title: Alterations of adrenomedullin and its receptor system components in calcified vascular smooth muscle cells.
abstract: Vascular calcification is a common finding in many cardiovascular diseases. Paracrine/autocrine changes in calcified vessels, and the secreted factors participate in and play an important role in the progress of calcification. Adrenomedullin (ADM) is a potent vasodilator peptide secreted by vascular smooth muscle cells (VSMCs) and vascular endothelial cells. Recently, receptor activity-modifying proteins (RAMPs) have been shown to transport calcitonin receptor-like receptor (CRLR) to the cell surface to present either as CGRP receptor or ADM receptor. In this work, we explored the production of ADM, alterations and significance of ADM mRNA and its receptor system components--CRLR and RAMPs mRNA in calcified VSMCs. Our results showed that calcium content, 45Ca2+ uptake and alkaline phosphatases (ALPs) activity in calcified VSMCs were increased, respectively, compared with control VSMCs. Content of ADM in medium was increased by 99% (p < 0.01). Furthermore, it was found that the levels of ADM, CRLR, RAMP2 and RAMP3 mRNA in calcified cells were elevated, respectively, compared with that of control. The elevated levels of CRLR, RAMP2 and RAMP3 mRNA were significant correlation with ADM mRNA (r = 0.83, 0.92 and 0.93, respectively, all p's < 0.01) in calcified VSMCs. The results show that calcified VSMCs generate an increased amount of ADM, up-regulate gene expressions of ADM and its receptor system components--CRLR, RAMP2 and RAMP3, suggesting an important role of ADM and its receptor system in the regulation of vascular calcification.
authors.affiliation: Institute of Cardiovascular Diseases, Peking University First Hospital, Beijing 100034, China.
authors.forename: Chun Shui
authors.initials: CS
authors.lastname: Pan
authors.forename: Yong Fen
authors.initials: YF
authors.lastname: Qi
authors.forename: Shu Heng
authors.initials: SH
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Ding Fang
authors.initials: DF
authors.lastname: Bu
authors.forename: Gui Zhong
authors.initials: GZ
authors.lastname: Li
authors.forename: Chao Shu
authors.initials: CS
authors.lastname: Tang
mesh_terms: D053607:Adrenomedullin; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002114:Calcinosis / Q000378:metabolism*; D058286:Calcitonin Receptor-Like Protein; D002118:Calcium / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D010455:Peptides / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D058261:Receptor Activity-Modifying Proteins; D018003:Receptors, Calcitonin / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D058286:Calcitonin Receptor-Like Protein; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D010455:Peptides; D012333:RNA, Messenger; D058261:Receptor Activity-Modifying Proteins; D018003:Receptors, Calcitonin; D053607:Adrenomedullin; D000469:Alkaline Phosphatase; D002118:Calcium