Abstract
Aims. To explore the effects and mechanisms of fluid shear stress on portal vein remodeling in a rat model of portal hypertension. Methods. Subcutaneous injections of CCl4 were given to establish a rat model of liver cirrhosis and portal hypertension. Biomechanical technology was adopted to determine the dynamic changes of haemodynamic indices and fluid shear stress. Nitric oxide (NO), synthase (NOS), and endothelin-1 (ET-1) of the portal vein blood were measured. Changes in geometric structure and ultrastructure of the portal vein were observed using optical and electron microscopy. Results. After the CC14 injections, rat haemodynamics were notably altered. From week 4 onwards, PVP, PVF, and PVR gradually and significantly increased (P < 0.05 versus baseline). The fluid shear stress declined from week 4 onwards (P < 0.01 versus control group). NO, NOS, and ET-1 increased after repeated CCI4 injections. Hematoxylin and eosin staining showed thickened portal vein walls, with increased inside and outside diameters. Electron microscopy revealed different degrees of endothelial cell degeneration, destruction of basement membrane integrity, proliferating, and hypertrophic smooth muscle cells. Conclusions. Fluid shear stress not only influenced the biomechanical environment of the portal vein but also participated in vascular remodeling.
Highlights
Portal hypertension results from elevations in both portal resistance and blood flow
Endothelial cells (ECs), located at the lining of the blood vessels, are the cells exposed to shear stress and have the capacity to respond to blood flow changes [14]
Abnormal endothelial cells (ECs) are a key indicator for vascular remodeling
Summary
Portal hypertension results from elevations in both portal resistance and blood flow. Vascular remodeling refers to environmental changes leading to structural and functional alteration of blood vessels [2]. This is mainly characterized by abnormal blood vessel gene expression and the migration, hyperplasia, hypertrophy, and apoptosis of the endothelial cells (ECs) and smooth muscle cells (SMCs). Stress factors acting on the blood vessels result in structural and functional remodeling of the arterial walls. Abnormal venous wall remodeling regulated by stress has become a topic of intense interest. The changes in vasoactive factors secreted by the portal vein and the remodeling of vascular walls were investigated under conditions of shear stress. This study aimed to further investigate portal venous remodeling in the pathogenesis of liver cirrhosis with portal hypertension, thereby guiding its prevention and treatment
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