Evidence map›Paper›PMID 42333643›Full record

ArticleJournal of the American Heart Association2026

Multiomic Reference Map of Endothelial Mechanosensitive Pathways Under Athero- and Erosion-Prone Flow.

Giulio Vidotto, Sara Luzzi, Jonathan D Humphries, Robert Beal, David G McVey, Christopher P Nelson, Thomas R Webb, Martin J Humphries, Graham R Smith, Stephen J White

Abstract read
In one paragraph

Article in Journal of the American Heart Association, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Giulio VidottoBioinformatics Support Unit, Faculty of Medical Sciences Newcastle University Newcastle upon Tyne United Kingdom.ORCID 0009-0007-1754-6439
Sara LuzziBiosciences Institute, Faculty of Medical Sciences Newcastle University Newcastle upon Tyne United Kingdom.ORCID 0000-0001-6337-7495
Jonathan D HumphriesDepartment of Life Sciences Manchester Metropolitan University Manchester United Kingdom.ORCID 0000-0002-8953-7079
Robert BealDepartment of Life Sciences Manchester Metropolitan University Manchester United Kingdom.
David G McVeyLeicester British Heart Foundation Centre of Research Excellence & Division of Cardiovascular Sciences University of Leicester and National Institute for Health Research Leicester Biomedical Research Centre Leicester United Kingdom.ORCID 0000-0002-6402-2546
Christopher P NelsonLeicester British Heart Foundation Centre of Research Excellence & Division of Cardiovascular Sciences University of Leicester and National Institute for Health Research Leicester Biomedical Research Centre Leicester United Kingdom.
Thomas R WebbLeicester British Heart Foundation Centre of Research Excellence & Division of Cardiovascular Sciences University of Leicester and National Institute for Health Research Leicester Biomedical Research Centre Leicester United Kingdom.ORCID 0000-0001-5998-8226
Martin J HumphriesWellcome Centre for Cell-Matrix Research, Faculty of Biology, Medicine & Health University of Manchester Manchester United Kingdom.ORCID 0000-0002-4331-6967
Graham R SmithBioinformatics Support Unit, Faculty of Medical Sciences Newcastle University Newcastle upon Tyne United Kingdom.ORCID 0000-0001-6967-7691
Stephen J WhiteBiosciences Institute, Faculty of Medical Sciences Newcastle University Newcastle upon Tyne United Kingdom.ORCID 0000-0003-0090-6358

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAtherosclerosis develops at arterial sites exposed to disturbed flow, whereas plaque rupture and plaque erosion predominantly occur in regions subjected to elevated flow. The impact of elevated flow on regulation of endothelial gene expression is less well studied; therefore, we undertook a comprehensive analysis of primary human coronary artery endothelial cell gene expression under elevated flow, comparing it to gene expression induced by normal physiological and oscillatory flow.

methodsAnalysis of human coronary artery endothelial cell messenger RNA, microRNA and protein expression cultured under oscillatory shear stress, physiological laminar shear stress, and elevated shear stress (ESS) for 72 hours. Identification of changes in RNA isoform expression and proximity of flow-responsive genes to established coronary artery disease risk loci were also performed.

resultsA total of 2175 shear-regulated genes were identified, with 665 uniquely responsive to ESS. Both ESS and oscillatory shear stress induced significant changes in RNA isoform selection, predicted to affect 848 and 580 genes respectively. Signaling pathways regulating coronary artery disease pathogenesis including Hippo, TGFβ/BMP (transforming growth factor beta/bone morphogenetic protein), and IRF (interferon regulatory factor), showed altered RNA isoform selection, which may influence plaque development and plaque erosion. A total of 65% of linkage disequilibrium-filtered coronary artery disease-associated genetic variants contained at least 1 oscillatory shear stress or ESS-regulated gene within 250 kb. Proteomic analysis identified 289 proteins differentially expressed under oscillatory shear stress and 171 under ESS, with notable discordance between messenger RNA and protein changes observed in 28.7% (oscillatory shear stress versus laminar shear stress) and 16.6% (ESS versus laminar shear stress) genes. Additionally, 40 shear-responsive microRNAs were identified.

conclusionsElevated flow elicits a distinct gene expression program in human coronary artery endothelial cells, modulating pathways central to coronary artery disease pathogenesis.

Indexed as

AtherosclerosisCoronary Artery DiseaseCoronary VesselsEndothelial CellsEndothelium, VascularMechanotransduction, CellularPlaque, AtheroscleroticCells, CulturedGene Expression ProfilingGene Expression RegulationHumansMicroRNAsMultiomicsRNA, MessengerStress, MechanicalMicroRNAsRNA, Messengerendothelial cellsgene expressionplaque erosionshear stress

Identifiers

PMID42333643
PMCPMC13477354

What Socratic 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 Socratic graph.