Evaluation of circulating osteoprotegerin as a new biomarker in the metabolic syndrome: cardiovascular risk assessment, analytical factors and circulating sources

• Autores: Carmen Pérez de Ciriza Villacampa
• Directores de la Tesis: Nerea Varo Cenarruzabeitia (dir. tes.)
• Lectura: En la Universidad de Navarra ( España ) en 2014
• Idioma: español
• Tribunal Calificador de la Tesis: José Antonio Páramo Fernández (presid.), Josune Orbe (secret.), Julio Sánchez Álvarez (voc.), Imma Caballé Martín (voc.), Allan Lawrie (voc.)
• Materias:
  • Química
    • Bioquímica
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• Resumen

  • Osteoprotegerin (OPG), an osteoclastogenesis inhibitor implicated in bone remodelling, has emerged as a potential biomarker for cardiovascular disease (CVD). The aims of the present study are: 1) To study the influence of preanalytical and analytical factors in OPG measurements. 2) To evaluate OPG concentration in patients with the MS and its association with subclinical atherosclerosis and coronary arterial calcification (CAC), 3) To establish the sources of circulating OPG among different cell types involved in the atherogenic process as well as the effects of elevated OPG in endothelial cells (ECs).

    Preanalytical and analytical conditions should be considered due to the impact on OPG. OPG levels vary depending on the specimen. Increasing centrifugation speed does not alter OPG concentration and serum separation after centrifugation should be performed within 30 minutes. Centrifuged samples are more stable and they should preferably be stored at 4ºC (maximum 24 hours). Longer storage may be done at -20ºC. Moreover, a maximum of three freeze-thaw cycles is suggested. Endogenous interferents can alter OPG levels specially haemoglobin (reducing OPG values) and triglycerides (increasing OPG concentration). Bilirubin, cholesterol and RANKL do not interfere with OPG measurements.

    OPG circulating levels are elevated in patients with the MS and are higher in diabetics, hypertensives, obese and non-smokers. OPG correlates with the number of cardiovascular risk factors, IMT and CAC. The data suggest that OPG may potentially be a biomarker for cardiovascular risk/damage.

    Adipose tissue, monocytes, platelets and ECs are potential sources of OPG in circulation. OPG expression was highly and significantly increased by IL-1β stimulation, insulin and glucose. OPG secretion to the supernatant was increased by IL-1β and PDGF. Besides, ECs stimulation with OPG further contributes to the proinflammatory state in MS patients.