Evidence map›Paper›PMID 29950403›Full record

ArticleCirculation2018

Genetic Regulation of Fibroblast Activation and Proliferation in Cardiac Fibrosis.

Shuin Park, Sara Ranjbarvaziri, Fides D Lay, Peng Zhao, Mark J Miller, Jasmeet S Dhaliwal, Adriana Huertas-Vazquez, Xiuju Wu, Rong Qiao, Justin M Soffer and 5 more

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

Article in Circulation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
4.9field-weighted citation impact, top 4% 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

48 citing papers in PubMed, 88 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Multi-organ phenotypes in mice lacking latent TGFβ binding protein 2 (LTBP2).Developmental dynamics : an official publication of the American Association of Anatomists · 2024
    Review
  19. Review
  20. 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

15 authors at 5 institutions in 4 countries.

Shuin ParkDivision of Cardiology, Department of Medicine, David Geffen School of Medicine (S.P., S.R., P.Z., M.J.M., J.S.D., A.H.-V., X.W., R.Q., J.M.S., A.J.L., R.A.), University of California, Los Angeles.
Sara RanjbarvaziriDivision of Cardiology, Department of Medicine, David Geffen School of Medicine (S.P., S.R., P.Z., M.J.M., J.S.D., A.H.-V., X.W., R.Q., J.M.S., A.J.L., R.A.), University of California, Los Angeles.
Fides D LayDivision of Cardiology, Department of Medicine, David Geffen School of Medicine (S.P., S.R., P.Z., M.J.M., J.S.D., A.H.-V., X.W., R.Q., J.M.S., A.J.L., R.A.), University of California, Los Angeles.
Peng ZhaoDivision of Cardiology, Department of Medicine, David Geffen School of Medicine (S.P., S.R., P.Z., M.J.M., J.S.D., A.H.-V., X.W., R.Q., J.M.S., A.J.L., R.A.), University of California, Los Angeles.
Mark J MillerDivision of Cardiology, Department of Medicine, David Geffen School of Medicine (S.P., S.R., P.Z., M.J.M., J.S.D., A.H.-V., X.W., R.Q., J.M.S., A.J.L., R.A.), University of California, Los Angeles.
Jasmeet S DhaliwalDivision of Cardiology, Department of Medicine, David Geffen School of Medicine (S.P., S.R., P.Z., M.J.M., J.S.D., A.H.-V., X.W., R.Q., J.M.S., A.J.L., R.A.), University of California, Los Angeles.
Adriana Huertas-VazquezDivision of Cardiology, Department of Medicine, David Geffen School of Medicine (S.P., S.R., P.Z., M.J.M., J.S.D., A.H.-V., X.W., R.Q., J.M.S., A.J.L., R.A.), University of California, Los Angeles.
Xiuju WuDivision of Cardiology, Department of Medicine, David Geffen School of Medicine (S.P., S.R., P.Z., M.J.M., J.S.D., A.H.-V., X.W., R.Q., J.M.S., A.J.L., R.A.), University of California, Los Angeles.
Rong QiaoDivision of Cardiology, Department of Medicine, David Geffen School of Medicine (S.P., S.R., P.Z., M.J.M., J.S.D., A.H.-V., X.W., R.Q., J.M.S., A.J.L., R.A.), University of California, Los Angeles.
Justin M SofferDivision of Cardiology, Department of Medicine, David Geffen School of Medicine (S.P., S.R., P.Z., M.J.M., J.S.D., A.H.-V., X.W., R.Q., J.M.S., A.J.L., R.A.), University of California, Los Angeles.
Christoph RauAnesthesiology and Perioperative Medicine (C.R., Y.W.), University of California, Los Angeles.
Yibin WangAnesthesiology and Perioperative Medicine (C.R., Y.W.), University of California, Los Angeles.
Hanna K A MikkolaEli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research (S.P., S.R., F.D.L., P.Z., M.J.M., J.S.D., R.Q., J.M.S., H.K.A.M., R.A.), University of California, Los Angeles.
Aldons J LusisDivision of Cardiology, Department of Medicine, David Geffen School of Medicine (S.P., S.R., P.Z., M.J.M., J.S.D., A.H.-V., X.W., R.Q., J.M.S., A.J.L., R.A.), University of California, Los Angeles.
Reza ArdehaliDivision of Cardiology, Department of Medicine, David Geffen School of Medicine (S.P., S.R., P.Z., M.J.M., J.S.D., A.H.-V., X.W., R.Q., J.M.S., A.J.L., R.A.), University of California, Los Angeles.
University of California, Los Angeles · USBroad Center · USJisc · GBWest Coast University · USYibin University · CN

Funding

Systems genomics of metabolic syndrome traitsP01HL028481 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LUSIS, ALDONS JAKE · 1985 to 2019
$50.2M
Vascular Biology Training GrantT32HL069766 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LUSIS, ALDONS JAKE · 2002 to 2022
$7.4M
A Systems Approach to Dissect Genetic Basis of Heart FailureR01HL123295 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LUSIS, ALDONS JAKE, WANG, YIBIN · 2014 to 2017
$2.6M
Exploring heterogeneity of cardiac fibroblasts to reverse fibrosisDP2HL127728 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARDEHALI, REZA · 2014 to 2014
$2.3M
NHLBI NIH HHS DP2 HL127728NHLBI NIH HHS P01 HL028481NHLBI NIH HHS R01 HL123295NHLBI NIH HHS T32 HL069766
6 · The paper itself

Abstract

backgroundGenetic diversity and the heterogeneous nature of cardiac fibroblasts (CFbs) have hindered characterization of the molecular mechanisms that regulate cardiac fibrosis. The Hybrid Mouse Diversity Panel offers a valuable tool to examine genetically diverse cardiac fibroblasts and their role in fibrosis.

methodsThree strains of mice (C57BL/6J, C3H/HeJ, and KK/HlJ) were selected from the Hybrid Mouse Diversity Panel and treated with either isoproterenol (ISO) or saline by an intraperitoneally implanted osmotic pump. After 21 days, cardiac function and levels of fibrosis were measured by echocardiography and trichrome staining, respectively. Activation and proliferation of CFbs were measured by in vitro and in vivo assays under normal and injury conditions. RNA sequencing was done on isolated CFbs from each strain. Results were analyzed by Ingenuity Pathway Analysis and validated by reverse transcription-qPCR, immunohistochemistry, and ELISA.

resultsISO treatment in C57BL/6J, C3H/HeJ, and KK/HlJ mice resulted in minimal, moderate, and extensive levels of fibrosis, respectively (n=7-8 hearts per condition). Isolated CFbs treated with ISO exhibited strain-specific increases in the levels of activation but showed comparable levels of proliferation. Similar results were found in vivo, with fibroblast activation, and not proliferation, correlating with the differential levels of cardiac fibrosis after ISO treatment. RNA sequencing revealed that CFbs from each strain exhibit unique gene expression changes in response to ISO. We identified Ltbp2 as a commonly upregulated gene after ISO treatment. Expression of LTBP2 was elevated and specifically localized in the fibrotic regions of the myocardium after injury in mice and in human heart failure patients.

conclusionsThis study highlights the importance of genetic variation in cardiac fibrosis by using multiple inbred mouse strains to characterize CFbs and their response to ISO treatment. Our data suggest that, although fibroblast activation is a response that parallels the extent of scar formation, proliferation may not necessarily correlate with levels of fibrosis. In addition, by comparing CFbs from multiple strains, we identified pathways as potential therapeutic targets and LTBP2 as a marker for fibrosis, with relevance to patients with underlying myocardial fibrosis.

Indexed as

Cell ProliferationGenetic VariationAnimalsCardiomyopathiesCells, CulturedDisease Models, AnimalFemaleFibroblastsFibrosisGenetic Predisposition to DiseaseIsoproterenolLatent TGF-beta Binding ProteinsMice, Inbred C3HMice, Inbred C57BLPhenotypeSpecies SpecificityIsoproterenolLatent TGF-beta Binding ProteinsLtbp2 protein, mousefibroblastsfibrosisisoproterenol

Identifiers

PMID29950403
PMCPMC6202226
OpenAlexW2809990901

What OpenQuestion holds

Textmetadata
LicenceTDM
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.