Evidence map›Paper›PMID 28562688›Full record

ArticlePloS one2017

Smooth muscle cell-specific Notch1 haploinsufficiency restricts the progression of abdominal aortic aneurysm by modulating CTGF expression.

Jaspreet Sachdeva, Advitiya Mahajan, Jeeyun Cheng, Jeremy T Baeten, Brenda Lilly, Helena Kuivaniemi, Chetan P Hans

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
4.7field-weighted citation impact, top 5% 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

30 citing papers in PubMed, 42 citations in OpenAlex.

  1. Article
  2. Review
  3. Proteome-Wide Genetic Investigation of Large Artery Stiffness.JACC. Basic to translational science · 2024
    Article
  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. Review
  19. Article
  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

7 authors at 4 institutions in 2 countries.

Jaspreet SachdevaOhio State University, Columbus, Ohio, United States of America.
Advitiya MahajanCardiology, Medical Pharmacology & Physiology and Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri, United States of America.
Jeeyun ChengCenter for Cardiovascular Research and The Heart Center, Nationwide Children's Hospital, Columbus, Ohio, United States of America.
Jeremy T BaetenCenter for Cardiovascular Research and The Heart Center, Nationwide Children's Hospital, Columbus, Ohio, United States of America.
Brenda LillyCenter for Cardiovascular Research and The Heart Center, Nationwide Children's Hospital, Columbus, Ohio, United States of America.
Helena KuivaniemiDivision of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa.
Chetan P HansOhio State University, Columbus, Ohio, United States of America.ORCID http://orcid.org/0000-0003-1830-9084
Nationwide Children's Hospital · USStellenbosch University · ZAThe Ohio State University · USUniversity of Missouri · US

Funding

Role of Notch1 Signaling in Abdominal Aortic AneurysmR01HL124155 · NHLBI · UNIVERSITY OF MISSOURI-COLUMBIA · PI HANS, CHETAN · 2015 to 2019
$1.9M
NHLBI NIH HHS R01 HL124155
6 · The paper itself

Abstract

aimsInfiltration of macrophages and apoptosis of vascular smooth muscle cells (VSMCs) promote the development of abdominal aortic aneurysm (AAA). Previously, we demonstrated that global Notch1 deficiency prevents the formation of AAA in a mouse model. Herein, we sought to explore the cell-specific roles of Notch1 in AAA development. METHODS AND

resultsCell-specific Notch1 haploinsufficient mice, generated on Apoe-/- background using Cre-lox technology, were infused with angiotensin II (1000 ng/min/kg) for 28 days. Notch1 haploinsufficiency in myeloid cells (n = 9) prevented the formation of AAA attributed to decreased inflammation. Haploinsufficiency of Notch1 in SMCs (n = 14) per se did not prevent AAA formation, but histoarchitectural traits of AAA including elastin degradation and aortic remodeling, were minimal in SMC-Notch1+/-;Apoe-/- mice compared to Apoe-/- mice (n = 33). Increased immunostaining of the contractile SMC-phenotype markers and concomitant decreased expression of synthetic SMC-phenotype markers were observed in the aortae of SMC-Notch1+/-;Apoe-/- mice. Expression of connective tissue growth factor (CTGF), a matrix-associated protein that modulates the synthetic VSMC phenotype, increased in the abdominal aorta of Apoe-/- mice and in the adventitial region of the abdominal aorta in human AAA. Notch1 haploinsufficiency decreased the expression of Ctgf in the aorta and in vitro cell culture system. In vitro studies on SMCs using the Notch1 intracellular domain (NICD) plasmid, dominant negative mastermind-like (dnMAML), or specific siRNA suggest that Notch1, not Notch3, directly modulates the expression of CTGF.

conclusionsOur data suggest that lack of Notch1 in SMCs limits dilation of the abdominal aorta by maintaining contractile SMC-phenotype and preventing matrix-remodeling.

Indexed as

HaploinsufficiencyAnimalsAortic Aneurysm, AbdominalCells, CulturedCoculture TechniquesConnective Tissue Growth FactorMatrix MetalloproteinasesMiceMuscle, Smooth, VascularReceptor, Notch1Connective Tissue Growth FactorMatrix MetalloproteinasesReceptor, Notch1

Identifiers

PMID28562688
PMCPMC5451061
OpenAlexW2618470987

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.