The Impact Mechanism Of Emotional Stress On Atherosclerotic Plaque Vulnerability By SDF-1/CXCR4 Biological Axis

Plaque rupture and thrombosis compose the main pathogenesis of ACS(acute coronary syndrome,ACS).There is substantial evidence that poor psychological factors are relevant to recurrent major adverse cardiac events and reduce the quality of life following ACS.Therefore,it is beneficial to reduce the incidence and mortality of acute cardiovascular events by further deepening the basic research on vulnerable plaque from the psychological level and clarifying the pathogenesis and influencing factors of plaque vulnerability.Abnormal lipid metabolism and inflammatory reaction are the two main characteristics of AS(atherosclerosis,AS)damage.Therefore,to reduce the incidence of atherosclerotic diseases,the improvement of lipid metabolism disorder and inhibition of inflammation should become the focus of AS research.SDF-1(stromal cell-derived factor 1,SDF-1)binding to the CXCR4(chemokine receptor-4,CXCR4)heterodimer or homodimer can activate downstream signalling pathways,such as FAK and PKC,ERK and NF-?B,thus modulating adhesion,migration,proliferation and survival of inflammatory cells.Chemotaxis of SDF-1/CXCR4 regulate the activation and recruitment of neutrophils and smooth muscle cells.Interaction between chemokine SDF-1 and CXCR4 aggravate the inflammatory response and accelerate the occurrence and development of AS.Therefore,based on the clinical practice of psycho-cardiology,and the correlation between AS and the pathophysiology of SDF-1/CXCR4 axis,we are going to intervene Apoe-/-mice and establish mice model of liver depression by emotional stimulation.Under the premise of the main target SDF-1/CXCR4 axis,we will observe the relationship of emotional stimulation,chemokine SDF-1/CXCR4 disorders with plaque vulnerability.Our study will have an important scientific significance for the early prevention and treatment of AS plaque vulnerability.Chapter 1 The impact mechanism of emotional stress on atherosclerotic plaque vulnerability by SDF-1/CXCR4 biological axisObjective:By studying SDF-1,CXCR4 expression in ApoE-/-mice's plasma,plaque,aorta,hippocampus and bone marrow which influenced by emotional stimulation,we would like to reveal the correlation of AS plaque vulnerability in mouse model of stagnation of liver qi with SDF-1/CXCR4 biological axis imbalance,and thereby providing a theoretical basis for treatment of heart disease by liver-based therapy theory of Traditional Chinese Medicine,and providing new ideas for clinical prevention and treatment of coronary heart disease.Methods:30 8-week-old male ApoE-/-mice were equally divided into normal control group,high-fat diet group and model group of stagnation of liver qi and 108-week-old inbred C57BL/6/J mice were used as the blank control group.Each mouse based on the 12 weeks of intervention was to detect levels of plasma lipids(TC,TG,LDL-C,HDL-C),NE,SDF-1 and CXCR4 levels,extent of aortic injury in pathology,SDF-1 and CXCR4 expression levels of peripheral blood platelet,aorta,hippocampus and bone marrow.Results:Results showed a significant increase in weight gain,lipid metabolism index of TC,TG,LDL-C and HDL-C,NE levels and expression of SDF-1 and CXCR4 in plasma detected by ELISA,and MOD value of immunohistochemistry in mouse model of stagnation of liver qi.The difference was statistically significant(P<0.05)when compareded with the blank control group,normal control group and the high fat diet group.The degree of atherosclerosis was also more serious in arcus aortae of mouse model of stagnation of liver qi detected by hematoxylin-eosin staining and immunohistochemistry.Compareded with normal control group and high fat diet group,western blotting results showed increased expression of SDF-1 and CXCR4 in platelet,aorta,hippocampus and reduced expression of SDF-1 and CXCR4 in bone marrow in mouse model of stagnation of liver qi,and the difference was statistically significant(P<0.01).Conclusion:1.Emotional stress causes SDF-1/CXCR4 biological axis dysfunction and thereby accelerates the progress of AS.This study confirms that liver qi stagnation is the important factor to cause atherosclerotic plaque instability and rupture.2.By detecting effect of the sympathetic nervous system on SDF-1/CXCR4 biological axis,the study reveals the target point of the effect of emotional stress on atherosclerotic vulnerable plaque from the perspective of chemotaxis effect,inflammatory reaction and other biological effects.And it further provides an experimental basis for elucidating the molecular mechanism of acute coronary syndrome induced by liver qi stagnation.