Evidence map›Paper›PMID 21490328›Full record

ArticleAmerican journal of physiology. Heart and circulatory physiology2011

Extracellular pyrophosphate metabolism and calcification in vascular smooth muscle.

Ricardo Villa-Bellosta, Xiaonan Wang, José Luis Millán, George R Dubyak, W Charles O'Neill

Open access · greenAbstract read
In one paragraph

Article in American journal of physiology. Heart and circulatory physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed, 1 pooled it
5.7field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

69 citing papers in PubMed, 1 synthesis or guideline pooled it, 136 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Elevated phosphate levels in CKD - a direct threat for the heart.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025
    Review
  4. Review
  5. Article
  6. Review
  7. Article
  8. Zinc Action in Vascular Calcification.Preventive nutrition and food science · 2024
    Review
  9. Article
  10. Review
  11. Review
  12. Article
  13. Article
  14. Review
  15. Review
  16. Article
  17. Review
  18. Review
  19. Article
  20. Review

9 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 3 institutions in 2 countries.

Ricardo Villa-BellostaEmory Univ., Renal Division WMB 338, 1639 Pierce Dr., Atlanta, GA 30322, USA.
Xiaonan Wang
José Luis Millán
George R Dubyak
W Charles O'Neill
Emory University · USCase Western Reserve University · USSanford Burnham Prebys Medical Discovery Institute · US

Funding

TRANSMEMBRANE SIGNALLING IN SMOOTH MUSCLE CELL LINESR01GM036387 · NIGMS · CASE WESTERN RESERVE UNIVERSITY · PI DUBYAK, GEORGE R · 1987 to 2014
$4.5M
Pyrosphate In Vascular Calcification of Renal FailureR01DK069681 · NIDDK · EMORY UNIVERSITY · PI O'NEILL, W CHARLES · 2006 to 2010
$1.6M
Leads and Target Validation for Vascular Calcification in Chronic Kidney DiseaseRC1HL101899 · NHLBI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI MILLAN, JOSE LUIS · 2009 to 2010
$977k
NHLBI NIH HHS HL-101899NHLBI NIH HHS RC1 HL101899NIDDK NIH HHS DK-069681NIGMS NIH HHS GM-36387NIGMS NIH HHS R01 GM036387
6 · The paper itself

Abstract

Extracellular inorganic pyrophosphate (ePP(i)) is an important endogenous inhibitor of vascular calcification, but it is not known whether systemic or local vascular PP(i) metabolism controls calcification. To determine the role of ePP(i) in vascular smooth muscle, we identified the pathways responsible for ePP(i) production and hydrolysis in rat and mouse aortas and manipulated them to demonstrate their role in the calcification of isolated aortas in culture. Rat and mouse aortas contained mRNA for ectonucleotide pyrophosphatase/phosphodiesterases (NPP1-3), the putative PP(i) transporter ANK, and tissue-nonspecific alkaline phosphatase (TNAP). Synthesis of PP(i) from ATP in aortas was blocked by β,γ-methylene-ATP, an inhibitor of NPPs. Aortas from mice lacking NPP1 (Enpp1(-/-)) did not synthesize PP(i) from ATP and exhibited increased calcification in culture. Although ANK-mediated transport of PP(i) could not be demonstrated in aortas, aortas from mutant (ank/ank) mice calcified more in culture than did aortas from normal (ANK/ANK) mice. Hydrolysis of PP(i) was reduced 25% by β,γ-methylene-ATP and 50% by inhibition of TNAP. Hydrolysis of PP(i) was increased in cells overexpressing TNAP or NPP3 but not NPP1 and was not reduced in Enpp1(-/-) aortas. Overexpression of TNAP increased calcification of cultured aortas. The results show that smooth muscle NPP1 and TNAP control vascular calcification through effects on synthesis and hydrolysis of ePP(i), indicating an important inhibitory role of locally produced PP(i). Smooth muscle ANK also affects calcification, but this may not be mediated through transport of PP(i). NPP3 is identified as an additional pyrophosphatase that could influence vascular calcification.

Indexed as

Adenosine TriphosphateAdenoviridaeAlkaline PhosphataseAnimalsArteriesCalcification, PhysiologicDiphosphatesDNA PrimersExtracellular SpaceHumansMiceMice, KnockoutMuscle, Smooth, VascularOrgan Culture TechniquesPhosphoric Diester HydrolasesPyrophosphatasesAdenosine TriphosphateAlkaline PhosphataseDiphosphatesDNA Primersectonucleotide pyrophosphatase phosphodiesterase 1Phosphoric Diester HydrolasesPyrophosphatasesRNA, Messenger

Identifiers

PMID21490328
PMCPMC3129914
OpenAlexW2158585939

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.