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Objective:To explore the effect of tanshinone ⅡA on myocardial remodeling in ischemia/reperfusion (I/R)-induced heart failure of rodent model.Methods:① In vivo, 30 SD rats were randomly divided into sham operation, heart failure and tanshinone ⅡA treatment group, with 10 rats in each group. The I/R model was established by ligating the left coronary artery until ST segment elevation for 30 minutes, then the ligation was removed for 2 hours as reperfusion. In the sham operation group, the rat chest was opened without artery ligation. Three days after model establishment, tanshinone ⅡA (10 mg/kg) were given intraperitoneal injected in tanshinone ⅡA group for 9 weeks. In the other two groups, normal saline was administrated in the same way. The behavioral manifestations of the rats in each group were observed; hemodynamic indexes were evaluated; Masson staining was performed to observe the degree of myocardial fibrosis; enzyme linked immunosorbent assay (ELISA) was used to detect the content of Galectin-3 in myocardial tissue; quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to detect the expressions of collagenⅢ, collagenⅠ, matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of metalloproteinase (TIMP-1). ② In vitro, rats primary cardiac fibroblasts were extracted and isolated, and divided into blank control group, angiotensinⅡ group (7-10 mmol/L angiotensinⅡ) and angiotensinⅡ+ tanshinoneⅡA group (7-10 mmol/L angiotensinⅡ+ 5-10 mmol/L tanshinone ⅡA). At 24 hours and 48 hours of culture, the cell proliferation in each group was detected by methyl thiazolyl tetrazolium (MTT); the expressions of collagenⅢ, collagenⅠ, MMP-2 and TIMP-1 were detected by qRT-PCR; the content of Galectin-3 in cardiac fibroblasts was detected by ELSIA. Results:① In vivo, the rats' activity status, hair conformity and food intake were ranked from good to bad in order of sham operation group, tanshinone ⅡA group and heart failure model group. Compared with the sham-operated group, the heart rate (HR) of the rats in the heart failure model group was significantly decreased and the heart function was significantly impaired. The mRNA and protein expression of collagenⅠ, collagenⅢ, TIMP-1 and Galectin-3 content were significantly increased, while the mRNA and protein expression of MMP-2 were significantly decreased. Compared with the heart failure model group, rats in the tanshinone ⅡA group showed significantly higher HR and improved cardiac function, significantly lower mRNA expression of collagenⅠ and collagenⅢ, significantly lower mRNA and protein expression of TIMP-1 and Galectin-3, and significantly higher mRNA and protein expression of MMP-2, and the most obvious changes were in the 9th weeks of modeling [collagenⅠ mRNA (2 -ΔΔCt): 4.70±1.19 vs. 10.21±1.62, collagenⅢ mRNA (2 -ΔΔCt): 3.03±0.46 vs. 13.84±1.93, TIMP-1 mRNA (2 -ΔΔCt): 1.90±0.19 vs. 4.55±0.43, TIMP-1/GAPDH: 0.33±0.04 vs. 0.67±0.05, Galectin-3 (ng/L): 489.93±79.30 vs. 821.72±94.09, MMP-2 mRNA (2 -ΔΔCt): 0.37±0.07 vs. 0.03±0.01, MMP-2/GAPDH: 0.69±0.09 vs. 0.21±0.04, all P < 0.05]. Masson staining showed that myocardial tissue fibrosis was obvious in the heart failure group, and the degree of fibrosis in the tanshinoneⅡA group was reduced. ② In vitro, compared with the blank control group, the proliferation rate, collagenⅠ, collagen Ⅲ and TIMP-1 expression and Galectin-3 content of myocardial fibroblasts were significantly increased, and MMP-2 expression was significantly decreased in the angiotensin group at 24 h and 48 h of culture. Compared with the angiotensin group, the proliferation rate of cardiac fibroblasts and the expression of collagenⅠ, collagen Ⅲ and TIMP-1 and the content of Galectin-3 were significantly decreased, and the expression of MMP-2 mRNA was significantly increased in the angiotensin + tanshinone ⅡA group, and the most significant changes were at 48 hours of culture [proliferation rate: (57.0±3.7)% vs. (67.0±2.4)%, collagenⅠmRNA (2 -ΔΔCt): 551.43±67.10 vs. 871.48±12.25, collagenⅢ mRNA (2 -ΔΔCt): 233.76±18.73 vs. 385.51±31.35, TIMP-1 mRNA (2 -ΔΔCt): 238.69±17.37 vs. 351.84±26.17, Galectin-3 (ng/L): 283.76±28.73 vs. 415.51±31.35, MMP-2 mRNA (2 -ΔΔCt): 108.54±12.10 vs. 51.47±6.25, all P < 0.05]. Conclusion:Tanshinone ⅡA can improve cardiac function, inhibit myocardial fibrosis and improve myocardial remodeling in rats with I/R-induced heart failure.
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Chronic hypertension evoked aberrant myocardial remodeling is the main reason for progressive death from heart failure. It is of great clinical significance to find effective prevention and treatment methods to block this pathological process. It has been shown that imbalance of the autonomic nervous system (ANS) induced by chronic hypertension, i.e., hyper-excitation of sympathetic nerve system and suppression of parasympathetic (vagal) nerve system, activates immune cells-mediated inflammatory responses, and exacerbates the pathological remodeling of cardiac tissue. Except the negative inotropic outcomes, excitation of vagal nerves also has an anti-inflammatory effect which is mediated by activating the cholinergic anti-inflammatory pathway (CAIP). Previous studies showed that electroacupuncture (EA) could exert anti-hypertensive and systematic anti-inflammatory effects by increasing vagal activity. In addition, preliminary study from our lab demonstrated that EA was able to alleviate the pathological progress from hypertension to cardiac hypertrophy. However, the potential role of CAIP in restoring hypertension induced aberrant myocardial remodeling is still unknown. Herein, based on the alteration of ANS function in hypertension and EA's impact on vagal activity, we propose novel research ideas that EA could attenuate the pathological process of hypertension induced abnormal myocardial remodeling via activating CAIP.
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Atorvastatin is proven to ameliorate cardiac hypertrophy induced by chronic intermittent hypoxia (CIH).However,little is known about the mechanism by which atorvastatin modulates CIH-induced cardiac hypertrophy,and whether specific hypertrophyrelated microRNAs are involved in the modulation.MiR-31 plays key roles in the development of cardiac hypertrophy induced by ischemia/hypoxia.This study examined whether miR-31 was involved in the protective role of atorvastatin against CIH-induced myocardial hypertrophy.H9c2 cells were subjected to 8-h intermittent hypoxia per day in the presence or absence of atorvastatin for 5 days.The size of cardiomyocytes,and the expression of caspase 3 and miR-31 were determined by Western blotting and RT-PCR,respectively.MiR-31 mimic or Ro 31-8220,a specific inhibitor of protein kinase C epsilon (PKCε),was used to determine the role of miR-31 in the anti-hypertrophic effect of atorvastatin on cardiomyocytes.PKCε in the cardiomyocytes with miR-31 upregulation or downregulation was detected using RT-PCR and Western blotting.The results showed that CIH induced obvious enlargement of cardiomyocytes,which was paralleled with increased atrial natriuretic peptide (ANP),brain natriuretic peptide (BNP),and slow/beta cardiac myosin heavy-chain (MYH7) mRNA levels.All these changes were reversed by the treatment with atorvastatin.Meanwhile,miR-31 was increased by CIH in vitro.Of note,the atorvastatin pretreatment significantly increased the mRNA and protein expression of PKCε and decreased that of miR-31.Moreover,overexpression of miR-31 abolished the anti-hypertrophic effect of atorvastatin on cardiomyocytes.Upregulation and downregulation of miR-31 respectively decreased and increased the mRNA and protein expression of PKCε.These results suggest that atorvastatin provides the cardioprotective effects against CIH probably via up-regulating PKCε and down-regulating miR-31.
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Atorvastatin is proven to ameliorate cardiac hypertrophy induced by chronic intermittent hypoxia (CIH).However,little is known about the mechanism by which atorvastatin modulates CIH-induced cardiac hypertrophy,and whether specific hypertrophyrelated microRNAs are involved in the modulation.MiR-31 plays key roles in the development of cardiac hypertrophy induced by ischemia/hypoxia.This study examined whether miR-31 was involved in the protective role of atorvastatin against CIH-induced myocardial hypertrophy.H9c2 cells were subjected to 8-h intermittent hypoxia per day in the presence or absence of atorvastatin for 5 days.The size of cardiomyocytes,and the expression of caspase 3 and miR-31 were determined by Western blotting and RT-PCR,respectively.MiR-31 mimic or Ro 31-8220,a specific inhibitor of protein kinase C epsilon (PKCε),was used to determine the role of miR-31 in the anti-hypertrophic effect of atorvastatin on cardiomyocytes.PKCε in the cardiomyocytes with miR-31 upregulation or downregulation was detected using RT-PCR and Western blotting.The results showed that CIH induced obvious enlargement of cardiomyocytes,which was paralleled with increased atrial natriuretic peptide (ANP),brain natriuretic peptide (BNP),and slow/beta cardiac myosin heavy-chain (MYH7) mRNA levels.All these changes were reversed by the treatment with atorvastatin.Meanwhile,miR-31 was increased by CIH in vitro.Of note,the atorvastatin pretreatment significantly increased the mRNA and protein expression of PKCε and decreased that of miR-31.Moreover,overexpression of miR-31 abolished the anti-hypertrophic effect of atorvastatin on cardiomyocytes.Upregulation and downregulation of miR-31 respectively decreased and increased the mRNA and protein expression of PKCε.These results suggest that atorvastatin provides the cardioprotective effects against CIH probably via up-regulating PKCε and down-regulating miR-31.
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@#The protective effect and mechanism of Oroxylin A, a naturally occurring compound in Scutellaria baicalensis Georgi, was investigated in this study. Isoproterenol administration to rats triggered classic cardiac failure, as demonstrated by objective parameters of cardiac dysfunction. Intragastric administration of oroxylin A at the dose of 25, 50 and 100 mg/(kg·d)significantly improved deranged cardiac parameters in the isoproterenol-induced heart failure model in a dose-dependent manner. At the same time, oroxylin A markedly ameliorated cardiac histological changes and down-regulated serum levels of various neuroendocrine factors including norepinephrine, aldosterone, brain natriuretic peptide, endothelin 1, angiotensin II and so on. Mechanistically, augmenting autophagy of myocardial cells via the inhibition of AKT1-RPS6KB1 signaling contributed to the improvement of isoproterenol-induced rat heart failure by oroxylin A. Taken together, these results suggest that oroxylin A ameliorates heart failure through promoting autophagy in myocardial cells.
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OBJECTIVE:To prospectively study the effects of trimetazidine on myocardial remodeling and oxidative stress in patients with hypertensive heart disease (HHD),in order to provide reference for clinical treatment of HHD.METHODS:Eighty-two HHD patients were selected from our hospital during Jan.2014-Jul.2016,and they were divided into control group and observation group by sortition randomization method,with 41 cases in each group.Control group received routine HHD chemical drug (antihypertensive drugs,lipid-lowering drugs,hypoglycemic agents and antiplatelet drugs,etc.) therapy.Observation group was additionally given trimetazidine 20 mg,tid,on the basis of control group.Both groups were treated for 3 months.Before treatment and after 3 months of treatment,SBP,DBP,New York Heart Association (NYHA) cardiac function grade,LVEF,LVESD,LVEDD,LVMI and the levels of GSH-Px,SOD,MDA and ROS were compared between 2 group.The occurrence of ADR was observed in 2 groups.RESULTS:Before treatment,there was no statistical significance in each index between 2 groups (P＞0.05).After 3 months of treatment,SBP and DBP of 2 groups were decreased significantly compared to before treatment (P＜0.01);there was no statistical significance between 2 groups (P＞0.05).There was no statistical significance in NYHA cardiac function grade compared to before treatment or between 2 groups (P＞0.05).LVESD,LVEDD and LVMI of observation group were decreased significantly compared to before treatment (P＜0.05);LVEF was increased significantly compared to before treatment (P＜0.05);LVEDD and LVMI of observation group were significantly lower than control group (P＜0.05).Compared to before treatment,SOD level of control group was decreased significantly,while the levels of GSH-Px and SOD in observation group were increased significantly;MDA and ROS of observation group were significantly lower than those of control group,with statistical significance (P＜0.05).No obvious ADR was found in 2 groups.CONCLUSIONS:Trimetazidine can improve cayocardial remodeling and reduce oxidative stress level of HHD patients with good safety.
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Cardiovascular remodeling or dysfunction-induced abnormal cardiac output,blood volume and peripheral vascular resistance is an important pathophysiological mechanism for the occurrence and development of hypertension.Cathepsins are widely expressed in human various tissue and cells and they are involved in the pathogenesis of hypertension through activation of renin-angiotensin system,degradation of cytoplasmic matrix,proliferation of smooth muscle cell and hypertrophy of myocyte.The clinical studies have found that cathepsins can be used as a biomarker for hypertension.In recent years,the studies on the functions and mechanisms of cathepsins have provided a new sight and strategy for treatment of hypertension.
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AIM: To investigate the effects of myocardial remodeling of aged left atrium (LA) on atrial ar-rhythmogenesis in rabbits .METHODS:The male New Zealand rabbits were divided into young LA and aged LA groups . By observing the changes of monophasic action potential ( MAP) and burst-pacing in LA of the rabbits in vivo, the main cardioelectrophysiological parameters such as resting membrane potential ( RMP) , action potential amplitude ( APA) , ma-ximum rise veloctiy of action potential (dv/dtmax), plateau potential and action potential duration at 30%, 50%and 90%( APD30 , APD50 and APD90 ) , as well as the inducibility and duration of atrial arrhythmias were recorded .L-type calcium current (ICa,L) was analyzed via whole-cell patch-clamp technique in enzymatically dissociated single rabbit LA myocytes . The myocardial collagen content was quantified after Masson staining , and the ultrastructure of the LA cells was observed under scanning electron microscope .The expression of Cav 1.2 in LA tissue of the 2 groups was detected by Western blot . RESULTS:Compared with young LA group , dv/dtmax and plateau potential were significantly decreased , APD30 and APD50 were shortened, and APD90 was notably prolongated in aged LA group (P<0.01).The inducibility or duration of atrial arrhythmias was severely increased or prolongated in aged LA group (P<0.01).With voltage clamp model, the den-sity of ICa,L in aged LA group was significantly decreased , and current-voltage curve was notably moved upward compared with young LA group.When the clamp potential was +20 mV, the density of ICa,L was notably modified from (11.72 ± 1.39) pA/pF in young LA group to (6.08 ±0.98) pA/pF in aged LA group ( P<0.01).Compared with young LA group, the protein level of collagen was significantly increased (P<0.01), and the arrange of atrial myocytes was irregular in LA of rabbits in aged LA group .The atrial myocytes of the LA wall in aged LA group exhibited abnormal ultrastructural alterations , such as karyopyknosis , irregular and swelling mitochondria with the presence of vacuoles , and mild and severe sarcomere degeneration .Compared with those in LA tissues of young rabbits , the expression levels of Cav 1.2 in the LA tis-sues of aged rabbits were severely reduced (P<0.01), and had a significant positive correlation with the reduction of ICa,L (r=0.83, P<0.01).CONCLUSION:The pathophysiological characteristics of aged LA are significantly altered , and might contribute to vulnerability and susceptibility of occurrence of atrial fibillation in aged rabbits .The mechanisms might completely attribute to the notable reduction of ICa,L , abnormal alterations of ultrastructures and obvious decrease in the ex-pression of Cav1.2 in the aged LA of aged rabbits .
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To investigate the inhibitory effect of Huangqi Danshen decoction (HDD) on isoproterenol (ISO)-induced myocardial remodeling and explore its effect on STIM1, TRPC1, CaN and NFATc3 expressions. ISO (2.5 mg•kg⁻¹•d⁻¹×14 d) was given by subcutaneous injection to establish myocardial remodeling models in rats, and then were randomly divided into control group, ISO model group, HDD5 group (HDD 5 g•kg⁻¹•d⁻¹+ISO), and HDD10 group (HDD 10 g•kg⁻¹•d⁻¹+ISO). After intervention for 4 weeks, the heart mass index (HW/BW) and the left ventricular mass index (LVW/BW) were calculated; the structure of myocardium was observed by echocardiography; the pathological changes of myocardium were observed by HE staining; levels of BNP, CaN and CaM kinases II in serum were detected by ELISA, and the protein expression levels of STIM1, TRPC1, p-CaN, p-NFATc3, and NFATc3 in left ventricular tissues were detected by Western blot. The results showed that the HW/BW and LVW/BW in ISO group were greater than those in HDD5 group and HDD10 group (P<0.05); Echocardiography showed that HDD inhibited ISO-induced increase in LVEDD and LVESD; ELISA results showed that HDD could significantly inhibit the increase of BNP, CaN and CaM kinases II levels in serum of rats with ISO-induced myocardial remodeling (P<0.01). Western blot results showed that STIM1, TRPC1, p-CaN, p-NFATc3 and NFATc3 expression levels were increased in the myocardial tissues of ISO group rats, and after HDD administration, the above expression levels were decreased in group ISO, HDD for myocardial tissue after administration of STIM1, TRPC1, p-CaN, p-NFATc3 and NFATc3 expression decreased (P<0.05). Our findings indicated that HDD can attenuate the myocardial remodeling induced by ISO, and its mechanism may be related to down-regulating the expression levels of STIM1, TRPC1, CaM kinases II, p-CaN/CaN and p-NFATc3/NFATc3.
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Objective To evaluate the value of QT dispersion in myocardial remodeling and prognosis in patients with chronic heart failure with preserved ejection fraction (HFpEF).Methods Totally 76 patients admitted to hospital due to HFpEF in the period between years 2013-2015 were recruited.A 12-lead ECG,chest radiograph,echocardiogram,and serum for biochemical analysis were obtained at baseline.Patients were followed for 10.3 ± 2.6 months,the basic information of patients,medication details,laboratory examination,echocardiography and other clinical data,and the mortality rate and the incidence of the disease were collected and analyzed.Results During the follow-up,11 patients died (14.5％) with QT dispersion for 81.6 ± 25.7ms.65 patients survived,including 27 cases of readmission for cardiovascular events (35.5％) with QT dispersion for 73.8 ± 24.7ms.The remaining 38 patients without cardiovascular events (50％) with QT dispersion 64.8 ± 28.7ms.Univariate analysis showed that QTcmax and QTcd were the risk factors for death and cardiovascular events in HFpEF patients (P ＜ 0.05).Cox's proportional hazards regression model analysis found that QTcd was the independent risk factors for death and cardiovascular events in HFpEF patients (P ＜ 0.05).Pearson's correlation analysis showed that QTcd was significantly related with left ventricular end systolic diameter (P ＜ 0.05),left ventricular end diastolic diameter (P ＜ 0.05).Conclusion QT dispersion has clinical value in the diagnosis of myocardial remodeling and prognosis in patients with HFpEF.
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In the 70s of last century, the treatment of chronic heart failure (CHF) mainly uses inotropic drugs, diuretic and vasodilators, which can improve the hemodynamic condition and have no change in mortality in patients. Since the end of 1980s, excessive activation of the renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system have demonstrated to play a key role in the pathophysiology of CHF. Blockade of these two systems can significantly reduce the mortality of CHF, which become a comerstone of the treatment of heart failure. Since 2010, three different types of drugs namely ivabradine, LCZ696 and a kind of traditional Chinese medicine have been shown confirmed the curative effects for heart failure, that means a new concept of CHF treatment, neurohormonal blockade/inducing and systematical regulation.
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Aim To investigate the effects of total gin-senosides ( TG) on microvascular regeneration and car-diac function in rat after acute myocardial infarction ( AMI ) . Methods The acute myocardial infarction model was created with left coronary artery ligated in male Sprague Dawley rats. The model rats were ran-domly divided into sham, model, TG low and high dose groups. TG groups were injected into abdominal cavity with TG(20 mg·kg-1·d-1, 40 mg·kg-1· d-1 ) . Sham and model groups were injected with e-qual-volume normal saline. On the 35th day post-opera-tion, heart function was examined by color doppler ul-trasoundination. HE, Masson and immunohistochemis-trical staining were used to observe the histopathologi-cal changes of myocardium and micro vessel density. The level of vascular endothelial growth factor( VEGF) and basic fibroblast growth factor( bFGF) mRNA were detected by real-time PCR. Results Compared with the model group, high and low dose TG obviously de-creased the left ventricular end diastolic dimension, the left ventricular end-systolic dimension, the left ventric-ular end-diastolic volume and the left ventricular end-systolic volume(P<0. 05 and P<0. 01), and signifi-cantly increased the ejection fraction and the fractional shortening ( P <0. 01 ) . The histopathological changes of myocardium on myocardial infarction and fibrosis were dramatically reduced by TG. But ventricular wall was thicker. Two dose TG remarkably increased the expressions of VEGF and bFGF mRNA and micro ves-sel density of compositive CD31 + cells in ischemic myocardial tissue and around of infarct area(P<0. 01, P <0 . 0 5 ) . Conclusions TG could improve the car-diac function of acute myocardial infarction rat. The mechanism may be related to the upregulation of VEGF and bFGF gene expression, the promotion angiogene-sis, then the improvement of blood supply in myocardi-al infarction area.
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Objective To study the expression of transforming growth factor -β1 (TGF -β1 )in myocardial tissue and the concentration of serum B -type natriuretic peptide (BNP)in myocardial remodeling of SD rats induced by isoproterenol (ISO)and the effects of carvedilol intervention.Methods According to random number table,30 male SD rats were divided into 3 groups:(1 )after 9 g/L saline was injected with 5 mL/(kg·d)for 1 0 days,9 g/L sa-line was used at the dose of 1 0 mL/(kg·d)by way of gavage for 4 weeks in the control group (n =1 0);(2)after ISO was injected with 5 mg/(kg·d)for 1 0 days,9 g/L saline was used at the dose of 1 0 mL/(kg·d)by way of gavage for 4 weeks in the model group (n =1 0);(3)after ISO was injected with 5 mg/(kg·d)for 1 0 days,carvedilol was used at the dose of 1 0 mg/(kg·d)by way of gavage for 4 weeks in the treatment group (n =1 0).Then,all the rats were killed and the cardiac weight index (CWI)was measured.The pathological changes of myocardial tissue were ob-served through HE staining and Masson staining.The mRNA expression of TGF -β1 was detected by adopting reverse transcription -polymerase chain reaction.The protein of TGF -β1 was detected by means of immunohistochemistry and Western blot.The concentration of serum BNP was tested by adopting enzyme -linked immuno sorbent assay.Results (1 )Pathological changes by light microscope:no significant pathological changes were observed in myocardial tissue of the control group.The denaturization,hypertrophy,edema,necrosis of myocardial cells and collagen fibers increased in myocardial tissue of the model group were more serious than those of the treatment group.(2)CWI:CWI of the model group[(3.31 ±0.07)mg/g]was significantly higher than that of the treatment group[(3.03 ±0.04)mg/g],and CWI of the treatment group was significantly higher than that of the control group[(2.98 ±0.1 0)mg/g].There was significant difference among 3 groups (F =54.383,P =0.000).There was also significant difference between any 2 groups (all P <0.01 ).(3)The level of TGF -β1 of myocardial tissue:the level of TGF -β1 of the model group was significantly higher than that of the treatment group,and the level of TGF -β1 of the treatment group was significantly higher than that of the control group by using three detection methods.There was significant difference among 3 groups (F=1 3.62,P =0.000).There was also significant difference between any 2 groups (all P <0.01 ).(4)The concentration of serum BNP:the concentration of serum BNP of the model group[(61 .1 3 ±2.00)ng/L]was significantly higher than that of the treatment group[(57.08 ±1 .52)ng/L],and the concentration of serum BNP of the treatment group was sig-nificantly higher than that of the control group[(51 .56 ±1 .80)ng/L].There was significant difference among 3 groups (F =72.81 ,P =0.000).There also was significant difference between any 2 groups (all P <0.01 ).Conclusions The expression of TGF -β1 in myocardial tissue was up -regulated and the concentration of serum BNP was increased in my-ocardial remodeling of SD rats induced by ISO.The carvedilol intervention can down -regulate the expression of TGF -β1 and decrease the concentration of BNP,then inhibit myocardial remodeling,and improve cardiac function.
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Objective To investigate the myocardial remodeling inhibition effect of bisoprolol combined with trimetazidine in the treatment of hypertensive myocardial hypertrophy.Methods 86 cases with hypertension and cardiac hypertrophy in Lingwu People’s Hospital of Ningxia from June 2015 to June 2016 were selected and randomly divided into two groups,43 cases in the control group received routine clinical treatment,43 cases in the experiment group received more with bisoprolol combined with trimetazidine treatment.Blood pressure,ultrasonic cardiogram,levels of serum TNF-α, MMP3 and CRP were compared before and after the treatment.Results Compared with before treatment,levels of blood pressure,IVST,LVPWT,LVMI, MMP3,TNF-αand serum CRP significantly decreased after treatment,and compared with the control group,levels of blood pressure,IVST,LVPWT, LVMI,MMP3,TNF-αand serum CRP in the experiment group were lower,the differences were statistically significant (P<0.05),and the effective rate in the experiment group was higher than the control group ( P<0.05 ) .Conclusion Bisoprolol combined with trimetazidine can effectively inhibit the remodeling of hypertension in patients with myocardial hypertrophy,has good clinical efficacy.
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Objective To investigate the effects of metoprolol on Myocardial remodeling and cardiac function in type 2 diabetic patients with chronic heart failure.Methods 70 type 2 diabetic patients with chronic heart failure were randomly divided into treatment group and control group.Both groups were given conventional anti-heart failure treatment.The patients in the treatment group were administered with oral metoprolol.Two groups were treated for 12 weeks.The changes of cardiac function, left ventricular posterior wall thickness (LVPWTH), left ventricular end diastolic diameter ( LVEDD ) , left ventricular end systolic diameter ( LVESD ) , left ventricular ejection fraction ( LVEF) and E/A were observed before and after treatment in both groups.Results After treatment, the total effec-tiveness rate of the clinical curative effect in the treatment group was 85.71%, significantly higher than the control group (p<0.05).LVPWTH, LVEDD and LVESD decreased after treatment, while LVEF and E/A increased. These changes were more significant in the treatment group, with statistically significant difference between two groups ( p<0.05) .There was no significant effect of metoprolol on glucose and lipid metabolism in patients with type 2 diabetes mellitus.No serious adverse drug reaction was observed in both groups.Conclusion Metoprolol can reverse or delay left ventricular remodeling in type 2 diabetic patients with chronic heart failure, and can also improve cardiac function.
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Objective To investigate the the molecular mechanism of telmisartan for myocardial remodeling in rats with renovascular hypertention. Methods The renovascular hypertensive myocardial hypertrophy model of rats were established by narrowing the left renal artery.The total of 45 mature male SD rats were divided into sham-operated group(n= 15),model control (n = 15 ) and telmisartan group ( n = 15 ) randomly. The rats in telmisartan group were treated with telmisartan (10 mg?kg-1?d-1 ) while those in the sham-operated and model control were reated with the same amounts of distilled water by intragastrical administration . At 8th week of administration, the myocardial structure and function were detected by ultrasonography.The blood pressure was measured by arterial catheterization and calculating the left ventricular mass index (LVMI) .The level of serum calcium and nerve phosphatase ( CaN) and the expression of β-myosin heavy chain ( β-MHC) mRNA were detected. Results The thickness of left ventricular,ejection fraction[(69.23± 1.09)% vs(73.77± 3.00)%], fractional shortening [(30.21±2.02)% vs(35.29±0.90)%],LVMI[(2.83±0.14) mg?g-1 vs(2.32±0.11) mg?g-1 ] were decreased,and the differences were statistically significant (P<0.05).The level of serum calcium and nerve phosphatase (CaN) and the expression of β-myosin heavy chain (β-MHC) mRNA were decreased in telmisartan treated rats,and the differences were statistically significant (P< 0.05) when compared with the model control group. Conclusion Telmisartan can improve the myocardial hypertrophy of renovascular hypertensive rats,and it may downregulate the expression of β-MHC by inactivating of the start signal CaN and its downstream signal pathway.
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OBJECTIVE: Chagas' disease has spread throughout Latin America because of the high rate of migration among these countries. Approximately 30% of Chagas' patients will develop cardiomyopathy, and 10% of these will develop severe cardiac damage leading to heart failure. Beta-blockade improves symptoms and survival in heart failure patients; however, its efficacy has not been well established in Chagas' disease. We evaluated the role of carvedilol in cardiac remodeling and mortality in a Chagas' cardiomyopathy animal model. METHODS: We studied Trypanosoma cruzi infection in 55 Syrian hamsters that were divided into three groups: control (15), infected (20), and infected + carvedilol (20). Animals underwent echocardiography, electrocardiography, and morphometry for collagen evaluation in ventricles stained with picrosirius red. RESULTS: The left ventricular diastolic diameter did not change between groups, although it was slightly larger in infected groups, as was left ventricular systolic diameter. Fractional shortening also did not change between groups, although it was slightly lower in infected groups. Collagen accumulation in the interstitial myocardial space was significantly higher in infected groups and was not attenuated by carvedilol. The same response was observed in the perivascular space. The survival curve showed significantly better survival in the control group compared with the infected groups; but no benefit of carvedilol was observed during the study. However, in the acute phase (up to 100 days of infection), carvedilol did reduce mortality. CONCLUSION: Carvedilol did not attenuate cardiac remodeling or mortality in this model of Chagas' cardiomyopathy. The treatment did improve survival in the acute phase of the disease.
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Animals , Cricetinae , Female , Adrenergic beta-Antagonists/therapeutic use , Carbazoles/therapeutic use , Chagas Cardiomyopathy/drug therapy , Propanolamines/therapeutic use , Ventricular Remodeling/drug effects , Chagas Cardiomyopathy/mortality , Chagas Cardiomyopathy/pathology , Collagen/analysis , Disease Models, Animal , Echocardiography , Heart Rate/drug effects , Heart Ventricles/physiopathology , Kaplan-Meier Estimate , Mesocricetus , Survival Rate , Time Factors , Treatment OutcomeABSTRACT
It has been recently shown that calcium channel blockers might have a protective effect on cardiac fibrogenesis induced by aldosterone. The objective of this study was to evaluate the protective effect of felodipine, a dihydropyridine calcium channel blocker, against heart and kidney damage caused by aldosterone-high sodium intake in uninephrectomized rats. Wistar rats were divided into three groups: CNEP (uninephrectomized + 1 percent NaCl in the drinking water, N = 9); ALDO (same as CNEP group plus continuous infusion of 0.75 µg/h aldosterone, N = 12); ALDOF (same as ALDO group plus 30 mg·kg-1·day-1 felodipine in the drinking water, N = 10). All results were compared with those of age-matched, untreated rats (CTL group, N = 10). After 6 weeks, tail cuff blood pressure was recorded and the rats were killed for histological analysis. Blood pressure (mmHg) was significantly elevated (P < 0.05) in ALDO (180 ± 20) and ALDOF (168 ± 13) compared to CTL (123 ± 12) and CNEP (134 ± 13). Heart damage (lesion scores - median and interquartile range) was 7.0 (5.5-8.0) in ALDO and was fully prevented in ALDOF (1.5; 1.0-2.0). Also, left ventricular collagen volume fraction ( percent) in ALDOF (2.9 ± 0.5) was similar to CTL (2.9 ± 0.5) and CNEP (3.4 ± 0.4) and decreased compared to ALDO (5.1 ± 1.6). Felodipine partially prevented kidney injury since the damage score for ALDOF (2.0; 2.0-3.0) was significantly decreased compared to ALDO (7.5; 4.0-10.5), although higher than CTL (null score). Felodipine has a protective effect on the myocardium and kidney as evidenced by decreased perivascular inflammation, myocardial necrosis and fibrosis.
Subject(s)
Animals , Rats , Calcium Channel Blockers/therapeutic use , Felodipine/therapeutic use , Hypertension/drug therapy , Kidney/pathology , Myocardium/pathology , Sodium Chloride , Aldosterone/pharmacology , Blood Pressure/drug effects , Disease Models, Animal , Fibrosis/prevention & control , Hypertension/pathology , Nephrectomy , Necrosis/prevention & control , Rats, WistarABSTRACT
Objective The purpose of the present study was to investigate the effect of peroxisome proliferator-activated receptors δ（PPAR δ）activation with dietary GW610742X on the expression of tenascin-C in the infarcted and remodeling myocardium.Methods Sixty male Wistar rats were divided into four groups,including control group,sham group,myocardial infarction（MI） group,and MI＋GW610742X（GW）group.The left coronary artery was ligated to establish the MI model.PPAR δ activator GW610742X（100mg/kg/d）was administrated into the rats of GW group.At 3 months after procedure,the expression and distribution of tenascin-C in left ventricular free wall from each group were examined by Western blotting and immunofluorescence,respectively.Results After 3 months following procedure,there were obvious necrosis and fibrosis in left ventricular free wall from MI group.The expression of tenascin-C in MI and GW group was significantly higher than those in control and sham group（P 〈 0.01）.Moreover,tenascin-C expression in GW group was remarkably decreased compared to MI group（P 〈 0.05）.Additionally,tenascin-C expression in sham group was similar to that in control group（P 〉 0.05）.Conclusion The tenascin-C is upregulated in infarcted myocardium during the remodeling process,which can be significantly attenuated by PPAR δ activation.
ABSTRACT
Objective To investigate the involvement of mitogen-activated protein kinase(MAPK)and PI3K(phosphatidylinositol 3 kinase)/ Protein kinase B(Akt) signal transduction pathways in the mechanism of myocardium remodeling in patients with congestive heart failure(CHF).Methods Thirty nine patients of mitral valve disease with CHF were randomly selected and 30 cases of healthy persons were included as controls.Cardiac function parameters were measured by echocardiography.Concentration of AngⅡ in plasma and myocardial tissues was determined by radio immunoassay.Activity of PKC was determined by using competive prote in binding method,activity of MAPK was detected by the methods of immunoprecitipation.Immunoprecitipation was used to assay the protein expression and phosphorylation of PI3K and Akt(Protein kinase B),protein expression of C-FOS and ?-skeletal-actin in myocardial tissues.Results Pathological changes of myocardial tissues in CHF with valvular heart diseaseshowed typical myocardial remodeling.The hypertrophy was dominant at early stagy of CHF,while at end stage the characteristics include disordered alignament of the myocytes,the discontinuity and dissolving of cardiomyofibrills,destroyed subcellular organs,and the hyperplasia of interstitial tissue.AngⅡ concentration in plasm and myocardial tissues in patients with CHF was higher than those in the control group(P