Changes Of Mitochondrial Coupling Factor 6 In Acute Myocardial Infarction And The Possible Mechanisms

Partâ… Changes of Mitochondrial Coupling Factor 6 in Patients with Acute Myocardial Infarction and its Clinical ComplicationsObjects: The objective of our study is to investigate the alterations in the plasma lever of mitochondrial coupling factor 6 (CF6), a novel endogenous inhibitor of prostacyclin, in patient with acute myocardial infarction (AMI) and to study the relationship between plasma CF6 and clinical trails in AMI.Methods: In total, 80 patients with AMI and 90 age and sex-matched healthy subjects were examined. Blood samples were collected in the next morning after patients were in hospital to detect the concentration of CF6 and other biochemical indicators. Circulating CF6 was measured by radioimmunoassay. The data were analyzed with the statistical software package SPSS11.0 and differences were considered statistically significant with P<0.05.Results: The plasma level of CF6 was significantly increased in patients with AMI ((297.70±46.15 pg/ml vs 200.23±20.93 pg/ml in controls, p<0.01) and the plasma level of CF6 was increased in the patients with higer coronary artery scores. Moreover, the level of CF6 has no relationship with age, sex, smoke, blood pressure, blood sugar, TNI and CK-MB lever, whereas plasma CF6 was significant correlated with triglyceride, cholesterol and low density lipoprotein.Conclusion: The results suggest that an increased CF6 level may play an important role in the pathophysiological process of AMI. As a potential risk factor for AMI, CF6 might have important clinical significance.Partâ…¡Role of PKC-MAPK Signal Transduction Pathway in the Changes of Mitochondrial Coupling Factor 6 Induced by Ischemia/hypoxiaObjective: To study the role of PKC-MAPK signal transduction pathway in the secretion and gene expression changes of CF6 in cultivated ischemia/hypoxia rat cardiomyocytes.Methods: Cultivated rat cardiomyocytes were randomly divided into 5 groups: group Control, group Ischemia/hypoxia, group Staurosprine, group U0126 and group SB202190. Cardiomyocytes in group Control were cultivated normally. Cardiomyocytes in group Ischemia/hypoxia Cardiomyocytes, Staurosprine, U0126 and SB202190 were exposed to stimulation of ischemia and hypoxia and different specific inhibitor of PKC, ERK1/2 and p38MAPK was added into the medium of last three groups respectively. Real-time PCR was used to detect the mRNA expression of CF6 and CF6 in medium was measured by radioimmunoassay. PKC activity was determined by measuring the incorporation of ³²P fromγ-³²P-ATP into protamine. Western Blots technique was performed to detect the protein expression of p-ERK1/2 and p-38MAPK.Results: Three hours after cardiomyocytes were stimulated by ischemia and hypoxia, the gene expression of CF6 were increased greatly vs Control (P<0.01). Six hours after the cells were stimulated, the expression of CF6 were increased to a peak. Ischemia/hypoxia could induce the cultured cardiomyocytes to secret CF6 in a time-dependent manner. The ERK1/2 and p38MAPK were significantly phosphorylated by exposure to ischemia/ hypoxia and the enhanced phosphorylations were obviously suppressed by the PKC inhibitor. Meanwhile r, the enhanced phosphorylation of ERK1/2 and p38MAPK could also be suppressed by ERK1/2 inhibitor and p38 MAPK inhibitor individually. Moreove, compared with cardiomyocytes cultured for 6 hours in normal circumstance alone, ischemia/hypoxia plus PKC inhibitor, ERK1/2 inhibitor or p38 MAPK inhibitor significantly suppressed the stimulatory effect of ischemia/hypoxia on CF6 production, the inhibition rate being 59.1 % (P<0.01),56.4 % (P<0.01)å’Œ58.9%(P<0.01). And the inhibitors could also decrease the mRNA expression of CF6 that induced by ischemia and hypoxia.Conclusion: The specific inhibitor of PKC, ERK1/2 and p38MAPK can reduce the increase in gene expression and protein release of CF6 induced by ischemia and hypoxia. This suggests that ischemia/hypoxia is one of the stimulator of endogenous CF6 in cardiomyocytes, which is regulated by PKC- MAPK signal transduction pathway. More studies about the correlation between CF6 and PKC, MAPK might provide new methods to the diagnosis and treatment of ischemic heart disease.