Evidence map›Paper›PMID 23814115›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2013

Endothelial cell sensing of flow direction.

Chong Wang, Brendon M Baker, Christopher S Chen, Martin Alexander Schwartz

Registry-linked trialAbstract read
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02982044 (Endothelial Function Responses to Manipulations in Blood Flow Pattern), which is not on this map. Cited by 162 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
162citing papers in PubMed, 1 pooled it
8.4field-weighted citation impact, top 2% 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.

NCT02982044 nacompletednot on this mapstarted 2017, after this paper: background citation

Endothelial Function Responses to Manipulations in Blood Flow Pattern

TypeinterventionalSponsorMcMaster UniversityRan2017 to 2017Enrolled10ConditionsEndothelial DysfunctionArmsSuprasystolic (300 mmHg) cuff compressions, Handgrip exercise, Passive heat stress
3 · Its place in the literature

Who cites it

162 citing papers in PubMed, 1 synthesis or guideline pooled it, 286 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Comparison of Cannulation Strategies for Minimally Invasive Mitral Valve Surgery.Interdisciplinary cardiovascular and thoracic surgery · 2026
    Article
  5. Article
  6. Hemodynamic Metrics and Arterial Dysfunction: Insights From a Novel Microfluidic Device.International journal for numerical methods in biomedical engineering · 2026
    Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Endothelial Nuclear and Cytoskeletal Responses to Mechanical Stresses.Advances in experimental medicine and biology · 2026
    Article
  12. Review
  13. Article
  14. Vascular endothelial integration of multiple biophysical stimuli.Frontiers in cardiovascular medicine · 2026
    Article
  15. Article
  16. Article
  17. Hemodynamics in carotid artery stenosis.International angiology : a journal of the International Union of Angiology · 2025
    Review
  18. Article
  19. Article
  20. Review

102 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

4 authors at 1 institution in 1 country.

Chong WangRobert M Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA, USA.
Brendon M Baker
Christopher S Chen
Martin Alexander Schwartz
University of Pennsylvania · US

Funding

RESBIO - the Technology Resource for Polymeric BiomaterialsP41EB001046 · NIBIB · RUTGERS THE ST UNIV OF NJ NEW BRUNSWICK · PI KOHN, JOACHIM B. · 2003 to 2017
$17.0M
REGULATION OF ANGIOGENESIS BY MICROENVIRONMENTAL CUESR01EB000262 · NIBIB · UNIVERSITY OF PENNSYLVANIA · PI CHEN, CHRISTOPHER S · 2002 to 2023
$6.2M
Integrins in the Endothelial Response to Fluid Shear StressR01HL075092 · NHLBI · YALE UNIVERSITY · PI SCHWARTZ, MARTIN A · 2004 to 2019
$5.1M
NHLBI NIH HHS R01 HL075092NHLBI NIH HHS R01 HL75092NIBIB NIH HHS P41 EB001046NIBIB NIH HHS R01 EB000262NIBIB NIH HHS R01 EB00262
6 · The paper itself

Abstract

objectiveAtherosclerosis-prone regions of arteries are characterized by complex flow patterns where the magnitude of shear stress is low and direction rapidly changes, termed disturbed flow. How endothelial cells sense flow direction and how it impacts inflammatory effects of disturbed flow are unknown. We therefore aimed to understand how endothelial cells respond to changes in flow direction. APPROACH AND

resultsUsing a recently developed flow system capable of changing flow direction to any angle, we show that responses of aligned endothelial cells are determined by flow direction relative to their morphological and cytoskeletal axis. Activation of the atheroprotective endothelial nitric oxide synthase pathway is maximal at 180° and undetectable at 90°, whereas activation of proinflammatory nuclear factor-κB is maximal at 90° and undetectable at 180°. Similar effects were observed in randomly oriented cells in naive monolayers subjected to onset of shear. Cells aligned on micropatterned substrates subjected to oscillatory flow were also examined. In this system, parallel flow preferentially activated endothelial nitric oxide synthase and production of nitric oxide, whereas perpendicular flow preferentially activated reactive oxygen production and nuclear factor-κB.

conclusionsThese data show that the angle between flow and the cell axis defined by their shape and cytoskeleton determines endothelial cell responses. The data also strongly suggest that the inability of cells to align in low and oscillatory flow is a key determinant of the resultant inflammatory activation.

Indexed as

HemodynamicsMechanotransduction, CellularActin CytoskeletonAnimalsAtherosclerosisCattleCell Culture TechniquesCells, CulturedCell ShapeEndothelial CellsEnzyme ActivationInflammationNF-kappa BNitric OxideNitric Oxide Synthase Type IIIOscillometryNF-kappa BNitric OxideNitric Oxide Synthase Type IIIProto-Oncogene Proteins c-aktReactive Oxygen Speciesatherosclerosishemodynamicsmechanotransduction, cellular

Identifiers

PMID23814115
PMCPMC3812824
OpenAlexW2143987563

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

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.