title: [Mechanism of losartan suppressing vascular calcification in rat aortic artery].
abstract: Objective To investigate the effect of the angiotensin II receptor 1 (AT1R) blocker losartan on vascular calcification in rat aortic artery and explore the underlying mechanisms. Methods SD rats were divided randomly into control group, vascular calcification model group and treatment group. Vascular calcification models were made by subcutaneous injection of warfarin plus vitamin K1 for two weeks. Rats in the treatment group were subcutaneously injected with losartan (10 mg/kg) at the end of the first week and consecutively for one week. We observed the morphological changes by HE staining and the calcium deposition by Alizarin red staining in the artery vascular wall. The mRNA expressions of bone morphogenetic protein 2 (BMP2) and Runt-related transcription factor 2 (RUNX2) were analyzed by reverse transcription PCR. The BMP2 and RUNX2 protein expressions were determined by Western blotting. The apoptosis of smooth muscle cells (SMCs) were detected by TUNEL. The AT1R expression was tested by fluorescent immunohistochemistry. Results The aortic vascular calcification was induced by warfarin and vitamin K1. Compared with the vascular calcification model group, the mRNA and protein expressions of BMP2 and RUNX2 were significantly downregulated in the aorta in the losartan treatment group. Furthermore, the apoptosis of SMCs and the AT1R expression obviously decreased. Conclusion AT1R blocker losartan inhibits the apoptosis of SMCs and reduces AT1R expression; it downregulates the BMP2 and RUNX2 expressions in the vascular calcification process.
authors.affiliation: Hubei Provincial Key Laboratory of Cardio-cerebrovascular and Metabolic Diseases, Hubei University of Science and Technology, Xianning 437100, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Shao
authors.affiliation: Hubei Provincial Key Laboratory of Cardio-cerebrovascular and Metabolic Diseases, Hubei University of Science and Technology, Xianning 437100, China.
authors.forename: Panfeng
authors.initials: P
authors.lastname: Wu
authors.affiliation: Hubei Provincial Key Laboratory of Cardio-cerebrovascular and Metabolic Diseases, Hubei University of Science and Technology, Xianning 437100, China. *Corresponding authors, E-mail: xywjl@163.com.
authors.forename: Jiliang
authors.initials: J
authors.lastname: Wu
authors.affiliation: Hubei Provincial Key Laboratory of Cardio-cerebrovascular and Metabolic Diseases, Hubei University of Science and Technology, Xianning 437100, China. *Corresponding authors, E-mail: mincaili@163.com.
authors.forename: Mincai
authors.initials: M
authors.lastname: Li
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001158:Arteries / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D007150:Immunohistochemistry; D019808:Losartan / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000473:pathology; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D061205:Vascular Calcification / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D010837:Vitamin K 1; D014859:Warfarin
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D050659:Core Binding Factor Alpha 1 Subunit; D044140:Receptor, Angiotensin, Type 1; C493717:Runx2 protein, rat; D014859:Warfarin; D010837:Vitamin K 1; D019808:Losartan