Endothelial shear stress signal transduction and atherogenesis: From mechanisms to therapeutics

He, Lei; Zhang, Chenglin; Chen, Qinghua; Wang, Li; Huang, Yü

doi:10.1016/j.pharmthera.2022.108152

Cited by 51 publications

(34 citation statements)

References 314 publications

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“…Further characterization of PlexinA4 ligands and signaling pathways should be of great importance and may open up a new field for specific therapeutic targeting to maintain vascular health. As mentioned above, shear stress imparted by blood flow ultimately leads to atheroprotective or atherogenic responses, 21,22 and the direct detection of molecular mechanosensors is the first step in the progression. The semaphorin‐binding receptor PlexinD1 has been identified as a novel force detector in ECs and exerts effects through forming a mechano‐complex with Nrp1 and vascular endothelial growth factor receptor 2 (VEGFR2) 34 .…”

Section: Semaphorins and Atherosclerosismentioning

confidence: 99%

“…Shear stress produced by blood flow is important for vascular development and can also initiate atherosclerosis. 21 In general, blood flow can be divided into steady flow (S-flow) and disturbed flow (D-flow). In the aorta, the greater curvature has less probability to develop plaque typically with S-flow; accordingly, the lesser aortic curvature is more preferable for plaque formation with D-flow.…”

Section: Endothelial Dysfunction and Leukocyte Infiltrationmentioning

confidence: 99%

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The role of semaphorins in cardiovascular diseases: Potential therapeutic targets and novel biomarkers

Yin

Zhang

et al. 2022

The FASEB Journal

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Semaphorins (Semas), which belongs to the axonal guidance molecules, include 8 classes and could affect axon growth in the nervous system. Recently, semaphorins were found to regulate other pathophysiological processes, such as immune response, oncogenesis, tumor angiogenesis, and bone homeostasis, through binding with their plexin and neuropilin receptors. In this review, we summarized the detailed role of semaphorins and their receptors in the pathological progression of various cardiovascular diseases (CVDs), highlighting that semaphorins may be potential therapeutic targets and novel biomarkers for CVDs.

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Section: Semaphorins and Atherosclerosismentioning

confidence: 99%

Section: Endothelial Dysfunction and Leukocyte Infiltrationmentioning

confidence: 99%

The role of semaphorins in cardiovascular diseases: Potential therapeutic targets and novel biomarkers

Yin

Zhang

et al. 2022

The FASEB Journal

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“…A large number of studies have shown that endothelial metabolic adaptation induced by VEC phenotypic changes, such as in ammation, oxidative stress, endoplasmic reticulum stress, apoptosis, autophagy, endothelial mesenchymal transition, endothelial permeability and epigenetic regulation, plays a fundamental role in the occurrence and development of atherosclerosis. Mechanical sensors, adaptor proteins, kinases and transcription factors work together to transfer external stimuli from plasma membrane to nucleus for regulation of gene expression [42].…”

Section: Effects Of Vascular Matrix Stiffness On Ec Functionmentioning

confidence: 99%

Matrix Stiffness, Endothelial Dysfunction and Atherosclerosis

Chen

Wang

et al. 2022

Preprint

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Background Atherosclerosis (AS) is the leading cause of the human cardiovascular disease (CVDs). Endothelial dysfunction promotes the monocytes infiltration and inflammation that participate fundamentally in atherogenesis. Endothelial cells (EC) have been recognized as mechanosensitive cells and have different responses to distinct mechanical stimuli. Emerging evidence shows matrix stiffness-mediated EC dysfunction plays a vital role in vascular disease, but the underlying mechanisms are not yet completely understood. Methods It is through literature search to introduce the detailed role of matrix stiffness in the EC dysfunction in the process of AS diseases. Results This article aims to summarize the effect of matrix stiffness on the pro-atherosclerotic characteristics of EC including morphology, rigidity, biological behavior and function as well as the related mechanical signal. The review also discusses and compares the contribution of matrix stiffness-mediated phagocytosis of macrophages and EC to AS progression. Conclusion These advances in our understanding of the relationship between matrix stiffness and EC dysfunction open the avenues to improve the prevention and treatment of now-ubiquitous atherosclerotic diseases.

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“…EndoMT is strongly implicated in the development of atherosclerotic plaques in mice and in huma patients ( 6 ). Endothelial homeostasis is regulated by several master transcription factors, such as KLF2, KLF4 and Nrf2, the activation of which leads to anti-inflammatory, anti-oxidant, anti-thrombotic and inflammation-resolution effects ( 10 , 19 ). Also, upon injurious stimuli exposure (such as aging, irradiation, anti-cancer therapy, inflammation, virus/bacterial infection and cigarette smoking etc.…”

Section: Vascular Wall Components In Vascular Homeostasis and Atheros...mentioning

confidence: 99%

“…In this article, we reviewed the biological functions of the structural components of the vessel wall in the vascular homeostasis and atherosclerosis. Considering that atherosclerosis is a focal disease that preferentially develops in regions where disturbed blood flow occurs, and the flow pattern is turbulent/oscillatory flow ( 10 , 19 ), the spatio-temporal and biomechanical basis of atherosclerosis remain to be validated ( 69 ). The focal nature of atherogenesis resembles the zonation phenomenon in the liver, which is coordinated by multiple cell types ( 70 , 71 ).…”

Section: Concluding Remarks and Future Perspectivesmentioning

confidence: 99%

Vascular homeostasis in atherosclerosis: A holistic overview

Lyu²,

Ilyas

et al. 2022

Front. Immunol.

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Atherosclerosis refers to the deposition of lipids and the co-existence of inflammation and impaired inflammation resolution in pan-vasculature, which causes lumen narrowing, hardening, plaque formation, and the manifestation of acute cardiovascular events. Emerging evidence has suggested that vascular circulation can be viewed as a complex homeostatic system analogous to a mini-ecosystem which consists of the vascular microenvironment (niche) and the crosstalk among phenotypically and functionally diverse vascular cell types. Here, we elucidate how cell components in the vascular wall affect vascular homeostasis, structure, function, and atherosclerosis in a holistic perspective. Finally, we discuss the potential role of vascular-stabilizing strategies including pharmacotherapies, natural substances and lifestyle modifications, in preventing cardiovascular diseases by preserving vascular integrity and homeostasis.

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Endothelial shear stress signal transduction and atherogenesis: From mechanisms to therapeutics

Cited by 51 publications

References 314 publications

The role of semaphorins in cardiovascular diseases: Potential therapeutic targets and novel biomarkers

The role of semaphorins in cardiovascular diseases: Potential therapeutic targets and novel biomarkers

Matrix Stiffness, Endothelial Dysfunction and Atherosclerosis

Vascular homeostasis in atherosclerosis: A holistic overview

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