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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.

Vascular calcification remains one of the main factors associated to morbidity and mortality in both ageing and chronic kidney disease. Both hyperphosphataemia, a well-known promoter of vascular calcification, and abnormal processing defects of lamin A/C have been associated to ageing. The main aim of this study was to analyse the effect of phosphorus load in the differential expression pattern of genes and proteins, particularly of lamin A/C, which are involved in phenotypic change of the vascular smooth muscle cells to osteoblast-like cells. The in vivo study of the calcified abdominal aortas from nephrectomized rats receiving a high phosphorus diet showed among others, a repression of muscle related proteins and overexpression of lamin A/C. Similar results were observed in vitro, where primary vascular smooth muscle cells cultured in calcifying medium showed increased expression of prelamin A and lamin A and abnormalities in the nuclear morphology. Co-immunoprecipitation assays showed novel and important physical interactions between lamin A and RUNX2 during the process of calcification. In fact, the knockdown of prelamin A and lamin A inhibited the increase of Runx2, osteocalcin and osteopontin gene expression, calcium deposition, nuclear abnormalities and the RUNX2 protein translocation into the nucleus of the cell. These in vivo and in vitro results highlight the important role played by lamin A in the process of vascular calcification., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Left ventricular hypertrophy (LVH), a common complication in chronic kidney disease (CKD), is associated with high cardiovascular mortality. The aim of this experimental study was to analyze the effect of different vitamin D receptor activators (VDRAs) on both LVH and myocardial fibrosis in chronic renal failure (CRF)., Methods: Male Wistar rats with CRF, carried out by 7/8 nephrectomy, were treated intraperitoneally with equivalent doses of VDRAs (calcitriol, paricalcitol and alfacalcidol, 5 days per week) during 4 weeks. A placebo group (CRF + vehicle) and a Sham group with normal renal function served as controls. Biochemical, morphological, functional and molecular parameters associated with LVH were evaluated, as well as cardiac fibrosis, collagen I, transforming growth factor β1 (TGFβ1) and matrix metalloproteinase-1 (MMP1) expression., Results: All VDRAs treatment prevented LVH, with values of cardiomyocyte size, LV wall and septum thickness and heart-body weight ratio similar to those observed in the Sham group. At molecular levels, all VDRAs attenuated atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) expression compared with CRF + vehicle. The phosphorylation of ERK1/2, a signal for activating growth, was stimulated in the CRF + vehicle group; VDRAs use prevented this activation. Paricalcitol was the only VDRA used that maintained in the normal range all parameters associated with myocardial fibrosis (total collagen, collagen I, TGFβ1 and MMP1)., Conclusions: Our findings demonstrated that the three VDRAs used induced similar changes in bone metabolic parameters and LVH. In addition, paricalcitol was the only VDRA which showed a relevant beneficial effect in the reduction of myocardial fibrosis, a key factor in the myocardial dysfunction in CKD patients.