Effects of high-frequency mechanical stimuli on flow related vascular cell biology

Abstract

Mechanical forces related to blood pressure and flow patterns play a crucial role in vascular homeostasis. Perturbations in vascular stresses and strain resulting from changes in hemodynamic may occur in pathological conditions, leading to vascular dysfunction as well as in vascular prosthesis, arteriovenous shunt for hemodialysis and in mechanical circulation support. Turbulent-like blood flows can induce high-frequency vibrations of the vessel wall, and this stimulus has recently gained attention as potential contributors to vascular pathologies, such as development of intimal hyperplasia in arteriovenous fistula for hemodialysis. However, the biological response of vascular cells to this stimulus remains incompletely understood. This review provides an analysis of the existing literature concerning the impact of high-frequency stimuli on vascular cell morphology, function, and gene expression. Morphological and functional investigations reveal that vascular cells stimulated at frequencies higher than the normal heart rate exhibit alterations in cell shape, alignment, and proliferation, potentially leading to vessel remodeling. Furthermore, vibrations modulate endothelial and smooth muscle cells gene expression, affecting pathways related to inflammation, oxidative stress, and muscle hypertrophy. Understanding the effects of high-frequency vibrations on vascular cells is essential for unraveling the mechanisms underlying vascular diseases and identifying potential therapeutic targets. Nevertheless, there are still gaps in our understanding of the molecular pathways governing these cellular responses. Further research is necessary to elucidate these mechanisms and their therapeutic implications for vascular diseases.

Keywords: Vascular cells; high-frequency; mechanobiology; tissue remodeling; vibration.

Figure 1.

Biological response of vascular cells to flow-induced high-frequency vibrations. The schematic diagram reports some of the morphological, functional, and gene expression changes observed in endothelial (ECs) and smooth muscle cells (SMCs) exposed to stimuli at high-frequencies. Morphological changes include actin fibers alignment and cell orientation, vascular tone regulation, formation of double-membrane limited vacuoles, and disruption of the internal elastic lamina (IEL). Vibrations induce the proliferation of smooth muscle cells leading to a thickening of the intimal layer and promote in ECs and SMCs the expression of factors and the activation of pathways related to inflammation, oxidative stress and vascular dysfunction, including extracellular signal-regulated kinase 1 and 2 (ERK1/2), endothelial nitric-oxide synthase (eNOS), nuclear factor-kB (NF-kB), soluble guanylate cyclase (sGC), Krüppel-like factor 2 (KLF-2), vascular endothelial growth factor (VEGF), tumour necrosis factor alpha (TNF-α), interleukin-8 (IL-8), interleukin-4 (IL-4), and interleukin-10 (IL-10). Early growth response 1 (Egr-1). This figure was created using Biorender.com