Differential Proteomics Research On LVH Of Rats With Abdominal Aortic Constriction And The Preventive Effects Of Telmisartan And Amlodipine On LVH

ObjectiveTo establish the rat model of left ventricular hypertrophy in hypertensive rats by Abdominal Aotic Constriction(AAC) and to investigate the preventive effects of Amlodipine and Telmisatan on animal model of LVH, AAC rats.MethodsAAC and Sham operation were performed on 8-week-old male Sprague Dawley rats. After one week of operation, AAC rats were randomly divided into three groups, Amlodipine, Telmisartan and control respectively. The first two groups were treated by Amlodipine and Telmisartan at the dosages of 5mg/kg/day respectively. Before treatment and before animal sacrificed, echocardiographic, hemodynamic and cardiac morphological data were collected again for comparison.Results1. The animal survival probability was 76.3% after AAC operation. Compared with Sham group, AAC group rats increased HR, SBP, DBP, LVESP with 10.7%,18.9%,8.8% and 19.2%(P<0.05) respectively. There was no significant difference on echocardiographic and pathologic index between the two groups. After 9 weeks of operation, there were 22.3%,38.1%,22.0%,40.9%increase in HR, SBP, DBP, LVESP(P<0.01), and 30.4%, 30.3%,40.4%,38.1%increase in IVS, LVPW, HW, HW/BW(P<0.01) respectively. The myocardial cells enlarged dramatically and arranged disorderly, the nuclei also enlarged and darken stained and malformed under microscope. EF,FS,LVEDP,±dp/dtmax there was no significant difference between two groups and no pulmonary edema under microscope.2. After treatment by Amlodipine for 8 weeks, SBP, DBP, LVESP decreased by 24.7%,17.5%,24.8%(P< 0.01) respectively in Amlodipine group compared with control group, and there was no significant difference with Sham group(P>0.05).1VS,LVPW,HW, HW/BW decreased by 11.5%,10.5%,17.1%,16.2%(P<0.05) respectively in Amlodipine group compared with controls, but increased compared with the Sham group (P<0.05).3. After treatment by Telmisartan for 8 weeks, IVS,LVPW,HW,HW/BW decreased by 15.5%,,6.3%,31.7%,33.3%(P<0.01)respectively in Telmisartan group compared with control group, and there was no significant difference with Sham group(P>0.05), SBP,DBP,LVESP decreased by 20.4%,15.4%,22.0%(P<0.01) respectively in Telmisartan group compared with controls, but increased compared with Sham group(P< 0.05).ConclusionThe rat model of left ventricular hypertrophy in hypertensive rats by Abdominal Aotic Constriction(AAC) was successed. Both amlodipine and telmisartan can decrease blood pressure and can prevent LVH formation of AAC rats. Telmisartan is more effective on prevention of LVH than Amlodipine based on the similar decreasing blood pressure effect. ObjectiveTo identify the differentially expressed proteins in the left ventricular hypertrophy of Abdominal Aortic Constriction (AAC) rats by proteomic approach and analyze the functions of these differential proteins associated with the mechanism of hypertensive hypertrophy.Methods8-week-old male Sprague Dawley rats were grouped randomly into AAC and Sham groups. Collected echocardiographic, hemodynamic, cardiac morphological data after 9 weeks and obtained animal heart muscle proteins for 2-D gel analysis. Differentially expressed proteins between two groups were confirmed by MODI-TOF-MS and further verified by western-blot.Results1. The protein spots on 2-D gels of AAC and Sham were 916±66,914±37 respectively. The matching rate within group was 90.3% and 86.1% between groups.2. In 2-D gel analysis, the spot's density if more than 2 times different, it will be considered difference (p<0.05). There were 35 different spots between AAC and Sham groups,17 differentially expressed protein spots were up-regulated and 8 were down-regulated.5 were appeared only in AAC group and 5 were absent in AAC group.3. Confirmed 21 protein spots by MOLDI-TOF-MS. There were 14 up-regulated,4 down-regulated and 3 were newly observed. Up-regulation proteins were myosin light polypeptide, cardiac muscle alpha actin l proprotein, beta-myosin heavy chain, mitochondrial ribosomal protein LI5, G protein-coupled receptor 34, Tyrosine-protein kinase ZAP-70, aspartyl-tRNA synthetase, et al. Down-regulation proteins were ATP synthase,L-3-hydroxyacyl-Coenzyme A dehydrogenase,3-hydroxybutyrate dehydrogenase, et al. The newly observed proteins in LVH group were IQ motif and ubiquitin domain containing,3-hydroxybutyrate dehydrogenase and unnamed protein product.4. Among the 21 confirmed proteins,6 were cell structure proteins (28.5%),6 metabolism related proteins,4 signal transduction proteins,3 post-translation modification proteins and 2 unknown proteins.ConclusionDifferentially expressed proteins in AAC rats associated with glycolysis, cell signaling and communication, gene expression and regulation, myocardial structure were increased and protein expression related to fat acid metabolism decreased, these changes led to left ventricular hypertrophy eventually. ObjectiveTo investigate the preventive effects of Telmisartan and Amlodipine on left ventricular hypertrophy (LVH) in the early stage of the hypertensive rats with abdominal aortic constriction (AAC), and to analyze protein expression changes in LVH by proteomic approach and to identify key proteins associated with Telmisartan and Amlodipine treatment.MethodsThe hypertensive rats with AAC were treated with Telmisartan and Amlodipine(5mg/kg) respectively for 8 weeks. Echocardiography, hemodynamic measurements and necropsy were performed to assess the degree of LVH. The differentially expressed proteins in all groups were separated by 2-DE and identified by MODI-TOF-MS. Alterations in protein expression were further confirmed by western-blot analysis.ResultsAmong 21 differential proteins between Sham and Control groups, there were 13 different spots between Telmisartan and Control groups. Down-regulation proteins were Zeroβ-globin, myosin, cardiac muscle alpha actin 1 proprotein, beta-myosin heavy chain, myosin light chain 2, glyceraldohyde-3-phosphate, aspartyl-tRNA synthetase, G protein-coupled receptor 34, Tyrosine-protein kinase ZAP-70, Up-regulation proteins were H(+)-transproting ATP synthase, L3-hydroxybutyrate dehydrogenase, ATP synthase,ATP synthase beta subunit. There were 5 different spots between Amlodipine and Control groups. Down-regulation proteins were cardiac muscle alpha actin 1 proprotein, beta-myosin heavy chain,3-hydroxybutyrate dehydrogenase, aspartyl-tRNA synthetase. Up-regulation proteins were H(+)- transproting ATP synthase, L3-hydroxybutyrate dehydrogenase, ATP synthase,ATP synthase beta subunit. The results of Western-blot showed that myosin light chain 2 was increased in control and amlodipine treatment group, and it was 1.98 and 1.70 fold of that in Sham group (P<0.05). There was no significant difference between those two groups. In Telmisartan treated group, the protein was 1.37 fold of that in Sham group, but it decreased 44% in AAC group (p<0.05).ConclusionIn addition to reducing BP, Telmisartan may prevent the development of LVH by down-regulating proteins associated with glycolysis, intracellular signalling of G protein-coupled receptor and tyrosine-protein kinase, gene expression, and eventually causing down-regulation of myocardial structure proteins. Amlodipine may prevent the development of LVH by down-regulating proteins associated with myocardial structure and increase the protein expression associated with glycolysis, gene expression. Telmisartan is more effective than Amlodipine on preventing of LVH proteins expression based on the similar blood pressure regulation.