The Role of Histone Protein Acetylation in Regulating Endothelial Function.

Qing R Miao,Wenquan Hu,Xiang Wang,Xiaoran Sun,Zhi Fang

doi:10.3389/fcell.2021.672447

Abstract

Endothelial cell (EC), consisting of the innermost cellular layer of all types of vessels, is not only a barrier composer but also performing multiple functions in physiological processes. It actively controls the vascular tone and the extravasation of water, solutes, and macromolecules; modulates circulating immune cells as well as platelet and leukocyte recruitment/adhesion and activation. In addition, EC also tightly keeps coagulation/fibrinolysis balance and plays a major role in angiogenesis. Therefore, endothelial dysfunction contributes to the pathogenesis of many diseases. Growing pieces of evidence suggest that histone protein acetylation, an epigenetic mark, is altered in ECs under different conditions, and the acetylation status change at different lysine sites on histone protein plays a key role in endothelial dysfunction and involved in hyperglycemia, hypertension, inflammatory disease, cancer and so on. In this review, we highlight the importance of histone acetylation in regulating endothelial functions and discuss the roles of histone acetylation across the transcriptional unit of protein-coding genes in ECs under different disease-related pathophysiological processes. Since histone acetylation changes are conserved and reversible, the knowledge of histone acetylation in endothelial function regulation could provide insights to develop epigenetic interventions in preventing or treating endothelial dysfunction-related diseases.

Highlights

Endothelial cells (ECs), mostly in the inner layer of blood vessels are co-existing with everchanging environmental conditions, such as fluid shear stress, fluctuations of blood pressure, glucose and cytokines, nutrition availability, as well as pollutant molecules (Potente and Makinen, 2017; Sturtzel, 2017)
HDAC inhibition with Trichostatin A (TSA) decreases eNOS mRNA while paradoxically increasing its promoter activity, suggesting a more complicated mechanism involving HDAC and histone acetylation mediated eNOS mRNA expression (Rossig et al, 2002)
The maternal nutrient restriction increases the acetylation of histone H3K9, H3K18, and H4 and hypoxia-inducible factor-1α (HIF-1α) binding levels at the gene promoter of ET1 in pulmonary vascular ECs (PVEC) of intrauterine growth retardation (IUGR) newborn rats and continues up to 6 weeks after birth

Summary

Introduction

Endothelial cells (ECs), mostly in the inner layer of blood vessels are co-existing with everchanging environmental conditions, such as fluid shear stress, fluctuations of blood pressure, glucose and cytokines, nutrition availability, as well as pollutant molecules (Potente and Makinen, 2017; Sturtzel, 2017). HDAC inhibition with TSA decreases eNOS mRNA while paradoxically increasing its promoter activity, suggesting a more complicated mechanism involving HDAC and histone acetylation mediated eNOS mRNA expression (Rossig et al, 2002). The maternal nutrient restriction increases the acetylation of histone H3K9, H3K18, and H4 and hypoxia-inducible factor-1α (HIF-1α) binding levels at the gene promoter of ET1 in pulmonary vascular ECs (PVEC) of intrauterine growth retardation (IUGR) newborn rats and continues up to 6 weeks after birth.

Results

Conclusion