The Plasma Level Of Apelin And The Relationship Between Apelin And ADM, AngⅡ In Patients With CHF

BackgroundMost cardiac diseases would show CHF at their end phase, which manifested as left ventricular dysfunction, activation of never and endocrine system, and disorder of peripheral hemodynamics. It was recognized that nervous and endocrine system played important roles in the occurrence, development and prognosis determination of CHF. Vasoactive agents produced by nervous and endocrine system, as well as the interaction between these agents, could influence cardiovascular system via multiple mechanisms. In recent years, a new type of vasoactive agent called Apelin had taken much focus. Apelin was first reported in 1998, and was a natural ligand of angiotensin receptor AT1 related protein(APJ). Apelin-36 consisted of 36 amino acids, molecular weight was about 3kD. Apelin was generally distributed in the body and had multiple biological effects, including positive inotropism and depressurization, and was elevated in pateints with CHF. The function of Apelin receptor (APJ receptor) was adverse to that of Ang II receptor. ADM was abundant in pheochromocytoma, adrenal medulla, heart, etc. Plasm ADM mainly produced by endothelium and smooth muscle cells from blood vessel. ADM's biological effects included increasing myocardial contractility, relaxing vascular tone and lowing the blood pressure, etc.Plasm ADM level rised marked in patients with CHF, and was increased with the advancing of heart failure, when heart failure was mitigated, it failed. Expression of ADM could be suppressed by antagonists of Angll receptor. Angll could be produced by circulatory RAS and independent RAS from cardiovascular organ (including myocardium, vascular smooth muscle cells, etc). Tissue RAS acted directly and seemed more important as compared with circulatory RAS. The biology effects of Ang II included vasoconstriction effect and vascular remodeling, contraction of coronary artery, positive inotropism, promoting the hypertrophic of myocardium, increasing of afterload, which resulted in decreasing of left ventricle compliance and relaxing function. Finally the heart become decompensation and enlargement of left ventricle cavity and decreasing of ejection fraction occured, causing the heart failure to advance. Some clinical data indicated that plasm Ang II level rised as heart failure progressed and fell when it mitigated. All these suggested that Apelin, ADM, Ang II might play important roles in the adjustment of Cardiac function, and co-effort and opposite functions might exist between these agents. Objective:We aimed to study the role of Apelin in the developing of CHF by determinating the different plasm Apelin, ADM and Angll levels between patient groups and controls and patients'auto-control as well, thus provided some theory basic for CHF evaluation and treatment. ADM and Angll, which had been well studied, were viewed as reference standard. And the correlation between Apelin and ADM, Ang II was studied to see whether ADM and Ang II could influence the synthesis and secretion of Apelin. Methods:1. 42 CHF patients and 12 healthy individuals entered the study, clinical data were collected, including left ventricle ejection factor, left ventricular end-diastolicvolume, E/A value, cardiothoracic ratio, etc.2. Venous blood was extracted and cryo-centrifugated, then the plasm was stored in -70 °C.3. Plasm Apelin, ADM, Angll were determinated using radio-immunity kits. Result:1. Clinical dataNo significant different was found between patient groups and control group in age, sex. LVEF in NYHA functional class HI and class IV was significantly lower than in control group (P<0.05) , and in class IV is lower in comparing with class II (P<0.05) . LVDd in class HI and class IV groups was significantly higher than in class II and control group (P<0.05) ; Class IE and class IV groups had higher cardiothoracic ratio than control group (P<0.05), but no different between class II and controls.2. Plasm Apelin, ADM, Angll levels between subgroups before the treatment of CHF:Plasm Apelin was significantly higher in class II and class III groups than in control group (P<0.05, P<0.01) , and was higher in class HI group than in class II group (P<0.01), but in class TV group was lower than in control group (P<0.05 ); Plasm ADM in class II-. EL IV groups increased gradually with highest value in class IV group, and were significantly higher in comparing with control group (P<0.01, P<0.001) ; Similar change was observed in plasm Ang II.3. Plasm Apelin ,ADM,Ang II levels after treatment of CHD with drugs: (1) Apelin:In Class n,in groups, plasm Apelin decreased when CHF improved (P<0.05 ), but in class HI group it's still higher, comparing the control group (P<0.05); Apelin in class IV was higher than before the treatment (P<0.05), but not different to controls.(2) ADM:Plasm ADM in all CHF groups decreased significantly after the treatment (P<0.05), but in class III,IV group remain higher in comparing with control groups, while class II group had no different with control group. (3)AngII:Plasm Ang II fell in class n,m,IV group, comparing before treatment (P<0.05), but in class IH,IV group was higher than in control group (P<0.01); No different existed between class II group and control group after improvement of CHF. 4. Correlation analysis of plasm Apelin, ADM and Ang II before treatment:Correlation analysis of plasm Apelin, ADM and Ang II before treatment showed that Apelin was positive correlated with ADM and Ang II. Conclusion:1. Plasm Apelin changed dynamicly with progress of CHF, increasing in Class II and class III group and falling to normal in class IV. So serum Apelin testing might be helpful to assist diagnose. Apelin was mainly secreted by endothelial cell, which suggested that endothelial cell might suffer serious impairment in advanced heart failure. So Apelin might be applied to CHF treatment in the future, plusing it's known physical function like enhancing myocardial contractility, vasodilatation, etc.2. Plasm ADM and Ang II remained high in Class EH and Class IV group after successful treatment, which suggested that never and endocrine system remain active despite of the improvement of cardiac function and symptom. These could cause heart failure to reappear due to adverse effect of Ang II.3.Apelin was positive correlation with ADM and Ang II in Class II and Class HI before drug treatment, which suggested that Apelin secretion might be partly influenced by ADM and Angll. In other words, Apelin might be able to facilitate the secretion of ADM and Ang II. In Class IV group, plasm Apelin was lower thancontrols, but ADM and Angll remain high, one explanation might be that endothelium impairment cause the reduction of Apenlin, while ADM and Angll secretion were not affected due to wild distribution.