significant correlation with SOD (r = 0.235, P < 0.001). Multivariate logistic regression analysis showed that higher plasma OPN was a protective factor for AMS [adjusted odds ratio (OR) 0.924, 95% confidence interval (CI) 0.884-0.966, P < 0.01]. Our results suggest that decreased plasma OPN is correlated with AMS, and oxidative stress may be implicated in this phenomenon. Decreased plasma SOD is also correlated with AMS.

Polymorphisms in the Osteopontin Are Associated with Susceptibility to Ankylosing Spondylitis in a Han Chinese Population.

The aim of this study was to investigate whether osteopontin (OPN) variants are associated with susceptibility to ankylosing spondylitis (AS) in a Chinese population. Polymorphisms at the 9175th position in exon 7 of OPN and rs17524488 were genotyped using direct sequencing in 186 unrelated AS patients and 188 ethnically matched healthy controls. Serum concentration of OPN was measured by enzyme-linked immunosorbent assay (ELISA) in all participants. AS patients displayed significantly higher OPN serum levels than the controls (P < 001). A heterozygous, novel 9175 T>A in exon 7 of the OPN gene was found in this study. In healthy controls, subjects carrying the rs17524488 G/G genotype of the OPN display significantly higher OPN serum levels than the GG/GG genotype (P < 0.05). Plasma OPN level is implicated as an early diagnostic marker of AS. The novel 9175th- (exon 7) position polymorphism of OPN and rs17524488 were related to susceptibility to AS in a Chinese population, the rs17524488 G/G genotype may be involved in the pathogenesis of AS, and the precise molecular mechanism underlying the influence of OPN polymorphisms on the development of AS remains to be determined in the further prospective studies.

Role of Plasma Osteopontin Level as a Predictor of Hepatic Fibrosis Regression and Response to Antiviral Treatment in Patients with Chronic HBV or Chronic HCV Infection

Background: Hepatitis B virus and Hepatitis C virus infection is one of the public health problems in Egypt. So we aimed to evaluate the efficacy of serum osteopontin as predictor of hepatic fibrosis regression and virological response in patients with chronic HBV or HCV infection. Methods: This study has been conducted on 74 HBeAg + ve chronic HBV infection, 74 chronic HCV infection and 74 healthy controls. HBV patients treated with Entecavir. HCV patients treated with sofosbuvir, daclatasvir with or without ribavirin. One year post HBeAg seroconversion and 3 months after end of regular antiviral treatment for patients with chronic HBV and chronic HCV infection respectively, hepatic condition was reevaluated. Results: 14.9% of patients with HBV, failed to achieve undetectable HBV DNA or HBeAg seroconversion and 2.7% of patients with HCV infection, failed to achieve SVR. In chronic HBV, pretreatment high serum osteopontin predict failure of virological response and hepatic fibrosis regression at a cutoff > 115.5, with 90.91% sensitivity, 82.54% specificity. Also high degree of liver stiffness predicts failure of hepatic fibrosis regression at a cutoff > 8.7, with 81.8% sensitivity, 73% specificity. Conclusions: In chronic HBV infection low osteopontin predicts good virological response and hepatic fibrosis regression. But it has no role in predicting SVR or hepatic fibrosis regression in chronic HCV infected patients.

Plasma osteopontin levels in patients with dilated and hypertrophic cardiomyopathy.

Osteopontin (OPN) is an extracellular matrix glycoprotein that plays arole in avariety of cellular activities associated with inflammatory and fibrotic responses. Increased OPN levels in myocardium and plasma have been demonstrated in patients with dilated cardiomyopathy (DCM). However, nothing is known about OPN levels in patients with hypertrophic cardiomyopathy (HCM). Therefore, the aim of our study was to compare plasma OPN levels in patients with these two most common cardiomyopathies. We examined plasma OPN as well as creatinine, C‑reactive protein (CRP), brain-type natriuretic peptide (BNP), and troponinI levels in 64patients with DCM, 43patients with HCM, and 75control subjects. Transthoracic echocardiography was also performed on all cardiomyopathy patients. Plasma OPN levels were significantly elevated in patients with DCM compared with HCM patients (95± 43 vs. 57± 21 ng/ml; p< 0.001) and control subjects (54± 19 ng/ml; p< 0.001); however, there was no difference between HCM patients and control subjects. New York Heart Association (NYHA) classIII orIV disease was more frequently present in DCM patients than in HCM subjects (44 % vs. 2 %, p< 0.0001). In multivariate analysis, BNP and CRP levels together with NYHA class were found to be significant predictors of plasma OPN levels in DCM patients (p= 0.002, p= 0.029, and p< 0.001 for BNP, CRP, and NYHA, respectively). Plasma OPN levels were associated with overall heart failure severity rather than with specific cardiomyopathy subtype in patients suffering from DCM or HCM, respectively.