The Level Of Serum HSP60 And Its Relationship With TNF-α In Patients With Acute Coronary Syndrome

The occurrence and development of atherosclerosis is affected by a lot of cooperative factors, among which immunoreaction and inflammation are the two mostly established. HSP60 is a highly conserved acute protein secreted and released by stimulated and dead endothelial cells and it may accelerate the development of acute coronary syndrome (ACS). Studies have shown that HSP60 is expressed in the block of atherosclerosis whose instability is the pathological foundation of ACS. In the block of atherosclerosis the antigen-present cells are greatly activated, which is a sign of immunoreaction and inflammation. Stimulated by stress, hypertension or infection can induce the secretion of HSP60 in artery endothelial cells. Then HSP60 is recognized as an auto-antigen by dendritic and Th cells through the TLR (Toll-like receptor) and this will finally result in the occurrence and development of atherosclerosis. TNF-α(Tumor Necrosis Factor- alpha) is an inflammatory factor which participates in the development of CHD(coronary heart disease), atherosclerosis, hypertension and heart failure. The inflammatory factor up-regulation in the serum has a critical relation with atherosclerosis instability, which has now become a prognostic index of acute heart disease. But the most studies show better correlation between TNF-αand the heart failure. With the further illustration of the immune mechanism in ACS, the relationship between HSP60, atherosclerosis and CHD has become a new hot topic.,but it had yet reported about the study of the HSP60 expression in ACS in domestic.HSP60 has been shown to stimulate the secretion of TNF-αby macrophage cells. But it was also suggested that HSP60 can down-regulate T cell migration and inhibit Th cell induced cytokine secretion (including TNF-α) through TLR-2. Now it is still controversial about how HSP60 regulates the expression of TNF-α. But a problem with these experiments is that they were all conducted in vitro. In the current study we investigated the expression of HSP60 and TNF-αin ACS and occurrence and development of ACS through detecting the level of them in vivo. Also, the relation between HSP60 and TNF-αwas studied.Methods:All inpatients were from the department of Cardiology and Emergency of the First Affiliated Hospital of Zhengzhou University. Totally 79 cases (52 males and 27 females) were selected and the mean age of them is 61±12. They are divided into three groups, the Normal group, the SAP (stable angina pectoris) group and the ACS group (including unstable angina pectoris and acute myocardial infarction). The number for each group are 20 (14 males, 6 females), 36 (22 males, 14 females) and 23 (16 males, 7 females) respectively. The mean age of them are 56±12 years (range, 40-77 years), 61±10 years (range, 40-79 years) and 62±11 years (range, 37-78 years). All CHD diagnoses are in accordance with the WHO standard on ischemic heart disease and some were further confirmed by PTCA. The normal group is individuals who have no CHD or even the major risk of it and there's no pathological change of brain or other important viscera and virulent diseases, which is confirmed by both medical and laboratory examination.5 ml venous blood was collected from limosis patient who has been in the hospital for one day. Then 2-3 ml serum was isolated by centrifugation for 5-10 minutes, 4000 rpm/min. The serum was put in EP(Eppendof,EP) and then stored at -80°C, later the levels of HSP60 and TNF-αwere detected by ELISA (Enzyme-Linked Immunosorbent Assay) method. Results:1. The serum HSP60 level of the ACS group [In(HSP60+1), 6.25±1.13] was significantly higher than that of the Normal group(3.91±2.13, t=0.000,P<0.001) and SAP group (3.74±1.88, t=0.000, P<0.001). There was no significant difference between the Normal and SAP group (t=0.751, P>0.05).2. There was a positive correlation between ACS and the serum HSP60 level when it exceeded 142.65ng/mL, the median level (x~2=17.98, P<0.001).3. There was no significant difference among the TNF-αlevel of the three groups, with the Normal group(In TNF-α, 2.22±0.52), the SAP group(2.32±0.75) and the ACS group(2.21±0.51) (F=0.287, P>0.05).4. There was no positively negative correlation between the level of serum HSP60 and TNF-α(r_s =-0.146, P>0.05).Conclusions:1. The serum HSP60 level increased significantly in the ACS group, which may has a correlation with the instability of the block.There was a positive correlation between the level of serum HSP60 and ACS, so it can be used to evaluate the state of immunity in ACS and this provides a new index for further clinical diagnosis and therapy.2. There was no significant difference among the TNF-αlevel of the three groups, which indicate that other index such as the receptor of TNF-αwas needed to evaluate the role of TNF-αin ACS.3. The levels of serum HSP60 and TNF-αhad no positive correlation and it seems that their relationship needs to be further studied.4. In the current study the levels of HSP60 and TNF-αin ACS were detected clinically and the mechanism of the development of ACS and its relationship with HSP60 was further discussed. Our study indicates that the serum HSP60 level has a great correlation with the instability of the block in ACS occurrence and it also reflects the status of human immunity as an antigen.