Aldosterone Blockade Ameliorates Vascular Calcification In Rats With Chronic Kidney Disease
INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE(2016)
Abstract
Vascular calcification (VC) is a common and serious cardiovascular complication in patients with chronic kidney disease (CKD). Aldosterone (Ald) plays a vital role in regulating cardiovascular function. It is known that patients with CKD suffer from hyperaldosteronism, suggesting Ald might regulate the development of VC in CKD. However, the role of endogenous Ald in the pathogenesis of VC in CKD is still unclear. In this study, we employed a model of adenine (ADN)-induced CKD in rats. The results showed that ADN-fed rats exhibited CKD, arterial media calcification, increased plasma levels of Ald and elevated serum biochemical parameters, including creatinine (Cr), blood urea nitrogen (BUN), phosphate and potassium. Serum calcium levels were not altered in rats with CKD. Compared with control aortas, alkaline phosphatase (ALP) activity and calcium content in calcified aortas were increased. The expression of osteogenic marker osteopontin (OPN) was up-regulated, and the expression of smooth muscle lineage marker alpha-smooth muscle actin (alpha-SMA) was down-regulated in aortas of rats with CKD. Furthermore, the Wnt/beta-catenin pathway was activated in calcified aortas and its activation led to the phosphorylation of glycogen synthase kinase 3 beta (GSK3 beta) and the increase of beta-catenin. Aldosterone antagonism with spironolactone (SPL) therapy mitigated aortic calcification, reduced serum Cr and BUN levels, and inhibited the activation of Wnt/beta-catenin pathway as well. These results indicate that hyperaldosteronism could promote the progression of VC via Wnt/beta-catenin pathway in rats with CKD. Ald blockade therapy may be effective in preventing the development of VC in patients with CKD.
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Key words
Aldosterone, vascular calcification, chronic kidney disease, GSK3 beta, beta-catenin
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