7076

TIMP1

CLGI|EPA|EPO|HCI|TIMP;TIMP metallopeptidase inhibitor 1;TIMP1;TIMP metallopeptidase inhibitor 1

TIMP-1|collagenase inhibitor|erythroid potentiating activity|erythroid-potentiating activity|fibroblast collagenase inhibitor|metalloproteinase inhibitor 1|tissue inhibitor of metalloproteinases 1

Xp11.3-p11.23

protein-coding

Count: TIMP; 116510

Pulmonary artery hypertension (PAH) causes right ventricular failure and possibly even death by a progressive increase in pulmonary vascular resistance. Bone marrow-derived mesenchymal stem cell therapy has provided an alternative treatment for ailments of various organs by promoting cell regeneration at the site of pathology. The purpose of this study was to investigate changes of pulmonary haemodynamics, pathology and expressions of various genes, including ET (endothelin)-1, ET receptor A (ERA), endothelial nitric oxide synthase (NOS) 3, matrix metalloproteinase (MMP) 2, tissue inhibitor of matrix metalloproteinase (TIMP), interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha in monocrotaline (MCT)-induced PAH rat models after bone marrow cell (BMC) transfusion. The rats were grouped as the control (C) group, monocrotaline (M) group, and BMC transfusion (B) group. M and B groups received subcutaneous (sc) injection of MCT (60 mg/kg). BMCs were transfused by intravenous injection at the tail 1 week after MCT injection in B group. Results showed that the average RV pressure significantly decreased in the B group compared with the M group. RV weight and the ratio of RH/LH+septum significantly decreased in the B group compared to the M group. Gene expressions of ET-1, ERA, NOS 3, MMP 2, TIMP, IL-6, and TNF-alpha significantly decreased in week 4 in the B group compared with the M group. In conclusion, BMC transfusion appears to improve survival rate, RVH, and mean RV pressure, and decreases gene expressions of ET-1, ERA, NOS 3, MMP 2, TIMP, IL-6, and TNF-alpha.

OBJECTIVE: To determine the effect of captopril and losartan on the expressions of matrix metalloproteinase-2,9 (MMP-2,9) and metalloproteinase-1 (TIMP-1) in rats with pulmonary arterial hypertension, and the mechanisms of captopril and losartan in intervening the development of pulmonary arterial hypertension. METHODS: Forty male Spraque-Dawley rats were divided into 4 groups randomly: pulmonary arterial hypertension (created by pneumonectomy plus MCT injection) model group (PAH Model), PAH model treated with captopril [PAH+Cap 10 mg/(kg x d)], losartan group [PAH+Los 15 mg/(kg x d)] and normal control group(Control). The mPAP, weight ratio of RV to LV+S, neointima formation, relative thickness of small pulmonary arteries, and degree of muscularization of non-muscular arterioles were measured at day 35. The expression of SM-a-actin in the PASMC was determined by immunochemistry stain. The expressions of MMP-2, 9, TIMP-1 and MMP-2, 9, TIMP-1 mRNA in the pulmonary tissues were determined by immunohistochemistry and FQ-PCR respectively. The enzymatic activity of MMP-2, 9 was measured by Gelatin zymography. RESULTS: Pneumonectomy plus MCT injection induced severe pulmonary arterial hypertension characterized by neointimal formation. Captopril or losartan suppressed the increase of mPAP, right ventricle weight, thickness of small pulmonary arteries and muscularization of peripheral pulmonary arterioles in the rats with PAH (P < 0.05). The PAH model group had higher expressions of MMP-2, 9, TIMP-1 mRNA and enzymatic activity of MMP-2, 9 in lung tissue than the other groups (P < 0.05). Captopril intervention had similar effects as losartan intervention. CONCLUSION: The captopril and losartan induced attenuation of PAH and pulmonary vascular remodeling is likely to be associated with the regulation of the expressions of MMP-2, 9, TIMP-1.