| [Background]Background]Dilated cardiomyopathy is an important cause of sudden death and heart failure,and it is the most important factor for children, young people’heart transplant in the world.The disease is often accompanied by malignant arrhythmias, sudden death, and has a high mortality rate.But the pathogenesis of DCM has not been clear at present, there is no specific treatment for DCM. Therefore, in patients with DCM, there is a huge difference in the prognosis and natural outcome.In recent years, it is generally considered that sustained inflammatory response is an important cause of DCM, acute and/or chronic inflammatory which lead to myocardial tissue damage and inflammatory cytokines mediated myocardial injury can be caused or induced dilated cardiomyopathy. So exploring new inflammatory cytokines has become the hot field of in research of DCM, it helps us to find exact intervention targets and applied to clinical practice so as to formulate a treatment plan for DCM, DCM will probably become a breakthrough treatment measures. CEACAM-1(Carcinoembryonic antigen cell adhesion molecule-1) is a new discovery of a new type of inflammatory molecules. Present study has demonstrated that CEACAM-1involved in the pathogenesis of inflammatory bowel disease by regulating T lymphocytes, and may become a new target for the treatment of inflammatory bowel disease.It is can be found that reduction in mononuclear cells and damage to lymphangiogenesis in dermal damage model in mice whose CEACAM-1gene was eliminated.Recent studies have also confirmed that CEACAM-1in mouse model whose cardiac received ischemic preconditioning is also highly expressed. Our lab has been the introduction of CEACAM-1knockout mice.Prior studies in our laboratory have demonstrated that CEACAM-1promote myocardial apoptosis by Bax/cytochrome C/caspase3pathway (mitochondrial dysfunction) implementation.CEACAM-1is a key cytokine mediated apoptosis after the heart ischemia/hypoxia injury.When CEACAM-1gene knockouted in mice, death rates declining and cardiac remodeling improved after myocardial infarction.The above indicate that CEACAM-1molecules via autocrine, paracrine pathway mediated inflammatory reaction role in dilated cardiomyopathy species. pathy,and for the prediction and prognosis playing a guide role in DCM patients.Based on previous studies and our laboratory studies, we hypothesized that CEACAM-1molecules which may act as an inflammatory factor mediated DCM occurs, development through one or multiple pathways, and participated in the process of ventricular remodeling and affected the patient’s condition and DCM prognosis.[Objectives]To explore serum expression levels of CEACAM-1in DCM patients, the relationship between CEACAM-1and the inflammatory response, condition and prognosis of patients with DCM.[Content]1. To investigate the expression of CEACAM-1in DCM patients’serum;2.To investigate CEACAM-1changes in patients with DCM after treatment Simultaneously,making comparision of DCM patient inflammation levels, severity of disease and cardiac function between different CEACAM-1change group before and after treatment;3. To investigate suckling rats cardiomyocytes CEACAM-1expression under inflammatory stimulation.[Methods]1.Choose between September2012and February2014during continuous selected, In Guang Zhou Nan Fang hospital cardiovascular medicine. A total of70cases in which patients diagnosed with DCM (a total of59cases,11cases were lost) accepted clinical follow-up. Follow by February15,2014.During hospitalization, collected the patient’s general condition including history of hypertension, diabetes, smoking history and family history; and fasting blood to detecting Pro-BNP (B-type natriuretic peptide precursor), lipids, C-reactive protein (CRP), Creatinine clearance (Creatinine clearance Ccr), Blood, CEACAM-1and other relevant indicators and on the same day do a echocardiogram to assess left ventricular ejection fraction study based on the object (LVEF), left ventricular end-diastolic diameter (LVEDD) and other indicators.At admission, each study subjects were rated cardiac function (NYHA classification), accepted follow-up of clinical indicators, changes in serum levels of CEACAM-1and medication after discharge conditions. Summing up follow-up results, analysis of the first level of serum CEACAM-1respectively, the second CEACAM-1serum concentration changes when following, DCM conditioning changes related to clinical indicators and the connection between the disease outcome related to clinical indicators. Experimental groups were as follows:(1) before treatment group+after treatment group+normal group:before treatment group:59patients with DCM in hospital for the first time(Whether or not in the past for the first diagnosis for DCM patients have defined as before treatment group) collecting their clinical data and fasting serum frozen spare CEACAM-1concentration prepare for testing. after treatment group:Total of59patients with DCM treatment all clinical indicators when the follow-up after discharge and fasting serum frozen spare CEACAM-1concentration prepare for testing. normal group:All of48people were under our hospital physical examination center qualified healthy people.(2)CEACAM-1lift set group+CEACAM-1drop set group:patients who accepted at least6months’treatment accpeted follow-up,then collected peripheral blood to detecting changes in CEACAM-1concentration. In contrast to the serum CEACAM-1concentrations at first admission, the CEACAM-1serum concentrations in patients with elevated compared to the first classified as a group named the lift set group, the serum concentration of CEACAM-1lower than the first group of patients classified as a name for the drop set group.2. Cardiomyocytes isolated and cultured in vitro, experimental groups were as follows:(1)control group+LPS group (50,400,1000mg/ml):LPS added to isolated cardiomyocytes were incubated for6hours, cells were extracted protein, Western-Blot Detecting the expression of CEACAM-1;(2) control group+H2O2group (50,100μM)+AngⅡ group (1uM) cells were extracted protein, Western-Blot Detecting the expression of CEACAM-1.[Results]1.In this study,a total of59cases follow-up for patients diagnosed with DCM, with an average follow-up time was11.49±4.74months.The total number of deaths occurred during follow-up were7cases, the rate was11.9%. All of them were cardiac death. The serum CEACAM-1concentrations were detected in59cases before and after treatment. Before treatment, CEACAM1-concentration was:2.77±2.33(mmol/L), after treatment serum CEACAM-1concentration:2.65±2.67(mmol/L), CEACAM-1concentration in all patients with DCM:2.77±2.33(mmol/L), CEACAM-1concentration in normal human was1.7±1.14(mmol/L).2.Comparison of CEACAM-1serum concentrations between normal subjects and patients with DCM:(1)Serum CEACAM-1concentration in DCM patients is significantly higher than normal before treatment.(p<0.001);(2)Serum concentrations of CEACAM-1has no statistically significant differences between normal and patients with DCM after treatment(p=0.018),shows that the peripheral blood CEACAM-1concentration of patients with DCM was significantly higher than normal.After treatment, its concentration is decreased.3.The relationship between CEACAM-1and inflammatory markers:(1)The relationship between CEACAM-1and CRP:①In CEACAM-1drop set group, the levels of CRP after treatment is lower than before treatment, there is a statistically significant difference (P=0.039), In CEACAM-1lift set group, CRP was no significant change after treatment, and no statistically significant difference. It shows that after treatment,the inflammation of CEACAM-1drop set group is improved,and the inflammation of CEACAM-1lift set group is no significant improvement.②Correlation analysis between CEACAM-1and CRP:A、The total serum CEACAM-1concentrations before treatment was positively correlated with the total CRP before treatment.(r=0.437, P=0.001); After treamet, there is no correaltion;B、In CEACAM-1drop set group, before treatment, serum CEACAM-1concentrations was positively correlated with CRP.(r=0.354, P=0.032);after treatment CEACAM-1concentrations were no obvious correlated with CRP; C、In CEACAM-1lift set group, before and after treatment, CEACAM-1concentrations were no obvious correlated with CRP; It indicates that in CEACAM-1drop set group, before treament,the CEACAM-1concentrations has positive correlation with the inflammation, and in CEACAM-1drop set group after treament, CEACAM-1lift set group before and after treament,the CEACAM-1concentrations has no correlation with inflammation.(2) The relationship between CEACAM-1and WBC:In CEACAM-1drop set group, the levels of WBC after treatment is lower than before treatment, there is a statistically significant difference (P=0.046),In CEACAM-1lift set group, WBC was no significant change after treatment, and no statistically significant difference. It shows that after treatment, the changes in WBC is consistent with the changes in CEACAM-1in CEACAM-1drop set group drop, and the inflammation of CEACAM-1lift set group is no significant improvement.4. The relationship between CEACAM-1and the clinical condition and prognosis of patients (1) The relationship between CEACAM-1and FS:In CEACAM-1drop set group, the levels of FS after treatment is higher than before treatment, there is a statistically significant difference (P=0.008).In CEACAM-1lift set group, after treatment, FS was no significant changes, after treatment and no statistically significant difference. It shows that after treatment,the cardiac function of CEACAM-1in drop set group is improved more than CEACAM-1in lift set group. The cardiac function of lift set group was no significant improvement after the treatments.(2)The relationship between CEACAM-1and LVEF:In CEACAM-1drop set group, the levels of LVEF after treatment is lower than before treatment, there is a statistically significant difference (P=0.005), In CEACAM-1lift set group, after treatment, LVEF has the rising trend,but no statistically significant difference. And CEACAM-1increasing trend in CEACAM-1drop set group is more obvious than lift set group, shows that after treatment,the cardiac function of CEACAM1in drop set group is improved more than in CEACAM-1lift set group. The cardiac function of lift set group was no significant improvement after the treatments.(3) The relationship between CEACAM-1and cardiac function:①the comparision of the NYHA class:the comparision of the NYHA class between CEACAM-1lift set group and CEACAM-1drop set group before and after treatment(NYHA class after treatment NYHA class before treatment)(P=0.006),In the CEACAM-1drop set group, the proportion of heart function improvement (67.6%) is higher than the CEACAM1lift set group(40.9%).In the CEACAM-1drop set group, cardiac function of8patients with NYHA class IV and10patients with NYHA class IV improved. Implying that the relation between the reduction of serum CEACAM-1concentration and improvement of the cardiac function of patients.②Correlation analysis between CEACAM-1and NYHA:A、Before treatment, the CEACAM-1concentrations was positively correlated with NYHA class (r=0.291, P=0.002); After treatment, the CEACAM-1concentrations was no obvious correlated with NYHA; B、In CEACAM-1drop set group, DCM patients before treatment, the CEACAM-1concentrations was positively correlated with NYHA class(r=0.336, P=0.026); after treatment, the CEACAM-1concentrations was no obvious correlated with NYHA; In CEACAM-1lift set group, before and after treatment, CEACAM-1concentrations were no obvious correlated with NYHA class; C^the CEACAM-1difference changes after treatment were positively correlated with improvement of cardiac function after treatment (r=0.51, P<0.001);(4) The relationship between CEACAM-1and Pro-BNP:①the comparision of Pro-BNP:In CEACAM-1drop set group, the levels of Pro-BNP after treatment is lower than before treatment, there is a statistically significant difference (P=0.001), In CEACAM-1lift set group, Pro-BNP was no significant change after treatment, and no statistically significant difference. It shows that in CEACAM-1drop set group, after treatment, patient’s condition improved, and in CEACAM-1lift set group, after treatment, patient’s condition was not obviously improved.②Correlation analysis between CEACAM-1and Pro-BNP:A. The total serum CEACAM-1concentrations before treatment was positively correlated with the total Pro-BNP before treatment.(r=0.415,P=0.001),after treatment, the CEACAM-1concentrations was no obvious correlated with Pro-BNP; B. In CEACAM-1drop set group, before treatment, serum CEACAM-1concentrations was positively correlated with Pro-BNP.(r=0.472,P=0.003), after treatment CEACAM-1concentrations were no obvious correlated with Pro-BNP; In CEACAM-1lift set group, before and after treatment, CEACAM1concentrations were no obvious correlated with Pro-BNP;5. LPS. H2O2, Ang-II stimulated cardiomyocytes testing expression of CEACAM-1were significantly higher than the control group (P<0.05), and with LPS, H2O2concentration gradient of different changes (P<0.05). Myocardial cell enhanced CEACAM-1expression after inflammatory stimulation.[Conclusion]CEACAM-1was associated with inflammation of DCM.CEACAM-1may be involved in the development and progression of DCM and the DCM patients’reaction to the treatment by regulating myocardial inflammation, and is expected to become a potential therapeutic target and prognostic indicators. |
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