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|Intermedin inhibits vascular calcification by increasing the level of matrix gamma-carboxyglutamic acid protein|
|Cai, Yan1; Xu, Ming-Jiang1; Teng, Xu1; Zhou, Ye Bo1; Chen, Li2; Zhu, Yi1,2; Wang, Xian1,2; Tang, Chao Shu1,2; Qi, Yong Fen1,2,3|
|关键词||Vascular Calcification Peptides Matrix Gamma-carboxyglutamic (Gla) Protein Phenotype Transition|
|WOS标题词||Science & Technology|
|类目[WOS]||Cardiac & Cardiovascular Systems|
|研究领域[WOS]||Cardiovascular System & Cardiology|
|关键词[WOS]||SMOOTH-MUSCLE-CELLS ; BONE MORPHOGENETIC PROTEIN-2 ; VITAMIN-D-3 PLUS NICOTINE ; HORMONE-RELATED PEPTIDE ; CHRONIC KIDNEY-DISEASE ; GLA PROTEIN ; ARTERIAL CALCIFICATION ; IN-VITRO ; PARATHYROID-HORMONE ; PROTECTIVE FACTOR|
Vascular calcification (VC) is highly associated with increased morbidity and mortality in patients with advanced chronic kidney disease. Paracrine/autocrine factors such as vasoactive peptides are involved in VC development. Here, we investigated the expression of the novel peptide intermedin (IMD) in the vasculature, tested its ability to prevent VC in vivo and in vitro, and examined the mechanism involved.
Rat VC was induced by administration of vitamin D-3 plus nicotine (VDN). IMD (100 ng kg(-1) h(-1)) was systemically administered by a mini-osmotic pump. VDN-treated rat aortas showed lower IMD content and increased expression of its receptors, along with increased vascular calcium deposition and alkaline phosphatase (ALP) activity. Low IMD levels were accompanied by increased calcium deposition in human atherosclerotic plaques. In vivo administration of IMD greatly reduced vascular calcium deposition and ALP activity in VDN-treated rats when compared with vehicle treatment, which was further confirmed in cultured vascular smooth muscle cells. Concurrently, the loss of smooth-muscle lineage markers and matrix gamma-carboxyglutamic acid (Gla) protein (cMGP) in aortas was ameliorated by administering IMD to rats with VC, and the increased phosphor-Smad(1/5/8) and core binding factor alpha-1 levels in calcified vasculature were also reduced. However, the inhibitory effects of IMD on VC were eliminated upon pre-treatment with warfarin or small interfering RNA to reduce cMGP.
Reduced endogenous IMD levels are associated with increased mineralization in vivo, and administration of IMD inhibits VC development by increasing cMGP levels. IMD may be an endogenous vasoprotective factor for VC.
|项目编号||30470693 ; 30770869 ; 30871013 ; 2006CB503807|
|资助机构||National Natural Science Foundation of China ; State Major Basic Research Development Program of the People&prime ; s Republic of China|
|作者单位||1.Peking Univ, Dept Physiol & Pathophysiol, Hlth Sci Ctr, Beijing 100191, Peoples R China|
2.Minist Educ Res, Key Lab Mol Cardiovasc Sci, Beijing 100191, Peoples R China
3.Peking Univ, Sch Basic Med Sci, Lab Cardiovasc Bioact Mol, Beijing 100191, Peoples R China
|Cai, Yan,Xu, Ming-Jiang,Teng, Xu,et al. Intermedin inhibits vascular calcification by increasing the level of matrix gamma-carboxyglutamic acid protein[J]. CARDIOVASCULAR RESEARCH,2010,85(4):864-873.|
|APA||Cai, Yan.,Xu, Ming-Jiang.,Teng, Xu.,Zhou, Ye Bo.,Chen, Li.,...&Qi, Yong Fen.(2010).Intermedin inhibits vascular calcification by increasing the level of matrix gamma-carboxyglutamic acid protein.CARDIOVASCULAR RESEARCH,85(4),864-873.|
|MLA||Cai, Yan,et al."Intermedin inhibits vascular calcification by increasing the level of matrix gamma-carboxyglutamic acid protein".CARDIOVASCULAR RESEARCH 85.4(2010):864-873.|
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