osteoprotegerin and Peripheral-Vascular-Diseases

To assess the association of circulating bone marrow-derived osteo-progenitors with vascular calcification in mouse models and patients with peripheral artery disease.. We estimated the percentage of circulating mononuclear cells expressing osteocalcin in 2 mouse models of aortic calcification developed in osteoprotegerin-deficient mice (OPG(-/-)) using flow cytometry. Aortic calcification was assessed in mice principally by a bioassay of harvested aortas. In patients with peripheral artery disease osteocalcin-positive cells (estimated by flow cytometry) were related to aortic calcification volume assessed from computed tomography.. The amount of extractable aortic calcium was increased in both mouse models used in comparison to controls. The percentage of circulating mononuclear cells expressing osteocalcin was correlated to the amount of extractable aortic calcium in male (r=0.525, p=0.02) and female OPG(-/-) (r=0.564, p=0.02) mice and also in animals in which calcification was accelerated using calcitriol (r=0.64, p=0.01). Patients with more severe aortic calcification had a greater percentage of circulating OCN(+) MNCs (median 4.07%, IQR 3.76-4.39, n=12) than those with less severe aortic calcification (median 3.10%, IQR 2.32-3.60, n=11, p=0.05).. This study demonstrates that aortic calcification can be robustly quantified in 2 mouse models. In these models and patients with peripheral artery disease circulating osteocalcin positive mononuclear cells are associated with the severity of aortic calcification.

Topics: Animals; Aorta; Aortic Diseases; Calcinosis; Calcium; Disease Models, Animal; Female; Flow Cytometry; Humans; Leukocytes, Mononuclear; Male; Mice; Osteocalcin; Osteoprotegerin; Peripheral Vascular Diseases; Severity of Illness Index; Stem Cells; Tomography, X-Ray Computed

Arterial stiffening is an independent predictor for cardiovascular mortality. Preliminary studies have shown that arterial calcification may have an impact on increased vascular stiffness. However, there are limited data about the role of calcification inhibitor osteoprotegerin (OPG) as an independent predictor for arterial stiffness in patients with peripheral arterial disease (PAD) and in healthy subjects. The aim of this study was to evaluate the association between OPG and arterial stiffness parameters in patients with PAD and in healthy subjects.. We studied 69 men with PAD (age 63 + or - 7 years) and 68 healthy subjects (age 54 + or - 8 years). Serum OPG and oxidized low-density lipoprotein (oxLDL) were measured using the enzyme-linked immunosorbent assay method. Radial and aortic pulse wave velocity (aPWV) and augmentation index (AIx) were determined by applanation tonometry.. The OPG (5.4 + or - 1.7 vs. 4.4 + or - 1.1 pmol/l; P < 0.001) and aPWV (10.1 + or - 2.5 vs. 7.6 + or - 1.6 m/s; P < 0.001) were different for the patients and for the controls. There was a linear relationship between OPG and aPWV in patients with PAD (R = 0.37; P = 0.003) and in healthy individuals (R = 0.40; P = 0.001). In multiple regression models after adjustment for potential confounders, OPG was independently associated with aPWV in the patients (R(2) = 0.47; P < 0.0001) and in the controls (R(2) = 0.44; P < 0.0001). The AIx or radial PWV was not correlated with OPG for either group.. The independent association between OPG and aPWV in patients with PAD and in controls suggests that the calcification inhibitor OPG may influence aortic stiffening in atherosclerosis and in clinically healthy subjects.

Topics: Aged; Aorta; Atherosclerosis; Blood Flow Velocity; Cross-Sectional Studies; Elasticity; Humans; Lipoproteins, LDL; Male; Middle Aged; Osteoprotegerin; Peripheral Vascular Diseases; Pulsatile Flow; Vascular Resistance

Patients infected with HIV have an increased risk for accelerated atherosclerosis. Elevated levels of osteoprotegerin, an inflammatory cytokine receptor, have been associated with a high incidence of cardiovascular disease (including peripheral arterial disease, or PAD), acute coronary syndrome, and cardiovascular mortality. The objective of this study was to determine whether PAD is prevalent in an HIV-infected population, and to identify an association with HIV-specific and traditional cardiovascular risk factors, as well as levels of osteoprotegerin.. One hundred and two patients infected with HIV were recruited in a cross-sectional study. To identify the prevalence of PAD, ankle-brachial indices (ABIs) were measured. Four standard ABI categories were utilized: < or = 0.90 (definite PAD); 0.91-0.99 (borderline); 1.00-1.30 (normal); and >1.30 (high). Medical history and laboratory measurements were obtained to determine possible risk factors associated with PAD in HIV-infected patients.. The prevalence of PAD (ABI < or = 0.90) in a young HIV-infected population (mean age: 48 years) was 11%. Traditional cardiovascular risk factors, including advanced age and previous cardiovascular history, as well as elevated C-reactive protein levels, were associated with PAD. Compared with patients with normal ABIs, patients with high ABIs had significantly elevated levels of osteoprotegerin [1428.9 (713.1) pg/ml vs. 3088.6 (3565.9) pg/ml, respectively, p = 0.03].. There is a high prevalence of PAD in young HIV-infected patients. A number of traditional cardiovascular risk factors and increased osteoprotegerin concentrations are associated with abnormal ABIs. Thus, early screening and aggressive medical management for PAD may be warranted in HIV-infected patients.

Topics: Adult; Ankle Brachial Index; Cross-Sectional Studies; Female; HIV Infections; Humans; Male; Middle Aged; Osteoprotegerin; Peripheral Vascular Diseases; Risk Factors

Osteoprotegerin (OPG), a member of the tumor necrosis factor receptor family, is involved in the process of bone turnover and also in the pathogenesis of osteoporosis and premature calcification of the vascular system. In the present study on patients with peripheral artery disease (PAD), we correlated plasma OPG concentrations with severity of disease and the presence of cardiovascular risk factors.. Sixty-seven consecutive inpatients (26 females; mean age 70 years (S.D.: 12), undergoing percutaneous transluminal angioplasty (PTA) because of advanced symptomatic PAD of the lower extremities were studied. Severity grade of disease (clinical stage after "Fontaine", functional measurements in terms of the ankle brachial index (ABI) and "Bollinger score" of angiographies), biochemical parameters and a detailed cardiovascular risk profile were documented. Fasting plasma concentrations of OPG were measured by a commercial sandwich enzyme immunoassay.. The mean plasma concentrations of OPG were 5.3 pmol/l (S.D.: 3.3). Plasma OPG concentrations in subjects with PAD, clinical stages III-IV (n=15) were 7.9 pmol/l (S.D.: 5.3) and were significantly higher than in patients without ischemic ulcerations (n=52; 4.6 pmol/l; S.D.: 2.0; p<0.01). The mean value of Bollinger score was 29.1 (S.D.: 19.8). OPG was positively correlated with Bollinger score of disease (r=0.31; p<0.02), age (r=0.58; p<0.01) and creatinine-values (r=0.32; p<0.01) and negatively correlated with ABI (r=-0.39; p<0.03).. In patients with PAD, plasma OPG concentrations were significantly higher in subjects with ischemic ulcerations than in those without and were positively correlated with higher severity grade of disease, age and creatinine-values. Further studies are required to analyze the role of OPG as a diagnostic marker for severity of atherosclerotic disease and to assess a possible therapeutic potential as "vasculoprotegerin".

Topics: Aged; Aged, 80 and over; Biomarkers; Female; Glycoproteins; Humans; Hypertension; Male; Middle Aged; Osteoprotegerin; Peripheral Vascular Diseases; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Risk Factors; Severity of Illness Index

Patients with vascular calcifications often have low bone mineral density (BMD), but it is still uncertain if osteoporosis and peripheral vascular disease (VD) are interrelated and linked by a common pathomechanism. Moreover, data on bone turnover in patients with advanced atherosclerosis are lacking. We measured BMD by dual-energy X-ray absorptiometry (DXA) and quantitative bone ultrasound (QUS), as well as the serum levels of osteocalcin (OC), bone-specific alkaline phosphatase (BAP), osteoprotegerin (OPG) and its ligand RANKL, and the urinary concentration of the C-terminal telopeptides of type I collagen (CrossLaps), in 36 patient (20 male and 16 female) with serious atherosclerotic involvement of the carotid and/or femoral artery to investigate the underlying mechanism of vascular and osseous disorders. Thirty age-matched and gender matched healthy individuals served as controls. After adjustment for age, BMD was significantly reduced at the lumbar spine in 23/36 (63%) patients (mean T score -1.71+/-1.42) and at the proximal femur in 34/36 (93%) patients (neck mean T score -2.5+/-0.88). Ten patients (27%) had abnormal QUS parameters. Gender and diabetes had no effect on the relationship between vascular calcification and bone density at any site measured. VD subjects had OC and BAP serum levels lower than controls (13.3+/-3.1 vs 27.7+/-3.3 ng/ml, P<0.01, and 8.4+/-2.3 vs 12.5+/-1.4 microg/l, P<0.01, respectively). Urinary CrossLaps excretion was not significantly different in patients with VD and in controls (257.9+/-138.9 vs 272.2+/-79.4 micro g/mmol Cr, respectively). Serum OPG and RANKL levels were similar in patients and in controls (3.5+/-1.07 vs 3.4+/-1.05 pmol/l, and 0.37+/-0.07 vs 0.36+/-0.06 pmol/l, respectively). We proved high occurrence of osteoporosis in VD, with evidence of age and gender independence. Negative bone remodelling balance would be a consequence of reduced bone formation, with no apparent increased activation of the OPG-RANKL system.

Topics: Absorptiometry, Photon; Aged; Arteriosclerosis; Biomarkers; Bone Density; Bone Remodeling; Calcinosis; Carotid Artery Diseases; Collagen; Female; Femoral Artery; Glycoproteins; Humans; Male; Middle Aged; Osteocalcin; Osteoporosis; Osteoprotegerin; Peptide Fragments; Peripheral Vascular Diseases; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Ultrasonography