osteoprotegerin and Heart-Valve-Diseases

Vitamin K is required for the activity of various biologically active proteins in our body. Apart from clotting factors, vitamin K-dependent proteins include regulatory proteins like protein C, protein S, protein Z, osteocalcin, growth arrest-specific gene 6 protein, and matrix Gla protein. Glutamic acid residues in matrix Gla protein are γ-carboxylated by vitamin K-dependent γ-carboxylase, which enables it to inhibit calcification. Warfarin, being a vitamin K antagonist, inhibits this process, and has been associated with calcification in various animal and human studies. Though no specific guidelines are currently available to prevent or treat this less-recognized side effect, discontinuing warfarin and using an alternative anticoagulant seems to be a reasonable option. Newer anticoagulants such as dabigatran and rivaroxaban offer promise as future therapeutic options in such cases. Drugs including statins, alendronate, osteoprotegerin, and vitamin K are currently under study as therapies to prevent or treat warfarin-associated calcification. Copyright © 2011 Wiley Periodicals, Inc. The authors have no funding, financial relationships, or conflicts of interest to disclose.

Topics: Anticoagulants; Calcinosis; Diphosphonates; Heart Valve Diseases; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperbaric Oxygenation; Muscle, Smooth, Vascular; Osteoprotegerin; Vitamin K; Warfarin

Cardiovascular disease is the leading cause of mortality in patients with end-stage renal disease (ESRD) and is attributed to a combination of traditional and non-traditional cardiovascular risk factors. In recent years, there has also been an increasing recognition of a very high prevalence of cardiovascular calcification in the ESRD population, including in patients receiving long-term peritoneal dialysis (PD). Numerous observational cohort studies have demonstrated the prognostic importance of cardiovascular calcifications in these patients. The mechanisms are not completely understood, but are likely multifactorial. The present article reviews the prevalence, clinical course, prognostic significance, and some contributing factors for vascular and valvular calcification in ESRD patients, including patients receiving PD therapy.

Topics: 1-Carboxyglutamic Acid; alpha-2-HS-Glycoprotein; Blood Proteins; Blood Vessels; C-Reactive Protein; Calcinosis; Calcium-Binding Proteins; Extracellular Matrix Proteins; Heart Valve Diseases; Heart Valves; Humans; Kidney Failure, Chronic; Matrix Gla Protein; Osteoprotegerin; Peritoneal Dialysis; Prevalence; Prognosis; Vascular Diseases

Postoperative atrial fibrillation (POAF), a frequent complication after cardiac surgery, causes morbidity and prolongs hospitalization. A significant association between circulating osteoprotegerin concentration and atrial fibrillation incidence had been identified. Osteoprotegerin/receptor activator of nuclear factor-κB/receptor activator of nuclear factor-κB ligand (RANKL) axis may also contribute to the development and progression of AF. Herein we sought to determine whether preoperative serum soluble RANKL and osteoprotegerin and soluble RANKL/osteoprotegerin ratio are associated with the incidence of POAF in cardiac surgery patients.. We enrolled 154 patients with preoperative sinus rhythm undergoing isolated cardiac valve surgery. Preoperative venous blood samples were obtained for measurement of serum soluble RANKL and osteoprotegerin. The POAF was defined as the characteristic arrhythmia lasting for at least 30 seconds before discharge. Comparison was made between patients without episode of POAF (sinus rhythm group, n=93) and patients experiencing POAF (atrial fibrillation group, n=61).. Serum levels of soluble RANKL and osteoprotegerin and soluble RANKL/osteoprotegerin ratio were significantly higher in the atrial fibrillation group than the sinus rhythm group. In multivariate survival regression, C-reactive protein, ejection fraction, left and right atrial diameters, preoperative use of beta-blocker, duration of ventilation, particularly serum soluble RANKL level, and soluble RANKL/osteoprotegerin ratio independently predicted POAF. According to receiver operating characteristic curve analysis, the best threshold values of serum soluble RANKL level and soluble RANKL/osteoprotegerin ratio for predicting POAF were 3.62 pmol/L and 0.51, respectively.. Elevated preoperative serum soluble RANKL level and soluble RANKL/osteoprotegerin ratio are independent predictors for POAF in patients undergoing cardiac valve surgery. These findings have important implications for identifying patients at higher risk of POAF who could be considered for prophylactic therapy.

Topics: Adult; Analysis of Variance; Atrial Fibrillation; Biomarkers; Cohort Studies; Female; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Humans; Male; Middle Aged; Osteoprotegerin; Postoperative Complications; Predictive Value of Tests; Preoperative Care; Proportional Hazards Models; Receptor Activator of Nuclear Factor-kappa B; Regression Analysis; Retrospective Studies; Risk Assessment; Solubility; Statistics, Nonparametric; Survival Rate; Treatment Outcome

Topics: Atrial Fibrillation; Female; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Humans; Male; Osteoprotegerin; Receptor Activator of Nuclear Factor-kappa B

Calcific aortic valve sclerosis involves inflammatory processes and occurs preferentially on the aortic side of endothelialized valve leaflets. Although the endothelium is recognized to play critical roles in focal vascular sclerosis, the contributions of valvular endothelial phenotypes to aortic valve sclerosis and side-specific susceptibility to calcification are poorly understood. Using RNA amplification and cDNA microarrays, we identified 584 genes as differentially expressed in situ by the endothelium on the aortic side versus ventricular side of normal adult pig aortic valves. These differential transcriptional profiles, representative of the steady state in vivo, identify globally distinct endothelial phenotypes on opposite sides of the aortic valve. Several over-represented biological classifications with putative relevance to endothelial regulation of valvular homeostasis and aortic-side vulnerability to calcification were identified among the differentially expressed genes. Of note, multiple inhibitors of cardiovascular calcification were significantly less expressed by endothelium on the disease-prone aortic side of the valve, suggesting side-specific permissiveness to calcification. However, coexisting putative protective mechanisms were also expressed. Specifically, enhanced antioxidative gene expression and the lack of differential expression of proinflammatory molecules on the aortic side may protect against inflammation and lesion initiation in the normal valve. These data implicate the endothelium in regulating valvular calcification and suggest that spatial heterogeneity of valvular endothelial phenotypes may contribute to the focal susceptibility for lesion development.

Topics: Animals; Antioxidants; Aortic Valve; Bone Morphogenetic Protein 4; Bone Morphogenetic Proteins; Calcinosis; Endothelial Cells; Gene Expression Profiling; Glycoproteins; Heart Valve Diseases; Hemodynamics; Inflammation; Male; NF-kappa B; Osteoprotegerin; Phenotype; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Swine