Studies Of CollagenⅠ,Ⅲ Pathomorphological And Serum Markers Changes In Myocardial Fibrosis

Background and Objectives Myocardial fibrosis is abnormal hyperplasia of collagen in cardiac interstitial , which attenuates severely cardiac function. The collagen types I and III are main components of the cardiac collagen network , The appropriate ratio between them is important in maintaining cardiac structure and function. The level of extracelluar matrix(ECM) in serum can reflect itself metabolism in vivo and be used to evaluate organs fibrosis. The structure, function, metabolism, regulation of the cardiac collagen network have been deeply studied and the remodeling of collagen network in hypertension, myocardial infarction(MI) and congestive heart failure was also reported. But it has not been studied how the pathomorphology of cardiac interstitial collagen changes and whether cardiac myocyte involves synthesis of collagen in dilated cardiomyopathy(DCM) and congenital heart disease (CHD). It also has not been reported whether changes of the serum ECM are significative in RHD and DCM. In order to comprehend better pathological mechanisms of myocardial fibrosis and provide bases for clinical prevention and therapy, the pathomorphological and quantitive changes of the collagen types I and III were investigated in this study. Meanwhile, the clinical values of the serum ECM was to be evaluated in rheumatic heart disease(RHD) and dilated cardiomyopathy(DCM).Methods 30 patients with RHD, including 12 with mitral stenosis(MS) and 8 with mitral regurgitation(MR), 7 patients with DCM and 10 patients with congential heart disease(CHD), including 6 Fallot tetralogy and 4 right ventricle outflow tract obstruction, were studied. Their myocardium specimenswere obtained in the operation, and the serum samples were harvested before operation. 5 healthy adult myocardium specimens and 20 serum samples of healthy adult composed the control groups. The cardiac myocyte and interstitial collagen pathological changes were observed by hematoxylin and eosin(HE) and Masson staining; The expression and distribution of collagen types I and III in cardiac interstitial were observed by Sirius Red F3B(SR) and immunohistochemistry staining, the area of myocardial fibrosis was measured by imaging analysis system;The procollagen mRNA was examined by in situ hybridization technology; The serum concentration of procollagen I(PCI), procollagen III(PCIII), laminin(LN)and hyaluronic(HA) were measured by radioimmunoassay.Results 1. Myocardial interstitial of RHD, DCM and CHD showed significant collagen hyperplasia, which surrounded and separated the cardiac myocyte; there were cardic myocytes with hypertrophy , atrophy , vacuole degeneration or local necrosis and endotheliosis with lumen stenosis. Imaging analysis results showed that the myocardial interstitial collagen volume fraction(CVF) (RHD group: 20.37±8.32, DCM group 18.34±2.84,CHD group 12.13±3.26) were significant more than that of healthy adult control group (5.47±1.68)(p<0.01). 2. The positive expression of collagen typeⅠand Ⅲand procollagen mRNA appeared in interstitial of all kinds of fibrosis myocardium, typeⅠcollagen also appeared in myocardial cell of RHD and DCM. It suggested that cardiac myocyte also involved myocardial fibrosis. 3.The levels of serum ECM(μg/L) in RHD group (PCI:64.24±21.28,PCIII:118.43±36.32,LN:116.77±16.65,HA118.29±37.69) and DCM group (PCI:60.56±19.58, PCIII:128.32±40.21,LN:115.66±15.36,HA:122.78±35.72) were significant higher than those of in healthy adult control group (PCI:49.08±14.54,PCIII:70.28±15.34,LN:82.68±13.60,HA:65.73±18.22)(p<0.01), meanwhile, the serum concentration of ECM were correlatedpositively with the area of myocardial fibrosis (p<0.05). Conclusions 1.The pathological changes of myocardial fibrosis are complex and variety and the mechanisms are different 2.The level of serum ECM can be used to reflect the degree of myocardial fibrosis and might be used to evalute the treatment effect and to predict pnognosis.