| Objective: To investigate the characteristic of the extracellular matrix remodeling induced by left ventricular pressure overload in valve disease. To analyze the gene expression of CTGF and MT1-MMP mRNA in cadiac muscle induced by pressure overload in valve disease, and the mechanism of CTGF and MT1-MMP in extracellular matrix remodeling. To identify the relationship between heart functional rehabilitation and the postoperative regression after the valve replacement in patients with aortic valve stenosis.Methods: 1.Of 45 patients, 16 cases were left ventricular pressure overload groups (PO), which were the multiple valve disease with predominately aortic valve stenosis,13 cases were left ventricular volume overload group (VO), which were the multiple valve disease with predominately aortic insufficiency,16 cases were mitral stenosis group (MS), which were composed of patients with simple mitral stenosis. Meanwhile, 5 normal persons were the control group, which died in accident. 2. The papillary muscles of left ventricle were collected during valve replacement operation and the sample tissues were divided into two parts, one for fixed embedding making paraffin section, another reserverd in liqid nitrogen for RT-PCR. In control group, ventricle muscles were collected in 0.5h after the death in accident, and reserved in -70℃freezer. 3. Histological features were studied by using Masson staining, and collagenous contents were quantitated with a computer-assisted imaging analysis system. The expression of CTGF mRNA and MT1-MMP mRNA were detected with RT-PCR methods. 4. 45 valve replacement patients were followed up by echocardiography and blood serum PICP were detected in all patients.Results: 1. Compare with MS group and control group, collagenous contents of left ventricle were significantly hyperplasia in PO group (P<0.01), vessel wall became thickening, and lumen of blood vessel got narrowing in PO group (P<0.05). Compare with VO group, the degree of myocardial fibrosis was higher in PO group (P<0.05). Compare with MS group and control group, the degree of myocardial fibrosis was higher in VO group (P<0.05). Compare with control group, collagenous contents of left ventricle were significantly hyperplasia in MS group (P<0.05). Pressure overload forms concentric hypertrophy in PO patients, volume overload forms eccentric hypertrophy in VO patients and myocardial hypertrophy was not found in MS group. 2. Compared with MS group and control group, the mean level of CTGF mRNA and MT1-MMP mRNA expression were significantly increased in PO group (P<0.01). Compared with MS group and control group, the mean level of MT1-MMP mRNA expression was significantly increased in VO group (P<0.05), there were no statistically difference of CTGF mRNA expression between PO group and VO group (P>0.05). The mean levels of CTGF mRNA and MT1-MMP mRNA expression in MS and control group were both lower. There were no statistically difference of MT1-MMP mRNA expression between MS group and control group (P>0.05), but CTGF mRNA expression was increased in MS group compare to control group (P<0.05). 3. After valve replacement, there were no statistically difference of heart functional rehabilitation between PO group and VO group (P>0.05). Compared with PO group, the heart functional rehabilitation was significantly improved (P<0.05) in MS group. After valve replacement, left ventricle chamber was significantly decreased; interventricular septum and LVPW were gradually thinningzed in PO group, there were no statistically difference between PO group and MS group (P>0.05). There was still existed higher valve pressure gradient, LVMI was increased obviously in PO group patients compared to MS group (P<0.05). 4. The concentration of serum PICP in valve replacement patients was higher than the control group (P<0.05). Compared with MS group, PICP was higher in PO and VO group (P<0.05). Postoperative (1mon) PICP decreased slowly, while postoperative (6mon, 12mon) PICP decreased obviously (P<0.05) in PO and VO group. In MS group, postoperative PICP decreased slightly (P<0.05). CVF,PVCA,CTGF mRNA,LVMI varied directly with preoperative PICP patients.Conclusion: 1. In PO group, the extracellular matrix remodeling of left ventricle is obviously, which is predominately with extracellular matrix proliferated and portion of each part changed, especially collagenous I and III deposited overacted, ventricular wall and blood vessel wall were thicked, and blood vessel get narrow, myocardial fibrosis is more seriously than in volume overload. Aortic valve stenosis induced pressure overload could form concentric hypertrophy, myocardial rigidity increased, thus to result in cardiac diastolic function decreased significantly. 2. As a fibrosis medium, CTGF mRNA expression was significantly increased in PO group, it`s maybe one of the key reason why left ventricle and LVMI were significantly hyperplasia and myocardial fibrosis was seriously. As a reverse fibrosis medium, MT1-MMP mRNA expression was increased both in VO and PO group, but it`s lower in PO group than in VO group, this maybe one reason why the fabrosis was sereasly in PO group than in VO group. 3. Based on the PICP concentration, it shows that the degree of myocardial fibrosis significantly decreased in postoperative than preoperative. But PICP concentrations were higher than those of control group. The result shows that the extracellular matrix remodeling by valve replacement in patients with aortic valve stenosis could not be completely reversed. The relation between the PICP concentration and the recovery of diastolic function is positive correlation.This show that myocardial fibrosis is the reason of the recovery of diastolic function.
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