Abstract:Atherosclerosis (As) is a pathological process which is tightly related to cardiovascular diseases. Because of its high risks to human health, Chinese scholars have carried out a large number of researches in recent 3 years, which focus on the model and the pathogenesis and risk factors of As, such as ferroptosis, pyroptosis, autophagy, gut microflora, exosomes, oxidative stress, low shear stress, non-coding RNA. Intensive and in-depth preclinical researches provide novel ideas for the selection of prevention and treatment strategies and drug research of As, in order to achieve clinical transformation. This paper reviews the preclinical researches on As conducted by Chinese scholars in recent 3 years.

Abstract:The process of atherosclerotic lesions is a proliferative response induced by arterial intimal injury, which occurs in the bifurcation and branching regions of the arteries with low shear stress (LSS). LSS regulates gene expression and phenotype transformation by activating membrane receptors and intracellular signal transduction on cells, and plays an important role in the occurrence and development of atherosclerosis. This article reviews the relationship between LSS and endothelial cell inflammation, endothelial-to-mesenchymal transition, endothelial cell autophagy and its regulatory mechanism, hoping to provide new ideas and strategies for the prevention and treatment of atherosclerosis.

Abstract:Aim To investigate the effect of low shear stress (LSS) on the expression of Bmi-1 in human umbilical vein endothelial cells (HUVEC) and its possible mechanism. Methods Human umbilical vein endothelial cells were cultured in vitro. Immunofluorescence was used to detect the localization of Bmi-1 in the cells. 0.5 h, 1 h, 2 h and 4 h were loaded into human umbilical vein endothelial cells by parallel plate flow chamber system. The expression of Bmi-1 mRNA was detected by real-time quantitative RT-PCR. The expression of Bmi-1 protein was detected by Western blot.Specific signal inhibitor SB2219 was used to investigate the signal transduction pathway. Results Immunofluorescence observation showed that Bmi-1 was mainly distributed in the nucleus of human umbilical vein endothelial cells. The expression of Bmi-1 was significantly increased after 0.5 h of LSS, the expression of Bmi-1 mRNA and protein decreased gradually with the prolongation of the time (1 h, 2 h and 4 h); the shear stress could significantly activate phosphorylated p38 expression; SB2219 could significantly inhibit the expression of Bmi-1. Conclusion LSS can induce the expression of Bmi-1 in human umbilical vein endothelial cells, the expression of Bmi-1 is closely related to the length of stimulation, this effect may be regulated by p38 signal.

Abstract:Aim To explore the effect of autophagy intervention on endothelial cells endothelial nitric oxide synthase （eNOS） and endothelin-1 （ET-1） expression under low shear stress. Methods ApoE－/－ mice were fed with high fat diet for 12 weeks. HE staining was used to detect the pathological changes of aortic sinus. Immunohistochemistry was applied to detect the protein expression of autophagy markers Beclin1, microtubule-associated protein 1 light chain 3 （LC3Ⅱ） and p62. Human umbilical vein endothelial cells （HUVEC） and separated New Zealand rabbits common carotid arteries were placed into an in vivo perfusion system with low shear stress （5 dyne/cm2） or normal shear stress （15 dyne/cm2） for 1 h, then the expression of Beclin1, LC3Ⅱ/LC3Ⅰ and p62 was measured using Western blot. After treated with 5 dyne/cm2 for 1 h followed with or without rapamycin or 3-methyladenine （3-MA） for 30 min, the expression of eNOS and ET-1 in human vascular endothelial cells and common arteries of New Zealand rabbits was detected. Results The expression of Beclin1, LC3Ⅱ and p62 was significantly increased in atherosclerotic plaque. Compared with 15 dyne/cm2 treatment group, the expression of Beclin1, LC3Ⅱ and p62 was significantly increased in 5 dyne/cm2 treatment group （P<0.05）. The autophagy inducer rapamycin up-regulated the eNOS expression and inhibited the ET-1 expression in both 5 dyne/cm2 treated HUVEC and common carotid arteries, whereas autophagy inhibitor 3-MA further inhibited eNOS expression and increased the ET-1 expression. Conclusion The inhibition of autophagy might contribute to the decreased expression of eNOS and the increased expression of ET-1 under low shear stress, which was improved by promoting autophagy.

Abstract:Aim To create an animal model for local change of shear stress to analyze the arterial wall response at different patterns of fluid shear stress. Methods 24 mice were equally randomized into three group (1 h group,4 h group and 24 h group) and one normal control group. A stenosis was set up with a cast attached to the wall of the abdominal aorta to change flow condition in test group. The parameters of hemodynamics and the internal diameter of blood vessel were measured by color Doppler flow imaging. The wall shear stress was calculated by Poiseiulle hydrodynamics formula (τm=η×4×Vm/D). Pathological examination and immunohistochemistry were performed to observe the arterial morphological changes and the endothelial P-selectin expression. The intimal-media thickness and adventitia thickness of the aorta were measured and endothelial P-selectin expression intensity was analyzed qualitatively. Results Regions of low shear stress and oscillatory shear stress were created upstream and downstream of the cast respectively. Vascular remodeling and P-selectin expression in the upstream arterial wall were much more severe than those in the downstream in all observed time-points (P><0.05). Conclusion Vascular remodeling and endothelial P-selectin expression could happen in a relative short time when it exposed under low shear stress,meanwhile the variant patterns of fluid shear stress may play different roles in the pathological process of artery.

Abstract:Aim Detected the expression of stromal cell-derived factor-1(SDF-1) in atherosclerotic lesions induced by low shear stress to research the roles of SDF-1 in atherosclerosis formation and development.MethodsWe set up a local stenosis in left carotid artery,then stimulated the local hemodynamics at the down-stream of stenosis with numerical simulation;HE staining was taken to identify the pathology of common carotid artery;Immunochistochemistry staining was used to detect the expression in atherosclerotic lesions.ResultsThere was a low shear stress region(0～0.3 Pa) at distal of ring where there was obvious atherosclerosis lesions formated.The intimal of control group (8±3μm) is obviously lowed than the treated group(4 weeks 38.5±12.7 μm,8 weeks 95.3±19.6 μm).Immunochistochemistry showed that SDF-1 highly expressed in atherosclerotic plaque without expression in control.ConclusionSDF-1 may play important roles in atherosclerosis formation and development induced by low shear stress.