The Role of Shear Stress on ET-1, KLF2, and NOS-3 Expression in the Developing Cardiovascular System of Chicken Embryos in a Venous Ligation Model

Physiology ◽  
2007 ◽  
Vol 22 (6) ◽  
pp. 380-389 ◽  
Author(s):  
Bianca C. W. Groenendijk ◽  
Kim Van der Heiden ◽  
Beerend P. Hierck ◽  
Robert E. Poelmann

In this review, the role of wall shear stress in the chicken embryonic heart is analyzed to determine its effect on cardiac development through regulating gene expression. Therefore, background information is provided for fluid dynamics, normal chicken and human heart development, cardiac malformations, cardiac and vitelline blood flow, and a chicken model to induce cardiovascular anomalies. A set of endothelial shear stress-responsive genes coding for endothelin-1 (ET-1), lung Krüppel-like factor (LKLF/KLF2), and endothelial nitric oxide synthase (eNOS/NOS-3) are active in development and are specifically addressed.

2016 ◽  
Vol 27 (25) ◽  
pp. 3972-3979 ◽  
Author(s):  
Xiangquan Kong ◽  
Liang Chen ◽  
Peng Ye ◽  
Zhimei Wang ◽  
Junjie Zhang ◽  
...  

Hyaluronan (HA) in the endothelial glycocalyx serves as a mechanotransducer for high-shear-stress–stimulated endothelial nitric oxide synthase (eNOS) phosphorylation and nitric oxide (NO) production. Low shear stress (LSS) has been shown to contribute to endothelial inflammation and atherosclerosis by impairing the barrier and mechanotransduction properties of the glycocalyx. Here we focus on the possible role of hyaluronidase 2 (HYAL2) in LSS-induced glycocalyx impairment and the resulting alterations in eNOS phosphorylation and NO production in human umbilical vein endothelial cells (HUVECs). We show that LSS strongly activates HYAL2 to degrade HA in the glycocalyx. The dephosphorylation of eNOS–Ser-633 under LSS was triggered after HA degradation by hyaluronidase and prevented by repairing the glycocalyx with high–molecular weight hyaluronan. Knocking down HYAL2 in HUVECs protected against HA degradation in the glycocalyx by inhibiting the expression and activity of HYAL2 and further blocked the dephosphorylation of eNOS–Ser-633 and the decrease in NO production in response to LSS. The LSS-induced dephosphorylation of PKA was completely abrogated in HYAL2 siRNA–transfected HUVECs. The LSS-induced dephosphorylation of eNOS–Ser-633 was also reversed by the PKA activator 8-Br-cAMP. We thus suggest that LSS inhibits eNOS–Ser-633 phosphorylation and, at least partially, NO production by activating HYAL2 to degrade HA in the glycocalyx.


Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 377
Author(s):  
Yunna Lee ◽  
Eunok Im

Cardiovascular diseases (CVDs) are the most common cause of morbidity and mortality worldwide. The potential benefits of natural antioxidants derived from supplemental nutrients against CVDs are well known. Remarkably, natural antioxidants exert cardioprotective effects by reducing oxidative stress, increasing vasodilation, and normalizing endothelial dysfunction. Recently, considerable evidence has highlighted an important role played by the synergistic interaction between endothelial nitric oxide synthase (eNOS) and sirtuin 1 (SIRT1) in the maintenance of endothelial function. To provide a new perspective on the role of natural antioxidants against CVDs, we focused on microRNAs (miRNAs), which are important posttranscriptional modulators in human diseases. Several miRNAs are regulated via the consumption of natural antioxidants and are related to the regulation of oxidative stress by targeting eNOS and/or SIRT1. In this review, we have discussed the specific molecular regulation of eNOS/SIRT1-related endothelial dysfunction and its contribution to CVD pathologies; furthermore, we selected nine different miRNAs that target the expression of eNOS and SIRT1 in CVDs. Additionally, we have summarized the alteration of miRNA expression and regulation of activities of miRNA through natural antioxidant consumption.


2007 ◽  
Vol 49 (25) ◽  
pp. 2379-2393 ◽  
Author(s):  
Yiannis S. Chatzizisis ◽  
Ahmet Umit Coskun ◽  
Michael Jonas ◽  
Elazer R. Edelman ◽  
Charles L. Feldman ◽  
...  

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