What question did this study set out to answer?

To identify the molecular mechanotransduction pathway through which fluid shear stress stimulates endothelial nitric oxide synthase activation via VEGFR2.

August 4, 2003Circulation ResearchOpen Access

Ligand-Independent Activation of Vascular Endothelial Growth Factor Receptor 2 by Fluid Shear Stress Regulates Activation of Endothelial Nitric Oxide Synthase

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Population

Cultured endothelial cells and in vivo arteriolar model

Comparison

Laminar flow (shear stress=12 dyne/cm2) vs Static conditions or inhibition of VEGFR2 and…

Design

Preclinical

Authors

ZJZheng‐Gen JinUniversity of Rochester HUHiroto UebaImperial Household Agency TTTatsuo TanimotoDaiichi Sankyo (United States)

Discussion

Member takes

Implication

Hypothesis-generating for endothelial mechanotransduction; leaves open translation to human vascular tone regulation.

Key Points

To identify the molecular mechanotransduction pathway through which fluid shear stress stimulates endothelial nitric oxide synthase activation via VEGFR2.
Subjected cultured endothelial cells to laminar fluid shear stress at 12 dyne/cm² in vitro.
Treated cells with selective VEGFR2 kinase inhibitors, antisense VEGFR2 oligonucleotides, and the Src kinase inhibitor PP2.
Assessed flow-mediated, nitric oxide-dependent arteriolar vasodilation under VEGFR2 inhibition in an in vivo model.
Laminar shear stress rapidly induced ligand-independent tyrosine phosphorylation of VEGFR2 via Src kinases, promoting downstream PI3K and Akt recruitment.
Selective inhibition or antisense knockdown of VEGFR2 blocked shear-induced Akt and eNOS activation and suppressed nitric oxide generation.
Pharmacological blockade of VEGFR2 kinase significantly decreased flow-induced, NO-dependent arteriolar dilation in vivo.

Structured PICO

Population

Cultured endothelial cells and in vivo arteriolar model

Intervention

Laminar flow (shear stress=12 dyne/cm2)

Comparator

Static conditions or inhibition of VEGFR2 (selective inhibitors, antisense oligonucleotides) and Src kinases (PP2)

Outcome

Activation of VEGFR2, Akt, eNOS, NO production, and NO-dependent arteriolar dilationsurrogate

Identifies VEGFR2 as a key mechanotransducer that activates eNOS in response to fluid shear stress, regulating vascular tone.

Cite This Study

Jin et al. (2003) studied this question.

synapsesocial.com/papers/6a72985d6ceb2bbd16e063ed https://doi.org/10.1161/01.res.0000089257.94002.96

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Ligand-Independent Activation of Vascular Endothelial Growth Factor Receptor 2 by Fluid Shear Stress Regulates Activation of Endothelial Nitric Oxide Synthase

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Ligand-Independent Activation of Vascular Endothelial Growth Factor Receptor 2 by Fluid Shear Stress Regulates Activation of Endothelial Nitric Oxide Synthase

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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