| Background Left ventricular hypertrophy (LVH) is regarded as a strong independent risk factor for the morbidity and mortality of essential hypertension (EH). It has been proved that the patients with EH and LVH die of myocardial infarction, heart failure, sudden death and other cardiovascular disease with 6~8 times more chances than that of patients with EH. Nowdays the reversal of LVH is one of main targets for the treatment of EH. Besides cardiomyocytes hypertrophy, the pathological basis of left ventricular hypertrophy shows cardiac fibroblasts (CFs) proliferation and excessive extracellular matrix (ECM) protein accumulation, which leads to myocardial fibrosis.It has been approved that statin can not only lower strikingly serum cholesterin and low-density lipoprotein , but also restrain VSMC from proliferation, prevent thrombosis and protect endothelium and its effect is far beyond that of regulate lipidemia. It remains unknown whether MF can be bettered by atorvastatin. The aim of study is to observe the effects of atorvastatin on the proliferation, the collagen synthesis, the activity of NOS-NO system, PTEN protein, the expression of NF- K. B and the matrix metalloproteinases and tissue inhibitors of metalloproteinases (MMPs/TIMPs) in the Spontaneously hypertensive rat (SHR) CFs, in hope of finding an new way for exploring theetiology and treatment of LVH associated with hypertension.Methods SHR CFs were isolated and cultured by collagenase-trypsin digestion and selective plating technique. (1) Cell proliferation was evaluated by MTT assay and cell cycle distribution was determined with flow cytometer (FCM). Collagen synthesis was measured by enzyme linked immuno-sorbent assay (ELISA). Nitric acid reductase method to detect NO contents, spectrophotometry was used to determine NOS activity. (2) Gelatinase activity was measured by gelatinase zymography. MMP-1, MMP-2, TIMP-1, TIMP-2 mRNA levels were detected by reversed transcription- polymerase chain reaction (RT-PCR). (3) PTEN, NF- K. B , MMP-1 and TIMP-1 protein levels were measured by western blot. (4) Immunofluorescence- interactive laser cytometer techniques was adopted to estimated the activation of NF- K B in SHR CFs with or without atorvastatin.. Results The results showed that: (1) A values of CFs from SHR measured with MTT assay in the 10-7mol/L, 10-6mol/L, 10-5mol/L and 10-4mol/L atorvastatin groups were 0.30 0.01, 0.26 0.01, 0.24 0.01 and 0.22 0.01, respectively, which were all significantly lower than that of control group (0.33 0.01, all P<0.01). A values of CFs from Wistar were 0.28 0.01, 0.26 0.01, 0.23 0.01 and 0.21 0.01, respectively, which were all remarkably lower than that of control group (0.30 0.01, all P<0.01). (2) 10-6mol/L atorvastatin could increase the percentage of G0/G1 stage and decrease the percentage of S stage , G2/M stage and proliferation index (PI). (3) The secretion of collagen I of SHR CFs in the 10-7mol/L-10-4mol/L atorvastatin groups were 0.80 0.01, 0.74 0.01, 0.68 0.01 and 0.62 0.02, respectively, all significantly lower than that of control group (0.97 0.02,all P<0.01). The secretion of collagen I of Wistar rats in 10-7mol/L~ 10-4mol/L atorvastatin groups were 0.73 0.01, 0.65 0.01, 0.60 0.02 and 0.56 0.02, respectively, all significantly lower than that of control group (0.81 0.01, all PO.01). (4) The PTEN protein level of SHR CFs in the 10-7mol/L-10-4mol/L atorvastatin groups were 1.63 0.12, 1.92 0.24, 2.75 0.19 and 3.08 0.27, respectively, all significantly higher than that of control group (1.47 0.16, all P<0.01). The PTEN protein level of Wistar rats in 10-7mol/L~ 10-4mol/L atorvastatin groups were 1.80 0.14, 2.34 0.21, 3.18 0.28 and 4.05 0.31, respectively, all significantly higher than that of control group10-6mol/L, 10-5mol/L and 10-4mol/L atorvastatin groups were 44.47 4.98 u mol/L, 51.70 5.0 In mol/L, 67.01 3.00 u mol/L and 73.81 2.29 w mol/L, respectively, 10-6mol/L, 10-5mol/L and 10-4mol/L atorvastatin groups were significantly higher than that of control group (39.78 4.48 mol/L, all P<0.01).
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