Mechanism of Astragalus methylside alleviating cardiomyocyte hypertrophy / 中华老年医学杂志

Objective:To investigate the protective effects and related mechanisms of Astragaloside Ⅳ(ASⅣ)alleviating Angiotensin II-induced cardiomyocyte hypertrophy.Methods:H9c2 cardiomyocytes were divided into six groups: normal control group, ASⅣ group(ASⅣ 100 μmol/L), AngⅡ group(AngⅡ 1 μmol/L), and three ASⅣ dose experiments(AngⅡ 1 μmol/L + ASⅣ 25 μmol/l group, AngⅡ 1 μmol/L+ ASⅣ 50 μmol/l group, AngⅡ1 μmol/L+ ASⅣ 100 μmol/L group), and simultaneously cultured for 24 hours.Cardiomyocyte viability was assessed by CCK8 assay, and surface area of culturedcardiomyocytes in each group was assessed by immunofluorescence assay.Atrial natriuretic peptide(ANP)mRNA expression was assessed by fluorescence real-time quantitative RT-PCR.And LC3 protein expression, an autophagy related protein, was assessed by Western blotting as well as immunofluorescence.Results:(1)AngⅡ decreased cardiomyocyte H9c2 viability in a dose-dependent manner( P<0.05). ASⅣ could inhibit the decrease of cardiomyocyte H9c2 viability in response to AngⅡ in a dose-dependent manner( P<0.05). (2)H9c2 cardiomyocytes induced by AngⅡ showed a significantly larger cell area and significantly higher ANP mRNA and ANP protein expression compared with controls.Different concentrations of ASⅣ intervention could reverse the increase of cardiomyocyte H9c2 area induced by AngⅡ and also decreased the expression of ANP protein induced by AngⅡ in a dose-dependent manner(all P<0.05). (3)Compared with the control group, the autophagy level and the expression of autophagy marker LC3II/I of H9c2 cardiomyocytes induced by AngⅡ were significantly increased(all P<0.05). ASⅣ could inhibit AngⅡ-activated autophagy, and the difference was statistically significant( P<0.05). ASⅣ inhibited the expression of LC3II/I in H9c2 cardiomyocytes stimulated by AngⅡ, and the difference was statistically significant( P<0.05). Conclusions:ASⅣ inhibits AngⅡ-induced cardiac hypertrophy by inhibiting autophagy of cardiomyocytes.

Rosmarinic acid inhibits high glucose-induced cardiomyocyte hypertrophy by activating Parkin-mediated mitophagy / 南方医科大学学报

OBJECTIVE@#To evaluate the effect of rosmarinic acid (RA) on mitophagy and hypertrophy of cardiomyocytes exposed to high glucose (HG).@*METHODS@#Rat cardiomyocytes (H9c2) exposed to HG (25 mmol/L) were treated with 50 μmol/L RA or with both RA treatment and Parkin siRNA transfection, with the cells cultured in normal glucose (5.5 mmol/L) and HG as the controls. The expressions of PINK1, Parkin and LC3II/LC3I in the cells were detected by Western blotting. The formation of mitochondrial autophagosomes was observed by transmission electron microscope. Flow cytometry was employed to detect the level of reactive oxygen species (ROS) and apoptotic rate of the cells. The activities of respiratory chain complex enzymes were measured by spectrophotometry. Fluorescence enzyme labeling and @*RESULTS@#RA treatment significantly increased the expression levels of PINK1, Parkin and LC3-II/I (@*CONCLUSIONS@#RA can protect rat cardiomyocytes against oxidative stress injury and cardiomyocyte hypertrophy induced by HG by activating Parkin-mediated mitophagy.

Overexpression of miR-130a-3p attenuates cardiomyocyte hypertrophy / 生物医学工程学杂志

This study aimed to explore the role of miR-130a-3p in cardiomyocyte hypertrophy and its underlying mechanisms. Pressure-overload induced myocardial hypertrophy mice model was constructed by thoracic aortic constriction (TAC). , norepinephrine (NE) was used to stimulate neonatal rat cardiomyocytes (NRCMs) and H9c2 rat cardiomyocytes to induce hypertrophic phenotypes. The expression of miR-130a-3p was detected in mice hypertrophic myocardium, hypertrophic NRCMs and H9c2 cells. The mimics and inhibitors of miR-130a-3p were transfected into H9c2 cells to observe the role of miR-130a-3p on the hypertrophic phenotype change of cardiomyocytes separately. Furthermore, whether miR-130a-3p regulated hypertrophic related signaling pathways was explored. The results showed that the expression of miR-130a-3p was significantly decreased in hypertrophic myocardium, hypertrophic NRCMs and H9c2 cells. After transfection of miR-130a-3p mimics, the expression of hypertrophic marker genes, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and β-myosin heavy chain (β-MHC), and the cell surface area were notably down-regulated compared with the control group (mimics N.C. + NE group). But after transfection of miR-130a-3p inhibitor, the expression of ANP, BNP and β-MHC in H9c2 cells increased significantly, and the cell area increased further. By Western blot, it was found that the protein phosphorylation level of Akt and mTOR were down-regulated after over-expression of miR-130a-3p. These results suggest that miR-130a-3p mimics may alleviate the degree of cardiomyocyte hypertrophy, meanwhile its inhibitor can further aggravate cardiomyocyte hypertrophy. Over-expression of miR-130a-3p may attenuate cardiomyocytes hypertrophy by affecting the Akt pathway.

Effect of Leonurine on p38 MAPK Signaling Pathway and miRNA-1 in Cardiomyocyte Hypertrophy Induced by AngⅡ / 中国实验方剂学杂志

Objective: To investigate the inhibitory effect of leonurine on cardiomyocyte hypertrophy induced by angiotensin Ⅱ(Ang Ⅱ) and its effect on p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway and miRNA-1.Method: Cardiomyocyte hypertrophy was induced by Ang Ⅱ (0.1 μmol·L-1) in primary neonatal cardiomyocytes. Experiments were designed in 6 groups as following:normal group, model group, p38 MAPK inhibitor group (SB203580, 10 μmol·L-1), low-dose(5 μmol·L-1), middle-dose(10 μmol·L-1) and high-dose(20 μmol·L-1) group. The cardiomyocyte surface area was measured by image software, and the protein contents were detected by Lowry. The concentrations of ANP in the culture supernatant were measured by enzyme-linked immunosorbent assay (ELISA). The expression level of miRNA-1 was detected by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR), and the protein expression levels of endothelin-1 (ET-1), p38 MAPK, p-p38 MAPK, myocyte enhancer factor 2 (MEF2), β-myosin heavy chain (β-MHC), α-myosin heavy chain (α-MHC) were detected by Western blot.Result: Compared with normal group, the surface area of cardiomyocyte, the protein contents, the concentrations of ANP, and the protein expression levels of ET-1, p38 MAPK, p-p38 MAPK, MEF2, β-MHC in model group were higher (Pα-MHC and miRNA-1 were lower than those in normal group (Pβ-MHC in high-dose group were lower (Pα-MHC and miRNA-1 were higher than those in model group (PConclusion: Leonurine (20 μmol·L-1) could inhibit cardiomyocyte hypertrophy induced by AngⅡ, and the mechanism is related to the inhibition of activation of p38 MAPK signaling pathway and up-regulation the expression of miRNA-1.

Effects of hydrogen sulfide (HS) on cardiac hypertrophy and miRNA-133a-mediated Ca/calcineurin/NFATc4 signal pathway in rats / 中国应用生理学杂志

OBJECTIVE@#To investigate the effects of hydrogen sulfide (HS) on the negatively regulation of cardiomyocyte hypertrophy and the relationship between the effect of HS with miRNA-133a-mediated Ca/calcineurin/NFATc4 signal pathway.@*METHODS@#Cardiomyocyte hypertrophy was induced by isoproterenol (ISO). The cell surface area was measured by image analysis system (Leica). The expression of brain natriuretic peptide(BNP), β-myosin heavy chain(β-MHC), cystathionase (CSE), miRNA-133a, calcineurin (CaN) were detected by qRT-PCR. The protein expressions of CaN、nuclear factors of activated T cells (NFATc4) were detected by Western blot. The concentration of HS in the cardiomyocyte was detected by Elisa. The concentration of intracellular calcium was measured by calcium imaging using confocal microscope. The nuclear translocation of NFATc4 was checked by immuno-fluorescence cell staining technique.@*RESULTS@#①The level of system of CSE/HS and expression of miRNA-133a were significantly reduced in cardiomyocyte hypertrophy. Pretreatment with NaHS increased the concentration of HS and the expression of miRNA-133a mRNA in cardiomyocytes, and suppressed cardiomyocyte hypertrophy. ②The concentration of intracellular calcium, the expression of CaN and nulear protein NFATc4 were significantly increased, and the nuclear translocation of NFATc4 were obviously enhanced in cardiomyocyte hypertrophy. NaHS pretreatment markedly inhibited these effects of ISO induced cardiomyocyte hypertrophy. ③Application of antagomir-133a reversed the inhibitory effects of NaHS on cardiomyocyte hypertrophy, and increased the influx of intracellular calcium, and elevated the expression of CaN and nuclear protein NFATc4, and enhanced the nuclear translocation of NFATc4.@*CONCLUSIONS@#HS can negatively regulate cardiomyocyte hypertrophy. The effects might be associated with HS increasing expression of miRNA-133a and inhibiting inactivation of Ca/calcineurin/NFATc4 signal pathway.

Effect of 5-AZA-2'-dC on angiotensin Ⅱ-induced cardiomyocyte hypertrophy / 中华急诊医学杂志

Objective To investigate the effect of 5-AZA-2'-dC on Angiotensin Ⅱ (Ang Ⅱ)-induced cardiomyocyte hypertrophy.Methods Cultured cells derived from neonatal heart of rat were divided into 5 groups:normal control,hypertrophic group,5-AZA-2'-dC treatment group,and 5-AZA-2'-dC pretreatment group.Neonatal rat cardiomyocyte hypertrophic response was assayed by the size of cardiomyocytes and atrial natriuretic polypeptide (ANP) expressive level.The level of sarcoplasmic reticulum Ca2+ ATPase (SERCA2a),total calmodulin kinase Ⅱ (CaMK Ⅱ) and phospho-CaMK Ⅱ (p-CaMK Ⅱ) detected by Western blot.The intracellular calcium changes of cardiomyocytes were imaged by confocal fluorescent microscopy.Results Cells treated with Ang Ⅱ at 10-6 mol/L for 48 h were chosen as hypertrophic cardiomyocyte model.The mRNA expression and protein level of ANP were significantly decreased in the treatment and pretreatment groups compared with hypertrophic group.The protein level of SERCA2a was significantly decreased in the hypertrophic group,and increased in the treatment and pretreatment group compared with hypertrophic group.The protein level of SERCA2a was significantly decreased in the hypertrophic group,and increased in the treatment and pretreatment group compared with hypertrophic group,whereas phospho-CaMK Ⅱ showed an opposite change tendency.The time required for increasing and declining to half of the intracellular calcium peak value were both delayed in hypertrophic group,as the treatment and pretreatment groups showed shorter time required compared with hypertrophic group.Conclusion 5-AZA-2'-dC could inhibit Ang Ⅱ-induced cardiomyocyte hypertrophy which might be related to regulate SERCA2a expression.Increased SERCA2a expression may maintain the calcium homeostasis through shortening the time of transfer Ca2+ from the cytosol of the cell to the lumen of the sarcoplasmic reticulum.

Effect of G Protein Coupled Estrogen Receptor 1 on Angiotensin Ⅱ-induced Hypertrophy of Cultured Neonatal Rat Cardiomyocytes / 中国循环杂志

Objectives: To observe the effect of activated G-protein coupled estrogen receptor 1 (GPER1) on Angiotensin II (AngII)-induced hypertrophy of cultured neonatal rat cardiomyocytes and explore related mechanisms. Methods: Primary cardiomyocytes derived from 2-to 3-day-old neonatal rats were cultured in vitro. Tandem mass tags (TMT) protein mass spectrometry was used to examine protein expressions; relevant bioinformatics analysis was performed to screen the possible regulatory mechanisms. Cardiomyocytes were divided into 6 groups: (1)Blank control group, (2) AngII group, (3)AngII+G1 (GPER1 activator) group, (4)AngII+G1+G15 (GPER1 inhibitor) group, (5)AngII+G1+U0126 (extracellular ERK inhibitor) group and (6)AngII+G1+MK2206 (AKT inhibitor) group (n=3 for each group). Cardiomyocytes GPER1 expressions, mRNA levels of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), protein levels of ERK, AKT with their interactions, autophagy-related proteins LC3II and LC3I were compared among different groups;impact of GPER1 on cardiomyocytes apoptosis was detected by flowcytometry. Results: AngII induced cardiomyocytes hypertrophy and upregulation of ANP and BNP mRNA levels in a dose-dependent manner (P<0.05). GPER1 expression could be detected on cardiomyocytes by Immunofluorescence technique. qRT-PCR results showed that GPER1 was activated by the specific activator G1 and mRNA expressions of ANP and BNP were inhibited in a dose-dependent manner by the specific activator G1 (P<0.05); mRNA levels of ANP and BNP were re-elevated in AngII+G1+G15 group (P<0.05). Western blotting results showed that protein expression of p-ERK and p-AKT was significantly higher in AngII group and AngII+G1 group than in blank control group (P<0.05), significantly reduced in AngII+G1+G15 group compared with AngII+G1 group (P<0.05); decreased expressions of p-ERK, p-AKT and mRNA levels of ANP,BNP were also detected in AngII+G1+MK2206 group (P<0.05). G1 induced protein expression was similar between AngII+G1 group and AngII+G1+U0126 group. Flowcytometry results indicated that cardiomyocytes apoptosis was similar between AngII+G1 group and AngII group (P>0.05). Ratio of LC3II/LC3I was significantly higher and autophagy levels were significantly enhanced in AngII group than in blank control group (P<0.01), these changes could be significantly reversed in AngII +G1 group (P<0.01 vs. AngII). Conclusions: Activation of GPER1 could inhibit neonatal cardiomyocytes hypertrophy, this effect might be related to AKT and ERK signaling pathway and cell autophagy.

Odanacatib Inhibits Resistin-induced Hypertrophic H9c2 Cardiomyoblast Cells Through LKB1/AMPK Pathway

ABSTRACT Odanacatib (ODN) is a selective inhibitor of cathepsin K. The cysteine protease cathepsin K has been implicated in cardiac hypertrophy. Resistine is an adipokine which is identified to promote cardiac hypertrophy. Here, we hypothesize that ODN mitigates resistin-induced myocyte hypertrophy. Cell surface area and protein synthesis were measured after treatment with resistin and ODN in H9c2 cells. The expression of cardiomyocyte hypertrophy marker BNP and β-MHC was detected by RT-qPCR. The expression and phosphorylation of AMPK and LKB1 were analyzed with Western blot. Resistin could significantly increase cardiomyocyte cell surface area, protein synthesis, and embryonic gene BNP and β-MHC expression, inhibit phosphorylation of AMPK and LKB1. ODN could significantly reverse the effects of resistin. Collectively, our data suggest that ODN can inhibit cardiomyocyte hypertrophy induced by resistin and the underlying mechanism may be involved in LKB1/AMPK pathway.

Role of ubiquitin E3 ligase TRIM10 in regulating cardiomyocyte hyper-trophy / 中国病理生理杂志

AIM:To explore the role of ubiquitin E3 ligase tripartite motif 10 (TRIM10) in the development of cardiomyocyte hypertrophy .METHODS: Primary cultured neonatal rat cardiomyocytes ( NRCMs ) were infected with siRNA-TRIM10, siRNA-control, Ad-TRIM10 or Ad-GFP for 24 h respectively, and then stimulated with phenylephrine ( PE) for additional 24 h.The protein levels of TRIM10, AKT and ERK1/2 were determined by Western blot .The size of the NRCMs was measured by immunofluorescence staining .The mRNA expression of atrial natriuretic peptide ( ANP) and brain natriuretic peptide ( BNP) was detected by RT-qPCR.RESULTS:Compared with the control , PE treatment signifi-cantly increased the protein expression of TRIM 10.Moreover, transfection of NRCMs with siRNA-TRIM10 markedly inhibi-ted cardiomyocyte size , the mRNA expression of ANP and BNP , and the phosphorylation levels of AKT and ERK as com-pared with siRNA-control after PE treatment.In contrast, overexpression of TRIM10 significantly enhanced PE-induced hy-pertrophic effect on NRCMs above .CONCLUSION:TRIM10 regulates cardiomyocyte hypertrophy partially through AKT and ERK signaling pathways .

The temporal expression patterns of the transcription factors and target genes in cardiomyocyte hypertrophy / 解放军医学杂志

Objective To investigate the temporal expression patterns of the related transcription factors and target genes in cardiomyocyte hypertrophy,and provide valuable clues for further researches on cardiomyocyte hypertrophy.Methods Isoproterenol (ISO) was used to induce ventricular myocytes hypertrophy in neonatal mice.The survival rate of cardiomyocyte was detected by CCK-8,and the average diameters and surface areas of cells were measured by computer photograph analysis system.The mRNA and protein expression levels of related genes were respectively measured by RT-PCR and Western blotting.Results The model of cardiomyocyte hypertrophy stimulated by ISO was constructed successfully.The expression levels of GATA4,MEF2C,GATA5,BNP and ANP increased 24 hours after ISO treatment,the expression levels of P300,α-MHC and TBX5 increased 12 hours after ISO treatment,and of SRF and β-MHC mRNA increased 6 hours after ISO treatment (P＜0.05).The expression levels of GATA4,α-MHC,β-MHC,SRF and P300 mRNA increased firstly,and then decreased in cardiomyocytes induced by ISO.The expression levels of GATA4,SRF,α-MHC,β-MHC and P300 mRNA were still higher than normal (P＜0.05),but of MEF2C decreased to normal (P＞0.0S) 72 hours after ISO treatment.The expression levels continuously elevated of GATA5,TBX5,ANP and BNP mRNA than that of controls (P＜0.05),while no fluctuation was found in NKX2.5 mRNA expression (P＞0.05).The expression of GATA4 protein increased,while of HEY2 protein decreased 48 hours after ISO treatment (P＜0.05).Conclusions In hypertrophic cardiomyocytes,the expression pattern of MEF2C is similar to,but the patterns of GATA5,GATA4,TBX5 and SRF are different with that in the development of heart,implying these genes are important during the process from compensatory stage to decompensation stage.The expression patterns of GATA4,MEF2C and SRF are similar to that of acetylase P300,implying the temporal expressions could be regulated by P300 in cardiomyocyte hypertrophy.

Activation of TGR5 reduces high glucose-induced cardiomyocyte hyper-trophy by inhibiting CaN/NFAT3 signaling / 中国病理生理杂志

AIM: To investigate the role of G-protein-coupled bile acid receptor 1 ( GPBR1; also known as TGR5) activation in high glucose-induced cardiomyocyte hypertrophy and calcineurin (CaN)/nuclear factor of activated T-cells 3 (NFAT3) signaling.METHODS:Primarily cultured mouse cardiomyocytes were used in the study .The cell surface areas of the cardiomyocytes were measured by an image analysis system .The cell protein content was detected by BCA meth-od.The expression of TGR5, CaN and NFAT3 at mRNA and protein levels was determined by RT-PCR and Western blot . RESULTS:The mouse cardiomyocytes were successfully cultured .High glucose significantly induced the increases in the cell surface area, the cell protein content and the expression of CaN and NFAT 3 (P<0.05) in the cardiomyocytes.TGR5 activation or a CaN antagonist cyclosporin A inhibited high glucose-induced cardiomyocyte hypertrophy and the expression of CaN and NFAT3 (P<0.05).These effects of TGR5 activation were abolished by TGR5 gene interference (P<0.05). CONCLUSION:TGR5 activation reduces high glucose-induced cardiomyocyte hypertrophy by inhibiting CaN /NFAT3 sig-naling.

Relationship Between Angiotensin Ⅱ , Secreted Frizzled-related Protein 5 and Rat's Cardiomyocyte Hypertrophy in Vitro / 中国循环杂志

Objective: To investigate the expression and effect of secreted frizzled-related protein 5 (sFRP5) in rat's cardiomyocyte hypertrophy in vitro. Methods: Neonatal rat's ventricular myocytes were cultured in vitro, cardiomyocyte hypertrophy was induced by Ang Ⅱ. Telmisartan and PD123319 were used to block angiotensin type 1 receptor (AT1R) and angiotensin type 2 receptor (AT2R) respectively. RT-PCR and Western-blot analysis were conducted to examine the expressions of sFRP5, BNP and TNF-α. Results: sFRP5 was expressed in cardiomyocytes. The mRNA and protein expressions of sFRP5, protein expression of BNP were increased by prolonged time of AngⅡ treatment, the maximum expression was observed at 48 h, P<0.05. Compared with Ang Ⅱ (10-6mol/L) group, the mRNA and protein expressions of sFRP5 in Ang Ⅱ +Telmisartan (10 μmol/L) group were decreased, P<0.05, those expressions were similar in Ang Ⅱ +PD123319 (10 μmol/L) group, P>0.05. Compared with AngⅡ (10-6 mo1/L)+sFRP5 (0 ng/ml) group, protein expressions of BNP and TNF-α were decreased inAng Ⅱ (10-6 mo1/L)+sFRP5 (10 ng/ml) group and in Ang Ⅱ (10-6 mo1/L)+sFRP5 (100 ng/ml) group respectively, P<0.05. Conclusion: For in vitro process of Ang Ⅱ induced neonatal rat's cardiomyocyte hypertrophy, using Ang Ⅱ receptor could up-regulate sFRP5 expression and sFRP5 plays an important role in cardiomyocyte hypertrophy.

Role of ubiquitin E3 ligase TRIM10 in regulating cardiomyocyte hyper-trophy / 中国病理生理杂志

AIM:To explore the role of ubiquitin E3 ligase tripartite motif 10 (TRIM10) in the development of cardiomyocyte hypertrophy .METHODS: Primary cultured neonatal rat cardiomyocytes ( NRCMs ) were infected with siRNA-TRIM10, siRNA-control, Ad-TRIM10 or Ad-GFP for 24 h respectively, and then stimulated with phenylephrine ( PE) for additional 24 h.The protein levels of TRIM10, AKT and ERK1/2 were determined by Western blot .The size of the NRCMs was measured by immunofluorescence staining .The mRNA expression of atrial natriuretic peptide ( ANP) and brain natriuretic peptide ( BNP) was detected by RT-qPCR.RESULTS:Compared with the control , PE treatment signifi-cantly increased the protein expression of TRIM 10.Moreover, transfection of NRCMs with siRNA-TRIM10 markedly inhibi-ted cardiomyocyte size , the mRNA expression of ANP and BNP , and the phosphorylation levels of AKT and ERK as com-pared with siRNA-control after PE treatment.In contrast, overexpression of TRIM10 significantly enhanced PE-induced hy-pertrophic effect on NRCMs above .CONCLUSION:TRIM10 regulates cardiomyocyte hypertrophy partially through AKT and ERK signaling pathways .

Resveratrol alleviates ISO-induced cardiomyocyte hypertrophy in rat / 基础医学与临床

Objective To explore the role of resveratrol (RES) on cardiomyocyte hypertrophy of rat induced by isoproternol (ISO) and the effect of Res on the expression of GRP78 and GRP94 in endoplasmic reticulum stress of cardiomyocyte hypertrophy.Methods Hypertrophic model of cardiomyocytes was induced by ISO.Cardiomyocytes was divided into four group: control group, the model group, RES+ISO group and RES group.Hypertrophy status of cardiomyocytes was determined by Leica 2Q500 image analysis system measuring the cell surface area and the gene expression of ANP.The content of LDH and MDA was measured in different groups, and the protein expressions of GRP78 and GRP94 were detected by Western blot.Results Compared with control group, ISO induced cardiomyocytes hypertrophy, endoplasmic reticulum stress related factors GRP78 and GRP94 protein expression were increased, compared with ISO group, RES intervention effectively suppressed the cardiomyocytes hyper-trophy induced by ISO, reduced the protein expression of GRP78 and GRP94, at the same time, reduced lactate dehydrogenase (LDH) and malondialdehyde (MDA) release in cell medium.Conclusions Treatment of RES may protect cardiomyocytes hypertrophy, which is partially mediated by inhibiting the expression of ERS factors GRP78 and GRP94.

Research progress in pharmacological effects of ginsenoside on cardiovascular diseases in last decade / 中草药

There are abundant active substances in ginsenoside, which have been used effectually in many fields. Ginseng saponins are the effective components in the treatment of cardiovascular diseases. Many kinds of ginseng saponins have a positive therapeutic effect on inhibiting cardiomyocyte hypertrophy, improving myocardial ischemia, protecting the ischemia-reperfusion myocardium, stimulating angiogenesis, and inhibiting myocardial apoptosis and anti-arrhythmia. This article summarized the research progress in the pharmacological effects of ginsenoside on cardiovascular diseases in the last decade.

Effects of fibroblast growth factor inducible 14 (Fn14) on high glucose induced-cardiomyocyte hypertrophy / 中华内分泌代谢杂志

Objective To investigate the effect and mechanisms of factor fibroblast growth factor inducible 14(Fn14)in the high glucose induced-cardiomyocyte hypertrophy. Method To observe the expression of collagenⅠ, connective tissue growth factor ( CTGF ) , transforming growth factor-β1 ( TGF-β1 ) , and Fn14 in high glucose induced-cardiomyocyte hypertrophy. Fn14 expressions was down-regulated by siRNA interference technique, and then the expressions of collagen Ⅰ, CTGF, and TGF-β1 were observed, and the mechanism was also explored. Results The expression of collagen I, CTGF and TGF-β1 was significantly up-regulated after high glucose induced-cardiomyocyte hypertrophy for 72 h. At the same time, the expression of Fn14 was increased after 72 h-treatment, and reached the peak at concentration of 30 mmol/L high glucose. High glucose could not up-regulated the expression of collagenⅠ, CTGF, and TGF-β1 after siFn14 interference, while the same result was observed in the expression of p-JNK. Conclusion The expressions of collagenⅠ, CTGF, TGF-β1, and Fn14 in cardiomyocyte of neonatal rats were induced by high glucose. While Fn14 expression was inhibited, the expressions of collagenⅠ, CTGF, and TGF-β1 were down-regulated, which seems to be involved with p-JNK signaling pathway.

Research progress of salvianolic acid B in cardiovascular diseases / 中国药理学通报

Cardiovascular disease is a serious threat to human health and quality of life ,and it has become the leading cause of death in human.Thus,looking for effective drugs to reduce the mortality and morbidity of such a disease has become a problem to be solved.Due to its good efficacy of activating blood circula-tion and dissipating blood stasis,salvia miltiorrhiza has been widely used in the treatment of cardiovascular disease and ob-tained a good curative effect.Salvianolic acid B is one of the main water-soluble components of salvia miltiorrhiza extract and studies have shown that salvianolic acid B possesses many biolog-ical activities,which not only has a good protective effect on my-ocardial infarction,but could significantly alleviate myocardial ischemia-reperfusion injury.This article reviews the research progress of salvianolic acid B in cardiovascular diseases,and al-so includes discussion about the mechanisms of salvianolic acid B in the regulation of cardiovascular diseases,which may provide references for follow-up research and clinical treatment.

PPARβ-related signal pathway involves in the effect of polydatin on high glucose-and insulin-induced cardiomyocyte hypertrophy / 中国药理学通报

Aim To investigate the effect of polydatin on cardiomyocyte hypertrophy induced by high glucose (25.5 mmol·L -1 )and insulin (0.1 μmol ·L -1 ) (HGI)and its possible influence on peroxisome prolif-erator-activated receptor-β (PPARβ)/nuclear tran-scription factor-κB (NF-κB)/nitric oxide (NO)signa-ling pathway.Methods The cardiomyocyte hypertro-phy was characterized in rat primary cardiomyocytes by measuring the cell surface area,protein content,and atrial natriuretic factor (ANF)mRNA expression.The mRNA and protein expressions were measured by qRT-PCR and Western blotting,respectively.The activity of NO synthase (NOS)and NO content were measured by reagent kit through ultraviolet spectroscopy.Results HGI significantly induced cardiomyocyte hypertrophy which increased the cell surface area,protein content and ANF mRNA expression (P <0.01 ).Meanwhile, the expressions of PPARβmRNA and protein reduced while the NF-κB p65 and iNOS expressions increased significantly which occurred in parallel with rising NOS activity and NO concentration (P <0.01 ).Polydatin (0.1,1,10 μmol·L -1 )inhibited the cardiomyocyte hypertrophy induced by HGI (P <0.01 ),and re-versed the mRNA and protein expressions of PPARβ, NF-κB p65 and iNOS,and NOS activity,as well as NO content.These effects of polydatin were abolished by GSK0660 (1 μmol·L -1 ),a selective PPARβan-tagonist (P <0.05 ).Conclusion Polydatin resists HGI-induced cardiomyocyte hypertrophy,which may be mediated by PPARβup-regulation,and then NF-κB-iNOS-NO pathway inactivation.

Regulation of miR-1 and miR-133 a on L-type calcium channel Cavβ2 and α1C subunits in rat cardiomyocyte hypertrophy / 基础医学与临床

Objective To investigate the regulation of miR-1 and miR-133 a on L-type calcium channel β2 subunit ( Cavβ2 ) and α1C subunit during rat cardiomyocyte hypertrophy .Methods Cardiomyocyte hypertrophy was in-duced by isoproterenol (ISO, 10μmol/L).The targets of miR-1 and miR-133a were predicted by online database microCosm and Targetscan , respectively .The 3′untranslated region sequences of Cavβ2 andα1C were respectively cloned into reporter vector and then transiently transfected into HEK 293 cells.The luciferase activities of samples were measured for demonstrating the expression of luciferase reporter vector .The protein expression of Cavβ2 andα1C were evaluated by Western blot .The expression levels of Cavβ2 andα1C were inhibited by RNAi to determine theeffectsofCavβ2andα1Concardiomyocytehypertrophy.Results 1)Cavβ2wasoneofpotentialtargetsof miR-1,α1C was the one of potential targets of miR-133a.2) The luciferase activities of HEK293 cells with the plasmid containing widetype Cavβ2 3′UTR sequence or α1 C significantly decreased ( P <0.05 , P <0.01 ) . 3 ) Upregulation of the miR-1 and miR-133 a by miR-1 mimic and miR-133 a mimic transfection suppressed pro-tein expression of Cavβ2 and α1C, respectively(P<0.01, P<0.05).4)Downregulation of Cavβ2 andα1C by RNAi could markedly inhibit the increase of cell surface area ( P<0.01 ) , mRNA expression of ANP andβ-MHC (P<0.05).Conclusions Cavβ2 is the target gene of miR-1 and α1C is the target gene of miR-133a.miR-1 and miR-133a can negatively regulate the expression of L-type calcium channel Cavβ2 andα1C subunit, inhibi-ting cardiomyocyte hypertrophy.

High glucose induces H9 c2 cardiomyocyte hypertrophy through Ca2+-CaN-NFAT3 signaling pathway / 中国病理生理杂志

AIM:To study the morphological changes of cardiac H9c2 cells during the developmental process of fetal rat.METHODS:Embryonic rat heart-derived H9c2 cells were maintained in DMEM supplemented with 10%fetal bovine serum.The H9c2 cells were plated at a density of 6 000 cells/cm and divided into 5 groups:H9c2 cells were trea-ted with 5 mmol/L glucose, 25 mmol/L glucose, 50 mmol/L glucose, Norvasc (25 nmol/L) +25 mmol/L glucose, or Norvasc (25 nmol/L)+50 mmol/L glucose for 48 h.The morphology of H9c2 cells was observed.The cell surface area was measured by Image-Pro Plus 6.1 software.Fluorescence spectrophotometry was used to detect the concentration of in-tracellular calcium ion ( [ Ca2+] i ) in the cardiomyocytes.The concentration of CaN in the cell was measured by ELISA. The mRNA expression of CaNAβ, NFAT3 and β-MHC in the cells was detected by real-time PCR.The protein levels of CaNAβ, NFAT3 and β-MHC in cultural H9c2 cells were detected by Western blot.RESULTS: The mean area of the cells, the mean fluorescence value of [ Ca2+] i and the concentration of CaN in 25 mmol/L glucose group were higher than those in 5 mmol/L glucose group, and those were lower than those in 50 mmol/L glucose group.After treated with Nor-vasc, those results decreased significantly.The expression of CaNAβ, NFAT3 andβ-MHC at mRNA and protein levels in 25 mmol/L glucose group was higher than those in 5 mmol/L glucose group, but was lower than those in 50 mmol/L glu-cose group .The expression of CaNAβ, NFAT3 andβ-MHC at mRNA and protein levels decreased significantly in Norvasc treatment group.CONCLUSION:Ca2+-CaN-NFAT3 signaling pathway is perhaps involved in high glucose-induced H9c2 cardiomyocyte hypertrophy.