BMP-2 promotes phosphate uptake, phenotypic modulation, and calcification of human vascular smooth muscle cells.


:Vascular calcification is associated with increased risk of cardiovascular events that are the most common cause of death in patients with end-stage renal disease. Clinical and experimental studies indicate that hyperphosphatemia is a risk factor for vascular calcification and cardiovascular mortality in these patients. Our previous studies demonstrated that phosphate transport through the type III sodium-dependent phosphate cotransporter, Pit-1, was necessary for phosphate-induced calcification and osteochondrogenic phenotypic change in cultured human smooth muscle cells (SMC). BMP-2 is a potent osteogenic protein required for osteoblast differentiation and bone formation that has been implicated in vascular calcification. In the present study, we have examined the effects of BMP-2 on human SMC calcification in vitro. We found that treatment of SMC with BMP-2 enhanced elevated phosphate-induced calcification, but did not induce calcification under normal phosphate conditions. mRNAs for BMP receptors, including ALK2, ALK3, ALK6, BMPR-II, ActR-IIA and ActR-IIB were all detected in human SMCs. Mechanistically, BMP-2 dose-dependently stimulated phosphate uptake in SMC (200 ng/ml BMP-2 vs. vehicle: 13.94 vs. 7.09 nmol/30 min/mg protein, respectively). Real-time PCR and Western blot revealed the upregulation of Pit-1 mRNA and protein levels, respectively, by BMP-2. More importantly, inhibition of phosphate uptake by a competitive inhibitor of sodium-dependent phosphate cotransport, phosphonoformic acid, abrogated BMP-2-induced calcification. These results indicate that phosphate transport via Pit-1 is crucial in BMP-2-regulated SMC calcification. In addition, BMP-2-induced Runx2 and inhibited SM22 expression, indicating that it promotes osteogenic phenotype transition in these cells. Thus, BMP-2 may promote vascular calcification via increased phosphate uptake and induction of osteogenic phenotype modulation in SMC.






Li X,Yang HY,Giachelli CM




Has Abstract


2008-08-01 00:00:00














  • Association of smoking and low serum bilirubin antioxidant concentrations.

    abstract::This study sought to examine the association between cigarette smoking and serum bilirubin antioxidant concentrations in 715 middle-aged men undergoing coronary angiography. The study involved 153 current smokers, 251 who quit smoking and 311 who never smoked. Serum bilirubin concentrations were divided into the follo...


    pub_type: 杂志文章


    authors: Schwertner HA

    更新日期:1998-02-01 00:00:00

  • Immune complexes containing modified lipoproteins are related to the progression of internal carotid intima-media thickness in patients with type 1 diabetes.

    abstract::Modified lipoproteins induce autoimmune responses including the synthesis of autoantibodies with pro-inflammatory characteristics. Circulating modified lipoprotein autoantibodies combine with circulating antigens and form immune complexes (IC). We now report the results of a study investigating the role of circulating...


    pub_type: 杂志文章


    authors: Lopes-Virella MF,McHenry MB,Lipsitz S,Yim E,Wilson PF,Lackland DT,Lyons T,Jenkins AJ,Virella G,DCCT\/EDIC Research Group.

    更新日期:2007-02-01 00:00:00

  • Apolipoprotein A-I and the molecular variant apoA-I(Milano): evaluation of the antiatherogenic effects in knock-in mouse model.

    abstract::No evidence of premature vascular disease is found in apolipoprotein A-I(Milano) (apoA-I(M)) human carriers, despite very low high density lipoprotein (HDL) cholesterol levels. Whether apoA-I(M) may impart a "gain of function" in atherosclerosis protection compared to wild-type apoA-I is hotly debated. To address this...


    pub_type: 杂志文章


    authors: Parolini C,Chiesa G,Gong E,Caligari S,Cortese MM,Koga T,Forte TM,Rubin EM

    更新日期:2005-12-01 00:00:00

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    abstract::The negative correlation between percent flow-mediated dilation (FMD%) and baseline diameter (D(base)) has only recently been recognised as a fundamental ratio-scaling problem, which is not resolved by significance-testing of D(base) inequality between groups/conditions, nor by covariate-adjusting FMD% itself by D(bas...


    pub_type: 杂志文章


    authors: Atkinson G,Batterham AM

    更新日期:2013-02-01 00:00:00

  • "Low dose" colestipol in children, adolescents and young adults with familial hypercholesterolemia.

    abstract::The effect of colestipol on plasma lipids and lipoproteins was studied in children, adolescents and young adults with familial hypercholesterolemia. O.125 g or 0.25 g/kg body weight were given in randomized sequence for period of 4 weeks. Total cholesterol was lowered by 13 and 18% with the smaller and larger dose , r...


    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Schlierf G,Mrozik K,Heuck CC,Middelhoff G,Oster P,Riesen W,Schellenberg B

    更新日期:1982-01-01 00:00:00

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    pub_type: 杂志文章


    authors: Alfon J,Guasch JF,Berrozpe M,Badimon L

    更新日期:1999-08-01 00:00:00

  • Cerivastatin: pharmacology of a novel synthetic and highly active HMG-CoA reductase inhibitor.

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    pub_type: 杂志文章


    authors: Bischoff H,Angerbauer R,Bender J,Bischoff E,Faggiotto A,Petzinna D,Pfitzner J,Porter MC,Schmidt D,Thomas G

    更新日期:1997-11-01 00:00:00

  • Severe atherosclerosis in the natural mummy of Girolamo Macchi (1648-1734), "major writer" of Santa Maria della Scala Hospital in Siena (Italy).

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    authors: Gaeta R,Fornaciari A,Izzetti R,Caramella D,Giuffra V

    更新日期:2019-01-01 00:00:00

  • A common methylenetetrahydrofolate reductase gene mutation and longevity.

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    pub_type: 杂志文章


    authors: Brattström L,Zhang Y,Hurtig M,Refsum H,Ostensson S,Fransson L,Jonés K,Landgren F,Brudin L,Ueland PM

    更新日期:1998-12-01 00:00:00

  • Genetic and nongenetic factors for moderate hyperhomocyst(e)inemia.

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    pub_type: 杂志文章,评审


    authors: Kang SS,Wong PW

    更新日期:1996-01-26 00:00:00

  • The SH2B1 obesity locus is associated with myocardial infarction in diabetic patients and with NO synthase activity in endothelial cells.

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    pub_type: 杂志文章,多中心研究


    authors: Prudente S,Morini E,Larmon J,Andreozzi F,Di Pietro N,Nigro A,Gervino EV,Mannino GC,Bacci S,Hauser TH,Bellacchio E,Formoso G,Pellegrini F,Proto V,Menzaghi C,Frittitta L,Pandolfi A,Sesti G,Doria A,Trischitta V

    更新日期:2011-12-01 00:00:00

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    authors: Dutta R,Singh U,Li TB,Fornage M,Teng BB

    更新日期:2003-07-01 00:00:00

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    authors: Clay MA,Pyle DH,Rye KA,Vadas MA,Gamble JR,Barter PJ

    更新日期:2001-07-01 00:00:00

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    pub_type: 临床试验,杂志文章


    authors: Lind L,Siegbahn A,Hulthe J,Elmgren A

    更新日期:2008-07-01 00:00:00

  • C-reactive protein gene variation and type 2 diabetes mellitus: a case-control study.

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    pub_type: 杂志文章


    authors: Zee RY,Germer S,Thomas A,Raji A,Rhees B,Ridker PM,Lindpaintner K,Williams GH,Nathan DM,Martin M

    更新日期:2008-04-01 00:00:00

  • The prognostic value of interleukin 6 in multiple chronic diseases and all-cause death: The Multi-Ethnic Study of Atherosclerosis (MESA).

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    authors: Cainzos-Achirica M,Enjuanes C,Greenland P,McEvoy JW,Cushman M,Dardari Z,Nasir K,Budoff MJ,Al-Mallah MH,Yeboah J,Miedema MD,Blumenthal RS,Comin-Colet J,Blaha MJ

    更新日期:2018-11-01 00:00:00

  • Plasma lipoprotein changes in humans induced by beta-interferon.

    abstract::Two groups of patients were administered either 4.5 X 10(6) U or 90 X 10(6) U each of recombinant DNA-derived interferon-beta serine (IFN-beta ser) i.v. daily for 10 days. IFN-beta ser affected lipoprotein lipids of patients in a dose dependent fashion. A decrease in plasma total cholesterol concentration occurred 24 ...


    pub_type: 临床试验,杂志文章


    authors: Rosenzweig IB,Wiebe DA,Borden EC,Storer B,Shrago ES

    更新日期:1987-10-01 00:00:00

  • Complement factor H Y402H gene polymorphism, C-reactive protein, and risk of incident myocardial infarction, ischaemic stroke, and venous thromboembolism: a nested case-control study.

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    pub_type: 杂志文章,随机对照试验


    authors: Zee RY,Diehl KA,Ridker PM

    更新日期:2006-08-01 00:00:00

  • Effect of chronic renal failure and methylprednisolone treatment on the uptake of labelled plasma cholesterol into the aorta of normocholesterolemic rabbits.

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    authors: Tvedegaard E,Szpirt W,Nielsen M

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  • Common promoter polymorphisms of inflammation and thrombosis genes and longevity in older adults: the cardiovascular health study.

    abstract::Inflammatory response genes may influence life span or quality at advanced ages. Using data from the population-based cardiovascular health study (CHS) cohort, we examined the associations between promoter polymorphisms of several inflammation and thrombosis genes with longevity. We ascertained genotypes for interleuk...


    pub_type: 杂志文章


    authors: Reiner AP,Diehr P,Browner WS,Humphries SE,Jenny NS,Cushman M,Tracy RP,Walston J,Lumley T,Newman AB,Kuller LH,Psaty BM

    更新日期:2005-07-01 00:00:00

  • Arterial endothelial function and wall thickness in familial hypercholesterolemia and familial combined hyperlipidemia and the effect of statins. A systematic review and meta-analysis.

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    authors: Masoura C,Pitsavos C,Aznaouridis K,Skoumas I,Vlachopoulos C,Stefanadis C

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    authors: Terasaka N,Miyazaki A,Kasanuki N,Ito K,Ubukata N,Koieyama T,Kitayama K,Tanimoto T,Maeda N,Inaba T

    更新日期:2007-02-01 00:00:00

  • Catheter-based adenovirus-mediated anti-monocyte chemoattractant gene therapy attenuates in-stent neointima formation in cynomolgus monkeys.

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    authors: Nakano K,Egashira K,Ohtani K,Zhao G,Funakoshi K,Ihara Y,Sunagawa K

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    authors: Nagaraj N,Matthews KA,Shields KJ,Barinas-Mitchell E,Budoff MJ,El Khoudary SR

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  • Impaired adaptive vascular growth in hypercholesterolemic rabbit.

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    pub_type: 杂志文章


    authors: Bucay M,Nguy J,Barrios R,Chen CH,Henry PD

    更新日期:1998-08-01 00:00:00

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    pub_type: 杂志文章


    authors: Kruk M,Kalińczuk L,Pregowski J,Przyłuski J,Janas J,Chmielak Z,Demkow M,Debski A,Ciszewski A,Otto B,Witkowski A,Ruzyłło W

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    pub_type: 杂志文章


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    更新日期:2002-12-01 00:00:00

  • Elevated CETP activity during acute phase of myocardial infarction is independently associated with endothelial dysfunction and adverse clinical outcome.

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    pub_type: 杂志文章


    authors: Carvalho LS,Virginio VW,Panzoldo NB,Figueiredo VN,Santos SN,Modolo RG,Andrade JM,Quinaglia E Silva JC,Nadruz-Junior W,de Faria EC,Sposito AC,Brasilia Heart Study Group.

    更新日期:2014-12-01 00:00:00

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    pub_type: 杂志文章


    authors: El Khoudary SR,Wildman RP,Matthews K,Thurston RC,Bromberger JT,Sutton-Tyrrell K

    更新日期:2012-11-01 00:00:00

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    authors: Basu A,Jenkins AJ,Zhang Y,Stoner JA,Klein RL,Lopes-Virella MF,Garvey WT,Lyons TJ,DCCT\/EDIC Research Group.

    更新日期:2016-01-01 00:00:00