The Expression And Significance Of Metalloproteinase And Apoptosis In The Calcific Aortic Valve

Degenerative aortic valve calcification is a common heart valve disease.With the development of health level,life length ening.The patients who require aortic valve replacement are increasing.The valve calcification will not only result in the valve function abnormal,but aslo heart failure infcetive endo carditis conduction block thromboembolism even the sudden death.In the early 1900s,eminent pathologists,such as Monckeberg, described aortic valve calcific disease as a passive process that is associated with rheumatic fever or aging.Over the past several decades,the etiology of aortic valve stenosis has changed considerably.Recent studies indicate that calcific aortic stenosis might be based on an active,chronic inflammatory process.But the precise pathomechanisms remain unclear. Matrix metallproteinases are a group of zinc-dependent endope ptidases that are secreted as inactive pro-enzymes by various cell types.They may co-ordinately degrade all components of the extracellular matrix including fibrillar collagen.The local equilibrium between MMP and TIMP expression and activation is thought to influence the extent of tissue remoding.Recently, it has been reported that apoptosis is almost certainly involved in the pathogenesis of a variety of human cardiovascular dise ase.Furthermore,apoptosis may play an important role in the structural remoding.Objective:The experiment is to investigate the expression and significance of metalloproteinase and apoptosis in the calcific aortic valve.To probe the pathogenetic mechanisms leading to the development of calcific aortic valve initially.Methods:Light and transmission electron microscopic observation of the calcific aortic valve during aortic valve replacement were carried out in 15 patients with senile calcific aortic stenosis and 10 patients with other reasons.And calculate the apoptosis index(AI)with TUNEL,were studied by immunohistochemistry for MMP-2 and TIMP-2.Result:1 Calcific valve the collagen fiber hyperplasia is compact, border blurred,degeneration,the lipid gather,the cell nuc leus strengthens visible disorderly arrangement mucus app earance to shrink falling off,elastic force fibre disinte gration,trivial calcium salt deposits first in the valve base degeneration and the lipid gather area,the endodermis is uneven,completeness destroys,the bast cell number falls off appearance the bottom,the collagen fiber mucus.2 The staining intensity in calcific valve showed was significantly increased.Positive cells were mostly localized subend othelial and the extracellular matrix,P＜0.01.Control valves exhibitied very weak staining of MMP-2 and TIMP-2 mostly localized in the extracelluar matrix. 3 The AI in the calcific valve showed was significantly increased(0.71±9.07 vs 0.21±6.83),P＜0.05.4 The cell component falls off obviously in the valve,fibre cell buckling grows up shuttle shape,cell nucleus solid shrink, visible degeneration mitochondria and empty space steep shape remains bodies in kytoplasm,extracellular matrix is hit by visible matrix vesicle.Interstitium calcification and aggregation.Various degree of endothelial alterations from disruption of individual endothelial cells to extensive denudation of ent ire endothelium were observed particularly on the aortic side of the valve.The apoptosis changes occurring in the nuclei of endothelial cells and fibroblasts in the calcified valve.Calcific deposits associated with the cellular fragments derived from apoptosis fibroblast.The degradation products and organelles results from apoptosis provided the substrates for calcific deposite.Conclusions:1 The unnormal expression of MMP-2 and TIMP-2 in the subendothelium breakdown the balance of MMP-2/TIMP-2. Matrix degradation increased and endothelium damaged. The expression of MMP-2 and TIMP-2 may play an impor tant role in the calcific aortic valve,they may be involved not only in matrix degradation but also in matrix remodling.2 Apoptosis of the fibroblasts was closely related to the severity of endothelial damage.Apoptosis may play an important role in the alterations of endothelial integrity leading to the increased filtration of calcium into the deeper layer of the valve tissue.3 The cellular degradation products and organelles extruded from the fibroblasts,mainly provided the substrates for calcium binding with progressive development of calcification in the valve tissue.4 Although the role of MMP and apoptosis in contribution to the pathogenesis of aortic valve calcification is evident,the mechanism of regulation and activation remain to be elucid ated.Further studies using modern molecular biotechnology are mandatory in order to clarify the mechanism for the initiation of apoptosis in the endothelial cells and fibroblasts.