Low Shear Stress Upregulates CX3CR1 Expression by Inducing VCAM-1 via the NF-κB Pathway in Vascular Endothelial Cells

Zhao, Yiwei; Ren, Peile; Li, Qiufang; Umar, Shafiu Adam; Tan, Yi; Dong, Yan; Yu, Fangming; Nie, Yongzhan

doi:10.1007/s12013-020-00931-4

Cited by 20 publications

(13 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Besides these primary and other risks, considering mechanical forces including shear stress in form of disturbed flow should also be crucial. Consistent with the accumulating evidence that specific plaque location is in the curved and branching regions of the arteries where the flow is low and disturbed, 129 and immune/inflammatory mechanisms involving Piezo1 signaling play critical role during the process, this shows that even newborn babies are counted in this risk, due to the branching and curved nature of blood vessels. This indicates the importance of turbulent shear, mediated by Piezo1 in the development and progression of atherosclerosis.…”

Section: Discussionsupporting

confidence: 75%

Mechanosensitive Piezo1 Channel Evoked-Mechanical Signals in Atherosclerosis

Shinge¹,

Zhang²,

Muluh³

et al. 2021

JIR

Self Cite

View full text Add to dashboard Cite

Recently, more and more works have focused and used extensive resources on atherosclerosis research, which is one of the major causes of death globally. Alongside traditional risk factors, such as hyperlipidemia, smoking, hypertension, obesity, and diabetes, mechanical forces, including shear stress, pressure and stretches exerted on endothelial cells by flow, is proved to be crucial in atherosclerosis development. Studies have recognized the mechanosensitive Piezo1 channel as a special sensor and transducer of various mechanical forces into biochemical signals, and recent studies report its role in atherosclerosis through different mechanical forces in pressure, stretching and turbulent shear stress. Based on our expertise in this field and considering the recent advancement of atherosclerosis research, we will be focusing on the function of Piezo1 and its involvement in various cellular mechanisms and consequent involvement in the development of atherosclerosis in this review. Also, we will discuss various functions of Piezo1 involvement in atherosclerosis and come up with new mechanistic insight for future research. Based on the recent findings, we suggest Piezo1 as a valid candidate for novel therapeutic innovations, in which deep exploration and translating its findings into the clinic will be a new therapeutic strategy for cardiovascular diseases, particularly atherosclerosis.

show abstract

Section: Discussionsupporting

confidence: 75%

Mechanosensitive Piezo1 Channel Evoked-Mechanical Signals in Atherosclerosis

Shinge¹,

Zhang²,

Muluh³

et al. 2021

JIR

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, if the otherwise rather high physiological shear stress is reduced, the expression of VCAM-1 and CX3CL1 is induced (27)(28)(29), which promotes the formation of atherosclerotic plaques (30). Here, the transcriptional induction of both iRhoms could significantly enhance the surface expression of ADAM17 and thus promote vascular permeability and immune cell recruitment through the shedding of VCAM-1 and CX3CL1.…”

Section: Discussionmentioning

confidence: 99%

Differential Induction of the ADAM17 Regulators iRhom1 and 2 in Endothelial Cells

Babendreyer

Rojas-González

Giese

et al. 2020

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

Background: Endothelial function significantly depends on the proteolytic release of surface expressed signal molecules, their receptors and adhesion molecules via the metalloproteinase ADAM17. The pseudoproteases iRhom1 and 2 independently function as adapter proteins for ADAM17 and are essential for the maturation, trafficking, and activity regulation of ADAM17. Bioinformatic data confirmed that immune cells predominantly express iRhom2 while endothelial cells preferentially express iRhom1.Objective: Here, we investigate possible reasons for higher iRhom1 expression and potential inflammatory regulation of iRhom2 in endothelial cells and analyze the consequences for ADAM17 maturation and function.Methods: Primary endothelial cells were cultured in absence and presence of flow with and without inflammatory cytokines (TNFα and INFγ). Regulation of iRhoms was studied by qPCR, involved signaling pathways were studied with transcriptional inhibitors and consequences were analyzed by assessment of ADAM17 maturation, surface expression and cleavage of the ADAM17 substrate junctional adhesion molecule JAM-A.Results: Endothelial iRhom1 is profoundly upregulated by physiological shear stress. This is accompanied by a homeostatic phenotype driven by the transcription factor KLF2 which is, however, only partially responsible for regulation of iRhom1. By contrast, iRhom2 is most prominently upregulated by inflammatory cytokines. This correlates with an inflammatory phenotype driven by the transcription factors NFκB and AP-1 of which AP-1 is most relevant for iRhom2 regulation. Finally, shear stress exposure and inflammatory stimulation have independent and no synergistic effects on ADAM17 maturation, surface expression and JAM-A shedding.Conclusion: Conditions of shear stress and inflammation differentially upregulate iRhom1 and 2 in primary endothelial cells which then results in independent regulation of ADAM17.

show abstract

“…Recent studies continue to elucidate a plethora of EC regulatory pathways that induce a proinflammatory and proatherogenic phenotype in response to disturbed flow ( Qu et al, 2020 ; Zhao et al, 2020 ; Xia et al, 2021 ) ( Figure 1 ). The mechanosensitive cation channel Piezo1, though essential for coordinating vascular morphogenesis under physiological shear stress in embryogenesis and adulthood ( Li J. et al, 2014 ), has been previously linked to altered flow-induced inflammation and leukocyte recruitment to the endothelium.…”

Section: Endothelial Cells Govern Site-specificity Of Atherogenesismentioning

confidence: 99%

Dysfunctional Vascular Endothelium as a Driver of Atherosclerosis: Emerging Insights Into Pathogenesis and Treatment

2021

View full text Add to dashboard Cite

Atherosclerosis, the chronic accumulation of cholesterol-rich plaque within arteries, is associated with a broad spectrum of cardiovascular diseases including myocardial infarction, aortic aneurysm, peripheral vascular disease, and stroke. Atherosclerotic cardiovascular disease remains a leading cause of mortality in high-income countries and recent years have witnessed a notable increase in prevalence within low- and middle-income regions of the world. Considering this prominent and evolving global burden, there is a need to identify the cellular mechanisms that underlie the pathogenesis of atherosclerosis to discover novel therapeutic targets for preventing or mitigating its clinical sequelae. Despite decades of research, we still do not fully understand the complex cell-cell interactions that drive atherosclerosis, but new investigative approaches are rapidly shedding light on these essential mechanisms. The vascular endothelium resides at the interface of systemic circulation and the underlying vessel wall and plays an essential role in governing pathophysiological processes during atherogenesis. In this review, we present emerging evidence that implicates the activated endothelium as a driver of atherosclerosis by directing site-specificity of plaque formation and by promoting plaque development through intracellular processes, which regulate endothelial cell proliferation and turnover, metabolism, permeability, and plasticity. Moreover, we highlight novel mechanisms of intercellular communication by which endothelial cells modulate the activity of key vascular cell populations involved in atherogenesis, and discuss how endothelial cells contribute to resolution biology – a process that is dysregulated in advanced plaques. Finally, we describe important future directions for preclinical atherosclerosis research, including epigenetic and targeted therapies, to limit the progression of atherosclerosis in at-risk or affected patients.

show abstract

Low Shear Stress Upregulates CX3CR1 Expression by Inducing VCAM-1 via the NF-κB Pathway in Vascular Endothelial Cells

Cited by 20 publications

References 33 publications

Mechanosensitive Piezo1 Channel Evoked-Mechanical Signals in Atherosclerosis

Mechanosensitive Piezo1 Channel Evoked-Mechanical Signals in Atherosclerosis

Differential Induction of the ADAM17 Regulators iRhom1 and 2 in Endothelial Cells

Dysfunctional Vascular Endothelium as a Driver of Atherosclerosis: Emerging Insights Into Pathogenesis and Treatment

Contact Info

Product

Resources

About