ABSTRACT
Objetivos: Evaluar el papel de la enzima antioxidante catalasa sobre el proceso de calcificación vascular asociada a insuficiencia renal crónica (IRC) y su efecto sobre la masa ósea. Material y métodos: Se utilizaron ratones C57/BL6J salvajes (WT) y transgénicos (TG), que sobreexpresan la enzima catalasa, a los que se les indujo IRC. Se utilizaron como control ratones WT y TG con intervención simulada. Transcurridas 16 semanas los animales se sacrificaron, obteniendo suero para analizar marcadores bioquímicos, el trozo residual de riñón, la aorta y las tibias. Se utilizó igualmente un modelo in vitro de cultivo primario de células de músculo liso vascular (CMLV) procedentes de aorta de ratón WT y TG sometidas durante 8 días a un medio calcificante con 3 mM de fósforo y 2 mM de calcio. Resultados: Solo en animales WT con IRC se observó un incremento significativo en la expresión génica de Runx2 y del depósito renal de calcio y un deterioro de la estructura ósea a nivel trabecular. Este efecto no se observó en ratones TG con IRC. Solo en las CMLV de ratones WT, la adición de medio calcificante produjo un aumento del contenido en calcio, de la expresión proteica de Runx2 y de las especies reactivas de oxígeno mitocondriales con una menor expresión proteica de la enzima catalasa. Conclusiones: La sobreexpresión de la enzima catalasa redujo el proceso de calcificación tanto in vivo como in vitro, mostrando in vivo que ese descenso se acompañó de una mejora en los parámetros óseos estudiados (AU)
Objetives: Assess the role of the catalase antioxidant enzyme in the vascular calcification process associated with chronic renal failure (CRF) and its effect on bone mass. Material and methods: Wild type C57/BL6J mice (WT) and transgenic mice (TG) were used, that overexpress the catalase enzyme, to which CRF was induced. Control WT and TG mice were used in simulated intervention. After 16 weeks, the mice were sacrificed, with serum samples taken for biochemical markers as well as residual pieces of kidney, aorta and tibias. An in vitro model of primary culture of smooth vascular muscle cells (SVMC) taken from the WT and TG aorta which underwent eight days of 3 mM phosphorus and 2 mM calcium calcifying medium. Results: A significant increase in Runx2 gene expression, calcium renal deposit and bone structure deterioration at trabecular level was only detected in WT mice with CRF. This was not observed in TG mice with CRF. Only in the case of WT mice SVMC, did added calcification medium raise calcium levels, proteic Runx2 expression and the reactive oxygen species of mitochondria with low catalase enzyme. Conclusions: Calcifying catalase over-expression was observed in both in vivo and in vitro, with in vivo showing that this reduction was accompanied by an improvement in bone parameters under study (AU)
Subject(s)
Animals , Mice , Vascular Calcification/enzymology , Vascular Calcification/metabolism , Bone Demineralization, Pathologic/enzymology , Bone Demineralization Technique , Catalase/therapeutic use , Antioxidants/analysis , Oxidative Stress , Mice, Transgenic , Gene Expression , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/enzymology , Renal Insufficiency, Chronic/veterinary , In Vitro Techniques , BiomarkersABSTRACT
UNLABELLED: In this observational study, we found a positive relationship between low calcidiol levels and the risk of aortic calcification progression. A 10-ng/mL increase of calcidiol was associated with a decrease in the risk of progression by 44%. This figure was higher than that observed if we increased age by 10 years. INTRODUCTION: The aim of this study was to investigate the relationship between serum calcidiol levels and the onset and progression of aortic calcifications in a community-based sample of ambulatory subjects. METHODS: Three hundred two men and women aged 50 and over underwent two lateral X-rays and were followed up for 4 years. Abdominal aortic calcifications were classified as absent, mild-moderate, and severe. The biochemical measurements of serum calcium, phosphorus, parathyroid hormone, total alkaline phosphatase, tartrate-resistant acid phosphatase, creatinine, calcidiol, calcitriol, and osteocalcin were determined. Subjects who had received anti-osteoporotic treatments were excluded from the analysis. RESULTS: Subjects with progression of aortic calcifications had significantly lower serum calcidiol levels than those without progression. In the multivariate analysis, using the agreed upon serum levels for calcidiol (>30 ng/mL) as the reference, those subjects with calcidiol levels between 10 and 20 ng/mL showed a higher risk of progression of aortic calcification (odds ratio (OR) = 3.95; 95% confidence interval (CI) = 1.16 to 13.40). An even higher OR was observed in subjects with calcidiol values <10 ng/mL (OR = 4.10; 95% CI = 1.12 to 14.99). In addition, an increase by 1 ng/mL in osteocalcin levels was associated with a 17% reduction of the risk of aortic calcification progression. CONCLUSIONS: An increase by 10 ng/mL of calcidiol was associated with a decrease in the risk of aortic calcifications progression by 44%. This figure was even higher than that observed if we increased age by 10 years. Levels of calcidiol higher than 30 ng/mL seem to be desirable to reduce the progression of aortic calcification and to maintain bone turnover.
