Target intelligence / Profile preview

Disturbed flow (d-flow) (d-flow)

Target
d-flow
Molecular classification
Hemodynamic condition, Mechanical stimulus
01

Overview

Disturbed flow (d-flow) refers to a hemodynamic state characterized by low and oscillatory wall shear stress, typically occurring at arterial branch points, bifurcations, and curvatures. Unlike steady laminar flow, which is atheroprotective, disturbed flow induces a pro-inflammatory and pro-thrombotic phenotype in the vascular endothelium, making these sites highly susceptible to the development of atherosclerotic plaques. Mechanotransduction at these sites involves various sensors, including Piezo1 ion channels, PECAM-1, and G protein-coupled receptors, which convert mechanical forces into biochemical signals like NF-kB activation. While not a single molecule or receptor itself, disturbed flow sites represent a localized physiological environment that is a primary driver of cardiovascular pathology. Therapeutic strategies often focus on modulating the molecular pathways activated at these sites, such as upregulating protective transcription factors like Kruppel-like factor 2 (KLF2) or inhibiting mechanosensitive microRNAs and inflammatory cascades.

Other names
Oscillatory shear stressLow shear stressNon-laminar flowRecirculating flowAtheroprone flow
02

Mechanism of action

Modulation of mechanosensitive signaling pathways, such as inhibition of Piezo1 or activation of Nrf2 and KLF2 to counteract pro-inflammatory endothelial activation induced by non-laminar shear stress.

03

Biological functions

MechanotransductionEndothelial cell activationLeukocyte recruitmentOxidative stress inductionVascular remodeling
04

Disease associations

AtherosclerosisCardiovascular diseaseIntimal hyperplasiaVascular inflammationAneurysm
05

Safety considerations

Systemic inhibition of mechanosensors may affect normal vascular tonePotential interference with lymphatic system functionOff-target effects on touch and proprioception (e.g., Piezo1 inhibition)
06

Interacting drugs

Atorvastatin

3 more in the full profile.

07

Biomarkers

Vascular cell adhesion molecule 1 (VCAM-1)Intercellular adhesion molecule 1 (ICAM-1)E-selectinMicroRNA-712Reactive oxygen species (ROS)

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