Osteoprotegerin, vascular calcification and atherosclerosis

Abstract

The association of bone pathologies with atherosclerosis has stimulated the search for common mediators linking the skeletal and the vascular system. Since its initial discovery as a key regulator in bone metabolism, osteoprotegerin (OPG) has become the subject of intense interest for its role in vascular disease and calcification. Studies in vitro and in animal models suggest that OPG inhibits vascular calcification. Paradoxically however, clinical studies suggest that serum OPG levels increase in association with vascular calcification, coronary artery disease, stroke and future cardiovascular events. This has led to extensive debate on the potential of OPG as a biomarker of vascular disease. However the exact significance and mechanisms by which this bone-regulatory protein influences cardiovascular pathophysiology is still unclear. The need for a more complete picture is being addressed in increasing valuable research indicating OPG as not only a marker but also a mediator of vascular pathology modulating osteogenic, inflammatory and apoptotic responses. By integrating the results of recent experimental research, animal models and clinical studies, this review summarises the present understanding of the role of OPG in vascular disease and calcification.

The balance of fetuin-A and osteoprotegerin is independently associated with diastolic dysfunction in hemodialysis patients

“…27 OPG also induces an anti-apoptotic effect by binding to tumor necrosis factor-related apoptosis-inducing ligands, which reduces the number of apoptotic bodies. 11 Although we could not demonstrate a significant positive relationship between Figure 3 The association between baPWV and AOCS in patients based on the balance between fetuin-A and OPG. After adjusting for age, sex, duration of dialysis, mean BP, heart rate, body mass index, hemoglobin, smoking, medication for hypertension, medication for diabetes, medication for dyslipidemia and prior CAD, significant differences in the baPWV (a) and AOCS (b) were observed across the four groups (Po0.05).…”

“…OPG could act as a survival factor for serum-deprived smooth muscle cells. 11 Hence, high OPG levels in patients with a high AOCS may reflect an incomplete defense mechanism against factors that promote heavy arterial calcification, 25 which ultimately results in increased ventricular stiffness, as explained above.…”

“…9,10 Osteoprotegerin (OPG), a soluble decoy receptor of the osteoclast receptor activator of the nuclear factor kB ligand (RANKL), acts as an important regulator of vascular calcification. 11 OPG-deficient mice develop severe osteoporosis and vascular calcification. 12 In contrast, elevated serum levels of OPG are associated with the progression of vascular stiffness and cardiovascular events in hemodialysis patients.…”

High Serum Osteoprotegerin Is Associated with Arterial Stiffness in Kidney Transplant Patients

“…Production of OPG is enhanced by inflammatory cytokines and may reflect endothelial dysfunction. Additionally, a failing myocardium, plaque rupture and the presence of other inflamed tissues, could contribute to an elevation in circulating OPG concentration (Van Campenhout and Golledge 2009;Venuraju et al 2010). Clinical studies have suggested that an increase in serum OPG levels is associated with renal events, CV events and mortality among KT patients (Hjelmesaeth et al 2006;Svensson et al 2012).…”

Prognostic Impact of Alkaline Phosphatase Measured at the Time of Presentation in Patients Undergoing Primary Percutaneous Coronary Intervention for St-Segment Elevation Myocardial Infarction

“…Calcific vasculopathy is one of the major contributors to atherosclerosis, and causes vascular hardening, aging, and finally, adverse cardiovascular events [1][2][3]. The development of calcification in atherosclerotic lesions is the result of osteogenic differentiation in subpopulations of vascular cells exposed to various stimuli [4].…”