[Significance and Expressions of MMP-1, TIMP-1 and TGF-ß1 in Valve Tissue of Rheumatic Heart Disease].

OBJECTIVES: To explore expressions of matrix metalloproteinase-1 (MMP-1), tissue inhibitor of metalloproteinases-1 (TIMP-1) and transforming growth factor-ß1 (TGF-ß1) in valve tissue of rheumatic heart disease (RHD), and to analyzed their roles in RHD. METHODS: The expressions of MMP-1, TIMP-1 and TGF-ß1 proteins and mRNAs were tested by Western blot and RT-PCR methods in valve tissues in participants with (experimental group, n=30) and without RHD (control group, n=15). Collagen fibers were detected by Masson staining, and collagen volume fraction (CVF) was caculated. The correlations of CVF and the expressions of MMP-1, TIMP-1 and TGF-ß1 were analyzed. RESULTS: The collagen fibers, CVF, and the protein and mRNA expressions of MMP-1 and TGF-ß1 in experimental group were higher than those in control group, while the protein and mRNA expressions of TIMP-1 in experimental group were lower than those in control group. The expression of TIMP-1 was negatively correlated with TGF-ß1 and CVF in valve tissues, while MMP-1 was positively correlated with them. The expression of TGF-ß1 was positively correlated with CVF in valve tissues. CONCLUSIONS: MMP-1, TIMP-1 and TGF-ß1 contribute to the progression of fibrosis in RHD.

Myocardial Injury in Rats Exposed to High-Intensity Exercise Evaluated by 2-D Speckle Tracking Imaging.

OBJECTIVE: The aim of the work described here was to evaluate strain and morphological change of the left ventricle in Sprague Dawley (SD) rats at different exercise intensities by 2-D speckle tracking imaging (STI). METHODS: Seventy-two 8-wk-old SD rats were divided into four groups on the basis of exercise intensity: sedentary (SED), low-intensity running, medium-intensity running (MIR) and high-intensity running (HIR). Each group was further sub-divided into three groups of different exercise lengths: 1, 4 and 8 wk. The structural measurements of the left ventricle and left ventricular ejection fraction (LVEF) were obtained by echocardiography. Systolic peak values of global longitudinal, circumferential and radial strains (GLS, GCS and GRS) were obtained. Histopathological results of the cross-sectional area (CSA) of myocardial cells, collagen volume fraction (CVF) of the myocardium and perivascular collagen area (PVCA) were also observed. RESULTS: Structural measurements of the left ventricle and LVEF did not change with different exercise intensities or lengths. GLS of the HIR8 wk sub-group was significantly lower than those of the SED8 wk and MIR8 wk sub-groups. Conversely, the GLS and GCS of the HIR8 wk sub-group were lower than those of the HIR1 wk and HIR4 wk sub-groups. Histopathologically, the CSA of myocardial cells significantly increased across all HIR sub-groups and the MIR4 wk and MIR8 wk sub-groups. CVFendo and PVCA were also significantly increased in the HIR4 wk and HIR8 wk sub-groups. The HIR8 wk group also had regional swelling and ill-defined boundaries of myocardial cells. CONCLUSION: Prolonged, high-intensity exercise may lead to exercise-induced injury of the myocardium. Two-dimensional STI can be used as a non-invasive early detection method for exercise-induced injury of myocardial function, compared with LVEF.

Value of segmental myocardial strain by 2-dimensional strain echocardiography for assessment of scar area induced in a rat model of myocardial infarction.

OBJECTIVES: Two-dimensional strain echocardiography (2DSE) technique has enabled accurate quantification of regional myocardial function. This experimental study was aimed to investigate the value of 2DSE in detection of segmental regional myocardial dysfunction induced by fibrosis following myocardial infarction in a small animal (rat) model. METHODS: A rat model of myocardial infarction was established by ligation of the proximal left anterior descending coronary artery in 17 SD rats. Regional myocardial function was detected by 2DSE at baseline and 4-weeks post-infarction, including end-systolic radial strain and strain rate (SR and SrR) and end-systolic circumferential strain and strain rate (SC and SrC) of each of six segments at papillary level. According to the size of scar found by histologic Masson staining, the optimal cutoff points of parameters for detecting scar area were analyzed and the sensitivity and specificity of every parameter to detect myocardial scar were obtained using ROC. RESULTS: (1) Comparing with parameters measured at baseline, there were significant decreases in SR, SrR, SC and SrC of each segment at 4 weeks post-infarction, with the worst in the infarct area (32.90 ± 8.79 vs 11.18 ± 3.89, 6.28 ± 1.35 vs 3.18 ± 0.47, -14.46 ± 2.21 vs -6.30 ± 2.17 and 4.93 ± 0.95 vs 2.59 ± 1.16, respectively) (all P < 0.05). (2)By 4 weeks, the myocardium of infarct area (anteroseptum, anterior and anterolateral) had fibrosis (31.33 ± 9.89, 73.42 ± 13.21 and 13.99 ± 3.24%, respectively) with minimal fibrosis in inferoseptal segment (0.32 ± 0.19%), no fibrosis was found in the inferior and inferolateral segments. (3)Significant negative correlations were found between the size of segmental scar and 2DSE parameters (r-value -0.61 ~ -0.80, all P < 0.01) with the strongest correlation in SR. SR less than 10% has 84% sensitivity and 98% specificity for detecting segments of scar area greater than 30% with AUC = 0.97. CONCLUSIONS: 2DSE is able to assess regional myocardial dysfunction in a rat model of myocardial infarction and has high accuracy in detecting infarct segments with scar area greater than 30%.

[Adverse cardiovascular effects of antiretrovirals in female mice during gestation].

Objective: To evaluate the effects of antiretrovirals on cardiovascular function and some biochemical indexes in gestational female rats. Methods: Nineteen 9-week-old female and six 10-week-old male SD rats were divided into normal control group (CON) and highly active antiretroviral therapy group (HARRT), 9/10 female rats and 3 male rats were combined into one cage, totally 2 cages. Female rats in CON group were intragastrically given with normal saline (NS, 10 ml/kg) every morning and evening, while female rats in HARRT group were treated with equal volume antiretrovirals (AZT 31.25 mg/kg + 3TC 15.63 mg/kg + LPV/r (41.67/10.42) mg/kg) for 3 months. The body weight and survival rate of female rats were recorded. Echocardiography and multichannel physiological recorder were used to detect arterial blood pressure and cardiac hemodynamic parameters. The levels of blood glucose, blood lipids, myocardial enzymes and liver enzymes were detected by corresponding kits. Myocardial collagen fibers were observed by Masson staining and the ultrastructure of myocardial cells were observed by transmission electron microscopy. Results: All female rats in CON group survived (9/9), while only 6 rats in HARRT group survived (6/10). Compared with CON group, the body weight of female rats in HAART group was decreased significantly(P＜0.01); the levels of left ventricular end diastolic diameter (LVDd), interventricular septal thickness (IVST), thickness of left ventricular posterior wall (LVPWT) , left atrial diameter (LAD) and arterial diastolic pressure were increased significantly (P＜0.05); the level of LVP+dP/dtmax was decreased (P＜0.01). The levels of triglyceride, creatine kinase, and glutamic oxaloacetic transaminase were decreased (P＜0.05 or P＜0.01), while the level of glucose was increased (P＜0.05). The collagen fibers were increased in myocardial tissue, and ultrastructure of myocardial cells was abnormal. Conclusion: Antiretrovirals during gestation can cause cardiovascular diseases in female rats.