Evidence map›Paper›PMID 27392969›Full record

ArticleThe American journal of pathology2016

Inflammation Drives Retraction, Stiffening, and Nodule Formation via Cytoskeletal Machinery in a Three-Dimensional Culture Model of Aortic Stenosis.

Jina Lim, Arshia Ehsanipour, Jeffrey J Hsu, Jinxiu Lu, Taylor Pedego, Alexander Wu, Chris M Walthers, Linda L Demer, Stephanie K Seidlits, Yin Tintut

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The American journal of pathology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
1.8field-weighted citation impact, top 14% 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

23 citing papers in PubMed, 34 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Review
  6. Models for calcific aortic valve disease in vivo and in vitro.Cell regeneration (London, England) · 2024
    Review
  7. Myeloid CCN3 protects against aortic valve calcification.Cell communication and signaling : CCS · 2023
    Article
  8. Review
  9. Review
  10. Review
  11. Calciprotein Particles: Balancing Mineral Homeostasis and Vascular Pathology.Arteriosclerosis, thrombosis, and vascular biology · 2021
    Review
  12. Review
  13. Tumor necrosis factor-α promotes and exacerbates calcification in heart valve myofibroblast populations.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021
    Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Review
  20. Effects of teriparatide on morphology of aortic calcification in aged hyperlipidemic mice.American journal of physiology. Heart and circulatory physiology · 2018
    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

10 authors at 1 institution in 1 country.

Jina LimDepartment of Pediatrics, University of California, Los Angeles, Los Angeles, California.
Arshia EhsanipourDepartment of Bioengineering, University of California, Los Angeles, Los Angeles, California.
Jeffrey J HsuDepartment of Medicine, University of California, Los Angeles, Los Angeles, California.
Jinxiu LuDepartment of Physiology, University of California, Los Angeles, Los Angeles, California.
Taylor PedegoDepartment of Medicine, University of California, Los Angeles, Los Angeles, California.
Alexander WuDepartment of Medicine, University of California, Los Angeles, Los Angeles, California.
Chris M WalthersDepartment of Bioengineering, University of California, Los Angeles, Los Angeles, California.
Linda L DemerDepartment of Bioengineering, University of California, Los Angeles, Los Angeles, California; Department of Medicine, University of California, Los Angeles, Los Angeles, California; Department of Physiology, University of California, Los Angeles, Los Angeles, California.
Stephanie K SeidlitsDepartment of Bioengineering, University of California, Los Angeles, Los Angeles, California.
Yin TintutDepartment of Medicine, University of California, Los Angeles, Los Angeles, California; Department of Physiology, University of California, Los Angeles, Los Angeles, California; Department of Orthopaedic Surgery, University of California, Los Angeles, Los Angeles, California. Electronic address: ytintut@mednet.ucla.edu.
University of California, Los Angeles · US

Funding

CARDIOVASCULAR SCIENTIST TRAINING PROGRAMT32HL007895 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SHIVKUMAR, KALYANAM, WATSON, KAROL E · 1998 to 2023
$9.2M
Regulation of PTH-induced Osteoanabolism by Inflammatory LipidsR01DK081346 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TINTUT, YIN · 2009 to 2013
$1.8M
Mechanisms of intermittent parathyroid hormone effects on calcific aortic diseaseR01HL121019 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DEMER, LINDA L., TINTUT, YIN · 2015 to 2018
$1.5M
Role of Inhibitory SMADs in Calcific Aortic Valve DiseaseR01HL114709 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DEMER, LINDA L., TINTUT, YIN · 2012 to 2015
$1.5M
NHLBI NIH HHS R01 HL114709NHLBI NIH HHS R01 HL121019NHLBI NIH HHS T32 HL007895NIDDK NIH HHS R01 DK081346
6 · The paper itself

Abstract

In calcific aortic valve disease, the valve cusps undergo retraction, stiffening, and nodular calcification. The inflammatory cytokine, tumor necrosis factor (TNF)-α, contributes to valve disease progression; however, the mechanisms of its actions on cusp retraction and stiffening are unclear. We investigated effects of TNF-α on murine aortic valvular interstitial cells (VICs) within three-dimensional, free-floating, compliant, collagen hydrogels, simulating their natural substrate and biomechanics. TNF-α increased retraction (percentage of diameter), stiffness, and formation of macroscopic, nodular structures with calcification in the VIC-laden hydrogels. The effects of TNF-α were attenuated by blebbistatin inhibition of myosin II-mediated cytoskeletal contraction. Inhibition of actin polymerization with cytochalasin-D, but not inhibition of Rho kinase with Y27632, blocked TNF-α-induced retraction in three-dimensional VIC hydrogels, suggesting that actin stress fibers mediate TNF-α-induced effects. In the hydrogels, inhibitors of NF-κB blocked TNF-α-induced retraction, whereas simultaneous inhibition of c-Jun N-terminal kinase was required to block TNF-α-induced stiffness. TNF-α also significantly increased collagen deposition, as visualized by Masson's trichrome staining, and up-regulated mRNA expression of discoidin domain receptor tyrosine kinase 2, fibronectin, and α-smooth muscle actin. In human aortic valves, calcified cusps were stiffer and had more collagen deposition than noncalcified cusps. These findings suggest that inflammation, through stimulation of cytoskeletal contractile activity, may be responsible for valvular cusp retraction, stiffening, and formation of calcified nodules.

Indexed as

AnimalsAortic ValveAortic Valve StenosisBlotting, WesternCalcinosisCell Culture TechniquesCells, CulturedCytoskeletonDisease Models, AnimalFluorescent Antibody TechniqueHumansHydrogel, Polyethylene Glycol DimethacrylateInflammationMiceMice, Inbred C57BLReal-Time Polymerase Chain ReactionHydrogel, Polyethylene Glycol DimethacrylateTumor Necrosis Factor-alpha

Identifiers

PMID27392969
PMCPMC5012467
OpenAlexW2464682896

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.