Abstract

Endothelial cell dysfunction is a term which implies the dysregulation of normal endothelial cell functions, including impairment of the barrier functions, control of vascular tone, disturbance of proliferative and migratory capacity of endothelial cells, as well as control of leukocyte trafficking. Endothelial dysfunction is an early step in vascular inflammatory diseases such as atherosclerosis, diabetic vascular complications, sepsis-induced or severe virus infection-induced organ injuries. The expressions of inflammatory cytokines and vascular adhesion molecules induced by various stimuli, such as modified lipids, smoking, advanced glycation end products and bacteria toxin, significantly contribute to the development of endothelial dysfunction. The transcriptional regulation of inflammatory cytokines and vascular adhesion molecules has been well-studied. However, the regulation of those gene expressions at post-transcriptional level is emerging. RNA-binding proteins have emerged as critical regulators of gene expression acting predominantly at the post-transcriptional level in microRNA-dependent or independent manners. This review summarizes the latest insights into the roles of RNA-binding proteins in controlling vascular endothelial cell functions and their contribution to the pathogenesis of vascular inflammatory diseases.

Highlights

  • The endothelium is the monolayer of endothelial cells (ECs) lining the lumen of blood vessels in every organ system

  • Normal EC function is critical for all aspects of vascular homeostasis [1 3]

  • Since the functions of miRNAs in vascular endothelial dysfunction have been comprehensively reviewed elsewhere [12 15], in the present review we summarize the latest insights into the roles of RNA-binding proteins in controlling vascular endothelial cell functions and their contributions to the pathogenesis of vascular inflammatory diseases

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Summary

Endothelial dysfunction in human diseases

The endothelium maintains normal vascular homeostasis with no or little expression of proinflammatory factors under normal homeostatic conditions. Both traditional and novel cardiovascular risk factors including smoking, aging, hypercholesterolemia, hypertension, hyperglycemia, and a family history of premature atherosclerotic disease are associated with alteration in endothelial function [4 6]. Infections with bacteria and viruses impair the blood-tissue barrier and result in tissue/organ injuries [16,17] This results in a chronic or acute inflammatory process accompanied by loss of antithrombotic factors and an increase in proinflammatory cytokines and prothrombotic products, in addition to abnormal vasoreactivity, elevating risk of cardiovascular events and organ injuries. Of the gene expression program in endothelium is an intensively studied area

Endothelial dysfunction and metabolic syndromes
Endothelial dysfunction and atherosclerosis
Endothelial dysfunction and septic shock
Endothelial dysfunction and severe virus infectious diseases
Post-transcriptional gene regulation
Tristetraprolin
MCPIP1
Drosha and DGCR8
Argonaute 2
Others
Conclusion and future direction
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