| Inflammation is closely related to the occurrence of acute myocardial infarction(AMI): inflammation can cause endothelial injury and secondary thrombosis of AMI.Neutrophils can aggravate endothelial injury,mediate more inflammatory cell infiltration,and mediate unstable plaque cap avulsion,which is one of the main causes of AMICCN1 is a secretory matrix protein with important physiological function.It has been found that it can promote the development of inflammation and autoimmune diseases,but whether it is involved in the inflammation and tissue damage of AMI has not been reported.This study analyzed the correlation between the expression level of serum CCN1 and the number of neutrophils in the circulating peripheral blood in AMI patients in combination with other clinical data in particular effects of the PCI treatment,to investigate the role of CCN1 in AMI.Furthermore,the association between the expression of CCN1 and the expression of MIP-2,and consequent causing the infiltration of neutrophils in the ischemic myocardial area were studied by using an myocardial infarction mouse model that is established by the ligation of left anterior descending branch.Finally,we analyzed the regulation tole and mechanism of CCN1 in mediating inflammation in AMI by using an in vitro human umbilical vein endothelial cell(UVEC)culture system.In this study,we had done some special research on the correlation between changes of serum CCN1 and myocardial ischemia such as ST-elevation myocardial infarction(STEMI),meanwhile the association between changes of serum CCN1 and the outcome after percutaneous coronary intervention(PCI)was alos analyzed.We found that: 1)the level of serum CCN1 in clinical samples of coronary heart disease(CHD)patients was elevated compared to those in non-CHD samples;2)the level of serum CCN1 in STEMI patients was significantly higher than that in non-st-segment elevation myocardial infarction(NSTEMI)patients before the PCI;3)after the PCI operation,the serum CCN1 level in STEMI patients dropped much more dramatically compared with that in NSTEMI patients.Taken together,these results suggest that serum CCN1 may be an auxiliary diagnostic indicator for CHD and MI,and may also be one of the prognosis indices of PCI.The main mechanism involves unbalanced lipid metabolism and adverse immune response,which leads to chronic inflammation of the arterial wall.To better investigated the role of CCN1 in AMI,we stiestabilished a mouse AMI model by ligating the left anterior descending branch of the coronary artery and found:.1)consistent with our findings in clinical samples,m RNA level and protein expression level of CCN1 in AMI model was raised.The same result was observed in MIP-2 on the m RNA level and protein expression level;2)the proportion of infiltrating neutrophils was higher than that in the control mice analyzed with the flow cytometry.3)by using CCN1 specific blocking antibody,the proportion of infiltrating neutrophils was lower compared to no blocking AMI mice.These results indicated that CCN1 had influence on recruitment of neutrophils to local lesion myocardium,and played an important role in promoting the CHD and in its prognosis.According to our research,CCN1 in synovial cells can up-regulate the expression of IL-8 and thereby recruiting neutrophils to the lesion area.In order to further study the role of CCN1 in the AMI caused by coronary artery stenosis,we carried out an in vitro study with UVEC culture.We found CCN1 was up-regulating IL-8 expression.In order to further analyze the serum CCN1 in the disease state,in this study,2514 cases of healthy donors' serum CCN1 distribution were analyzed,and the preliminary establish a normal reference range of serum CCN1.In conclusion,the inflammatory initiation of CCN1 in myocardial ischemic injury was investigated,and through the analysis of the clinical samples and animal models and in vitro studies,preliminary illustrates the mechanism of regulation of CCN1 participates in AMI by raising inflammatory cytokines,chemokines and neutrophil infiltration.It was provided a experimental data for the further relationship between serum CCN1 and AMI. |
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