Bone Morphogenetic Proteins 2/4 Are Upregulated during the Early Development of Vascular Calcification in Chronic Kidney Disease.

Xiao Wei,Li Li,Weihua Wu,Jiaru Lin,Qi Liu,Linwang Gan,Santao Ou

doi:10.1155/2018/8371604

Xiao Wei, Li Li + Show 5 more

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https://doi.org/10.1155/2018/8371604

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Abstract

Vascular calcification is a main cause of increased cardiovascular morbidity and mortality in chronic kidney disease (CKD) patients. This study aimed to investigate the role of the bone morphogenetic protein (BMP) signaling pathway in the early development of vascular calcification in CKD. A CKD vascular calcification rat model was established by providing rats with a 1.8% high-phosphorus diet and an intragastric administration of 2.5% adenine suspension. The kidney and aortic pathologies were analyzed. Blood biochemical indicators, serum BMP-2 and BMP-4 levels, and aortic calcium content were determined. The expression levels of BMP-2, BMP-4, bone morphogenetic protein receptor-IA (BMPR-IA), and matrix Gla protein (MGP) in aorta were examined by quantitative real-time polymerase chain reaction and immunohistochemistry. Compared with the normal control (Nor) rats, the CKD rats exhibited a significantly decreased body weight and an increased kidney weight as well as abnormal renal function and calcium-phosphorus metabolism. Aortic von Kossa and Alizarin red staining showed massive granular deposition and formation of calcified nodules in aorta at 8 weeks. The aortic calcium content was significantly increased, which was positively correlated with the serum BMP-2 (r = 0.929; P < 0.01) and serum BMP-4 (r = 0.702; P < 0.01) levels in CKD rats. The rat aortic BMP-2 mRNA level in the CKD rats was persistently increased, and the BMP-4 mRNA level was prominently increased at the 4th week, declining thereafter. Strong staining of BMP-2, BMP-4, BMPR-IA, and MGP proteins was observed in the tunica media of the aorta from the 4th week after model induction. In conclusion, activation of the BMP signaling pathway is involved in the early development of vascular calcification in CKD. Therefore, elevated serum BMP-2 and BMP-4 levels may serve as serum markers for CKD vascular calcification.

Highlights

The prevalence of chronic kidney disease (CKD) has increased every year and has become a global public health problem, affecting 8–16% of adults worldwide [1,2,3]
The rats were kept under observation for ten days prior to the start of the experiment. They were randomly divided into two groups, that is, normal controls (Nor group, n = 20) and CKD rats with vascular calcification (CKD group, n = 35)
The kidney weights were significantly increased in the CKD group, which led to a remarkable increase in the kidney/body weight index, compared with the Nor group

Summary

Introduction

The prevalence of chronic kidney disease (CKD) has increased every year and has become a global public health problem, affecting 8–16% of adults worldwide [1,2,3]. Vascular calcification has been found as an independent risk factor for cardiovascular morbidity and mortality in CKD patients [7]. A variety of risk factors, such as hyperphosphatemia, secondary hyperparathyroidism, chronic inflammation, and oxidative stress, may induce the formation of vascular calcification in CKD patients [12, 13] and are accompanied by the increased expression of bone matrix proteins, including bone morphogenetic proteins (BMPs), osteopontin, osteoprotegerin, and osteocalcin.

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