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September 5, 2026ACS Applied Materials & Interfaces

High shear stress enhances stiffness-dependent endothelial TRPV4 sensitivity, limiting inflammation to support vascular adaptation.

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Population

Endothelial cells in a microfluidic model of vascular stiffening, and human aortic tissues stratified by…

Comparison

Exposure to varying substrate stiffness and… vs Static conditions, soft substrates/aortas, and…

Design

Preclinical

Key result

High shear stress enhanced endothelial TRPV4 sensitivity in a stiffness-dependent manner, and TRPV4 inhibition increased inflammatory responses, supporting a protective role in vascular adaptation.

Authors

ALAustin LaiYZYing ZhouPIPanagiotis Paraskevas Iliopoulos

Discussion

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Overview

TRPV4 may protect stiff vessels from inflammation under flow; leaves open therapeutic targeting in human vascular aging.

Key Points

  • To investigate how substrate stiffness and shear stress interact to regulate endothelial TRPV4 expression, function, and downstream vascular adaptation during aging.
  • Employed a microfluidic model of vascular stiffening to examine endothelial TRPV4 expression and calcium responses under static and high shear stress conditions.
  • Performed immunohistochemical analysis of human aortic tissue samples stratified by vascular stiffness (stiff versus soft aortas).
  • Evaluated stiffness-dependent actin remodeling, cell alignment, and inflammatory responses using the selective TRPV4 inhibitor GSK2193874.
  • Under static conditions, increased substrate stiffness downregulated TRPV4 expression and attenuated TRPV4-mediated calcium responses in endothelial cells.
  • High shear stress enhanced TRPV4 sensitivity to selective agonists in a stiffness-dependent manner, matching increased endothelial TRPV4 expression observed in stiff human aortas.
  • TRPV4 activation regulated stiffness-dependent actin remodeling and cell alignment, whereas pharmacological inhibition with GSK2193874 elevated endothelial inflammatory responses.

Structured PICO

P
Population
Endothelial cells in a microfluidic model of vascular stiffening, and human aortic tissues stratified by vascular stiffness.
E
Exposure
Exposure to varying substrate stiffness and shear stress; pharmacological inhibition of TRPV4 using GSK2193874.
C
Comparator
Static conditions, soft substrates/aortas, and uninhibited controls.
O
Outcome
Endothelial TRPV4 expression and TRPV4-mediated calcium responses.surrogate

TRPV4 plays a protective role in endothelial adaptation to pathological mechanical environments like vascular stiffening, highlighting its potential as a therapeutic target for vascular aging.

Cite This Study

Lai et al. (2026) studied Vascular aging and cardiovascular disease. Substrate stiffness and shear stress vs. Static conditions and soft substrates was evaluated on Endothelial TRPV4 expression and calcium responses. High shear stress enhanced endothelial TRPV4 sensitivity in a stiffness-dependent manner, and TRPV4 inhibition increased inflammatory responses, supporting a protective role in vascular adaptation.

synapsesocial.com/papers/6a9bd4126b95aff0620eb7a3https://doi.org/10.1021/acsami.6c10999
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Abstract Thu115: TRPV4 Regulates Aortic Root Stiffening, Cell Heterogeneity, and Transcriptional Dynamics in Atherosclerosis2025
  2. 2Abstract Thu114: TRPV4 Contributes to Valve Stiffening, Cell Heterogeneity, and Transcriptional Reprogramming in Aortic Valve Stenosis2025
  3. 3Finding a Link Between the TRPV4 Ion Channel and Angiogenesis: A Potential Therapeutic Target for Vascular Remodeling2025
  4. 4TRPV1 Deletion in Male Mice Alters Cardiomyocyte Ultrastructure Without Affecting Baseline Cardiac Function2025
  5. 5Decoding vascular aging: Substrate stiffness and shear stress orchestrate endothelial inflammation and remodelling via mechanosensitive pathways2025