Abstract
The vascular system is largely exposed to the effect of changing flow conditions. Vascular cells can sense flow and its changes. Flow sensing is of pivotal importance for vascular remodeling. In fact, it influences the development and progression of atherosclerosis, controls its location and has a major influx on the development of local complications. Despite its importance, the research community has traditionally paid scarce attention to studying the association between different flow conditions and vascular biology. More recently, a growing body of evidence has been accumulating, revealing that ncRNAs play a key role in the modulation of several biological processes linking flow-sensing to vascular pathophysiology. This review summarizes the most relevant evidence on ncRNAs that are directly or indirectly responsive to flow conditions to the benefit of the clinician, with a focus on the underpinning mechanisms and their potential application as disease biomarkers.
Highlights
The vascular system and the bloodstream interact in several ways
MiR-143 and miR-145 can be transported from vascular smooth muscle cells (VSMCs) to endothelial cells (ECs) through membrane protrusions known as tunneling nanotubes, a process modulated by the transforming growth factor-β (TGFβ) pathway [93]
In line with this evidence, recent experiments showed that fluid shear stress conditions obtained through femoral artery ligation in rats lead to the upregulation of miR-143-3p, contributing to the reorganization of extracellular matrix through the inhibition of the synthesis of V-α2 collagen [94]
Summary
The vascular system and the bloodstream interact in several ways. The vessel wall is able to modulate flow conditions but is influenced by flow [1,2]. Laminar shear stress is a key regulator of arterial endothelium and induces the expression of different molecules to stabilize the endothelial atheroprotective and anti-inflammatory function [11]. Platelet endothelial cell adhesion molecule (PECAM)-1, VE-cadherin and vascular endothelial growth factor (VEGF) receptors are examples of how shear stress variation is associated with gene expression change in ECs [23]. These proteins form a mechanosensory complex at cell-cell junctions that is essential for the activation of several shear-sensitive signaling pathways [24]. L-type calcium channels, the Rho-pathway, and the Notch signaling are among the most relevant signal transduction pathways that mediate the effects of flow alterations on VSMCs [25,26,27,28,29]
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