| Background: Heart Failure is the final destination of most cardiovascular diseases and the main cause of death in cardiopaths.Coronary heart disease is the most common cause of heart failure.Complement C1q/tumor necrosis factor related proteins(CTRPs)as adiponectin paralog,mainly secreted by adipose tissue expression.Among them,CTRP1 can reduce blood glucose,increase insulin sensitivity,and enhance the oxidation of fatty acids in skeletal muscle.In addition,it is closely related to blood pressure regulation and thrombosis.However,the association between CTRP1 and heart failure is unclear.Objective: To investigate the relationship and mechanism between CTRP1 and coronary heart disease accompanied with heart failureMethods: 1.Detection of plasma CTRP1 level in patients with coronary heart disease complicated with heart failure:a total of 100 subjects were divided into coronary heart disease with heart failure group(n = 50),and the normal control group(n = 50).The blood lipid、blood glucose、liver function、BNP、renal function、aldosterone、cardiac ultrasound、body height、body weight、blood pressure were measured,and body mass index(BMI)was calculated.Determination of CTRP1 in plasma by ELISA.2.Study on CTRP1 in mice with heart failure after myocardial infarction:to make 48 male KM mices of 10 weeks old were randomly divided into sham operation group group(24 members)and operation group(24 members)that ligated the anterior descending coronary artery to make myocardial infarction model.To use operation time as the cutoff point,the two groups of mices were divided into the operation 3 days group(group A,n = 8),the sham 3 days group(group D,n = 8);the operation 7 days group(group B,n = 8),the sham 7 days group(group E,n = 8);the operation 24 days group(group C,n = 8),the sham 24 days group(group F,n = 8).Cardiac function was evaluated by echocardiography,and the changes of cardiac function and morphology were compared.The expression of CTRP1 in cardiac tissues of mice in each group was compared by immunohisto chemistry and protein blotting.The levels of plasma aldosterone were measured by ELISA.3.Cell experiment:(1)The H295 R cells were stimulated by 40 ng/ml CTRP1 for 6 hours,12 hours,24 hours,then the expression of CYP11B2 in the cells was measured.(2)The H295 R cells were stimulated with BNP 1 μM,CTRP1 40 ng/ml,BNP+CTRP1(CTRP1 40 ng/ml after BNP 1 μM 30min)for 24 hours,the expression of CYP11B2 was measured in cells.Aldosterone levels in cells of all goups culture medium were determined by ELISA.Results: 1.Results the level of plasma CTRP1:(1)The CTRP1 levels in patients was significantly higher than the normal group(p<0.01).(2)The CTRP1 level in cardiac function grade Ⅳ group is the highest,followed by cardiac function Ⅲ group,and cardiac function Ⅱ group is the lowest(p<0.05).The CTRP1 level of ≥55mm(left ventricular volumes)group is obviously higher than <55 mm group’s(p<0.01).Between different left ventricular ejection fraction goups,the CTRP1 levels were no statistically significant difference(P > 0.05).(3)The CTRP1’s level of plasma in patients is positively related to the level of hsTnI、lgALT、lgBNP、 Uricacid、lghs-CRP、Aldosterone in patients and their left ventricular volume(p<0.05).The BNP level of plasma in patients is an independent factor of CTRP1 level of plasma(β=1.040,p<0.05).2.Animal experimental results:(1)The results of echocardiography showed that LVEF,LVFS and LVPW were significantly lower in the operation groups compared with the sham operation groups(P<0.05).LVIDd was significantly increased in the operation 24 d group compared with the sham operation 24 d goup(P<0.05).(2)The expression of CTRP1 in myocardial cells and the level of aldosterone in the operation 3 d group and the operation group 7 d group were significantly higher than those in the sham operation groups respectively(P<0.05).However,there was no significant difference in the two groups of 24 d(P >0.05).3.Cell experiment results:(1)H295R cells were stimulation by 40 ng/ml CTRP1 for different times,and then CYP11B2 expression and each aldosterone level in cell cultures of 24 h and 12 h group were significantly higher than the control group,which the 24 h group is the highest(P < 0.05 or P < 0.01).There was no statistically significant difference between the 6 h group and the control group(P > 0.05).(2)Respectively using CTRP1 40 ng/ml,BNP 1uM,BNP1 um after CTRP1 40 ng/ml 30 min,stimulate H295 R cells for 24 hours.Comparing with control group,the expression of CYP11B2 and aldosterone’s levels in the BNP group is significantly decreased(P < 0.01),and those in the CTRP1、BNP + CTRP1 groups are significantly increased(P < 0.01),which the CTRP1 group is more than the BNP+CTRP1 group(P < 0.05).Conclusion:1.The CTRP1’s level of plasma in patients with coronary heart disease accompanied with heart failure was significantly increased,and the level gradually decreased with the improvement of the disease.The CTRP1’s level was closely related to the deterioration of cardiac function and left ventricular volume.The BNP’s level of plasma was an independent factor of CTRP1’s level.2.The model of heart failure after myocardial infarction was established by ligating the anterior descending branch of coronary artery in mice.Due to the occurrence of heart failure in mice with myocardial infarction,the expression of CTRP1 and the level of plasma aldosterone were significantly increased in mice with acute heart failure.No changes were observed in the recovery period of heart failure in mice.3.After H295 R cells were stimulated with CTRP1,The expression of CYP11B2 and the synthesis of aldosterone increased gradually with the stimulation time.The promoting synthesis effect of CTRP1 on CYP11B2 can be antagonized by BNP. |
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