Effects Of Low Shear Stress On Apoptosis Of Vascular Smooth Muscle Cell Of Common Carotid Atherosclerosis

Objective: To explore the biomechanical effects and mechanisms of low shear stress on apoptosis of VSMC of common carotid atherosclerosis. Materials and methods: We established the atherosclerotic model of left common carotid artery that presented low shear stress by the operation of ligating the left external carotid artery in the rabbits. 86 male New Zealand rabbits were randomly divided into 5 groups. 24 rabbits (group HCLS) not only were fed on high-cholesterol diet but also kept in low shear stress in their left common carotid arteries and the others included control group (group C, 6), sham operation group (group SO, 8), only low shear stress group (group LS, 24) and only high cholesterol group (group HC, 24). The morphological changes of atherosclerosis were observed by light microscopy. The expression of some proteins and genes interrelated with apoptosis, the changes of phenotype, proliferation and apoptosis of VSMC in AS under low shear stress were studied by immunohistochemistry, in situ hybridization and computer image processing methods. Results: (1)The typical carotid atherosclerosis was observed and the atherosclerotic lesion was obviously accelerated under low shear stress. (2) The expression of alpha-actin downregulated and the phenotype of VSMC converted from contractile phenotype into synthetic phenotype. (3)The rate of apoptosis in AS increased. (4)The expression of P53, Bax and c-Myc proteins increased. (5)The expression of Bcl-2 protein and bcl-2 mRNA decreased. Conclusion: The results mentioned above showed that the model of AS under low shear stress was successfully established. Not only proliferation but also apoptosis of VSMC in ASwere affected by low shear stress that probably regulated the expressions of proteins and genes interrelated with proliferation and apoptosis. The apoptosis of VSMC was probably regulated by P53, c-Myc, Bax and bcl-2 in transcription level, which influence signal transduction pathway of low shear stress-induced apoptosis of VSMC of AS.