Background:Hypertrophy of the ligamentumflavum(HLF)is a common contributor to spinal stenosis which results in significant neurological impairments.Circular RNA(circRNA)circ_0003609 has been linked to HLF;however,the ex...Background:Hypertrophy of the ligamentumflavum(HLF)is a common contributor to spinal stenosis which results in significant neurological impairments.Circular RNA(circRNA)circ_0003609 has been linked to HLF;however,the exact mechanism by which it causes this disease is unclear.Methods:Circ_0003609 expressions were regulated in HLF cells by overexpression vectors and RNA interference.Cell proliferation andfibrosis-related gene expression were checked by the Cell Counting Kit-8(CCK-8)assay and western blotting.CircBank’s prediction of the association between miR-155 and circ_0003609 was supported by a dual-luciferase reporter experiment.The function of the miR-155/sirtuin 1(SIRT1)axis in controlling HLFfibrosis was further examined.Results:Overexpression of circ_0003609 suppressed HLF cell propagation andfibrosis compared to its silencing.It was found that circ_0003609 served as the sponge for miR-155 and that the circ_0003609/miR-155 axis controlled thefibrosis of HLF cells.It was found that circ_0003609 acted as a sponge for miR-155,regulating thefibrosis of HLF cells.Further,miR-155 targets SIRT1,and the miR-155/SIRT1 axis promotes HLF cellfibrosis.Conclusion:Circ_0003609 ameliorates hypertrophied ligamentumflavum(LF)by modulating the miR-155/SIRT1 axis,indicating a potential treatment approach for HLF.展开更多
Objective:To study the correlation between expression of Wnt and NCXl and cardiomyocyte apoptosis in mouse with myocardial hypertrophy.Methods:C57B/16 male mice were given the subcutaneous injection of 1 mg/kg isopren...Objective:To study the correlation between expression of Wnt and NCXl and cardiomyocyte apoptosis in mouse with myocardial hypertrophy.Methods:C57B/16 male mice were given the subcutaneous injection of 1 mg/kg isoprenaline to build the myocardial hypertrophy model.After 14 d of model building,mice were executed by cervical vertebra luxation.The ratio of heart weight/body weight(HW/BW) and heart weight/tibia length(HW/TL) was observed and proved using HE staining mat detected the size of eaidiomyocytes.40 male C57B/16 mice were randomly divided into the sham group(normal saline) and model group(isoprenaline),with 20 mice in each group.The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling was applied to detect the cardiomyocyte apoptosis;while Western blot and immunohistochemistry were employed to detect the expression of Wnt and NCX1.Meanwhile,the correlation between these two proteins and cardiomyocyte apoptosis was explored.Results:Compared with the sham group,the ratio of HW/BW and HW/TL was increased in the model group,as well as the bigger and hypertrophied cardiomyocytes,decreased number and increased apoptosis of eaidiomyocytes,and increased positive expression of Wnt3 a,WntSa and NCXl in the cardiac muscle tissue.Besides,there was positive correlation between the expression of Wnt and NCXl and the cardiomyocyte apoptosis.Conclusions:The expression of Wnt3 a,Wnt5a and NCXl in mouse with myocardial hypertrophy is increased and positively correlated with the cardiomyocyte apoptosis.展开更多
To investigate the molecular mechanism by which Tanshinone Ⅱ A （TSN Ⅱ A） prevents left ventricular hypertrophy （LVH）, we examined the expression of AT1R, TGF-β1 and Smads gene in the hypertrophic myocardium of ...To investigate the molecular mechanism by which Tanshinone Ⅱ A （TSN Ⅱ A） prevents left ventricular hypertrophy （LVH）, we examined the expression of AT1R, TGF-β1 and Smads gene in the hypertrophic myocardium of hypertensive rats with abdominal aorta constriction. LVH model was established by creating abdominal aorta constriction. Four weeks later, animals were randomly divided into 4 groups with 8 animals in each. One group was used as model control, the other three groups were treated with TSN ⅡA （20 mg/kg）, TSN ⅡA （10 mg/kg） and valsartan （10 mg/kg）, respectively. Another 8 SD rats were subjected to sham surgery and served as blank control. After 8- week treatment, the caudal artery pressure of the animals was measured. The tissues of left ventricle were taken for the measurement of the left ventricular mass index （LVMI） and pathological sectioning and HE-staining were used for determining the myocardial fiber dimension （MFD）. The mRNA expression of AT1R, protein expression of TGF-betal and activity of Smad-2, 4, 7 were detected by RT-PCR and Western blotting, respectively. Our results showed that （1） the blood pressure of rats treated with TSN Ⅱ A, either at high or low dose, was significantly higher than those in the control and valsartan-treated group （P〈0.01, P〈0.05）; （2） LVMI and MFD in TSN Ⅱ A and valsartan-treated rats were higher than those in the control group （P〈0.05） but significantly lower than those in the model control （P〈0.01）; （3） the high doses of TSN Ⅱ A and valsartan significantly down-regulated the mRNA expression of AT 1R and protein expression of TGF-beta l and Smad-3 in the hypertrophic myocardium （P〈0.01）, and TGF-betal in valsartan-treated animals was more significantly lower than that in rats treated with TSN Ⅱ A; （4） the two doses of TSN Ⅱ A and valsartan significantly up-regulated the protein expression of Smad-7 in the hypertrophic myocardium （P〈0.01）, and Smad-7 in the animals treated with high-dose TSN Ⅱ A was significantly higher than that in rats treated with valsartan. It is concluded that inhibition of myocardial hypertrophy induced by TSN ⅡA independent of blood pressure. The underlying mechanism might be the down-regulated expression of AT1R mRNA and Smad-3, increased production of Smad-7, and blocking effect of TSN Ⅱ A on TGF betal/Smads signal pathway in local myocardium.展开更多
Background The induced pluripotent stem cell （iPSC） has shown great potential in cellular therapy of myocardial infarction （MI）, while its application is hampered by the low efficiency of cardiomyocyte differentia...Background The induced pluripotent stem cell （iPSC） has shown great potential in cellular therapy of myocardial infarction （MI）, while its application is hampered by the low efficiency of cardiomyocyte differentiation. The present study was designed to investigate the effects of cardiotrophin-1 （CT-1） on cardiomyocyte differentiation from mouse induced pluripotent stem cells （miPSCs） and the underlying mechanisms involved. Methods The optimal treatment condition for cardiomyocyte differentiation from miPSCs was established with ideal concentration （10 ng/mL） and duration （from day 3 to day 14） of CT-1 administration. Up-regulated expression of cardiac specific genes that accounted for embryonic cardiogenesis was observed by quantitative RT-PCR. Elevated amount of a-myosin heavy chain （ct-MHC） and cardiac troponin I （cTn I） positive cells were detected by immunofluorescence staining and flow cytometry analysis in CT- 1 group. Results Transmission electron microscopic analysis revealed that cells treated with CT- 1 showed better organized sacromeric structure and more mitochondria, which are morphological characteristic of matured cardiomyocytes. Western blot demonstrated that CT-1 promotes cardiomyocyte differentiation from miPSCs partly via JAK2/STAT3/Pim-1 pathway as compared with control group. Conclusions These findings suggested that CT-1 could enhance the cardiomyocyte differentiation as well as the maturation of mouse induced pluripotent stem cell derived cardiomyocytes by regulating JAK2/STAT3/Pim-1 signaling pathway.展开更多
Objective： To observe the effect of different combination antihypertensive therapies on plasma endothelin-1 （ET-1） concentration and left ventricular diastolic function of essential hypertension patients with left ...Objective： To observe the effect of different combination antihypertensive therapies on plasma endothelin-1 （ET-1） concentration and left ventricular diastolic function of essential hypertension patients with left ventricular hypertrophy （LVH） Methods： A total of 111 patients with essential hypertension were selected, including 60 cases （34 males, 26 females） aged （60.7±5.6） years with simple hypertension, and 51 cases （28 males, 23 females） aged （61.8±7.0） years with essential hypertension complicated with LVH. Essential hypertension patients with LVH were randomly divided into the group of amlodipine （2.5 mg/d） combined with telmisartan （40 mg/d, n=26） and the group of amlodipine （2.5 mg/d） combined with amiloride （half tablet/d, n=25）,and the treatment lasted for 1 year. Echocardiography was performed before and after the treatment. Left ventricular mass index （LVMI）, left ventricular isovolumic relaxation time （IVRT） and other indicators were detected, and plasma ET-1 concentrations were measured for comparative analysis. And 56 patients （31 males, 25 females） aged （59.3±6.7） years with normal blood pressure in the same period in our hospital were selected as the normal control group. Results： The general clinical characteristics were similar between hypertensive LVH group, simple hypertensive group and normal healthy control group. Plasma ET-1 concentrations, LVMI and IVRT of hypertensive LVH group were significantly higher than those of normal control group and simple hypertension group, and the difference was statistically significant. The patients＇ baseline blood pressure, ET-1, LVMI, interventricular septal thickness （IVST）, left ventricular posterior wall thickness （LVPWT）, left ventricular end-diastolic diameter （LVEDd） and other clinical parameters showed no significant difference （P〉0.05） between the group of amlodipine combined with telmisartan and the group of amlodipine combined with amiloride. It was found that compared with that before treatment, blood pressure could be effectively controlled （P〈0.05）, and LVMI, IVST, LVPWT and IVRT （P〈0.05） were all lowered, and ET-1 （P〈0.01） was significantly reduced after 1 year of antihypertensive therapy in both the group of amlodipine combined with telmisartan and the group of amlodipine combined with amiloride. The group of amlodipine combined with telmisartan was better in lowering blood pressure and reducing LVMI, IVST, LVPWT, IVRT and ET-1 than the group of amlodipine combined with amiloride （P〈0.05）. Conelus｜on： Amlodipine-based combination antthypertensive therapy could reverse LVH and improve left ventricular diastolic function partly by lowering blood pressure and ET-1, and the effect of amlodipine combined with telmisartan was superior to that ofamlodipine combined with amiloride展开更多
Cardiotrophin-1 （CT-1） activates a distinct form of cardiac muscle cell hypertrophy in which the sarcomeric units are assembled in series. The aim of the study was to determine the expres- sion pattern of sarcomeric...Cardiotrophin-1 （CT-1） activates a distinct form of cardiac muscle cell hypertrophy in which the sarcomeric units are assembled in series. The aim of the study was to determine the expres- sion pattern of sarcomeric contractile protein α-actin, specialized eytoskeletal protein α-actinin and mitochondrial uncoupling protein-2 （UCP2） in myocardial remodeling induced by chronic exposure to CT-1. Kunming mice were intraperitoneally injected with carboxy-terminal polypeptide （CP） of CT-1 （CT-1-CP, 500 μg·kg-1·day^-1） for 1, 2, 3 and 4 week （s）, respectively （4 groups obtained according to the injection time, n=10 each, with 5 males and 5 females in each group）, Those injected with physiological saline for 4 weeks served as controls （n=10, with 5 males and 5 females）. The heart tissues of mice were harvested at 1, 2, 3 or 4 week （s）. Immunohistochemistry （IHC） and Western blotting （WB） were used to detect the distribution and expression of sarcomeric α-actin, α-aetinin and mitoehondrial UCP2 in myocardial tissues. IHC showed that α-actin was mainly distributed around the nuclei of cardiomyo- cytes, α-actinin concentrated around the striae and UCP2 scattered rather evenly in the plasma. The ex- pression of α-actin was slightly greater than that of α-actinin and UCP2 in the control group （IHC： χ^2=6.125; WB： F=0.249, P〉0.05） and it gradually decreased after exposure to CT-1-CP. There was no significant difference in the expression of α-actin between the control group and the CT-1-CP-treated groups （χ^2=7.386, P〉0.05）. But Western blotting revealed significant difference in the expression of α-actin between the control group and the 4-week CT-1-CP-treated group （F=2.912; q=4.203, P〈0.05）. Moreover, it was found that the expression of α-actinin increased stepwise with the exposure time in CT-1-CP-treated groups and differed significantly between CT-1-CP-treated groups and the control group （ICH： χ^2=21.977; WB： F=50.388; P〈0.01）. The expression of UCP2 was initially increased （WB： control group vs. 1- or 2-week group, q values： 5.603 and 9.995, respectively, P〈0.01） and then de- creased （WB： control group vs. 3-week group, q=4.742, P〈0.01; control group vs. 4-week group, q=0.558, P〉0.05）. It was suggested that long-term exposure to CT-1-CP could lead to the alteration in the expression of sarcomeric α-actin, α-actinin and mitochonclrial UCP2. The different expressions of sarcomeric structure proteins and mitochondrial UCP2 may be involved in myocardial remodeling.展开更多
Objective To investigate the impact of 1, 25-(OH)2D3 on left ventricular hypertrophy(LVH) in type 2 diabetic rats. Methods Type 2 diabetic mellitus(DM) model rats were established by intraperitoneally injecting with 3...Objective To investigate the impact of 1, 25-(OH)2D3 on left ventricular hypertrophy(LVH) in type 2 diabetic rats. Methods Type 2 diabetic mellitus(DM) model rats were established by intraperitoneally injecting with 30 mg/kg streptozotocin. After 8 weeks, 19 male rats were identified as diabetic with left ventricular hypertrophy(LVH) by ultrasound examination, and randomly assigned into three groups: untreated(DM-LVH, n=7), treated with insulin(DM-LVH+INS, n=6), and treated with 1, 25-(OH)2D3(DM-LVH+VD, n=6). Healthy male rats were used as the controls group(n=6). The fasting blood glucose and the insulin level were determined weekly. The left ventricular mass index, myocardial collagen content, collagen volume fraction, and 1, 25-(OH)2D3-receptor level were determined by 4 weeks later. Results In the DM-LVH model group, the insulin level was significantly decreased compared with the non-diabetic control group(P<0.05), whereas the blood glucose, left ventricular mass index, myocardial collagen content, collagen volume fraction, and 1, 25-(OH)2D3-receptor expression were significantly increased(all P<0.05). In the DM-LVH+INS and DM-LVH+VD groups, the insulin levels were significantly increased compared with the DM-LVH model group(P<0.05), whereas the other parameters were significantly decreased(all P<0.05). Conclusion 1, 25-(OH)2D3 could reverse LVH in diabetic rats and that the mechanism may involve stimulating insulin secretion and reducing blood glucose via direct up-regulation of 1, 25-(OH)2D3-receptor expression.展开更多
Participation of angiotensin II in chronic kidney diseases including diabetic nephropathy (DN) has been extensively described. Similarly, several studies support a protective role for angiotensin-(1-7). However, other...Participation of angiotensin II in chronic kidney diseases including diabetic nephropathy (DN) has been extensively described. Similarly, several studies support a protective role for angiotensin-(1-7). However, other studies suggest that some of the cellular effects of angiotensin-(1-7) may be deleterious. The objective of this study was to determine the role of exogenous angiotensin-(1-7) on renal hypertrophy development in rats with streptozotocin-induced diabetes. A control group and three groups of rats with streptozotocin-induced diabetes: untreated diabetic rats, diabetic rats treated with captopril, and diabetic rats treated with angiotensin-(1-7), were studied. After two weeks of treatment, the kidneys were removed under anesthesia with pentobarbital. The kidneys were weighed and the renal cortex was separated for analysis of AT<sub>1</sub>R, TGF-β<sub>1</sub>, MASR, and ACE2 expression by western blot. Rats in the three groups with diabetes had hyperglycemia, increased food and water consumption, and higher urinary volume than control rats. Treatment with captopril or angiotensin-(1-7) reversed streptozotocin-induced renal hypertrophy, measured by kidney weight, protein/DNA ratio in renal cortex, glomerular area, or proximal tubular cells area, proteinuria, and creatinine clearance reduction. AT<sub>1</sub>R, TGF-β<sub>1</sub>, and MAS receptor expression in renal cortex of diabetic rats increased significantly as compared to controls (p展开更多
MicroRNAs(miRNAs) are a class of endogenous small noncoding RNAs that regulate gene expression post-transcriptionally. Recent studies have demonstrated that miRNAs are involved in the pathogenesis of hypertrophy.We in...MicroRNAs(miRNAs) are a class of endogenous small noncoding RNAs that regulate gene expression post-transcriptionally. Recent studies have demonstrated that miRNAs are involved in the pathogenesis of hypertrophy.We investigated miR-16 expression and their potential roles in a rat model of hypertrophy induced by abdominal artery constriction (AAC).miR-16 expression was significantly decreased, and CCND1 and CCND2 protein were markedly increased without obvious change of its mRNA level after hypertrophy induction.CCND1 and CCND2 levels were increased without changing their transcript levels in neonatal rat ventricular cardiomyocytes(NRVC) induced by PE,and miR-16 was down-regulated in this process with significantly up-regulatedβ-MHC,ANF and MLC-2 expression.Conversely,introduction of functional miR-16,CCND1 siRNA or CCND2 siRNA into NRVCs could repress cardiomyocyte hypertrophy.These results implicate that miR-16 is involved in contributing to cardiac hypertrophy,one of the mechanisms may be resulted from post-transcriptional regulation of CCND1 and CCND2.展开更多
基金This research was supported by the Shanghai Natural Science Fund(No.21ZR1447500)Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital Baoshan Branch Medical Key Specialty Construction Project(No.rbzdzk-2023-001).
文摘Background:Hypertrophy of the ligamentumflavum(HLF)is a common contributor to spinal stenosis which results in significant neurological impairments.Circular RNA(circRNA)circ_0003609 has been linked to HLF;however,the exact mechanism by which it causes this disease is unclear.Methods:Circ_0003609 expressions were regulated in HLF cells by overexpression vectors and RNA interference.Cell proliferation andfibrosis-related gene expression were checked by the Cell Counting Kit-8(CCK-8)assay and western blotting.CircBank’s prediction of the association between miR-155 and circ_0003609 was supported by a dual-luciferase reporter experiment.The function of the miR-155/sirtuin 1(SIRT1)axis in controlling HLFfibrosis was further examined.Results:Overexpression of circ_0003609 suppressed HLF cell propagation andfibrosis compared to its silencing.It was found that circ_0003609 served as the sponge for miR-155 and that the circ_0003609/miR-155 axis controlled thefibrosis of HLF cells.It was found that circ_0003609 acted as a sponge for miR-155,regulating thefibrosis of HLF cells.Further,miR-155 targets SIRT1,and the miR-155/SIRT1 axis promotes HLF cellfibrosis.Conclusion:Circ_0003609 ameliorates hypertrophied ligamentumflavum(LF)by modulating the miR-155/SIRT1 axis,indicating a potential treatment approach for HLF.
基金supported by National Natural Science Foundation of China(81070655)
文摘Objective:To study the correlation between expression of Wnt and NCXl and cardiomyocyte apoptosis in mouse with myocardial hypertrophy.Methods:C57B/16 male mice were given the subcutaneous injection of 1 mg/kg isoprenaline to build the myocardial hypertrophy model.After 14 d of model building,mice were executed by cervical vertebra luxation.The ratio of heart weight/body weight(HW/BW) and heart weight/tibia length(HW/TL) was observed and proved using HE staining mat detected the size of eaidiomyocytes.40 male C57B/16 mice were randomly divided into the sham group(normal saline) and model group(isoprenaline),with 20 mice in each group.The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling was applied to detect the cardiomyocyte apoptosis;while Western blot and immunohistochemistry were employed to detect the expression of Wnt and NCX1.Meanwhile,the correlation between these two proteins and cardiomyocyte apoptosis was explored.Results:Compared with the sham group,the ratio of HW/BW and HW/TL was increased in the model group,as well as the bigger and hypertrophied cardiomyocytes,decreased number and increased apoptosis of eaidiomyocytes,and increased positive expression of Wnt3 a,WntSa and NCXl in the cardiac muscle tissue.Besides,there was positive correlation between the expression of Wnt and NCXl and the cardiomyocyte apoptosis.Conclusions:The expression of Wnt3 a,Wnt5a and NCXl in mouse with myocardial hypertrophy is increased and positively correlated with the cardiomyocyte apoptosis.
基金supported by a grant from the National Natural Science Foundation of China(No.30500657)
文摘To investigate the molecular mechanism by which Tanshinone Ⅱ A （TSN Ⅱ A） prevents left ventricular hypertrophy （LVH）, we examined the expression of AT1R, TGF-β1 and Smads gene in the hypertrophic myocardium of hypertensive rats with abdominal aorta constriction. LVH model was established by creating abdominal aorta constriction. Four weeks later, animals were randomly divided into 4 groups with 8 animals in each. One group was used as model control, the other three groups were treated with TSN ⅡA （20 mg/kg）, TSN ⅡA （10 mg/kg） and valsartan （10 mg/kg）, respectively. Another 8 SD rats were subjected to sham surgery and served as blank control. After 8- week treatment, the caudal artery pressure of the animals was measured. The tissues of left ventricle were taken for the measurement of the left ventricular mass index （LVMI） and pathological sectioning and HE-staining were used for determining the myocardial fiber dimension （MFD）. The mRNA expression of AT1R, protein expression of TGF-betal and activity of Smad-2, 4, 7 were detected by RT-PCR and Western blotting, respectively. Our results showed that （1） the blood pressure of rats treated with TSN Ⅱ A, either at high or low dose, was significantly higher than those in the control and valsartan-treated group （P〈0.01, P〈0.05）; （2） LVMI and MFD in TSN Ⅱ A and valsartan-treated rats were higher than those in the control group （P〈0.05） but significantly lower than those in the model control （P〈0.01）; （3） the high doses of TSN Ⅱ A and valsartan significantly down-regulated the mRNA expression of AT 1R and protein expression of TGF-beta l and Smad-3 in the hypertrophic myocardium （P〈0.01）, and TGF-betal in valsartan-treated animals was more significantly lower than that in rats treated with TSN Ⅱ A; （4） the two doses of TSN Ⅱ A and valsartan significantly up-regulated the protein expression of Smad-7 in the hypertrophic myocardium （P〈0.01）, and Smad-7 in the animals treated with high-dose TSN Ⅱ A was significantly higher than that in rats treated with valsartan. It is concluded that inhibition of myocardial hypertrophy induced by TSN ⅡA independent of blood pressure. The underlying mechanism might be the down-regulated expression of AT1R mRNA and Smad-3, increased production of Smad-7, and blocking effect of TSN Ⅱ A on TGF betal/Smads signal pathway in local myocardium.
基金This work was supported by the National Funds for Distinguished Young Scientists of China （No. 81325009） and National Nature Science Foundation of China （No. 81270168, No. 81227901）, （Feng Cao BWS12J037）, Innovation Team granted by Ministry of Education PRC （IRT1053）, National Basic Research Program of China （2012CB518101）. Shaanxi Province Program （2013K12-02-03, 2014KCT-20）. The authors declare no conflict of interest.
文摘Background The induced pluripotent stem cell （iPSC） has shown great potential in cellular therapy of myocardial infarction （MI）, while its application is hampered by the low efficiency of cardiomyocyte differentiation. The present study was designed to investigate the effects of cardiotrophin-1 （CT-1） on cardiomyocyte differentiation from mouse induced pluripotent stem cells （miPSCs） and the underlying mechanisms involved. Methods The optimal treatment condition for cardiomyocyte differentiation from miPSCs was established with ideal concentration （10 ng/mL） and duration （from day 3 to day 14） of CT-1 administration. Up-regulated expression of cardiac specific genes that accounted for embryonic cardiogenesis was observed by quantitative RT-PCR. Elevated amount of a-myosin heavy chain （ct-MHC） and cardiac troponin I （cTn I） positive cells were detected by immunofluorescence staining and flow cytometry analysis in CT- 1 group. Results Transmission electron microscopic analysis revealed that cells treated with CT- 1 showed better organized sacromeric structure and more mitochondria, which are morphological characteristic of matured cardiomyocytes. Western blot demonstrated that CT-1 promotes cardiomyocyte differentiation from miPSCs partly via JAK2/STAT3/Pim-1 pathway as compared with control group. Conclusions These findings suggested that CT-1 could enhance the cardiomyocyte differentiation as well as the maturation of mouse induced pluripotent stem cell derived cardiomyocytes by regulating JAK2/STAT3/Pim-1 signaling pathway.
基金Supported by the National Natural and Science Foundation of China(30871042)
文摘Objective： To observe the effect of different combination antihypertensive therapies on plasma endothelin-1 （ET-1） concentration and left ventricular diastolic function of essential hypertension patients with left ventricular hypertrophy （LVH） Methods： A total of 111 patients with essential hypertension were selected, including 60 cases （34 males, 26 females） aged （60.7±5.6） years with simple hypertension, and 51 cases （28 males, 23 females） aged （61.8±7.0） years with essential hypertension complicated with LVH. Essential hypertension patients with LVH were randomly divided into the group of amlodipine （2.5 mg/d） combined with telmisartan （40 mg/d, n=26） and the group of amlodipine （2.5 mg/d） combined with amiloride （half tablet/d, n=25）,and the treatment lasted for 1 year. Echocardiography was performed before and after the treatment. Left ventricular mass index （LVMI）, left ventricular isovolumic relaxation time （IVRT） and other indicators were detected, and plasma ET-1 concentrations were measured for comparative analysis. And 56 patients （31 males, 25 females） aged （59.3±6.7） years with normal blood pressure in the same period in our hospital were selected as the normal control group. Results： The general clinical characteristics were similar between hypertensive LVH group, simple hypertensive group and normal healthy control group. Plasma ET-1 concentrations, LVMI and IVRT of hypertensive LVH group were significantly higher than those of normal control group and simple hypertension group, and the difference was statistically significant. The patients＇ baseline blood pressure, ET-1, LVMI, interventricular septal thickness （IVST）, left ventricular posterior wall thickness （LVPWT）, left ventricular end-diastolic diameter （LVEDd） and other clinical parameters showed no significant difference （P〉0.05） between the group of amlodipine combined with telmisartan and the group of amlodipine combined with amiloride. It was found that compared with that before treatment, blood pressure could be effectively controlled （P〈0.05）, and LVMI, IVST, LVPWT and IVRT （P〈0.05） were all lowered, and ET-1 （P〈0.01） was significantly reduced after 1 year of antihypertensive therapy in both the group of amlodipine combined with telmisartan and the group of amlodipine combined with amiloride. The group of amlodipine combined with telmisartan was better in lowering blood pressure and reducing LVMI, IVST, LVPWT, IVRT and ET-1 than the group of amlodipine combined with amiloride （P〈0.05）. Conelus｜on： Amlodipine-based combination antthypertensive therapy could reverse LVH and improve left ventricular diastolic function partly by lowering blood pressure and ET-1, and the effect of amlodipine combined with telmisartan was superior to that ofamlodipine combined with amiloride
文摘Cardiotrophin-1 （CT-1） activates a distinct form of cardiac muscle cell hypertrophy in which the sarcomeric units are assembled in series. The aim of the study was to determine the expres- sion pattern of sarcomeric contractile protein α-actin, specialized eytoskeletal protein α-actinin and mitochondrial uncoupling protein-2 （UCP2） in myocardial remodeling induced by chronic exposure to CT-1. Kunming mice were intraperitoneally injected with carboxy-terminal polypeptide （CP） of CT-1 （CT-1-CP, 500 μg·kg-1·day^-1） for 1, 2, 3 and 4 week （s）, respectively （4 groups obtained according to the injection time, n=10 each, with 5 males and 5 females in each group）, Those injected with physiological saline for 4 weeks served as controls （n=10, with 5 males and 5 females）. The heart tissues of mice were harvested at 1, 2, 3 or 4 week （s）. Immunohistochemistry （IHC） and Western blotting （WB） were used to detect the distribution and expression of sarcomeric α-actin, α-aetinin and mitoehondrial UCP2 in myocardial tissues. IHC showed that α-actin was mainly distributed around the nuclei of cardiomyo- cytes, α-actinin concentrated around the striae and UCP2 scattered rather evenly in the plasma. The ex- pression of α-actin was slightly greater than that of α-actinin and UCP2 in the control group （IHC： χ^2=6.125; WB： F=0.249, P〉0.05） and it gradually decreased after exposure to CT-1-CP. There was no significant difference in the expression of α-actin between the control group and the CT-1-CP-treated groups （χ^2=7.386, P〉0.05）. But Western blotting revealed significant difference in the expression of α-actin between the control group and the 4-week CT-1-CP-treated group （F=2.912; q=4.203, P〈0.05）. Moreover, it was found that the expression of α-actinin increased stepwise with the exposure time in CT-1-CP-treated groups and differed significantly between CT-1-CP-treated groups and the control group （ICH： χ^2=21.977; WB： F=50.388; P〈0.01）. The expression of UCP2 was initially increased （WB： control group vs. 1- or 2-week group, q values： 5.603 and 9.995, respectively, P〈0.01） and then de- creased （WB： control group vs. 3-week group, q=4.742, P〈0.01; control group vs. 4-week group, q=0.558, P〉0.05）. It was suggested that long-term exposure to CT-1-CP could lead to the alteration in the expression of sarcomeric α-actin, α-actinin and mitochonclrial UCP2. The different expressions of sarcomeric structure proteins and mitochondrial UCP2 may be involved in myocardial remodeling.
基金Supported by the Research Fund for Public Health of the Health and Family Planning Commission of Wuhan Municipality(WG13B12)
文摘Objective To investigate the impact of 1, 25-(OH)2D3 on left ventricular hypertrophy(LVH) in type 2 diabetic rats. Methods Type 2 diabetic mellitus(DM) model rats were established by intraperitoneally injecting with 30 mg/kg streptozotocin. After 8 weeks, 19 male rats were identified as diabetic with left ventricular hypertrophy(LVH) by ultrasound examination, and randomly assigned into three groups: untreated(DM-LVH, n=7), treated with insulin(DM-LVH+INS, n=6), and treated with 1, 25-(OH)2D3(DM-LVH+VD, n=6). Healthy male rats were used as the controls group(n=6). The fasting blood glucose and the insulin level were determined weekly. The left ventricular mass index, myocardial collagen content, collagen volume fraction, and 1, 25-(OH)2D3-receptor level were determined by 4 weeks later. Results In the DM-LVH model group, the insulin level was significantly decreased compared with the non-diabetic control group(P<0.05), whereas the blood glucose, left ventricular mass index, myocardial collagen content, collagen volume fraction, and 1, 25-(OH)2D3-receptor expression were significantly increased(all P<0.05). In the DM-LVH+INS and DM-LVH+VD groups, the insulin levels were significantly increased compared with the DM-LVH model group(P<0.05), whereas the other parameters were significantly decreased(all P<0.05). Conclusion 1, 25-(OH)2D3 could reverse LVH in diabetic rats and that the mechanism may involve stimulating insulin secretion and reducing blood glucose via direct up-regulation of 1, 25-(OH)2D3-receptor expression.
文摘Participation of angiotensin II in chronic kidney diseases including diabetic nephropathy (DN) has been extensively described. Similarly, several studies support a protective role for angiotensin-(1-7). However, other studies suggest that some of the cellular effects of angiotensin-(1-7) may be deleterious. The objective of this study was to determine the role of exogenous angiotensin-(1-7) on renal hypertrophy development in rats with streptozotocin-induced diabetes. A control group and three groups of rats with streptozotocin-induced diabetes: untreated diabetic rats, diabetic rats treated with captopril, and diabetic rats treated with angiotensin-(1-7), were studied. After two weeks of treatment, the kidneys were removed under anesthesia with pentobarbital. The kidneys were weighed and the renal cortex was separated for analysis of AT<sub>1</sub>R, TGF-β<sub>1</sub>, MASR, and ACE2 expression by western blot. Rats in the three groups with diabetes had hyperglycemia, increased food and water consumption, and higher urinary volume than control rats. Treatment with captopril or angiotensin-(1-7) reversed streptozotocin-induced renal hypertrophy, measured by kidney weight, protein/DNA ratio in renal cortex, glomerular area, or proximal tubular cells area, proteinuria, and creatinine clearance reduction. AT<sub>1</sub>R, TGF-β<sub>1</sub>, and MAS receptor expression in renal cortex of diabetic rats increased significantly as compared to controls (p
文摘MicroRNAs(miRNAs) are a class of endogenous small noncoding RNAs that regulate gene expression post-transcriptionally. Recent studies have demonstrated that miRNAs are involved in the pathogenesis of hypertrophy.We investigated miR-16 expression and their potential roles in a rat model of hypertrophy induced by abdominal artery constriction (AAC).miR-16 expression was significantly decreased, and CCND1 and CCND2 protein were markedly increased without obvious change of its mRNA level after hypertrophy induction.CCND1 and CCND2 levels were increased without changing their transcript levels in neonatal rat ventricular cardiomyocytes(NRVC) induced by PE,and miR-16 was down-regulated in this process with significantly up-regulatedβ-MHC,ANF and MLC-2 expression.Conversely,introduction of functional miR-16,CCND1 siRNA or CCND2 siRNA into NRVCs could repress cardiomyocyte hypertrophy.These results implicate that miR-16 is involved in contributing to cardiac hypertrophy,one of the mechanisms may be resulted from post-transcriptional regulation of CCND1 and CCND2.
