1.Effects of Fenofibrate on neonatal rat hypertrophic cardiomyocyte in vitro
Journal of Medical Postgraduates 2003;0(08):-
Objective:To study the inhibitory effects of peroxisome proliferator-activated receptor ? activator Fenofibrate on the angiotensin Ⅱ(Ang Ⅱ)-induced cardiac hypertrophy in vitro. Methods: A model of hypertrophy of neonatal rat cardiac myocytes was established with Ang Ⅱ stimulation.With the aid of Leca Qwin Image software,the surface areas of cardiac myocytes were analyzed.The mRNA expression of ?、?-myosin heavy chains(?-MHC、?-MHC) and PPAR? was measured by reverse transcription-polymerase chain reaction(RT-PCR),and the cultured myocyte viability was estimated by MTT assay. Results:Fenofibrate pretreatment 24 h prior to Ang ⅡSignificantly reduced Ang Ⅱ-induced cardiac hypertrophy,inhibited the effect of AngⅡ on the cardiac myocyte viability and increased expression of?/?-MHC mRNA and PPAR? mRNA in a dose-dependent manner.In contrast,Fenofibrate had no significant effect on Ang Ⅱ treated cardiac myocytes when Fenofibrate treatment was concomitant with Ang Ⅱ. Conclusion: PPAR?-dependent pathway was involved in the inhibition of cardiac hypertrophy,but chronic treatment was needed.
2.Activators of peroxisome proliferator-activated receptors inhibit cultured AngⅡ-induced hypertrophic cardiomyocyte from neonatal rats
Journal of Third Military Medical University 2003;0(18):-
Objective To investigate the inhibitory effects of the ligands of peroxisome proliferator-activated receptors(PPARs),fenofibrate(PPAR? activator) and pioglitazone(PPAR? activator)on the angiotensin Ⅱ(Ang Ⅱ)-induced cardiac hypertrophy in vitro.Methods A model of hypertrophy of neonatal rat cardiac myocytes was established with AngII stimulation.With the aid of Leca Qwin Image software,the surface area of cardiac myocytes was analyzed.The mRNA expression of ?-MHC,?-MHC was measured by reverse transcription-polymerase chain reaction(RTPCR) and the cultured myocyte viability was estimated by MTT assay.Results Fenofibrate or pioglitazone pretreatment 24 h prior to AngⅡ stimulation,significantly reduced the cardiac hypertrophy(P
3.The comparative study of calcium-dependent and calcium-independent of dephosphorylation of myosin light chain and its effect on pulmonary artery pressure and right ventricular remodeling in rats
Yongyao YANG ; Tianhe YANG ; Qing'an JIANG ;
Chinese Journal of Applied Clinical Pediatrics 2015;(13):1016-1018
Objective To investigate the effects of calcium - dependent and calcium - independent in myosin light chain(MLC)dephosphorylation on pulmonary hemodynamics and right ventricular remodeling,and to observe whether there is a superimposition effect while intervention is conducted in two ways at the same time. Methods Ac-cording to random number table,50 rats were divided into 5 groups:sham operation group,model group,3 mg/(kg·d) ML - 7[MLC kinase(MLCK)inhibitor]treating group(M group),20 mg/(kg·d)Fasudil(Rho kinase inhibitor) treating group(F group)and 3 mg/(kg·d)ML - 7 plus 20 mg/(kg·d)Fasudil treating group(M + F group). The shunt between the abdominal aorta and inferior vena cava was used to establish rat models of pulmonary hypertension in-duced by high pulmonary flow in group of C and the experimental groups. The sham operation group was given a sham operation. MLCK and Rho kinase inhibitor were administrated intraperitoneally to rats with the shunt. After 8 weeks of shunting,mean right ventricular pressure(MRVP),mean pulmonary arterial pressure(MPAP),right ventricular hyper-trophy index(RVHI)and width of inferior venacava were evaluated by the right cardiac catheterization procedure. Results Compared with the sham operation group,MRVP,MPAP,and RVHI were obviously elevated in the model group [(2. 65 ±0. 57)kPa vs(4. 19 ±0. 67)kPa;(2. 42 ± 0. 48)kPa vs(4. 04 ± 0. 61)kPa,F = 295. 368,263. 912,all P ﹤0. 01;(0. 21 ±0. 01)g/ g vs(0. 41 ±0. 03)g/ g,F =247. 024,P ﹤0. 01]. Compared with model group,the MRVP,MPAP and RVHI in M group and F group were decreased significantly[(3. 51 ± 0. 47)kPa vs(4. 19 ± 0. 67)kPa;(3. 68 ± 0. 55)kPa vs(4. 19 ±0. 67)kPa,all P ﹤0. 01;M group:(0. 29 ±0. 02)g/ g,model group:(0. 41 ± 0. 03)g/ g,F group (0. 30 ±0. 03)g/ g,F =247. 024,P ﹤0. 05]. But the MRVP,MPAP and RVHI in M group and F group were higher than those of rats in the sham operation group. The MRVP,MPAP and RVHI of M + F group were elevated much obviously compared with those of the M or F group(P ﹤0. 05). Conclusions The calcium - dependent and calcium - independent in MLC dephosphorylation can respectively restrain the development of pulmonary hypertension and right ventricular re-modeling,and the obvious additive effect can be observed when the 2 drugs are used jointly.
4.Influence of transcatheter closure for atrial septal defects on heart remodeling and ventricular function in patients at different ages
Tianhe YANG ; Yongyao YANG ; Qingan JIANG ; Shan YU
Chinese Journal of Tissue Engineering Research 2009;13(39):7707-7710
OBJECTIVE: To investigate the geometric changes and ventricular function of heart after percutaneous closure of atrial septal defect according to patient age at the time of the procedure. METHODS: A total of 109 patients with atrial septal defect admitted to Department of Cardiology, Guizhou Provincial People's Hospital between June 1998 and October 2008 were retrospectively analyzed, including 53 males and 56 females aged 3.5-70 years. According to their age, the patients were divided into child group (aged=7 years, n=31), adolescent group (n=42, aged 8 18years) and adult group (n=36, aged > 18 years). Cardiac remodeling was assessed by transthoracic echocardiography before ASD closure and 6 months after atrial septal defect closure, including lateral diameter of left and right atrium (LALD, RALD), ratio of LALD/RALD, diastolic diameter of left and right ventricle (LVDD, RVDD), RVDD/LVDD ratio, and pulmonary diameter (PD), ejection fraction (EF) of LV and RV. RESULTS: 109 patients were all included in final analysis. Compared with preoperative results, the right atrium, RALD, RVDD,RALD/LALD, RVDD/LVDD ratio and PD were significantly decreased, while the left atrium and LALD significantly increased,and EF of left and right atrium was remarkably improved 6 months following atrial septal defect closure (P< 0.05-0.01).Moreover, the heart remodeling and heart function amelioration after atrial septal defect closure of child group were better than adolescent and adult groups (P < 0.05), but there were no significant differences between adolescent and adult groups (P>0.05).CONCLUSION: Transcatheter closure of atrial septal defect is safe and effective for all patients of different ages; in particular,results at children stage are better than adolescent and adult stages.
5.Role of PPARα/PGC-1αin doxorubicin induced mouse dilated cardio-myopathy
Xuesheng WANG ; Yongyao YANG ; Tianhe YANG ; Qingan JIANG
Chinese Journal of Pathophysiology 2015;(7):1160-1165
[ ABSTRACT] AIM:To investigate the changes of peroxisome proliferator-activated receptors ( PPAR)α/peroxi-some proliferator activated receptor coactivator 1 alpha ( PGC-1α) in doxorubicin ( DOX) induced dilated cardiomyopathy ( DCM) and its effect on the energy metabolism and myocardial function in mice .METHODS:Forty mice were randomly divided into 4 groups:control group, DOX group, PPARαinhibitor group and PPARαagonist group.The DCM model was established by injection of DOX.The protein levels of PPARα/PGC-1αwere detected.The PPARαinhibitor and PPARαagonist were used 2 weeks beforeinjection of DOX.The contents of adenine acid and phosphocreatine ( Pcr) in the mito-chondria were measured by high-performance liquid chromatography ( HPLC) .The ANT activity was analyzed by the atrac-tyloside-inhibitor stop technique.The changes of the echocardiography and hemodynamics were also observed.RESULTS:DOX induced DCM model was successfully established.The protein levels of PPARαand PGC-1αin control group were significantly higher than those in DOX group (P<0.05).Both of the high-energy phosphate contents and the transport ac-tivity of ANT were decreased in DOX group (P<0.05), and the hemodynamic parameters were disordered (P<0.01). Compared with DOX group, PPARαinhibitor pre-treatment significantly reduced the PPARα/PGC-1αexpression.Mean-while, high-energy phosphate contents in the mitochondria and the ANT transport activity of the mitochondria decreased, as well as the left ventricular function ( P<0.05) .On the other hand, PPARαagonist significantly increased the expression of PPARαand PGC-1α, and improved the transport activity of ANT.In addition, the hemodynamic parameters were amel-iorated, but the high-energy phosphate contents of the mitochondria did not significantly change.CONCLUSION:PPARα/PGC-1αplays an important role in the regulation of ANT transport activity in dilated cardiomyopathy induced by DOX, and the activation of PPARα/PGC-1αhas protective effects on the DCM induced by DOX.
6.Analysis on 567 cases of adverse events of the vaginal dilator.
Yongyao JIAN ; Tiezhu WANG ; Jianlin YANG ; Feng WANG ; Ping HUANG
Chinese Journal of Medical Instrumentation 2014;38(6):439-441
OBJECTIVETo investigate the risk factors of vaginal dilators by 567 adverse event reports, and to provide a reference for the reasonable use.
METHODSWith retrospective case study, analyzed 567 reports induced by vaginal dilators by National Adverse Drug Reaction Monitoring Center in 2012.
RESULTSExpected treatment of disease might be relevant with severity of adverse events, while age was not the related factor; the influencing factor of consequences of grading was the classification of the cause of adverse events.
CONCLUSIONMonitoring should be strengthen in order to reduce or avoid the vaginal dilator adverse events.
Adverse Drug Reaction Reporting Systems ; Dilatation ; adverse effects ; Drug-Related Side Effects and Adverse Reactions ; epidemiology ; Female ; Humans ; Retrospective Studies ; Risk Factors ; Vagina ; pathology
7.Effects of inhibiting myosin light chain kinase on endothelin-1 induced proliferation and apoptosis of pulmonary arterial smooth muscle cells in rats
Yongyao YANG ; Tianhe YANG ; Qingan JIANG ; Long YANG ; Feng TANG ; Hongwen TAN
Chinese Journal of Pathophysiology 2015;(2):256-260
AIM: To investigate the effect of inhibiting myosin light chain kinase ( MLCK) on endothelin-1 (ET-1) induced proliferation and apoptosis of rat pulmonary artery smooth muscle cells (PASMCs).METHODS: Rat PASMCs were cultured and stimulated with ET-1.The cells were randomly divided into control group , ET-1 group and ET-1+MLCK inhibitor group (ET-1+M).Western blotting, MTT assay, [3H]-TdR incorporation and flow cytometry were employed to test the expression of myosin light chain (MLC) and MLCK, cell proliferation, cell cycle and apoptotic rate of PASMCs ,respectively .The phosphorylation of MLC was determined by glycerol-PAGE coupled with Western blotting .RE-SULTS:Compared with control group , the protein expression of MLCK and MLC phosphorylation significantly enhanced af -ter ET-1 stimulation.ET-1 markedly induced the proliferation and decreased the percentage of apoptotic rate in the PASMCs.However, pretreatment with ML-7, a MLCK inhibitor, significantly reversed the above effects induced by ET-1. CONCLUSION:MLCK inhibitor effectively inhibits the ET-1-induced proliferation and the cell cycle progression .
8.Effects and mechanism of fenofibrate and pioglitazone on ventricular remodelingin in pressure overload rats
Qiang WU ; Yongyao YANG ; Tianhe YANG ; Yunchang CAI ; Longgui LI ; Qin HU
Chinese Journal of Pathophysiology 1999;0(09):-
AIM:To study the effects and mechanism of peroxisome proliferator-activated receptors(PPARs)ligands,fenofibrate and pioglitazone,on ventricular remodeling in pressure overload rats.METHODS:A pressure overload model was established by the constriction of abdominal aorta in Wistar rats.The hemodynamics and ventricular remodeling parameters,plasma and myocardial renin activity,angiotensin Ⅱ and aldosteron,the mRNA expression of angiotensin Ⅱ type 1 receptor(AT1)were investigated in the constriction of abdominal aorta group(CAA group,n=7)at 12-week after operation and treated experimental groups in which rats were treated with fenofibrate(F group,n=8),pioglitazone(P group,n=7),concomitant fenofibrate and pioglitazone(F+P group,n=6)for 12 weeks since 2 days after operation.The sham-operated rats served as controls(n=8).RESULTS:The ratio of left ventricular weight to body weight,mean arterial pressure,left ventricular systolic pressure,left ventricular end diastolic pressure,left ventricular systolic pressure and heart rate were significantly lower,the maximum left ventricular pressure rising and declining rates(?dp/dtmax)were significantly higher in all treated experimental groups than those in CAA group.Fenofibrate or pioglitazone had no effect on plasma and myocardial levels of renin,angiotensin Ⅱand aldosteron.The mRNA expression of AT1 was downregulated in treated groups except F group.CONCLUSION:PPAR ligands have no effect on plasma and myocardial levels of renin,angiotensin Ⅱand aldosteron,but fenofibrate and pioglitazone inhibit ventricular remodeling,decrease preload and afterload,increase ?dp/dtmax in pressure overload rats.The expression of mRNA of AT1 is downregulated in myocardium of pressure overload rats by the PPAR? signaling pathway.
9.Irisin Enhances Angiogenesis of Mesenchymal Stem Cells to Promote Cardiac Function in Myocardial Infarction via PI3k/Akt Activation
Fan YANG ; Zhi WANG ; Bing LI ; Youfu HE ; Fawang DU ; Shui TIAN ; Yu ZHANG ; Yongyao YANG
International Journal of Stem Cells 2021;14(4):455-464
Background and Objectives:
With the growing incidence of acute myocardial infarction (MI), angiogenesis is vital for cardiac function post-MI. The role of bone marrow mesenchymal stem cells (BMSCs) in angiogenesis has been previously confirmed. Irisin is considered a potential vector for angiogenesis. The objective of the present study was to investigate the potential role of irisin in the angiogenesis of BMSCs.
Methods:
and Results: In vivo, irisin-treated BMSCs (BMSCs+irisin) were transplanted into an MI mouse model. On day 28 post-MI, blood vessel markers were detected, and cardiac function and infarct areas of mice were evaluated. In vitro, paracrine effects were assessed by examining tube formation in human umbilical vein endothelial cells (HUVECs) co-cultured with the BMSCs+irisin supernatant. The scratch wound-healing assay was performed to evaluate HUVEC migration. Western blotting was performed to determine PI3k/Akt pathway activation in the BMSCs+irisin group. Transplantation of BMSCs+irisin promoted greater angiogenesis, resulting in better cardiac function in the MI mouse model than in controls. In the BMSC+irisin group, HUVECs demonstrated enhanced tube formation and migration. Activation of the PI3k/Akt pathway was found to be involved in mediating the role of irisin in the angiogenesis of BMSCs.
Conclusions
In cardiovascular diseases such as MI, irisin administration can enhance angiogenesis of BMSCs and pro-mote cardiac function via the PI3k/Akt pathway, optimizing the therapeutic effect based on BMSCs transplantation.