Evidence map›Paper›PMID 40439151›Full record

ArticleJournal of the American Heart Association2025

Smooth Muscle Cell-Derived Fibronectin Promotes an Atheroprotective Smooth Muscle Cell Phenotype Associated With Altered NO-cGMP Signaling.

Susanne Feil, Maria T K Zaldivia, Jacek Kiesel, Malte Roessing, Andreas Peter, Daniel Morales-Cano, Jacob F Bentzon, Moritz Lehners, Robert Feil

Abstract read
In one paragraph

Article in Journal of the American Heart Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. 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

9 authors.

Susanne FeilInterfakultäres Institut für Biochemie University of Tübingen Tübingen Germany.ORCID 0000-0003-2148-8773
Maria T K ZaldiviaInterfakultäres Institut für Biochemie University of Tübingen Tübingen Germany.
Jacek KieselInterfakultäres Institut für Biochemie University of Tübingen Tübingen Germany.
Malte RoessingInterfakultäres Institut für Biochemie University of Tübingen Tübingen Germany.
Andreas PeterInstitute for Clinical Chemistry and Pathobiochemistry, Department for Diagnostic Laboratory Medicine University Hospital Tübingen Tübingen Germany.ORCID 0000-0001-5732-2287
Daniel Morales-CanoCentro Nacional de Investigaciones Cardiovasculares Madrid Spain.ORCID 0000-0002-1692-4633
Jacob F BentzonCentro Nacional de Investigaciones Cardiovasculares Madrid Spain.ORCID 0000-0002-3020-5002
Moritz LehnersInterfakultäres Institut für Biochemie University of Tübingen Tübingen Germany.
Robert FeilInterfakultäres Institut für Biochemie University of Tübingen Tübingen Germany.ORCID 0000-0002-7335-4841

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCoronary artery disease due to atherosclerosis is the leading cause of death worldwide. Recent studies revealed an important role of smooth muscle cell (SMC) phenotypic switching in atherogenesis. How the extracellular matrix affects SMC phenotype in atherosclerotic lesions is not well understood. Fibronectin (Fn1) is an abundant component of the extracellular matrix in plaques and has been linked to coronary artery disease risk in humans.

methodsWe used mouse genetics combined with single-cell analyses, cell lineage tracing, and immunostaining of murine and human atherosclerotic lesions.

resultsGenetic ablation of SMC-derived Fn1 in mice led to a decrease of alpha smooth muscle actin-positive cells in atherosclerotic lesions and a reduced collagen content in the fibrous cap indicative of decreased plaque stability. Plaques lacking SMC-derived Fn1 contained more modulated SMCs with relatively low collagen expression. Interestingly, a subset of the modulated SMCs showed high expression of NO-sensitive guanylyl cyclase (NO-GC). NO-GC is a major cGMP generator in SMCs and like Fn1 has been implicated in coronary artery disease. Fn1 knockout SMCs showed increased cell growth and activity of the NO-cGMP pathway. Expression of Fn1 and NO-GC was also detected in modulated SMCs of human atherosclerotic lesions.

conclusionsSMC-derived Fn1 promotes plaque stability through suppression of SMC phenotypes with low alpha smooth muscle actin and collagen expression. This atheroprotective effect might be mediated, at least in part, by a crosstalk between Fn1 and the NO-cGMP axis in SMCs. Our study identifies a mechanistic link between 2 coronary artery disease risk genes, Fn1 and NO-GC, which explains how the extracellular matrix regulates SMC phenotype and plaque stability.

Indexed as

AtherosclerosisCyclic GMPFibronectinsMuscle, Smooth, VascularMyocytes, Smooth MuscleNitric OxideActinsAnimalsCell ProliferationCells, CulturedCollagenDisease Models, AnimalHumansMaleMiceMice, Inbred C57BLActinsCollagenCyclic GMPFibronectinsFN1 protein, humanNitric Oxideatherosclerosisfibronectinmodulated smooth muscle cellsNO‐cGMP signalingscRNA‐seqvascular disease

Identifiers

PMID40439151
PMCPMC12229189

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.