title: Adrenomedullin(27-52) inhibits vascular calcification in rats.
abstract: Adrenomedullin (ADM) has the vasodilatory properties and involves in the pathogenesis of vascular calcification. ADM could be degraded into more than six fragments in the body, including ADM(27-52), and we suppose the degrading fragments from ADM do the same bioactivities as derived peptides from pro-adrenomedullin. The present study carries forward by assessing the effects on vascular calcification of the systemic administration of ADM(27-52). The rat vascular calcific model was replicated with vitamin D3 and nicotine. ADM or/and ADM(27-52) were systemically administrated with mini-osmotic pump beginning at seventh day after the model replication for 25 days. Vascular calcific nodules histomorphometry, vascular calcium content, vascular calcium uptake, alkaline phosphatase activity, and osteopontin-mRNA quantification in aorta were assessed. ADM limited 40.2% vascular calcific nodules (P<0.01), did not effect on calcium content (P>0.05), reduced 44.4% calcium uptake (P<0.01), lowered 21.1% alkaline phosphatase activity (P<0.01), and regulated 40.9% downwards osteopontin-mRNA expression (P<0.01) in the aorta of rats with vascular calcification. ADM(27-52) receded 32.0% vascular calcific nodules (P<0.01), taken from 55.5% calcium content (P<0.01), did not affect calcium uptake (P>0.05), inhibited 22.5% alkaline phosphatase activity (P<0.01), and restrained 21.9% osteopontin-mRNA expression (P<0.01) in the aorta of rats with vascular calcification. Both of ADM and ADM(27-52) did interact on vascular calcification each other. ADM could partially antagonize the effects of ADM(27-52) in taking from calcium content (17.5%, P<0.01) and in receding vascular calcific nodules (18.6%, P<0.01). ADM could obviously enhance the action of ADM(27-52) in inhibiting alkaline phosphatase activity (14.4%, P<0.01) and in reducing calcium uptake (11.4%, P<0.01). ADM(27-52) could partially antagonize the effects of ADM on regulating downwards osteopontin-mRNA expression (17.0%, P<0.01). It is concluded that ADM(27-52) derived from ADM acts as an inhibitory agent on vascular calcification, with special mechanisms different from ADM derived from ADM progenitor molecule.
authors.affiliation: Institute of Cardiovascular Disease, Peking University First Hospital, Beijing 100034, China.
authors.forename: Da-Yong
authors.initials: DY
authors.lastname: Cai
authors.forename: Fang
authors.initials: F
authors.lastname: Yu
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.forename: Hong-Feng
authors.initials: HF
authors.lastname: Jiang
authors.forename: Chun-Shui
authors.initials: CS
authors.lastname: Pan
authors.forename: Yong-Feng
authors.initials: YF
authors.lastname: Qi
authors.forename: Lin
authors.initials: L
authors.lastname: Chang
authors.forename: Jin
authors.initials: J
authors.lastname: Zhao
authors.forename: Jin-Hui
authors.initials: JH
authors.lastname: Yang
authors.forename: Ming-Jia
authors.initials: MJ
authors.lastname: Zhu
authors.forename: Yue-Xia
authors.initials: YX
authors.lastname: Jia
authors.forename: Bin
authors.initials: B
authors.lastname: Geng
authors.forename: Tie-Min
authors.initials: TM
authors.lastname: Ma
authors.forename: Yong-Zheng
authors.initials: YZ
authors.lastname: Pang
authors.forename: Chao-Shu
authors.initials: CS
authors.lastname: Tang
mesh_terms: D053607:Adrenomedullin; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism* / Q000473:pathology; D002114:Calcinosis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D002762:Cholecalciferol / Q000633:toxicity; D008297:Male; D009538:Nicotine / Q000633:toxicity; D018722:Nicotinic Agonists / Q000633:toxicity; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018722:Nicotinic Agonists; D010446:Peptide Fragments; C432594:adrenomedullin (27-52); D053607:Adrenomedullin; D002762:Cholecalciferol; D009538:Nicotine