Evidence map›Paper›PMID 19406912›Full record

ArticleCardiovascular research2009

Rho kinase-1 mediates cardiac fibrosis by regulating fibroblast precursor cell differentiation.

Sandra B Haudek, Damon Gupta, Oliver Dewald, Robert J Schwartz, Lei Wei, JoAnn Trial, Mark L Entman

Open access · bronzeAbstract read
In one paragraph

Article in Cardiovascular research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed
4.8field-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

65 citing papers in PubMed, 100 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Review
  6. Review
  7. Article
  8. Cardiac fibrosis.Cardiovascular research · 2021
    Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. HaploinsufficientCells · 2020
    Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review

5 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

7 authors at 5 institutions in 2 countries.

Sandra B HaudekDeBakey Heart Center, Baylor College of Medicine and The Methodist Hospital, One Baylor Plaza F620, Houston TX 77030, USA. shaudek@bcm.tmc.edu
Damon Gupta
Oliver Dewald
Robert J Schwartz
Lei Wei
JoAnn Trial
Mark L Entman
Houston Methodist · USIndiana University – Purdue University Indianapolis · USLife & Brain (Germany) · DEMethodist Hospital · USTexas A&M University System · US

Funding

REGULATION OF CARDIOMYOCYTE SURVIVALP01HL085098 · NHLBI · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI FIRULLI, ANTHONY B. · 2007 to 2011
$10.9M
ROLE OF INFLAMMATION IN EARLY MYOCARDIAL ISCHEMIAP01HL042550 · NHLBI · BAYLOR COLLEGE OF MEDICINE · PI ENTMAN, MARK L · 1990 to 2004
$10.4M
Role of Blood-Borne Fibroblast Precursors in Ischemic CardiomyopathyR01HL089792 · NHLBI · BAYLOR COLLEGE OF MEDICINE · PI ENTMAN, MARK L · 2007 to 2016
$3.4M
Discovery of Mendelian Dyslipidemia and Heart Attack Genes Using Exome SequencingR01HL107816 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI KATHIRESAN, SEKAR · 2011 to 2015
$2.7M
ANGIOTENSIN II-SMAD SIGNALING IN CARDIAC FIBROSISR01HL076661 · NHLBI · BAYLOR COLLEGE OF MEDICINE · PI ENTMAN, MARK L · 2005 to 2009
$1.6M
NHLBI NIH HHS HL089792NHLBI NIH HHS HL42550NHLBI NIH HHS P01 HL042550NHLBI NIH HHS P01 HL085098NHLBI NIH HHS R01 HL076661NHLBI NIH HHS R01HL076661NHLBI NIH HHS R01 HL089792NHLBI NIH HHS R01 HL107816NHLBI NIH HHS T32HL107816
6 · The paper itself

Abstract

aimsHighly proliferative, CD34+/CD45+ fibroblasts derived from monocytic, blood-borne precursor cells play a critical role in the development of fibrosis in a murine ischaemic/reperfusion cardiomyopathy (I/RC) model. The differentiation of human monocytes into fibroblasts in vitro occurs after transendothelial migration (TEM) induced by monocyte chemoattractant protein 1 (MCP-1). Because Rho-associated kinase-1 (ROCK-1) has been implicated in fibrosis and leukocyte TEM, we investigated its involvement in I/RC. METHODS AND

resultsWe subjected mice with genetic deletion of ROCK-1 to I/RC. We found that ROCK-1(-/-) mice did not develop the fibrosis and cardiac dysfunction characteristic for I/RC: compared with wild-type, ROCK-1(-/-) hearts showed markedly lower numbers of I/RC-induced alpha-smooth muscle actin+ fibroblasts and CD34+/CD45+ fibroblast precursors. Isolated cardiac fibroblasts from ROCK-1(-/-) mice undergoing I/RC were large and slowly proliferating, similar to fibroblasts isolated from sham-treated hearts. We also performed in vitro assays in which human peripheral blood mononuclear cells (PBMC) migrated through endothelial cells in response to MCP-1. Prior to migration, PBMC were incubated with ROCK-1-targeting small interfering RNA to silence ROCK-1 expression. We found that an 80% reduction of ROCK-1 protein did not inhibit TEM, but significantly reduced the amount of mononuclear cells that differentiated into fibroblasts by >20-fold.

conclusionOur data implicate an important role for ROCK-1 in the differentiation, but not in the TEM of monocytes that mature into cardiac fibroblasts. These cells mediate non-adaptive fibrosis.

Indexed as

Cell TransdifferentiationAnimalsCardiomyopathiesCells, CulturedChemokine CCL2Disease Models, AnimalFibroblastsFibrosisHumansLeukocyte RollingLeukocytes, MononuclearMiceMice, KnockoutMyocardial Reperfusion InjuryMyocardiumrho-Associated KinasesChemokine CCL2rho-Associated KinasesROCK1 protein, humanRock1 protein, mouseROCK2 protein, human

Identifiers

PMID19406912
PMCPMC2709463
OpenAlexW2037227062

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.