The high incidence and prevalence of end-stage renal disease (ESRD) in Taiwan has been an important public health problem. In Taiwan, 90.96% of these patients are managed on maintenance hemodialysis. An autogenous arteriovenous fistula (AVF) has been commonly used as the vascular access in hemodialysis but there are significant problems associated with AVF failure. The main complications of AVF include thrombosis, stenosis, and vascular access infections. AVF operation causes hemodynamic environmental changes such as shear stress. The shear stress has been identified as playing important roles in regulating the vascular endothelial dysfunction. Histone deacetylases (HDACs) are important epigenetic factors that regulate cellular functions involving inflammatory and proliferative. Recent studies show that their expressions in endothelial cells are regulated by shear stress. Thus, we hypothesize that HDACs may play critical roles in venous endothelial cells (ECs) dysfunction and AVF failure. In this project, we have identified flow patterns and the expressions of HDACs in different locations of the AVF vessels (anastomosis and distal vein) by Doppler ultrasound and immunostaining. In addition, we generated rat AVF model to simulate human AVF condition and checked the relationship between the activation of HDACs and flow patterns. In Doppler ultrasound results, we found that high velocities and oscillatory shear stress (HOSS) existed in the anastomosis of the human and rat AVF vessels, whereas corresponding low velocities and laminar flow existed in the normal vein. In immunostaining results, HDAC-1/2/3 were activated in the anastomosis and proximal vein ECs in the venous limb of the human and rat AVF model. These results indicated that high and oscillatory shear stress can cause HDAC activation in venous ECs which may play some important roles in the development of AVF failure.
Date:
2014-04
Relation:
FASEB Journal. 2014 Apr;28(1 Suppl.):Article number LB218.
