Research Topic

Biomechanics in Translation: From Vascular Biology to Cardiovascular Drug Discovery

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The vascular endothelium comprises the innermost layer of cells lining the vessel lumen and functions as a direct interface between blood flow and tissues of the body. Due to its barrier function, as well as being a key player in the maintenance of vascular homeostasis, the vascular endothelium exhibits a ...

The vascular endothelium comprises the innermost layer of cells lining the vessel lumen and functions as a direct interface between blood flow and tissues of the body. Due to its barrier function, as well as being a key player in the maintenance of vascular homeostasis, the vascular endothelium exhibits a pivotal role in contributing to the overall function and health of the cardiovascular system. Thus, disruption of the diverse vascular signaling processes that are regulated by the endothelium may underpin the pathogenesis of cardiovascular disease.

Arteries are exposed to multiple mechanical forces that are exerted on the vessel wall, including shear stress and mechanical strain, both of which may impact the initiation and progression of atherosclerotic plaques. The growing body of evidence suggests that atherosclerosis preferentially develops at arterial regions exposed to complex disturbed blood flow, rather than unidirectional laminar flow. Moreover, different patterns of shear stress associated with blood flow elicit different cellular responses by altering mechanotransduction pathways and mechanosensitive transcription factors (TF), such as the recently reported YAP/TAZ, HIF1α, and TLR4 factors. Typically, steady laminar flow promotes vascular homeostasis and provides atheroprotection, whilst disturbed blood flow promotes atherosclerosis.

Emerging evidence has provided new insights into the cellular mechanisms of shear stress and strain-dependent regulation of vascular function that, upon dysregulation, lead to aberrant cardiovascular events such as atherosclerosis, atherothrombosis, and myocardial infarction. In particular, shear stress can differentially modulate epigenetic chromatin remodeling factors (such as DNMTs, TET2 and EZH2), and mechanosensitive transcription factors (KLF2, KLF4, NRF2, NF-kB, YAP/TAZ, HIF1α, and TLR4 etc). In addition, plaque vulnerability and eventual rupture results from a complex interaction between biological factors (such as lipid, hypoxia, oxidative stress etc) and mechanical factors (such as shear stress and strain), the interplay of which is still largely unknown.

Whilst we understand that this intricate interaction regulates plaque composition and vulnerability, a deeper understanding of the biomechanical mechanisms underlying cardiovascular disease is essential for designing new therapeutic strategies in order to prevent plaque development, and to promote plaque stability. The future direction of this area should be focused on elucidating novel mechanosensitive long non-coding RNAs, new TFs, and the role of these novel regulators in regulating vascular tone, inflammation, and endothelial cell metabolism. New technological advances such as RNA-sequencing, single cell RNA-sequencing, and ChIP-sequencing will be of benefit to elucidate the novel biomechanical regulators of gene expression in vascular homeostasis and diseases.

This Research Topic provides a comprehensive overview of the role of biomechanical mechanisms in cardiovascular disease, with an aim to accelerate cardiovascular drug discovery by targeting biomechanical regulatory factors. The Topic Editors welcome various types of articles, such as original research, review articles, methodology articles or other article types regarding the emerging role of biomechanics in atherosclerosis-related cardiovascular diseases.


Keywords: Biomechanics, shear stress, mechanobiology, mechanical strain, drug discovery


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