Evidence map›Paper›PMID 24530784›Full record

ArticleAtherosclerosis2014

Mono-allelic and bi-allelic ENPP1 deficiency promote post-injury neointimal hyperplasia associated with increased C/EBP homologous protein expression.

Ramon L Serrano, Weifang Yu, Robert Terkeltaub

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Atherosclerosis, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
–field-weighted citation impact
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

10 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Review
  6. Article
  7. Development (Cambridge, England) · 2018
    Article
  8. Review
  9. Review
  10. Article
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

3 authors.

Ramon L SerranoSan Diego VA Healthcare System and Department of Medicine, University of California, 111K, 3350 La Jolla Village Dr., San Diego, CA 92161, USA.
Weifang YuSan Diego VA Healthcare System and Department of Medicine, University of California, 111K, 3350 La Jolla Village Dr., San Diego, CA 92161, USA.
Robert TerkeltaubSan Diego VA Healthcare System and Department of Medicine, University of California, 111K, 3350 La Jolla Village Dr., San Diego, CA 92161, USA. Electronic address: rterkeltaub@ucsd.edu.

Funding

TISSUE ACQUISITION, MORPHOLOGY, AND CELL CULTUREP01AG007996 · NIA · UNIVERSITY OF CALIFORNIA SAN DIEGO · PI SAH, ROBERT L · 1989 to 2016
$26.0M
NPP1 and Molecular Mechanisms in Artery CalcificationR01HL077360 · NHLBI · VETERANS MEDICAL RESEARCH FDN/SAN DIEGO · PI TERKELTAUB, ROBERT A. · 2004 to 2012
$2.2M
Innate Inflammation in OsteoarthritisI01BX001660 · VA · VA SAN DIEGO HEALTHCARE SYSTEM · PI TERKELTAUB, ROBERT A. · 2012 to 2020
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BLRD VA I01 BX001660NHLBI NIH HHS HL077360NHLBI NIH HHS R01 HL077360NIA NIH HHS P01 AG007996PHS HHS PAGO7996
6 · The paper itself

Abstract

objectiveBi-allelic function-inactivating ENPP1 mutations cause artery media calcification (AMC) with associated severe myointimal hyperplasia in generalized arterial calcification of infancy (GACI), whereas mono-allelic ENPP1 deficiency is phenotypically normal. Here, we tested if ENPP1 deficiency promotes abnormal vascular smooth muscle cell (VSMC)-driven responses to injury, with or without calcification. The ER stress mediator C/EBP homologous protein (CHOP) affects neointimal hyperplasia and atherosclerosis, and has paradoxical effects on bone formation. Hence, we assessed relationships between ENPP1 and CHOP in VSMCs.

methodsWe studied ENPP1-deficient mice and control littermates subjected to left carotid artery ligation, and isolated and studied VSMCs from these and Chop-/- mice, or with CHOP siRNA treatment.

resultsNormal Enpp1-/+ mice, in addition to Enpp1-/- mice prior to AMC development, had accelerated neointimal hyperplasia in response to carotid artery ligation at 7-8 weeks age. Neointimal hyperplasia was linked with robust artery media CHOP expression in situ, but with marked AMC only in injured Enpp1-/- arteries. Cultured, ENPP1-deficient and CHOP-deficient VSMCs had increased migration and proliferation to PDGF. Cultured Chop-/- VSMCs demonstrated increased Pi donor-induced calcification. CHOP was significantly increased in Pi donor treated Enpp1-/- and Enpp1-/+ cultured VSMCs. CHOP siRNA treatment of Enpp1-/- VSMCs increased calcification, associated with elevated expression of tissue nonspecific alkaline phosphatase and the master osteoblastic transcription factor RUNX2.

conclusionsBoth mono-allelic and bi-allelic ENPP1 deficiency promote dysregulated VSMC function, with robust lesion CHOP expression and enhanced neointimal hyperplasia after injury in vivo, but marked post-injury calcification limited to Enpp1-/- mice. Intimal hyperplasia in GACI appears regulated by biologic effects of ENPP1 deficiency other than calcification, including ER stress. VSMC CHOP excess in ENPP1 deficiency may primarily function to limit VSMC calcification.

Indexed as

Alkaline PhosphataseAllelesAnimalsCarotid StenosisCell DifferentiationCore Binding Factor Alpha 1 SubunitDisease Models, AnimalGenotypeHyperplasiaLigationMiceMice, Inbred C57BLMice, KnockoutMyocytes, Smooth MuscleNeointimaPhosphoric Diester HydrolasesAlkaline PhosphataseALPL protein, mouseCore Binding Factor Alpha 1 Subunitectonucleotide pyrophosphatase phosphodiesterase 1Phosphoric Diester HydrolasesPyrophosphatasesRunx2 protein, mouseTranscription Factor CHOPArtery media calcificationCHOPER stressGeneralized arterial calcification of infancyUnfolded protein response

Identifiers

PMID24530784
PMCPMC4386864

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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.