Analysis Of The Rule Of Anti-cardiac Myosin Heavy Chain Autoantibody IgG Subclasses Level In Heart Failure Rat Model

Background and objectsMyocardial damage, cellular necrosis and Apoptosis are found in heart failure patient. Cardiac myosin is the main protain of muscle contraction and its structure is clear.The functions of its isodynamic enzymes and fragments are complicated. Very strong antigenicity and immunogenicity are found with cardiac myosin heavy chains by many studies [1-9]. Immunologic mechanism participates and influences nearly all cardiovascular diseases. Anti-cardiac myosin autoantibody participates in the development of hear failure [10-14]. But the relationship between the change of anti-cardiac myosin heavy chain autoantibody IgG Subclasses level and heart function is not clear yet.The present study intends to determine anti-cardiac myosin heavy chain autoantibody IgG Subclasses level in heart failure rat model, to observe dynamic rule of anti-cardiac myosin heavy chain autoantibody IgG Subclasses, to analyze the relationship between AMHCA IgG Subclasses and heart failure, and to explore the mechanism patho-physio process of immunity participating in hear failure, so as to provid evidences in improving preventative and diagnostic level of heart failure, and in enforcing effective interventions from Immunologic aspect. MethodsPartⅠ: To establish chronic heart failure rat model after abdominal aorta constriction.To make animal model of chronic heart failure in rats, abdominal aorta was constricted. To determine criterions of chronic heart failure rat model, echocardiagraph, hemodynamics parameters, pathology examination and immunohistochemistry were performed to evaluate the cardiac function.PartⅡ: To determine anti-cardiac myosin heavy chain autoantibody IgG Subclasses level in heart failure rat model.1.Collection of blood serum: At 7, 20, 50, 90, 120, 150 and 180 days after operation, blood serum was collected and conserved at - 20℃. 2. The levels of serum IgG AMHCA Subclasses were also measured by Indirect-enzyme linked immunosorbent assay.Results1.In sham operation group, echocardiagraph indexes such as LVPWD,IVS,LVESD,LVEDD,EF and FS had no statistical significance compared to those of normal control group at 3 months and 6 months. In operation group, echocardiagraph indexes such as LVPWD,IVS,LVESDand LVEDD increased, EF and FS decreased, but had no statistical significance compared to those of normal control group at 3 months except LVEDD. In operation group at 6 months, LVPWD,IVS,LVESD, LVEDD ,EF and FS increased, and had statistical significance compared to those of normal control group.2. In sham operation group, hemodynamics parameters such as LVEDP,LVSP,±dp/dt max and HR had no statistical significance compared to those of normal control group at 3 months and 6 months. In operation group, LVSP and±dp/dtmax decreased but had no statistical significance compared to those of normal control group at 3 months. But LVEDP increased and had statistical significance compared to normal control group. In operation group, LVSP and ±dp/dtmax decreased,HR and LVEDP increased, had statistical significance compared to normal control group at 6 months.3. There was no cardiac muscle pathological change in sham operation group. In operation group of 3 months, Myocardium of left ventricle had myocardium hypertrophy,nucelus thick dyed, myocardial cell disordered , cardiac muscle interstitial edema, small vessel wall thickened and inflammatory cell infiltrate. At 6 months post operation, cardiac muscle fibers broken, endochylema glassy degeneration, granulo-necrosis and fibrosis could be seen.4. Normal control group and sham operation group had negative immunohistochemistry results. The expression of ERK1 increased and the expression of p38MAPK was found only in a few cells at 3 months in operation group.The endochylema were brown. The expression of ERK1 decreased obviously and the expression of p38MAPK increased gradually 6 months in operation group. 5.IgG1 and IgG2 AMHCA were not detated in the blood serum of normal rats. One week post operation IgG2b AMHCA masc rate increased obviously in 12 heart failure rats of operation group. IgG AMHCA was negative in 18 rats which did not occur heart failure in sham-operation group. The masc rates of IgG2a and IgG2b AMHCA were kineticly developed in heart failure rats. IgG1 and IgG2b AMHCA were deteceted most during 50-90 days after operation. And IgG2a was during 150-180 days. IgG2a and IgG2b antibody titers were also kineticly developed. The highest antibody titers of IgG1 and IgG2b occurred at 50-90 days after operation, but IgG2a occurred at 150-180 days after operation.Conclusion1. The rats were in cardiac compensation period during the first 3 months after abdominal aorta constriction and were in cardiac decompensation period 6 months after the operation which according to echocardiagraph, hemodynamics parameters, cardiac muscle pathological change and immunohistochemistry.2. The reliable echocardiography enrollment criterions of heart failure rats model were: LVESD>0.55,LVEDD>0.6, EF<0.60,FS<0.25.3. During the process of myocardial hypertrophy developed to heart failure, hemodynamics changed, myocardial function was damaged, interstitial fiber cell accrementition. AMHCA IgG subclass transformed during this period. These transforms were influenced by T cells and cell factors. The production of IgG2b mainly regulated by Th2 cells. Th2 cells excrete cell factors which stimulate the generation and antibody formation of B cells. Th2 cells accommodate humoral immunity. The production of IgG2a was mainly regulated by Th1 cells, which mainly accommodate cell immunity. During the first 3 months after abdominal aorta constriction, IgG2b increased obviously and 6 months after the operation, IgG2a increased.That hints immunologic mechanism changed with heart failure proceeding. During cardiac compensation period, humoral immunity played an important role. But, during cardiac decompensation period, cell immunity did so.