Meta-analysis of statin combined with trimetazidine on the regulation of inflammatory factors in coronary atherosclerotic heart disease and improvement of ventricular remodeling

Objective:To systematically evaluate the effects of statins combined with trimetazidine on the regulation of inflammatory factors and the improvement of ventricular remodeling in coronary atherosclerotic heart disease based on the inflammasomes/immune damage response theory.Methods:Using computer to search for EMbase,The Cochrane Library,Web of Science,MEDLINE,PubMed,WanFang Data,CNKI,China Biomedical Document Service System(CBM),VIP database(VIP),9 databases in total.The search time limit is from the inception of the databases to June 7,2021.All reference documents included in the study were manually searched.According to the Cochrane systematic review method,the information on atorvastatin combined with trimetazidine and conventional treatment(antiplatelet,control blood pressure,diuresis,coronary artery dilation and other expectant treatments)contrast the use of trimetazidine or stains combined with expectant treatment of coronary atherosclerotic heart disease patients in Chinese and English randomized controlled trials(RCT),and conduct the extraction and quality evaluation of the included literature data,using RevMan5.4 software for Meta analysis.Outcome indicators include inflammatory factors:C-reactive protein(CRP),IL-6(interleukin 6),tumor necrosis factor(TNF-α),and ventricular remodeling related outcome indicators:left ventricular end diastolic diameter(LVEDD),left Ventricular end systolic diameter(LVESD).Results:12 randomized controlled trials were included,a total of 1120 patients with coronary heart disease.Meta-analysis results:(1)inflammatory factors:the statin combined with trimetazidine group can significantly reduce the CRP,IL-6,TNF-α’s expression degree in the blood of patients with coronary heart disease compared with the control group(only statins or trimetazidine).CRP[n=770,SMD=-2.70,95%CI(-2.55,-1.40),P<-0.00001],TNF-α[n=678,SMD=-2.25,95%CI(-3.39,-1.12),P<-0.0001],IL-6[n=770,SMD=-2.10,95%CI(-3.10,-1.10),P<0.00001].(2)Ventricular remodeling:Compared with the control group(using statins or trimetazidine alone),the statin combined with trimetazidine group can significantly reduce the left ventricular end-systolic diameter of patients with coronary heart disease before treatment[n=626,SMD=-1.55,95%CI(-2.10,-0.99),P<-0.00001]and leftVentricular end diastolic diameter[n=626,SMD=-1.18,95%CI(-1.56,-0.80),P<-0.00001].Conclusion:Compared with the control group,statins combined with trimetazidine can significantly reduce the level of inflammatory factors based on the inflammasomes/immune injury response theory,and improve the ventricular remodeling in patients with coronary heart disease.

Shengmai Yin formula promotes ventricular remodeling in chronic heart failure rats by inhibiting excessive autophagy via activating AKT/mTOR pathway

Background:Shengmai Yin(SMY)formula,a traditional Chinese medicine,shows a definite therapeutic effect on chronic heart failure(CHF)in clinical practice,but the molecular mechanism remains largely unknown.The PI3K/Akt/mTOR pathway is a classic pathway of autophagy and plays a pivotal role in the occurrence and development of CHF.Here,we aimed to investigate whether SMY formula treat CHF rats by inhibiting excessive autophagy.Methods:Echocardiography was conducted to evaluate cardiac function.Transmission electron microscopy was used to observe the arrangement of myocardial cells.Enzyme linked immunosorbent assay analysis was performed to quantitative detecting the content of N-terminal pro-B-type natriuretic peptide,stromelysin-2,TNF-α in rat serum.Western blotting was used to detect the expression of AKT,p-AKT,mTOR,p-mTOR,light chain 3(LC3),and p62.In vitro,myocardial cells were treated with hypoxia reoxygenation and then intervened with SMY.Cell counting kit-8 method was used to measure the cell viability.The immunofluorescence expression of LC3 protein were also examined.Results:In vivo,SMY intervention assisted in the ventricular remodeling,reduced the levels of N-terminal pro-B-type natriuretic peptide,stromelysin-2,TNF-αin serum,and recovered myocardial cell structure in CHF rats.Treatment with SMY significantly promoted the ratio of p-AKT/AKT,p-mTOR/mTOR,and down-regulated the expression level of p62 and the ratio of LC3-Ⅱ/LC3-Ⅰ.In vitro,when the concentration of SMY containing serum reached 40% in the medium,the activity of myocardial cells reached the highest at 135.14%.SMY inhibited the expression of LC3 in hypoxic-reoxygenation embryonic ventricular myocytes cells.When the hypoxic reoxygenation cells treated with p-mTOR inhibitor,rapamycin,or p-AKT inhibitor,API-1,SMY could also down-regulated the LC3 expression level.Conclusions:SMY formula functions in restoring cardiac function and promoting myocardial ultrastructural recovery by reducing autophagy activity through up-regulating the ratio of p-AKT/AKT,p-mTOR/mTOR,and down-regulating the expression level of p62 and the ratio of LC3-Ⅱ/LC3-Ⅰ in CHF rats.

MicroRNA-29a attenuates angiotensin-Ⅱ induced-left ventricular remodeling by inhibiting collagen,TGF-β and SMAD2/3 expression

Background Left ventricular(LV)remodeling is the most common target organ damage in hypertension.Previously,our study found that plasma microRNA-29a(miR-29a)level was associated with the LV remodeling in hypertensive patients.However,the causal relationship between miR-29a and LV remodeling remains unknown.Thus,the aim of this study was to investigate the regulation mechanism of miR-29a in LV remodeling.Methods&Results Overexpression and knockdown miR-29a mice were generated by tail-intravenous injection of miR-29a-mimic and inhibitor lentivirus for one week respectively.Then the mice were subjected to angiotensin-II(AngII)induced LV remodeling by subcutaneous AngII capsule osmotic pumping into AngII for four weeks.AngII-induced LV remodeling mice as the model group(n=9).Age-matched male SPF C57/BL6J mice(6–8 weeks old)were treated with the pumping of saline as a vehicle(n=6).In vivo,overexpression miR-29a ameliorated AngII-induced LV remodeling,while knockdown miR-29a deteriorated LV remodeling.Simultaneously,we observed that overexpression miR-29a mice inhibited but knockdown miR-29a mice increased cardiac cross-sectional area,indicating that miR-29a has an antagonistic effect on cardiac hypertrophy.Further studies found that overexpression miR-29a inhibited the content of the LV collagen including collagen I and III.Moreover,the expression of transforming growth factor-β(TGF-β)and phosphorylated SMAD2/3 decreased with the down-regulation of collagen I and III in overexpression miR-29a mice.Conclusions Our finding indicates that overexpression miR-29a attenuates LV remodeling by inhibiting collagen deposition,TGF-β,and phosphorylated SMAD2/3 expression.Thus,intervention miR-29a may be a therapeutic target for attenuating LV remodeling.

Effect of exercise training on left ventricular remodeling in patients with myocardial infarction and possible mechanisms

BACKGROUND A growing amount of evidence provides support for the hypothesis that acute myocardial infarction(AMI)patients should go through cardiopulmonary exercise testing(CPET)about 3-5 d after AMI is diagnosed,make reasonable exercising prescription,and conduct exercise training under guidance.AIM To investigate the effect of exercise training(ET)on left ventricular systolic function and left ventricular remodeling(LVRM)and to study the possible mechanisms of LVRM by the changes of matrix metallopeptidase 9(MMP-9)and tissue inhibitor of metalloproteinases 1(TIMP-1)in patients with acute STsegment elevation myocardial infarction(STEMI).METHODS Sixty patients with first STEMI undergoing direct percutaneous coronary intervention from February 2008 to October 2008 were randomly assigned to an exercise group(n=30)and a control group(n=30).The levels of MMP-9 and TIMP-1 were measured in all patients at 1 d,10-14 d,30 d,and 6 mo after admission.Two-dimensional echocardiography and cardiopulmonary exercise testing were done in patients at 10-14 d and 6 mo after admission.RESULTS There was no significant difference in CPET at baseline between the exercise group and the control group.At 6 mo,the time of exercise,peak and anaerobic threshold values of O2 uptake,and metabolic equivalents increased in both groups,but markedly increased in the exercise group.At baseline,there were no significant differences in left ventricular ejection fraction(LVEF)between the two groups.At 6 mo,LVEF increased in the exercise group,but not in the control group.At 6 mo,the percentage of patients with positive result of LVRM was 26.6%in the exercise group and 52.6%in the control group(P<0.05).The levels of plasma MMP-9 and TIMP-1 and the ratio of MMP-9 to TIMP-1 in both groups had no significant difference at 1 d and 10-14 d after AMI,but at 30 d and 6 mo,the levels of plasma MMP-9 and TIMP-1 in the exercise group were significantly lower than those in the control group;the ratio of MMP-9 to TIMP-1 in the exercise group was significantly higher than that in the control group.CONCLUSION ET under supervision based on home condition in early and recovery stage of AMI can improve exercise cardiopulmonary function and prevent the LVRM.Therefore,it may reduce unfavorable remodeling response by decreasing the levels of plasma MMP-9 and TIMP-1 and adjusting the ratio of MMP-9 to TIMP-1 hereafter.

Effects of astragalus polysaccharides on ventricular remodeling and miRNA-21 in rats with acute myocardial infarction

Objective:To investigate the effect of Astragalus polysaccharides(APS)on myocardial remodeling and expression of miR-21 after myocardial infarction.Methods:Sixty SPF grade healthy male rats were divided into the sham operation group,the model group,astragalus polysaccharide low,medium and high dose groups and atorvastatin group randomly with 10 rats in each group.The left anterior descending coronary artery(LAD)was ligated to establish myocardial infarction model in rats,and the corresponding drug intervention was given for 4 weeks.The changes of myocardial morphology and collagen were observed by HE and Masson staining.The levels of IL-1β,IL-6,TNF-αand IL-10 were detected by ELISA.The mRNA expressions of miR-21,MMP2,TIMP-2,Col-I,and Col-III was detected by RT-PCR.The protein expressions of TLR4,MyD88 and NF-κB p65 were detected by Western blot.Results:Compared with the model group,APS could improve the pathological morphology of myocardial tissue,increase the level of IL-10 in myocardial tissue,reduce the staining area of collagen and the contents of IL-1β,IL-6 and TNF-α(P<0.05).At the same time,APS could decreased the expression of MMP2,Col-I and Col-ⅢmRNA and the ratio of MMP2/TIMP-2,and increased the expression of TIMP-2 mRNA and miR-21 significantly(P<0.05).Furthermore,APS could significantly reduce the expression of TLR4,p-NF-κB p65 and MyD88 protein in myocardial tissue of rats with myocardial infarction,and the differences were statistically significant when compared with the model group(P<0.05).Conclusion:APS can inhibit the activation of TLR4/MyD88/NF-κB signaling pathway by upregulating the expression of miR-21,which plays a therapeutic role in ventricular remodeling after acute myocardial infarction.

Effect of angiotensin receptor neprilysin inhibitor on ventricular remodeling after myocardial infarction in rats

Objective:To investigate the effect of Angiotensin Receptor Neprilysin Inhibitor(ARNI)on ventricular remodeling after AMI in rats.Methods:Sixty male SD rats were randomly divided into Control group,AMI group,AMI-valsartan group,AMI-ARNI group,15 rats in each group,ligating the left coronary anterior descending artery to establish the rat model of AMI.Valsartan group and ARNI group were treated with valsartan(34mg/kg/day)and ARNi(68mg/kg/day)for 6 weeks,the Control group and AMI group were given the same amount of normal saline.LVIDd,LVIDs,EF were measured by color doppler echocardiography before and 6 weeks after treatment.After 6 weeks,the rats were sacrificed,the hearts were weighed,then myocardial tissue Masson staining was performed to calculate the collagen volume fraction(CVF).Results:compared with the control group,LVIDs increased significantly with the reduction of EF in the AMI group,valsartan group and ARNI group(P<0.05).After 6 weeks of treatment,compared with the AMI group,LVIDd and LVIDs both reduced significantly with the increase of EF in the ARNI group(P<0.05).Compared with the control group,the left ventricular weight,right ventricular weight and atrial weight all increased significantly in the AMI group,valsartan group,and ARNI group(P<0.05);compared with the AMI group,the left ventricular weight,right ventricular weight,atrial weight and CVF reduced significantly in the valsartan group and ARNI group(P<0.05);compared with the valsartan group,the left ventricular weight and CVF further reduced in the ARNI group.(P<0.05).Conclusions:ARNI has the effect of reversing ventricular remodeling after AMI in rats,which can reduce left ventricular volume,increase myocardial contractility,and inhibit myocardial cell hypertrophy and fibrosis.

Yiqi Huoxue traditional Chinese decoction affect ventricular remodeling in rats with heart failure after myocardial infarction by regulating osteopontin expression

Objective:To investigate the mechanism of Yiqi Huoxue traditional Chinese medicine affecting the osteopontin(OPN)level in myocardial tissue and improving ventricular remodeling in heart failure rats after myocardial infarction.Methods:Forty SPF-grade SD male rats were prepared,and 10 rats were reserved as blank controls.The remaining rats were prepared by anterior descending coronary artery ligation combined with reduced diet and exhausted swimming to prepare a rat model of heart failure after myocardial infarction.The rats in the blank group and the model group were orally administered with distilled water,the Chinese medicine group was administered with Yiqi Huoxue Chinese medicine decoction,and the western medicine group was administered with captopril.After 6 weeks of treatment,small animal ultrasound was used to detect changes in ventricular structure and function in rats.Kill all the rats,and take myocardial tissue,observe the morphological changes of myocardial tissu under a light microscope.Use real-time quantitative PCR to detect the expression of OPN mRNA in rat myocardial tissue,and use immunohistochemical method to detect the expression of OPN protein in myocardial tissue.Results:Compared with the blank group,the left ventricular ejection fraction(EF),left ventricular short axis shortening fraction(FS)of the model group were significantly reduced,and the left ventricular end-diastolic diameter(LVEDD)and left ventricular end-systolic diameter(LVESD)were significantly increased,OPN mRNA and protein expression were significantly up-regulated(P<0.01),and myocardial structure disorder was seen under light microscope.Compared with the model group,the EF and FS of the Chinese medicine group and the Western medicine group were both significantly increased,the LVEDD and LVESD were significantly reduced,the expressions of OPN mRNA and protein were significantly reduced(P<0.01),and the myocardial structure was significantly improved under light microscopy.There was no statistically significant difference between the western medicine group and the traditional Chinese medicine group(P>0.05).Conclusion:Yiqi Huoxue Chinese medicine may reduce the expression of OPN in myocardial tissue,improve ventricular remodeling,improve cardiac function and prevent heart failure after myocardial infarction.

Effects of Compound Danshen Dripping Pills on Ventricular Remodeling and Cardiac Function after Acute Anterior Wall ST-Segment Elevation Myocardial Infarction(CODE-AAMI):Protocol for a Randomized Placebo-Controlled Trial

Background:Ventricular remodeling after acute anterior wall ST-segment elevation myocardial infarction(AAMI)is an important factor in occurrence of heart failure which additionally results in poor prognosis.Therefore,the treatment of ventricular remodeling needs to be further optimized.Compound Danshen Dripping Pills(CDDP),a traditional Chinese medicine,exerts a protective effect on microcirculatory disturbance caused by ischemia-reperfusion injury and attenuates ventricular remodeling after myocardial infarction.Objective:This study is designed to evaluate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function after AAMI on a larger scale.Methods:This study is a multi-center,randomized,doubleblind,placebo-controlled,parallel-group clinical trial.The total of 268 patients with AAMI after primary percutaneous coronary intervention(pPCI)will be randomly assigned 1:1 to the CDDP group(n=134)and control group(n=134)with a follow-up of 48 weeks.Both groups will be treated with standard therapy of ST-segment elevation myocardial infarction(STEMI),with the CDDP group administrating 20 tablets of CDDP before pPCI and 10 tablets 3 times daily after pPCI,and the control group treated with a placebo simultaneously.The primary endpoint is 48-week echocardiographic outcomes including left ventricular ejection fraction(LVEF),left ventricular end-diastolic volume index(LVEDVI),and left ventricular end-systolic volume index(LVESVI).The secondary endpoint includes the change in N terminal pro-B-type natriuretic peptide(NT-proBNP)level,arrhythmias,and cardiovascular events(death,cardiac arrest,or cardiopulmonary resuscitation,rehospitalization due to heart failure or angina pectoris,deterioration of cardiac function,and stroke).Investigators and patients are both blinded to the allocated treatment.Discussion:This prospective study will investigate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function in patients undergoing pPCI for a first AAMI.Patients in the CDDP group will be compared with those in the control group.If certified to be effective,CDDP treatment in AAMI will probably be advised on a larger scale.(Trial registration No.NCT05000411)

GuanxinⅤRelieves Ventricular Remodeling by Inhibiting Inflammation:Implication from Virtual Screening,Systematic Pharmacology,Molecular Docking,and Experimental Validation

Objective:To reveal the anti-inflammatory mechanism of GuanxinⅤ,which is prescribed for ventricular remodeling in clinical practice.Methods:GuanxinⅤ-,ventricular remodeling-,and inflammationrelated targets were obtained through an integrated strategy of virtual screening and systematic pharmacology,and then the shared targets were visualised with a Venn diagram.GuanxinⅤnetwork and the protein-protein interaction network were drawn,and enrichment analysis was conducted.Finally,the main results obtained from the integrated strategy were validated by molecular docking and in vivo experiments.Results:A total of 251,11,425,and 15,246 GuanxinⅤ-,ventricular remodeling-,and inflammation-related targets were acquired,respectively.Then,211 shared targets were considered to contribute to the mechanism of ventricular remodeling treated by GuanxinⅤ.Guanxin network and the protein-protein interaction network were drawn,and enrichment analysis showed some cardiovascular-related biological processes and signaling pathways.Molecular docking revealed that the GuanxinⅤ-derived compounds could align with key targets.Final in vivo experiments proved that GuanxinⅤreverses ventricular remodeling by inhibiting inflammation.Conclusion:GuanxinⅤrelieves ventricular remodeling by regulating inflammation,which provides new ideas for the anti-ventricular remodeling mechanism of GuanxinⅤ.

Panax Notoginseng Saponins Inhibits Ventricular Remodeling after Myocardial Infarction in Rats Through Regulating ATF3/MAP2K3/p38 MAPK and NFκB Pathway

Objective:To explore whether Panax notoginseng saponins(PNS)exhibits heart protective effect in myocardial infarction(MI)rats and to identify the potential signaling pathways involved.Methods:MI rats induced by ligating the left anterior descending(LAD)coronary artery were assigned to sham coronary artery ligation or coronary artery ligation.Totally 36 Sprague-Dawley rats were randomly divided into sham group(distilled water,n=9),MI group(distilled water,n=9),PNS group(PNS,40 mg/kg daily,n=9)and fosinopril group(FIP,1.2 mg/kg daily,n=9)according to a random number table.The left ventricular morphology and function were conducted by echocardiography.Histological alterations were evaluated by the stainings of HE and Masson.The serum levels of C reactive protein(CRP),tumor necrosis factorα(TNF-α),growth differentiation factor-15(GDF-15)and the ratio of metalloproteinase-9(MMP-9)and tissue inhibitor of MMP-9(TIMP-1)were determined by ELISA.The levels of activating transcription factor 3(ATF3),mitogen-activated protein kinase kinase 3(MAP2 K3),p38 mitogen-activated protein kinase(p38 MAPK),phosphorylation of p38 MAPK(p-p38 MAPK),transforming growth factor-β(TGF-β1),collagenⅠ,nuclear factor kappa B p65(NFκB p65),phosphorylation of NFκB p65(p-NFκB p65),and phosphorylation of inhibitory kappa Bα(p-IκBα)in hearts were measured by Western blot and immunohistochemical staining,respectively.Results:PNS improved cardiac function and fibrosis in MI rats(P<0.05).The serum levels of CRP,TNF-α,GDF-15 and the ratio of MMP9/TIMP1 were reversed by PNS in MI rats.The expressions of TGF-β1,collagenⅠ,MAP2 K3,p38 MAPK,p-p38 MAPK,NFκB p65,p-NFκB p65,and p-IκBαwere down-regulated,while ATF3 increased with the treatment of PNS(P<0.05).Conclusions:PNS may improve cardiac function and fibrosis in MI rats via regulating ATF3/MAP2 K3/p38 MAPK and NFκB signaling pathways.These results suggest the potential of PNS in preventing the development of ventricular remodeling in MI rats.

Effect of supplementing Qi and promoting blood circulation therapy on left ventricular remodeling: a systematic review and Meta-analysis

OBJECTIVE: To evaluate the effectiveness of an adjuvant therapy from Traditional Chinese Medicine for supplementing Qi and promoting blood circulation(CMSQPBC) on left ventricular remodeling in patients after myocardial infarction(MI).METHODS: Randomized controlled trials were identified in the Cochrane Library, Embase, Web of Science, PubMed, China National Knowledge Infrastructure Database, Chinese Biomedical Literature Database, China Science and Technology Journal Database, Wanfang databases, reviews, and reference lists of relevant articles. The weighted mean difference(WMD) was calculated for changes in the left ventricular ejection fraction(LVEF), LV end-diastolic volume(LVEDV) and LV end-systolic volume(LVESV) from baseline to follow-up(> 3 months) by using random-effects Meta-analysis. The primary outcome was change in LVEF, and secondary outcomes were changes in LV dimensions including LVEDV and LVESV.RESULTS: A total of 10 trials(enrolling 854 participants, median follow-up six months) evaluated the association between CMSQPBC and changes in LV function and volume. Compared with the control group, CMSQPBC significantly improved LVEF(854 patients;WMD: 4.97%, 95% CI: 3.78-6.15;P < 0.001)and attenuated the enlargement of LVEDV(607 patients;WMD:-7.89 mL, 95% CI:-11.54 to-4.24;P<0.001) and LVESV(364 patients;WMD =-5.80 mL,95% CI,-9.60 to-2.01;P < 0.01).CONCLUSION: CMSQPBC may reverse deleterious pathological remodeling after myocardial infarction. Higher quality and more rigorous randomized trials with larger sample sizes are needed to further confirm the findings.

Effect of spironolactone on cardiac remodeling after acute myocardial infarction

BACKGROUND:Few studies have reported the effect of aldosterone receptor antagonist(ARA) on myocardial remodeling after acute myocardial infarction(AMI).This study was undertaken to investigate the preventive effect of ARA on myocardial remodeling after AMI.METHODS:A total of 616 patients who had been admitted into the CCU of the First Affiliated Hospital of Harbin Medical University from January 2008 to January 2010 were studied prospectively.Only 528 patients were observed completely,including 266 of the control group and 262 of the treatment group.There was no statistical difference in age,gender,medical history,admission situation,and treatment between the two groups(P>0.05).The preventive effects of spironolactone on cardiac remodeling,left ventricular function,renal function and blood levels of potassium were evaluated by echocardiography,serum potassium and serum creatinine at one-month and one-year follow-up.RESULTS:The echocardiography indicators such as LVESD,LVEDD,LVEF,LAD-ML and LADSI were significantly improved in the treatment group compared with the control group at one year(P<0.05).In the treatment group,LVESD,LVEDD,LVPWT,LVEF,LAD-ML and LAD-SI were more significantly improved at one year than one month(P<0.05,P=0.007 to LVEF),and in the control group LVEF was more significantly improved at one year than one month(P=0.0277).There were no significant differences in serum potassium and serum creatinine levels between the two groups.CONCLUSION:On the basis of conventional treatment,the early combination of low-dose spironolactone(20 mg/d) could inhibit cardiac remodeling at late stage and prevent heart fadure.

Comparison of Arrhythmias among Different Left Ventricular Geometric Patterns in Essential Hypertension

The differences of arrhythmias among distinct left ventricular geometric patterns in the patients with essential hypertension were studied. 179 patients with essential hypertension received 24 h dynamic ECG recording, ambulatory blood pressure monitoring, echocardiography examination, etc. According to the examinations, left ventricular geometric patterns and arrhythmias were identified. The comparison of morbidity of arrhythmias between the left ventricular remodeling group and the normal geometric pattern group was performed. The multiple stepwise regression analysis was carried out to identify the independent determinants of arrhythmias. After these predictors were controlled or adjusted, the severity of arrhythmias among different left ventricular geometric patterns was compared. It was found that the morbidity of atrial arrhythmia, ventricular arrhythmia and complex ventricular arrhythmias in the left ventricular remodeling group was significantly higher than in the normal geometric pattern group respectively. There were many independent factors influencing on arrhythmias in essential hypertension. Of all these factors, some indices of left ventricular anatomic structure, grade of hypertension, left atrial inner dimension, E/A, diastolic blood pressure load value at night and day average heart rate and so on were very important. After the above mentioned factors were adjusted, the differences of the orders of arrhythmias between partial geometric patterns were reserved, which resulted from the differences of the geometric patterns. Many factors contributed to arrhythmias of essential hypertension, such as grade of hypertension, LVMI, LA, PWT and so on. The severity of arrhythmias was different in different left ventricular geometric patterns.

Changes in Reverse Cardiac Remodeling after Percutaneous Atrial Septal Defect Closure in Children and Adults

Background:The influence of the timing of transcatheter atrial septal defect(ASD)closure on ventricular remodeling at 6 months after ASD closure is unclear.This study investigated changes in cardiac remodeling after transcatheter closure of large ASDs according to patient age at the time of the procedure.Methods:In this study,41 children and 43 adults underwent percutaneous closure of a large ASD.Cardiac remodeling was assessed by two-dimensional echocardiography and electrocardiography before and at 6 months after ASD closure.Results:The age of the children and adults were 2.8±3.1 and 50.0±15.6 years,respectively.The Qp/Qs ratio of all patients was 2.24±0.67.The right atrial(RA)maximal dimension and right ventricular(RV)transverse diameter were significantly decreased and the left ventricular(LV)dimension was significantly increased at 6 months after ASD closure.However,the difference in RA and RV dimension changes between the groups was not statistically significant.The difference in left atrial(LA)dimension changes between the groups was also not statistically significant,but the LV dimension significantly increased in children compared with that in adults(P=0.018).The RV/LV ratio was decreased after ASD closure,and a significant difference was found in the RV/LV ratio changes between the groups.In ECG,the PR interval was significantly more decreased in adults than in children(P=0.003).Conclusions:In conclusion,the LV diameter was significantly more increased in children than in adults at 6 months after percutaneous ASD closure.Thus,cardiac remodeling after percutaneous ASD closure varies in children and adults.

Effects of omacor^®on left ventricular remodelling consecutive to post myocardial infarction special issue-myocardial infarction

Ventricular remodelling is the main trigger of the development of heart failure. Therefore, the reduction of structural remodelling is known to prevent the development of heart failure. The aim of the present study was to investigate the effects of OMACOR?, a well known mixture of EPA and DHA in an experimental model of heart failure induced by occlusion of left descending coronary artery and the reperfusion within 2 months. After a long term treatment of 2 months;OMACOR? (100 mg/kg) statistically significantly reduced the expansion of infarcted zone (35% ± 4%, P ± 3% in the vehicle group). The phosphorylation of Cx43 as biomarker of the cardiac remodelling was visualised by immunofluorescence in rat’s heart at the end of the study. In the vehicle-infarcted group, a significant de-phosphorylation of Cx43 was observed (8.2 ± 1.0 u.a, n = 8 compared to 11.8 ± 1.3 u.a in the sham group, n = 9) confirming a remodelling process in the infarcted group. In the group treated with OMACOR?,the de-phosphorylation of Cx43 was no longer observed compared to the sham group (16.4 ± 2.9 u.a, n = 9, NS). The present results demonstrate that a long term treatment with OMA-COR? reduced the infarcted size in experimental models of heart failure and that these anti-remodelling effects are due at least in part by resynchronizing the gap junction activity.

Research progress of related signal pathways in the prevention and treatment of heart failure with traditional Chinese medicine

Heart failure(HF)is a kind of continuous development syndrome of cardiac insufficiency caused by various heart diseases.Not only does the prevalence continue to rise,but the mortality rate and readmission rate remain high.Heart failure is also the end-stage of cardiovascular disease and the main cause of death of patients,which seriously affects the health and quality of life of people all over the world.Ventricular remodeling plays a key role in the occurrence and development of heart failure.Therefore,by improving ventricular remodeling,it is of important research value to explore the intervention of traditional Chinese medicine in the development of heart failure.Studies have shown that the mediation of multiple signaling pathways can lead to progressive aggravation of ventricular remodeling,and experimental studies often confirm the therapeutic effects of traditional Chinese medicine.Traditional Chinese medicine usually achieves the therapeutic effect of heart failure through multiple targets and multiple approaches.In recent years,there have been more and more researches on the role and mechanism of Chinese medicine intervention in heart failure.However,it is concluded that Chinese medicine intervention has less influence on heart failure signal pathways.This article summarizes the understanding of Chinese medicine on heart failure and the five signal pathways related to Chinese medicine intervention in heart failure.The 5 signaling pathways in the world,namely transforming growth factor-β1(TGF-β1)/signal transduction protein(Smads)signaling pathway,Toll-like receptor(TLR)/nuclear transcription factor-κB(NF-κB)inflammation signaling pathway,Renin-angiotensinaldosterone(RAAS)system,phosphoinositide 3-kinase(PI3K)-serine/threonine protein kinase(AKT)signaling pathway and mitogen-activated protein kinase(MAPK)dependent signaling pathway.

Association of circadian blood pressure pattern and left heart chamber enlargement in hypertensive patients:A cross-sectional study

Background Non-dipping blood pressure(BP)pattern is a potential risk factor contributing to cardiac geometry change.Relationship between BP pattern and left atrium(LA)enlargement besides left ventricle(LV)structural change is seldom studied.Methods A total of 237 hypertensive and hospitalized adults were enrolled.Left heart chamber parameters were measured by 2-dimensional echocardiography,and BP circadian rhythm was evaluated by 24-hour ambulatory blood pressure monitoring.Night-day ratios of systolic BP(NDR-SBP)were calculated and BP patterns were classified into dippers,reduced-dippers,and risers,which were defined as NDR-SBP<0.9,≥0.9 and<1,≥1,respectively.Multiple logistic regression analyses were performed to identify the factors associated with increased left ventricular end-diastolic internal diameter and left atrial diameter.Results Among enrolled participants,there were 62(26.2%)dippers,136(57.4%)reduced-dippers and 39(16.5%)risers.Briefly,57.8%were male and the mean age was 57.0±13.9 years.Compared to the dippers,both left ventricular end-diastolic diameter(44.4±4.3 mm in dippers,45.5±4.0 mm in reduced-dippers,46.5±4.5 mm in risers,P=0.045)and left atrial diameter(32.7±4.1 mm in dippers,34.3±4.7 mm in reduced-dippers,35.7±4.3 mm in risers,P=0.004)were progressively increased in reduced-dippers and risers.Logistic regression analyses showed that after adjusted for age,male gender,history of diabetes,blood lipid profiles,mean diurnal BP and estimated glomerular filtration rate,the association between increased LV diameter and riser BP pattern was significant(OR:2.621,95%CI:1.030-6.678)while the association between increased LA diameter and riser BP pattern was marginally significant.Conclusions The riser BP pattern is associated with the enlargement of LV and probably that of LA in hypertensive patients independent of 24-hour systolic BP level.

Cell sheet formation enhances the therapeutic effects of human umbilical cord mesenchymal stem cells on myocardial infarction as a bioactive material

Stem cell-based therapy has been used to treat ischaemic heart diseases for two decades.However,optimal cell types and transplantation methods remain unclear.This study evaluated the therapeutic effects of human umbilical cord mesenchymal stem cell(hUCMSC)sheet on myocardial infarction(MI).Methods:hUCMSCs expressing luciferase were generated by lentiviral transduction for in vivo bio-luminescent imaging tracking of cells.We applied a temperature-responsive cell culture surface-based method to form the hUCMSC sheet.Cell retention was evaluated using an in vivo bio-luminescent imaging tracking system.Unbiased transcriptional profiling of infarcted hearts and further immunohistochemical assessment of monocyte and macrophage subtypes were used to determine the mechanisms underlying the therapeutic effects of the hUCMSC sheet.Echocardiography and pathological analyses of heart sections were performed to evaluate cardiac function,angiogenesis and left ventricular remodelling.Results:When transplanted to the infarcted mouse hearts,hUCMSC sheet significantly improved the retention and survival compared with cell suspension.At the early stage of MI,hUCMSC sheet modulated inflammation by decreasing Mcp1-positive monocytes and CD68-positive macrophages and increasing Cx3cr1-positive non-classical macrophages,preserving the cardiomyocytes from acute injury.Moreover,the extracellular matrix produced by hUCMSC sheet then served as bioactive scaffold for the host cells to graft and generate new epicardial tissue,providing mechanical support and routes for revascularsation.These effects of hUCMSC sheet treatment significantly improved the cardiac function at days 7 and 28 post-MI.Conclusions:hUCMSC sheet formation dramatically improved the biological functions of hUCMSCs,mitigating adverse post-MI remodelling by modulating the inflammatory response and providing bioactive scaffold upon transplantation into the heart.Translational perspective:Due to its excellent availability as well as superior local cellular retention and survival,allogenic transplantation of hUCMSC sheets can more effectively acquire the biological functions of hUCMSCs,such as modulating inflammation and enhancing angiogenesis.Moreover,the hUCMSC sheet method allows the transfer of an intact extracellular matrix without introducing exogenous or synthetic biomaterial,further improving its clinical applicability.