Cardiac Hypertrophy In Rats Research Articles

Attenuation of microRNA-16 derepresses the cyclins D1, D2 and E1 to provoke cardiomyocyte hypertrophy.

Cyclins/retinoblastoma protein (pRb) pathway participates in cardiomyocyte hypertrophy. MicroRNAs (miRNAs), the endogenous small non-coding RNAs, were recognized to play significant roles in cardiac hypertrophy. But, it remains unknown whether cyclin/Rb pathway is modulated by miRNAs during cardiac hypertrophy. This study investigates the potential role of microRNA-16 (miR-16) in modulating cyclin/Rb pathway during cardiomyocyte hypertrophy. An animal model of hypertrophy was established in a rat with abdominal aortic constriction (AAC), and in a mouse with transverse aortic constriction (TAC) and in a mouse with subcutaneous injection of phenylephrine (PE) respectively. In addition, a cell model of hypertrophy was also achieved based on PE-promoted neonatal rat ventricular cardiomyocyte and based on Ang-II-induced neonatal mouse ventricular cardiomyocyte respectively. We demonstrated that miR-16 expression was markedly decreased in hypertrophic myocardium and hypertrophic cardiomyocytes in rats and mice. Overexpression of miR-16 suppressed rat cardiac hypertrophy and hypertrophic phenotype of cultured cardiomyocytes, and inhibition of miR-16 induced a hypertrophic phenotype in cardiomyocytes. Expressions of cyclins D1, D2 and E1, and the phosphorylated pRb were increased in hypertrophic myocardium and hypertrophic cardiomyocytes, but could be reversed by enforced expression of miR-16. Cyclins D1, D2 and E1, not pRb, were further validated to be modulated post-transcriptionally by miR-16. In addition, the signal transducer and activator of transcription-3 and c-Myc were activated during myocardial hypertrophy, and inhibitions of them prevented miR-16 attenuation. Therefore, attenuation of miR-16 provoke cardiomyocyte hypertrophy via derepressing the cyclins D1, D2 and E1, and activating cyclin/Rb pathway, revealing that miR-16 might be a target to manage cardiac hypertrophy.

Effect of Aqueous Extract of Tephrosia purpurea on Cardiovascular Complications and Cataract Associated with Streptozotocin-induced Diabetes in Rats.

Tephrosia purpurea has been reported to possess antidiabetic activity, however, its effects on cardiovascular complications and cataract associated with diabetes have not been studied. The objective of the present study was to investigate the effects of aqueous extract of Tephrosia purpurea on cardiovascular complications and cataract associated with streptozotocin-induced diabetes in rats. Sprague Dawley rats of either sex were made diabetic with streptozotocin (45 mg/kg, i.v.). Treatment of aqueous extract of Tephrosia purpurea was given in the dose of 300 and 500 mg/kg/day, p.o for 8 weeks. Various hemodynamic (blood pressure, heart rate, +dp/dt, -dp/dt) and biochemical (serum glucose, cholesterol, triglycerides, creatinine, urea, lactate dehydrogenase and creatinine kinase) parameters were recorded after 8 weeks of the treatment. To evaluate cataract, various biochemical estimations were done in eye lens. Streptozotocin produced hyperglycemia; hypoinsulinemia; hyperlipidemia; increased blood pressure; increased creatinine, cardiac enzymes, reduction in heart rate and cardiac hypertrophy in rats and all these changes were prevented by the treatment with aqueous extract of Tephrosia purpurea in both the doses. Streptozotocin also produced decrease in soluble protein and reduced glutathione in lens of rats that was prevented by aqueous extract of Tephrosia purpurea. Our data suggest that aqueous extract of Tephrosia purpurea prevents not only the streptozotocin-induced metabolic abnormalities but also cardiovascular complications as well as reduce the risk of development of cataract.

Increased clearance of reactive aldehydes and damaged proteins in hypertension-induced compensated cardiac hypertrophy: impact of exercise training.

Background. We previously reported that exercise training (ET) facilitates the clearance of damaged proteins in heart failure. Here, we characterized the impact of ET on cardiac protein quality control during compensated ventricular hypertrophy in spontaneously hypertensive rats (SHR). Methods and Results. SHR were randomly assigned into sedentary and swimming-trained groups. Sedentary SHR displayed cardiac hypertrophy with preserved ventricular function compared to normotensive rats, characterizing a compensated cardiac hypertrophy. Hypertensive rats presented signs of cardiac oxidative stress, depicted by increased lipid peroxidation. However, these changes were not followed by accumulation of lipid peroxidation-generated reactive aldehydes and damaged proteins. This scenario was explained, at least in part, by the increased catalytic activity of both aldehyde dehydrogenase 2 (ALDH2) and proteasome. Of interest, ET exacerbated cardiac hypertrophy, improved ventricular function, induced resting bradycardia, and decreased blood pressure in SHR. These changes were accompanied by reduced cardiac oxidative stress and a consequent decrease in ALDH2 and proteasome activities, without affecting small chaperones levels and apoptosis in SHR. Conclusion. Increased cardiac ALDH2 and proteasomal activities counteract the deleterious effect of excessive oxidative stress in hypertension-induced compensated cardiac hypertrophy in rats. ET has a positive effect in reducing cardiac oxidative stress without affecting protein quality control.

Combinational effect of resveratrol and atorvastatin on isoproterenol-induced cardiac hypertrophy in rats

Introduction:Resveratrol is a natural polyphenol present mainly in grapes. It has been shown to offer strong cardio protection in animal models due to its ability to correct lipid peroxidation and maintain antioxidants level. Atorvastatin, a HMG-CoA reductase inhibitor, lowers cholesterol level and is commonly prescribed to heart patients. Our aim in this study was to see the combination effect of these two drugs against Isoproterenol-induced cardiac hypertrophy in rats.Materials and Methods:Wister Albino rats were treated with resveratrol (20 mg/kg/day, p.o), atorvastatin (20 mg/kg/day, p.o) and in combination (resveratrol [10 mg/kg/day, p.o] + atorvastatin [10 mg/kg/day, p.o]) for a period of 25 days and from 15th till 25th day Isoproterenol (5 mg/kg/day, s.c) was co-administered to rats to induce cardiac hypertrophy.Results:A significant increase in creatine kinase, lactate dehydrogenase, aspartate transaminase and lipid peroxidation with the significant decrease in reduced glutathione, superoxide dismutase and catalase were observed in Isoproterenol treated rats. Resveratrol, atorvastatin and their combination significantly reversed the effect. The histopathological studies and myocardial infarct size evaluation also confirmed the protection.Conclusion:Comparing the data we came to this conclusion that atorvastatin although showed the protection along all the parameters, the extent of protection offered by resveratrol alone and in combination were more effective. Hence, it can be concluded that resveratrol, an herbal nutritional supplement, alone and in combination is better against cardiac hypertrophy.

Polydatin prevents angiotensin II-induced cardiac hypertrophy and myocardial superoxide generation.

Our studies and others recently demonstrate that polydatin, a resveratrol glucoside, has antioxidative and cardioprotective effects. This study aims to investigate the direct effects of polydatin on Ang II-induced cardiac hypertrophy to explore the potential role of polydatin in cardioprotection. Our results showed that in primary cultured cardiomyocytes, polydatin blocked Ang II-induced cardiac hypertrophy in a dose-dependent manner, which were associated with reduction in the cell surface area and [(3)H]leucine incorporation, as well as attenuation of the mRNA expressions of atrial natriuretic factor and β-myosin heavy chain. Furthermore, polydatin prevented rat cardiac hypertrophy induced by Ang II infusion, as assessed by heart weight-to-body weight ratio, cross-sectional area of cardiomyocyte, and gene expression of hypertrophic markers. Further investigation demonstrated that polydatin attenuated the Ang II-induced increase in the reactive oxygen species levels and NADPH oxidase activity invivo and invitro. Polydatin also blocked the Ang II-stimulated increases of Nox4 and Nox2 expression in cultured cardiomyocytes and the hearts of Ang II-infused rats. Our results indicate that polydatin has the potential to protect against Ang II-mediated cardiac hypertrophy through suppression of NADPH oxidase activity and superoxide production. These observations may shed new light on the understanding of the cardioprotective effect of polydatin.

Effects of stachydrine on norepinephrine-induced neonatal rat cardiac myocytes hypertrophy and intracellular calcium transients.

BackgroundLeonurus heterophyllus sweet has been suggested to have cardioprotective effects against heart diseases, including ischemic diseases and ventricular remodeling. However, the active ingredients of the herb and the underlying mechanisms are poorly understood. The aim of the present study was to investigate the effects of stachydrine (STA), a major constituent of Leonurus heterophyllus sweet, on norepinephrine (NE) induced hypertrophy and the changes of calcium transients in neonatal rat cardiomyocytes.MethodsVentricular myocytes from 1-day-old Wistar rats were isolated and cultured in DMEM/F12 with 1 μmol/L norepinephrine in the presence or absence of 10 μmol/L STA for 72 h. Cardiomyocytes hypertrophy was evaluated by cell surface area, total protein/DNA content, β/α-MHC mRNA ratio. While calcium handling function was evaluated by Ca2+-transient amplitude and decay, SERCA2a activity and expression, PLN expression and phosphorylation. β1-adrenergic receptor system activation was evaluated by the content of cAMP and the activation of PKA.ResultsNE treatment increases the cell surface area, protein synthesis, the expression level of β-MHC and β/α-MHC ratio. These effects were attenuated by STA. NE-induced hypertrophy was associated with increased Ca2+-transient amplitude, accelerated decay of the Ca2+-transient, increased phospholamban expression, hyper-phosphorylation at both the serine-16 and threonine-17 residues, increased intracellular cAMP level, and PKA overactivation. All of which were significantly inhibited by STA.ConclusionThese data suggest that STA attenuates norepinephrine-induced cardiomyocyte hypertrophy and has potential protective effects against β-adrenergic receptor induced Ca2+ mishandling.

Effects of Shenmai injection on afterdepolarization and triggered activities in left ventricular papillary muscle in rat cardiac hypertrophy

This study is to evaluate the effects of Shenmai injection on the temporal alterations of action potential (AP), early afterdepolarization (EAD) and delayed afterdepolarization (DAD) in papillary muscles. The action potentials were recorded by a glass electrode. APD at 90% repolarization (APD9 ) was measured, and spontaneous EAD and DAD were observed. The results show APD90 was significantly prolonged in model group compared with sham-operated group, whereas it was remained unchanged in Shenmai injec- tion treatment group and amiodarone group. The spontaneous EADs and DADs were frequently visible in model group. In conclusion, EAD, DAD and trigger activities increase gradually during pathological progression of rat cardiac hypertrophy, and Shenmai injection could improve the action potential change in rat cardiac hypertrophy.

Ascending Aortic Constriction in Rats for Creation of Pressure Overload Cardiac Hypertrophy Model

Ascending aortic constriction is the most common and successful surgical model for creating pressure overload induced cardiac hypertrophy and heart failure. Here, we describe a detailed surgical procedure for creating pressure overload and cardiac hypertrophy in rats by constriction of the ascending aorta using a small metallic clip. After anesthesia, the trachea is intubated by inserting a cannula through a half way incision made between two cartilage rings of trachea. Then a skin incision is made at the level of the second intercostal space on the left chest wall and muscle layers are cleared to locate the ascending portion of aorta. The ascending aorta is constricted to 50-60% of its original diameter by application of a small sized titanium clip. Following aortic constriction, the second and third ribs are approximated with prolene sutures. The tracheal cannula is removed once spontaneous breathing was re-established. The animal is allowed to recover on the heating pad by gradually lowering anesthesia. The intensity of pressure overload created by constriction of the ascending aorta is determined by recording the pressure gradient using trans-thoracic two dimensional Doppler-echocardiography. Overall this protocol is useful to study the remodeling events and contractile properties of the heart during the gradual onset and progression from compensated cardiac hypertrophy to heart failure stage.

Ascending Aortic Constriction in Rats for Creation of Pressure Overload Cardiac Hypertrophy Model

Ascending aortic constriction is the most common and successful surgical model for creating pressure overload induced cardiac hypertrophy and heart failure. Here, we describe a detailed surgical procedure for creating pressure overload and cardiac hypertrophy in rats by constriction of the ascending aorta using a small metallic clip. After anesthesia, the trachea is intubated by inserting a cannula through a half way incision made between two cartilage rings of trachea. Then a skin incision is made at the level of the second intercostal space on the left chest wall and muscle layers are cleared to locate the ascending portion of aorta. The ascending aorta is constricted to 50–60% of its original diameter by application of a small sized titanium clip. Following aortic constriction, the second and third ribs are approximated with prolene sutures. The tracheal cannula is removed once spontaneous breathing was re-established. The animal is allowed to recover on the heating pad by gradually lowering anesthesia. The intensity of pressure overload created by constriction of the ascending aorta is determined by recording the pressure gradient using trans-thoracic two dimensional Doppler-echocardiography. Overall this protocol is useful to study the remodeling events and contractile properties of the heart during the gradual onset and progression from compensated cardiac hypertrophy to heart failure stage.

Ameliorative role of gemfibrozil against partial abdominal aortic constriction-induced cardiac hypertrophy in rats.

Fibrates are peroxisome proliferator-activated receptor-α agonists and are clinically used for treatment of dyslipidemia and hypertriglyceridemia. Fenofibrate is reported as a cardioprotective agent in various models of cardiac dysfunction; however, limited literature is available regarding the role of gemfibrozil as a possible cardioprotective agent, especially in a non-obese model of cardiac remodelling. The present study investigated the role of gemfibrozil against partial abdominal aortic constriction-induced cardiac hypertrophy in rats. Cardiac hypertrophy was induced by partial abdominal aortic constriction in rats and they survived for 4 weeks. The cardiac hypertrophy was assessed by measuring left ventricular weight to body weight ratio, left ventricular wall thickness, and protein and collagen content. The oxidative stress in the cardiac tissues was assessed by measuring thiobarbituric acid-reactive substances, superoxide anion generation, and reduced glutathione level. The haematoxylin-eosin and picrosirius red staining was used to observe cardiomyocyte diameter and collagen deposition, respectively. Moreover, serum levels of cholesterol, high-density lipoproteins, triglycerides, and glucose were also measured. Gemfibrozil (30 mg/kg, p.o.) was administered since the first day of partial abdominal aortic constriction and continued for 4 weeks. The partial abdominal aortic constriction-induced cardiac oxidative stress and hypertrophy are indicated by significant change in various parameters used in the present study that were ameliorated with gemfibrozil treatment in rats. No significant change in serum parameters was observed between various groups used in the present study. It is concluded that gemfibrozil ameliorates partial abdominal aortic constriction-induced cardiac oxidative stress and hypertrophy and in rats.

Dystrophin absence is implicated in the transition from physiological to pathological cardiac hypertrophy (547.4)

Hypertension causes cardiac hypertrophy, cardiac dysfunction, and heart failure (HF). The mechanisms implicated in the transition from physiological to pathological hypertrophy are still unknown. Growing evidence points out to the role of inappropriate mechanical coupling in the pathogenesis of HF and the cytoskeletal proteins as the most obvious candidates for intracelular remodeling. We investigated dystrophin and its potential role in the transition from physiological to pathological cardiac hypertrophy in rats submitted to chronic abdominal aorta stenosis. Wistar rats were submitted to abdominal aorta stenosis and killed at 30, 60 and 90 days post surgery (dps). The hearts were collected and Western blot and immunofluorescence were performed for dystrophin and calpain. Blood pressure was evaluated and cardiac function evaluate by echocardiography. Data were considered significant when p<0.05. At 90 dps 70% presented hypertrophied hearts (HH) and 30% hypertrophied+dilated hearts (DH), as evaluated by echocardiography. Blood pressure increased 53,42% (30d), 50,8% (60d) and 64,36% at 90dps. Dystrophin expression at 30, 60 dps and HH animals was the same as control, but decreased in DH animals. The ejection fraction was the same as control at 30 and 60dps, however it was reduced 35% at 90d in HH and 48% in DH. Loss of dystrophin could be partly responsible for the development of heart failure in rats submitted to chronic abdominal aorta stenosis. Thus, it is essential to define the mechanistic aspects of the pathophysiological processes involved in deterioration of cardiac function and design develop strategies to inhibit and/or reverse evolution of heart hypertrophy from compensated to decompensated phase. Grants from FAPESP 09/17787‐8; 10/19216‐5.Grant Funding Source: Supported by FAPESP 09/17787‐8; 10/19216‐5

Expression of nucleolin in pressure overload-induced cardiac hypertrophy rats

To detect the expression of nucleolin in cardiac hypertrophy rats induced by pressure overload. A total of 40 SD rats with body weight 180 g and 220 g were recruited and randomly divided into 2 groups: a transverse aortic constriction (TAC) group and a sham surgery group. Cardiac hypertrophy model was employed by transverse aortic constriction surgery. Then 2 weeks and 4 weeks after the experiment, the heart mass index (HMI), left ventricle mass index (LVMI) were measured. β-MHC mRNA in the heart tissue was detected with RT-PCR. Nucleolin in the heart, brain and kidney was respectively detected with Western blot. Compared with the sham surgery group, HMI, LVMI in the TAC group increased significantly (P<0.01) 4 weeks after the surgery; the expression of β-MHC mRNA in the heart tissue increased (P<0.05) in the TAC group 4 weeks after the surgery; and the expression of nucleolin protein in the heart tissue of the TAC group was remarkably upregulated (P<0.05) 2 weeks after the surgery, with no change in the brain and kidney tissue between the 2 groups. Expression of nucleolin protein has been upregulated in response to pressure overload, which may suggest that nucleolin plays a role in cardiac hypertrophy induced by pressure overload.

Long-term passive wheel running-induced rat model of physiological cardiac hypertrophy

Objective To explore a novel animal model of physiological cardiac hypertrophy induced by long-term passive wheel running.Methods Forty male Sprague-Dawley rats were randomly divided into four groups(n=10):normal control group,passive wheel running(PWR)group,sham operation group,and transverse aortic constriction(TAC)group.PWR group received passive wheel movement training,TAC group received aortic arch narrow operation,sham operation group did not receive ligature thoracic aorta,and other treatments were similar to that of TAC group;no treatment was given to the normal control group.Five weeks after training or operation,a comparison was made between different groups.The modeling results of PWR were assessed by echocardiography,morphology,and molecular hypertrophic-markers for heart failure.Results Echocardiography findings showed that thickness of the left ventricle wall in PWR group was significantly increased compared with the normal control group,and that in the TAC group was significantly increased compared with the sham operation group(P0.01);the stroke volume and ejection fraction were also significantly different between PWR and normal control group and between the TAC group and sham operation group(P0.01).The left ventricle internal diameter at enddiastole was not significantly different from that of normal control group,but that in the TAC group was decreased by 38%compared with the sham operation group(P0.01),indicating that the cardiac structures were significantly different betweenPWR and TAC groups.Compared with the normal control group,the heart weight/body weight ratio,left ventricular weight/body weight ratio and lung weight/body weight ratio were increased by 25.0%,37.3% and 23.8% in PWR rats,respectively;compared with the sham group,the above indicators were increased by 31.6%,38.8% and 56.6% in TAC rats,respectively(P0.05or P0.01).Compared with the normal control group,the expression levels of atria natriuretic peptide(ANP)and brain natriuretic peptide(BNP)were 0.67-fold and 0.48-fold of those in PWR group(P0.05),and those in the TAC group were 1.98-fold and 2.03-fold those of the sham operation group(P0.05).Conclusion Long-term PWR training can induce physiological cardiac hypertrophy in rats,which may provide a novel way for establishing physiological cardiac hypertrophy animal models.

Endothelin receptor blocker bosentan inhibits hypertensive cardiac fibrosis in pressure overload-induced cardiac hypertrophy in rats

significantly attenuated (P<0.05 and <0.001) by bosentan (50 and 100mg/kg perorally) treatment. An upregulation in the mRNA expression of endothelin-1 was significantly (P<0.05 and <0.001) attenuated by bosentan (50 and 100mg/kg perorally) treatment. Histological aberration induced after pressure overload was restored by bosentan treatment. Conclusion Bosentan attenuates the development of cardiac hypertrophy by blocking the endothelin-1 receptor and improving left ventricular function; it also ameliorates endogenous biomarkers in pressure overload-induced cardiac hypertrophy in rats. Cardiovasc Endocrinol 2:85–97 � c 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Inhibition of DNA methylation reverses norepinephrine-induced cardiac hypertrophy in rats.

The mechanisms of heart failure remain largely elusive. The present study determined a causative role of DNA methylation in norepinephrine-induced heart hypertrophy and reduced cardiac contractility. Male adult rats were subjected to norepinephrine infusion for 28 days, some of which were treated with 5-aza-2'-deoxycytidine for the last 6 days of norepinephrine treatment. At the end of the treatment, hearts were isolated and left ventricular morphology and function as well as molecular assessments was determined. Animals receiving chronic norepinephrine infusion showed a sustained increase in blood pressure, heightened global genomic DNA methylation and changes in the expression of subsets of proteins in the left ventricle, left ventricular hypertrophy, and impaired contractility with an increase in the susceptibility to ischaemic injury. Treatment of animals with 5-aza-2'-deoxycytidine for the last 6 days of norepinephrine infusion reversed norepinephrine-induced hypermethylation, corrected protein expression patterns, and rescued the phenotype of heart hypertrophy and failure. The findings provide novel evidence of a causative role of increased DNA methylation in programming of heart hypertrophy and reduced cardiac contractility, and suggest potential therapeutic targets of demethylation in the treatment of failing heart and ischaemic heart disease.

Metabonomic Profiling Revealed an Alteration in Purine Nucleotide Metabolism Associated with Cardiac Hypertrophy in Rats Treated with Thiazolidinediones

Thiazolidinediones (TZDs) including rosiglitazone (RSG) and pioglitazone (PIO) are synthetic agonists selective for peroxisome proliferator-activated receptor-γ (PPARγ) and have been clinically used to treat type-II diabetes as insulin sensitizers. Recent meta-analyses have shown that TZDs are associated with an increased risk for the development of heart failure. To elucidate the mechanism underlying such a cardiac adverse effect, we used a (1)H NMR-based approach to examine the metabonomic profiles in the cardiac tissues treated with RSG (15 mg/kg body weight/day) or PIO (45 mg/kg/day) for 4 weeks and found that the TZD treatments resulted in a significantly altered metabolic profile in hearts, which was associated with cardiac hypertrophy. Multivariate analysis demonstrated that TZDs led to an accumulation in adenosine monophosphate (AMP) and a depletion of inosine. Consistently, AMP kinase, a signal pathway sensitive to the change in the intracellular concentrations of AMP, was activated in the cardiac tissues from the TZDs-treated rats. Quantitative real-time reverse-transcriptase polymerase chain reaction showed a significant induction of the genes involved in the de novo synthesis of purine nucleotide but a reduction of those for the catabolism. Furthermore, the putative PPAR-responsive elements were identified in the 5'-flanking regions of the TZD-up-regulated genes such as adenylosuccinate synthase gene (Adss) and phosphoribosl pyrophosphate synthetase 1 (Prps1), and the binding of PPARγ to these motifs was confirmed by using chromatin immunoprecipitation assay. In conclusion, these results demonstrated that TZDs induced alterations in purine nucleotide metabolism in rat hearts via transcriptional regulation of the PPARγ-target genes, which may play an important role in the development of cardiac hypertrophy associated with TZDs.

Inhibitory effect of nitric oxide-induced total ginsenosides on right ventricular hypertrophy in rats

To observe the effect of total ginsenosides (TG) on right ventricular hypertrophy induced by monocrotaline (MCT) in rats, and study its relationship with the nitric oxide pathway. Male Sprague Dawley rats were randomly divided into the control group, the MCT model group, TG-treated (20, 40, 60 mg kg-1 d-1) groups, and the L-arginine (L-arg) th NO release, T + L-N and L-a + L-N groups were wi th NOS into study TG's effect 200 mg kg-1 d-1 group. Besides, and its relationship wi also set, intraperitoneally injected with TG 40 mg kg-1 d -1 and L-arg 200 mg kg-1 - d-1, and orally administered hibitor L-NAME 20 mg kg-1 d-1. After all of the groups were given drugs for 18 d, their right ventricular peak systolic pressure (RVSP) ventricular hypertrophy index (RVHI) and RVW/BW were determined. Ultra-structure of myocardial cells was observed with transmission electron microscope. The NO2 -/NO3 - content in myocardial tissues were detected with the nitrate reduction method. ANF and eNOS mRNA expressions in right ventricle tissues were detected by using real-time RT-PCR. Low, middle and high doses of TG and L-arg preventive administration could significantly reduce RVSP, RVHI, RVW/BW and ANF mRNA expressions (P < 0. 05) , and ameliorate cellular mitochondrial swelling and degeneration. L-NAME could prevent the effect of L-arg on above indexes, whereas L-NAME of the same dose could not impact the reducing effect of TG 40 mg kg -1 on above indexes. TG 60 mg kg -1 could raise eNOS mRNA expression, but TG 20 mg kg-1 and 40 mg kg-1 showed no effect. TG can significantly attenuate MCT-induced right cardiac hypertrophy in rats. Its anti-hypertrophic effect is partially realized through NO.

Amelioration of cardiac hypertrophy induced by abdominal aortic banding in ferulic acid treated rats

The objective of the present study was to investigate the beneficial effects of treatment of the abundant phytochemical Ferulic acid (FA), alone or in combination with angiotensin II receptor antagonist telmisartan on pressure overload–induced cardiac hypertrophy in rats. Albino Wistar rats were divided into 6 groups: Sham, abdominal aorta constriction (AAB) and three FA (20mg/kg) treatment groups given as a pretreatment or post-treatment or in combination with telmisartan (Tel; 10mg/kg). The standard drug used was Tel (10mg/kg). The pretreatment was given for 35 days while the other treatments were started from the 29th day of surgery for a period of 7 days orally. After recording the exercise testing and hemodynamic parameters, animals were sacrificed for biochemical and histopathological studies. The AAB group had a significant increase in left ventricular weight (LVW) (p<0.001), elevated blood pressure (p<0.001), a significant increase in reactive oxygen species (ROS) (p<0.001) and serum creatinine kinase-MB (CK-MB) (p<0.001), significantly lowered glutathione concentration and superoxide dismutase (SOD) (p<0.001). Pretreatment with FA alone or post-treatment of FA in combination with telmisartan attenuated the rise in LVW and blood pressure (p<0.001). It eliminated the ROS significantly (p<0.01), reduced CK-MB, raised the glutathione and SOD (p<0.001). These findings confirm the protective role of pretreatment of FA and post-treatment of FA with telmisartan in pressure overload–induced cardiac hypertrophy mediated through its integrated effect of potent antioxidative, anti-hypertensive and anti-inflammatory activity.

Hydroxysafflor yellow A attenuates left ventricular remodeling after pressure overload-induced cardiac hypertrophy in rats

Context: Hydroxysafflor yellow A (HSYA), the main chemical component of the safflower yellow pigments, is used extensively in traditional Chinese medicine for the treatment of cerebrovascular and cardiovascular diseases.Objective: The present study determined the effects of HSYA on left ventricular hypertrophy after pressure overload and investigated the underlying mechanisms.Materials and methods: Cardiac hypertrophy was induced by the ligation of abdominal aorta in male Wistar rats. The rats were then divided into five groups and treated with captopril (100 mg/kg) or HSYA at different doses (0, 10, 20 and 40 mg/kg). Six weeks after treatment, the weight of left ventricle, LVMI (left ventricular mass index) and pathological changes were measured. MMP-2 (metalloproteinase 2) and MMP-9 (metalloproteinase 9) levels were determined by ELISA. Protein expressions of Bcl-2 and Bax were evaluated by immunohistochemistry.Results: HSYA (20, 40 mg/kg) significantly attenuated the increase of LVMI (ventricular weight/body weight) by 13.04 and 30.43% respectively, when compared with the model group. This was associated with the amelioration of pathological lesion, such as cardiac muscle fibers were smaller and the nuclei of cardiomyocytes were lightly stained in animals treated with HSYA (20, 40 mg/kg). In addition, the administration of HSYA at doses of 20 and 40 mg/kg increased the Bcl-2/Bax ratio (1.17 ± 0.08 and 1.39 ± 0.07 versus 0.71 ± 0.06). In addition, the serum MMP-2 and MMP-9 levels were blocked by the treatment at doses of 20 and 40 mg/kg HSYA (MMP-2, 76.1 ± 9.2 and 65.6 ± 6.8 versus 82.9 ± 6.2, ng/ml; MMP-9, 66.6 ± 4.8 and 57.5 ± 5.0 versus 83.5 ± 6.0, ng/ml).Conclusion: These findings indicated that HSYA has beneficial effects on hypertensive ventricular remodeling, which may involve mechanisms of inhibiting cell apoptosis and suppressing metalloproteinases expression.

MicroRNA-26 Was Decreased in Rat Cardiac Hypertrophy Model and May Be a Promising Therapeutic Target

MicroRNA (miR)-26 was found to be downregulated in cardiac diseases. In this study, the critical role of miR-26 in myocardial hypertrophy in both in vivo and in vitro was investigated. Sixteen male Wistar rats that underwent sham or transverse abdominal aortic constriction (TAAC) surgery were divided into control or TAAC group. Cardiomyocytes were isolated from neonatal Sprague-Dawley rats. Our study demonstrated that miR-26a/b was downregulated in both TAAC rat model and cardiomyocytes. The results of luciferase assays also suggested that glycogen synthase kinase 3β (GSK3β) may be a direct target of miR-26. The overexpression of miR-26 attenuated GSK3β expression and inhibited myocardial hypertrophy. The downregulation of miR-26 reversed these effects. Furthermore, silence of GSK3β gene phenocopied the anti-hypertrophy effects of miR-26, whereas overexpression of this protein attenuated the effects of miR-26. Taken together, these data suggest that miR-26 regulates pathological structural changes in the rat heart, which may be associated with suppression of the GSK3β signaling pathway, and implicate the potential application of miR-26 in diagnosis and therapy of cardiac hypertrophy.