osteoprotegerin and Angina--Unstable

 Osteoprotegerin (OPG), receptor activator of nuclear factor-kappa B (RANK) and receptor activator of nuclear factor-kappa B ligand (RANKL), the members of the tumor necrosis factor (TNF) family, have multiple effects on bone metabolism, endocrine functions and, as an inflammatory pathway, in the immune system. This study tried to determine the association of the OPG/RANKL/RANK axis with the severity of unstable angina (UA) as an inflammatory condition. Our study involved 50 patients with UA and 50 healthy people. Serum and peripheral blood mononuclear cells were isolated from all participants. Serum levels and gene expression of OPG, RANKL, and RANK in mononuclear cells were measured by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (RT-PCR), respectively. For each patient with UA, the thrombolysis in myocardial infarction (TIMI) and the global registry of acute coronary events (GRACE) scores were determined to evaluate the severity of the disease. Then we analyzed the relation of OPG, RANKL, and RANK levels with TIMI and GRACE scores in patients with UA. Discriminate analysis was used to predict the combinational models of such factors on the prediction of UA. Serum levels of OPG and RANKL (p<0.001) and gene expression of RANKL (p<0.001) were significantly more in patients than those in healthy ones. No relation was seen between the OPG/RANKL/RANK axis and the severity of UA according to TIMI and GRACE scores. Our study shows that serum level, as well as gene expression of OPG/RANKL/RANK axis neither, predicts the occurrence of UA nor shows any relationship with its severity.

Topics: Angina, Unstable; Biomarkers; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Gene Expression; Humans; Inflammation Mediators; Osteoprotegerin; Prognosis; RANK Ligand; Real-Time Polymerase Chain Reaction; Receptor Activator of Nuclear Factor-kappa B; Severity of Illness Index; Signal Transduction

Osteoprotegerin (OPG), an inhibitor of osteoclastogenesis, has recently been under the spotlight in studies regarding the pathophysiology of atherosclerosis.. To evaluate the value of serum OPG in the diagnosis and severity in patients with stable angina pectoris (SA) and unstable angina pectoris/non ST elevation myocardial infarction.. This study involved 160 patients, SA (n = 65), acute coronary syndrome (NSTE-ACS; n = 65), and a control group (n = 30). Blood samples were collected in the first hour, after 24 hours and on the fifth day. The prevalence of coronary artery atherosclerotic lesions was determined using the Gensini scoring system.. A statistically significant difference was observed in the first hour OPG levels between the control group and both the SA and NSTE-ACS group (p < 0.001). When the cut-off value was determined as 247.71 pg/mL, the sensitivity and specificity of the first hour OPG levels indicating coronary artery disease were 91.54% and 46.67%, respectively, while the positive predictive value was 88.1% and the negative predictive value was 56%. No correlations were observed between the first, 24th hour and the fifth day OPG levels and the Gensini scores. No relation was denoted between the OPG levels and number of diseased coronary arteries.. In our study, serum OPG level seemed to be unrelated to the severity or the degree of coronary artery disease in patients with SA and unstable angina pectoris/non ST elevation myocardial infarction. OPG may only be accepted as an indicator of coronary atherosclerosis.

Topics: Acute Coronary Syndrome; Angina, Stable; Angina, Unstable; Biomarkers; Comorbidity; Coronary Angiography; Coronary Artery Disease; Female; Humans; Male; Middle Aged; Multivariate Analysis; Osteoprotegerin; Predictive Value of Tests; Prevalence; Sensitivity and Specificity

This study was designed to evaluate the biological significance of simultaneous changes in the circulating levels of osteoprotegerin (OPG) and TNF-related apoptosis inducing ligand (TRAIL) in patients with coronary artery disease (CAD), and, in particular, with acute myocardial infarction (AMI).. Total levels of OPG and TRAIL were measured by ELISA in patients with AMI (n=113), unstable angina (UA, n=21) and healthy controls (n=120).. Since OPG was elevated during the acute phase (first 12-24-48h) after AMI and in patients with UA with respect to healthy controls, while TRAIL was decreased in acute AMI patients, CAD patients were characterized by an increased OPG/TRAIL ratio. Moreover, the OPG/TRAIL ratio was significantly (p<0.05) higher in the acute AMI patients who developed heart failure (HF) than in those who did not develop HF in the follow-up.. An impaired OPG/TRAIL ratio after AMI is related to a higher risk of HF.

Topics: Angina, Unstable; Coronary Disease; Enzyme-Linked Immunosorbent Assay; Female; Heart Failure; Humans; Male; Myocardial Infarction; Osteoprotegerin; TNF-Related Apoptosis-Inducing Ligand

This study was designed to assess the association between osteoprotegerin (OPG) levels on admission and long-term prognosis in patients with acute coronary syndromes (ACS).. Osteoprotegerin, a member of the tumor necrosis factor receptor superfamily, has pleiotropic effects on bone metabolism, endocrine function, and the immune system.. Serum samples for OPG analysis were obtained within 24 h of admission in 897 ACS patients (median age 66 years, 71% men) and related to the incidence of death, heart failure (HF) hospitalizations, myocardial infarction (MI), and stroke.. A total of 261 patients died during a median follow-up of 89 months. The baseline OPG concentration was strongly associated with increased long-term mortality (hazard ratio [HR] for HR per 1 SD increase in logarithmically transformed OPG level 1.7 [range 1.5 to 1.9] p < 0.0001) and HF hospitalizations (HR 2.0 [range 1.6 to 2.5]; p < 0.0001) but weaker with recurrent MI (HR 1.3 [range 1.0 to 1.5]; p = 0.02) and not with stroke (HR 1.2 [range 0.9 to 1.6]; p = 0.35). After adjustment for conventional risk markers, including troponin I, C-reactive protein (CRP), B-type natriuretic peptide (BNP), and ejection fraction, the association remained significant for mortality (HR 1.4 [range 1.2 to 1.7]; p < 0.0001) and HF hospitalization (HR 1.6 [range 1.2 to 2.1]; p = 0.0002), but not recurrent MI. By comparison of the area under the receiver-operating characteristics curves, OPG performed similarly to BNP and ejection fraction and significantly better than CRP and troponin I as a predictor of death.. Serum OPG is strongly predictive of long-term mortality and HF development in patients with ACS, independent of conventional risk markers.

Topics: Acute Coronary Syndrome; Aged; Angina, Unstable; Biomarkers; Bone and Bones; Endocrine System; Female; Hospitalization; Humans; Immune System; Incidence; Male; Middle Aged; Osteoprotegerin; Prognosis; Prospective Studies; Time Factors

Based on its role in inflammation and matrix degradation, we hypothesized a role for osteoprotegerin (OPG), RANK, and RANK ligand (RANKL) in coronary artery disease.. We examined the expression of various members of the OPG/RANKL/RANK axis in patients with stable and unstable angina and in the atherosclerotic lesions of apolipoprotein E-deficient (apoE(-/-)) mice. Our findings were: (1) Serum levels of OPG were raised in patients with unstable angina (n=40), but not in those with stable angina (n=40), comparing controls (n=20); (2) mRNA levels of RANKL were increased in T-cells in unstable angina patients accompanied by increased expression of RANK in monocytes; (3) strong immunostaining of OPG/RANKL/RANK was seen within thrombus material obtained at the site of plaque rupture during acute myocardial infarction; (4) OPG/RANKL/RANK was expressed in the atherosclerotic plaques of apoE(-/-) mice, with RANKL located specifically to the plaques; and (5) RANKL enhanced the release of monocyte chemoattractant peptide-1 in mononuclear cells from unstable angina patients, and promoted matrix metalloproteinase (MMP) activity in vascular smooth muscle cells.. We show enhanced expression of the OPG/RANKL/RANK system both in clinical and experimental atherosclerosis, with enhanced T-cell expression of RANKL as an important feature of unstable disease.

Topics: Adult; Aged; Angina, Unstable; Animals; Apolipoproteins E; Atherosclerosis; Carrier Proteins; Cell Line; Female; Glycoproteins; Humans; Male; Matrix Metalloproteinases; Membrane Glycoproteins; Mice; Mice, Knockout; Middle Aged; Monocytes; Muscle, Smooth, Vascular; Osteoprotegerin; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Rupture, Spontaneous; T-Lymphocytes