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Losartan Inhibits Vascular Calcification by Suppressing the BMP2 and Runx2 Expression in Rats In Vivo

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Abstract

The blockade of renin–angiotensin II system has been shown to reduce morbidity and mortality in hypertension, atherosclerosis, diabetes and chronic kidney disease. Since vascular calcification (VC) is commonly found in these diseases, the aim of this study was to examine whether or not losartan, a widely used angiotensin II receptor blockers, inhibits VC in rats in vivo. A rat model of VC was generated by treating rats with a combination of warfarin and vitamin K1. Two weeks after the treatments, the rats were treated with vehicle or without losartan (100 ng/kg/day) for 2 weeks. At the end of the experiments, aortic arteries were isolated for the examination of calcification morphology, mRNA and protein expression of BMP2 and Runx2, and osteoblast differentiation. Warfarin and vitamin K instigated vascular remodeling with calcified plaques in the aortic arteries in rats. Losartan significantly attenuated warfarin- and vitamin K-induced vascular injury and calcification. Consistently, losartan suppressed the levels of mRNA and protein expression of BMP2 and Runx2, two key factors for VC. Further, vascular calcified lesion areas expressed angiotensin II 1 receptor (AT1R). Finally, losartan treatment significantly inhibited apoptosis in vascular smooth muscle cell (VSMC) in rat arteries. We conclude that losartan suppresses VC by lowering the expression of AT1R, Runx2 and BMP2, and by inhibiting the apoptosis of VSMC in rat aortic arteries.

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Acknowledgments

This work was supported by the grant from the National Natural Science Foundation of China (No. 81270355) and the grants from the Fund of the Science and Technology Department of Hubei Province, China (2014CFB211). We thank Dr. Ming-Hui Zou for his critical review of the manuscript.

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The authors have declared that no competing interests exist.

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Authors and Affiliations

  1. Hubei Province Key Laboratory on Cardiovascular, Cerebrovascular and Metabolic Disorders, Hubei University of Science and Technology, Xianning, 437100, People’s Republic of China

    Mincai Li, Panfeng Wu, Juan Shao, Zhiqiang Ke, Dan Li & Jiliang Wu

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  1. Mincai Li
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Correspondence to Mincai Li or Jiliang Wu.

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Li, M., Wu, P., Shao, J. et al. Losartan Inhibits Vascular Calcification by Suppressing the BMP2 and Runx2 Expression in Rats In Vivo. Cardiovasc Toxicol 16, 172–181 (2016). https://doi.org/10.1007/s12012-015-9326-y

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