title: Losartan Inhibits Vascular Calcification by Suppressing the BMP2 and Runx2 Expression in Rats In Vivo.
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.
authors.affiliation: Hubei Province Key Laboratory on Cardiovascular, Cerebrovascular and Metabolic Disorders, Hubei University of Science and Technology, Xianning, 437100, People's Republic of China. mincaili@163.com.
authors.forename: Mincai
authors.initials: M
authors.lastname: Li
authors.affiliation: Hubei Province Key Laboratory on Cardiovascular, Cerebrovascular and Metabolic Disorders, Hubei University of Science and Technology, Xianning, 437100, People's Republic of China.
authors.forename: Panfeng
authors.initials: P
authors.lastname: Wu
authors.affiliation: Hubei Province Key Laboratory on Cardiovascular, Cerebrovascular and Metabolic Disorders, Hubei University of Science and Technology, Xianning, 437100, People's Republic of China.
authors.forename: Juan
authors.initials: J
authors.lastname: Shao
authors.affiliation: Hubei Province Key Laboratory on Cardiovascular, Cerebrovascular and Metabolic Disorders, Hubei University of Science and Technology, Xianning, 437100, People's Republic of China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Ke
authors.affiliation: Hubei Province Key Laboratory on Cardiovascular, Cerebrovascular and Metabolic Disorders, Hubei University of Science and Technology, Xianning, 437100, People's Republic of China.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.affiliation: Hubei Province Key Laboratory on Cardiovascular, Cerebrovascular and Metabolic Disorders, Hubei University of Science and Technology, Xianning, 437100, People's Republic of China. xywjl@163.com.
authors.forename: Jiliang
authors.initials: J
authors.lastname: Wu
mesh_terms: D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D050659:Core Binding Factor Alpha 1 Subunit / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D019808:Losartan / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D061205:Vascular Calcification / Q000188:drug therapy* / Q000378:metabolism*
chemical_list: D057911:Angiotensin Receptor Antagonists; C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D050659:Core Binding Factor Alpha 1 Subunit; C493717:Runx2 protein, rat; D019808:Losartan
keywords: BMP2; Runx2; Vascular calcification; Warfarin