Mechanism Of Hypertension And Low Shear Stress On Carotid Remodeling In Rat

Vascular remodeling defines as a progress in which the vessel morphology and function accommodate the environment during the period of growth, development, ageing, and diseases. The enormous studies have shown that mechanical forces such as stretch and shear stress play crucial roles in vascular remodeling. Undersanding mechanisms of the vascular remodeling induced by hypertension and/or low shear stress could not only reveal the biomechanics of circulation, but also be of benefit to the prevention, diagnosis and treatment of cardiovascular diseases.In present study, the model of the low shear stress in carotid or hypertension was established by the ligation of partial distal branches of the left common carotid (LCA) or the coarctation of aorta in SD rats respectively. In some rats the low shear stress in carotid was accompanied by the hypertension. The media and intimal thickness, as well as the ratio of vessel thickness to inner diameter were determined by morphometrical approach. The MMP-2 activity was dectected by zymogram, the expression of proteins, including p-Akt, p-p38, Rho GDIα, p53, p21, p27, bcl-2 and BAX, were verified by Western blotting in LCA. Then, tyributyrin, a HDAC inhibitor, was used to interfere in the low shear stress-mediated carotid remodeling in rats.The results showed that (1) MMP-2 activity, the media and intimal thickness, and the ratio of vessel thickness to inner diametee were increased when LCA subjected to hypertension or low shear stress, they were further enhanced when both of hypertension and low shear stress were existed, (2) Low shear stress induced the expression of p-Akt. However, the highest expression of p-Akt was observed in LCA of low shear stress accompanied by hypertension. (3) The expression of p-p38 and Rho GDIαwas upregulated in LCA by either low shear stress or hypertension. However, the highest expression of p-p38 and Rho GDIαwas observed in LCA of low shear stress accompanied by hypertension. (4) Effect of low shear stress on both decreasing apoptosis and increasing proliferation of VSMCs in LCA was reversed by tributyrin, a HDAC inhibitor.The results suggested that vascular remodeling was the most prominent in LCA subjected to low shear stress accompanied by hypertension, which is regulated through the changing expression of p-Akt, p-p38, Rho GDIα. Tributyrin could affect the flow mediated carotid remodeling by both increasing apoptosis and decreasing proliferation of VSMCs through PI-3K/Akt, bcl-2, p53, p27. Tributyrin could have potential roles in treatment of vascular diseases, such as artherosclerosis and vascular restenosis, etc.