Electroacupuncture improves myocardial fibrosis in heart failure rats by attenuating ECM collagen deposition through modulation of TGF-β1/Smads signaling pathway

Background: To explore the effects of electroacupuncture on cardiac function and myocardial fibrosis in rat models of heart failure, and to elucidate the underlying mechanism of electroacupuncture in heart failure treatment. Methods: Healthy male Sprague-Dawley rats were allocated into three groups: Sham group, Model group, and electroacupuncture (Model + EA) group, with each group comprising 8 rats. The model underwent a procedure involving the ligation of the left anterior descending coronary artery to induce a model of heart failure. The Model + EA group was used for 7 consecutive days for electroacupuncture of bilateral Shenmen (HT7) and Tongli (HT5), once a day for 30 min each time. Left ventricular parameters in rats were assessed using a small-animal ultrasound machine to analyze changes in left ventricular end-diastolic volume, left ventricular end-systolic volume, left ventricular ejection fraction, and left ventricular fractional shortening. Serum interleukin-1β (IL-1β), cardiac troponin (cTn), and N-terminal brain natriuretic peptide precursor levels were measured using ELISA. Histopathological changes in rat myocardium were observed through HE staining, while collagen deposition in rat myocardial tissue was assessed using the Masson staining method. Picro sirius red staining, immunohistochemical staining, and RT-qPCR were utilized to distinguish between the various types of collagen deposition. The expression level of TGF-β1 and SMAD2/3/4/7 mRNA in rat myocardial tissues was determined using RT-qPCR. Additionally, western blot analysis was conducted to assess the protein expression levels of TGF-β1, SMAD3/7, and p-SMAD3 in rat myocardial tissues. Results: Compared with the Sham group, the left ventricular ejection fraction and left ventricular fractional shortening values of the Model group were significantly decreased (P < 0.01);the left ventricular end-diastolic volume and left ventricular end-systolic volume values were remarkably increased (P < 0.01);serum N-terminal brain natriuretic peptide precursor content was increased (P < 0.01);serum IL-1β and cTn levels were increased (P < 0.01);myocardial collagen volume fraction were increased (P < 0.01);and those of the expression of TGF-β1 and SMAD2/3/4 mRNA was increased (P < 0.01);the expression of SMAD7 mRNA was decreased (P < 0.01);the protein expression levels of TGF-β1, SMAD3, and p-Smad3 were increased (P < 0.01);the protein expression level of SMAD7 was decreased (P < 0.01) in the Model group. Compared to the Model group, the expression levels of the proteins TGF-β1, SMAD3, and p-Smad3 in myocardial tissue were found to be decreased (P < 0.01), and the expression level of the protein SMAD7 was found to be increased (P < 0.01) in the Model + EA group;the collagen volume fraction and deposition of type Ⅰ /Ⅲ collagen were decreased (P < 0.01) in the Model + EA group. Conclusion: Electroacupuncture alleviates myocardial fibrosis in rats with heart failure, and this effect is likely due to attributed to the modulation of the TGF-β1/Smads signaling pathway, which helps reduce collagen deposition in the extracellular matrix.

Notum protects against myocardial infarction-induced heart dysfunction by alleviating cardiac fibrosis

Background and Objective:Cardiac fibrosis is a pathological reparative process that follows myocardial infarctionand is associated with compromised cardiac systolic and reduced cardiac compliance.The Wnt signaling pathway is closely implicated in organ fibrosis,and Notum,a highly conserved secreted inhibitor,modulates Wnt signaling.The objective of this study was to explore the role and mechanism of Notum in cardiac fibrosis.Methods:A mouse model of cardiac remodeling was established through left coronary artery ligation surgery,with the addition of Notum injection following myocardial infarction surgery.The protective effect of Notum on myocardial infarction was assessed by evaluating cardiac function,including survival rate,echocardiographic assessment,and cardiac contraction analyses.Inflammatory cell necrosis and infiltration were confirmed through H&E and Masson staining.The expression of fibrosis-related genes andβ-catenin pathway markers was detected using Western blot quantificational RT-PCR(qRT-PCR).Additionally,EdU,wound healing,and immunofluorescence staining analyses were performed to detect the effect of Notum's in transforming growth factor beta-1(TGF-β1)induced myofibroblast transformation.Results:The administration of Notum treatment resulted in enhanced survival rates,improved cardiac function,and decreased necrosis and infiltration of inflammatory cells in mice subjected to left coronary artery ligation.Furthermore,Notum effectively impeded the senescence of cardiac fibroblasts and hindered their pathological transformation into cardiac fibroblasts.Additionally,it significantly reduced collagen production and attenuated the activation of the Wnt/β-catenin pathway.Our preliminary investigations successfully demonstrated the therapeutic potential of Notum in both fibroblasts in vitro and in a mouse model of myocardial infarction-induced cardiac fibrosis in vivo.Conclusion:Notum inhibition of the Wnt/β-catenin signaling pathway and cardiac fibroblast senescence ultimately hampers the onset of cardiac fibrosis.Our findings suggest that Notum could represent a new therapeutic strategy for the treatment of cardiac fibrosis.

Liraglutide Suppresses Myocardial Fibrosis Progression by Inhibiting the Smad Signaling Pathway

Objective Liraglutide is a commonly used hypoglycemic agent in clinical practice,and has been demonstrated to have protective effects against the development of cardiovascular disease.However,its potential role in myocardial fibrosis remains unexplored.The present study aims to assess the impact of liraglutide on the activation of cardiac fibroblasts.Methods Primary rat adult fibroblasts were isolated,cultured,and randomly allocated into 4 groups:control group,transforming growth factor beta1(TGFβ1)stimulation group,liraglutide group,and TGFβ1+liraglutide group.Fibroblast activation was induced by TGFβ1.Cell proliferation activity was assessed using the CKK-8 kit,and cellular activity was determined using the MTT kit.Reverse transcrition-quantitative polymerase chain reaction(RT-qPCR)was utilized to quantify the level of collagen transcription,immunofluorescence staining was performed to detect the expression level of type III collagen andα-smooth muscle protein(α-SMA),and immunoblotting was conducted to monitor alterations in signal pathways.Results The addition of 10,25,50 and 100 nmol/L of liraglutide did not induce any significant impact on the viability of fibroblasts(P>0.05).The rate of cellular proliferation was significantly higher in the TGFβl stimulation group than in the control group.However,the treatment with 50 and 100 nmol/L of liraglutide resulted in the reduction of TGFβl-induced cell proliferation(P<0.05).The RT-qPCR results revealed that the transcription levels of type I collagen,type III collagen,andα-SMA were significantly upregulated in the TGFβl stimulation group,when compared to the control group(P<0.05).However,the expression levels of these aforementioned factors significantly decreased in the TGFβl+liraglutide group(P<0.05).The immunofluorescence staining results revealed a significant increase in the expression levels of type III collagen andα-SMA in the TGFβl stimulation group,when compared to the control group(P<0.05).However,these expression levels significantly decreased in the TGFβl+liraglutide group,when compared to the TGFβl stimulation group(P<0.05).The Western blotting results revealed that the expression levels of phosphorylated smad2 and smad3 significantly increased in the TGFβl stimulation group,when compared to the control group(P<0.05),while these decreased in the TGFβl+liraglutide group(P<0.05).Conclusion Liraglutide inhibits myocardial fibrosis development by suppressing the smad signaling pathway,reducing the activation and secretion of cardiac fibroblasts.

Atorvastatin ameliorated myocardial fibrosis in db/db mice by inhibiting oxidative stress and modulating macrophage polarization

BACKGROUND People with diabetes mellitus(DM)suffer from multiple chronic complications due to sustained hyperglycemia,especially diabetic cardiomyopathy(DCM).Oxidative stress and inflammatory cells play crucial roles in the occurrence and progression of myocardial remodeling.Macrophages polarize to two distinct phenotypes:M1 and M2,and such plasticity in phenotypes provide macrophages various biological functions.AIM To investigate the effect of atorvastatin on cardiac function of DCM in db/db mice and its underlying mechanisms.METHODS DCM mouse models were established and randomly divided into DM,atorvastatin,and metformin groups.C57BL/6 mice were used as the control.Cardiac function was evaluated by echocardiography.Hematoxylin and eosin and Masson staining was used to examine the morphology and collagen fibers in myocardial tissues.The expression of transforming growth factor-β1(TGF-β1),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),M1 macrophages(iNOS^(+)),and M2 macrophages(CD206^(+))were demonstrated by immunohistochemistry and immunofluorescence staining.The levels of TGF-β1,IL-1β,and TNF-αwere detected by ELISA and real-time quantitative polymerase chain reaction.Malondialdehyde(MDA)concentrations and superoxide dismutase(SOD)activities were also measured.RESULTS Treatment with atorvastatin alleviated cardiac dysfunction and decreased db/db mice. The broken myocardialfibers and deposition of collagen in the myocardial interstitium were relieved especially by atorvastatin treatment.Atorvastatin also reduced the levels of serum lactate dehydrogenase, creatine kinase isoenzyme, and troponin;lowered the levels of TGF-β1, TNF-α and IL-1β in serum and myocardium;decreased the concentration of MDAand increased SOD activity in myocardium of db/db mice;inhibited M1 macrophages;and promoted M2macrophages.CONCLUSION Administration of atorvastatin attenuates myocardial fibrosis in db/db mice, which may be associated with theantioxidative stress and anti-inflammatory effects of atorvastatin on diabetic myocardium through modulatingmacrophage polarization.

Hyperglycemia-induced myocardial fibrosis may be associated with pyroptosis and apoptosis of cardiomyoctes in diabetic mice

Myocardial fibrosis is an important manifestation of diabetic cardiomyopathy.This study investigated the potential mechanism of diabetic myocardial fibrosis.Male C57BL/6J and db/db mice aged 8 weeks were randomly divided into the diabetic(DB)and control groups.At 20 weeks,the mouse heart was harvested and subjected to hematoxylin-eosin staining(HE)and Masson staining to investigate the degree of fibrosis.The expressions of transforming growth factor-beta 1(TGF-β1),collagen-III,B-cell lymphoma-2(Bcl2),Bcl2-associated X protein(Bax),cleaved gasdermin D(GSDMD),cysteinyl aspartate specific proteinase-1(caspase-1),apoptosis-associated speck-like protein containing a CARD(ASC),and nucleotide-binding oligomerization domain(NOD)-like receptor 3(NLRP3)were measured by western blotting.Immunohistochemistry and TdT-mediated dUTP nick end labeling(TUNEL)staining were performed to analyze the development of apoptosis and pyroptosis.A significant increase in body weight and blood glucose in the DB group was observed.Myocardial pathological injury,fibrosis,apoptosis,and pyroptosis were more obvious and serious in the DB group.The expression of anti-apoptotic Bcl2 significantly decreased,while the expression levels of pro-apoptotic Bax,caspase-3,and pyroptosis-related proteins,such as cleaved GSDMD,and caspase-1 in the DB group were significantly increased.Pyroptosis and apoptosis were probably the main mechanisms that caused myocardial fibrosis in mice with diabetes.

Xinfuli Granule improves post-myocardial infarction ventricular remodelingand myocardial fibrosis in rats by regulating TGF-β/Smads signaling pathway

Recent clinical and experimental studies have confirmed the effects of Xinfuli Granule (XG), a compound Chinese medicine in the prevention and treatment of heart failure (HF). This study aimed to investigate the effects and the mechanisms of XG on ventricular reconstruction in rats with acute myocardial infarction (AMI).MethodsSprague-Dawley rats were subjected to left anterior descending branch ligation. The rats that survived 24 h were randomly assigned to five groups: medium-dose of XG group (MI+XGM), high-dose of XG group (MI+XGH), carvedilol group (MI+C), medium-dose of XG + carvedilol group (MI+C+XGM). Fourteen rats underwent identical surgical procedures without artery ligation, serving as sham controls. At 28 days, left ventricular weight to body weight (LVW/BW) and heart weight to body weight (HW/BW) were calculated; left ventricular ejection fraction (LVEF), left ventricular shortening fraction (LVFS), left ventricular internal diameter at systole (LVIDS) were measured by ultrasound; HE staining, Masson staining, and Sirius red staining were used to assess the myocardial pathological and physiological changes as well as myocardial fibrosis area and non-infarct zone I/III collagen ratio. Expression of Smad3 were detected and analyzed by Western blot, immunohistochemistry and immunofluorescence. P-Smad3, Smad2 and Smad7 in the TGF-β/Smads signaling pathway were also analyzed by Western blot.ResultsThe LVIDS (P < 0.01), HW/BW (P < 0.05), type I/III collagen ratio (P < 0.01) and myocardial collagen (P < 0.01) decreased significantly while the LVW/BW, LVFS (P < 0.05) increased significantly in MI+XGM group as compared with those in other groups. The expression of key signal molecules of the TGF-β/Smads signaling pathway, including Smad3, P-Smad3 and Smad2 protein were decreased, while the expression of Smad7 increased in both XG and carvedilol treatment groups as compared to those of the MI group (all P < 0.01). Immunohistochemistry and immunofluorescence further confirmed the down-regulated Smad3 expression.ConclusionXG can improve ventricular reconstruction and inhibit myocardial fibrosis in rats with AMI by regulating TGF-β/Smads signaling pathway.

“Burnt-Out” Endomyocardial Fibrosis—An Overview

Tropical endomyocardial fibrosis (EMF) is a public health problem affecting the children, young adults and elderly individuals in an epidemic fashion in the coastal districts of south India. Due to lack of resources for research in these endemic areas, its etiology remains elusive and hypotheses ranging from infections and allergic causes to malnutrition and toxins have not been tested rigorously. The disease is characterized by endocardial fibrosis and the right ventricle is the cardiac chamber most frequently affected. Patients may present clinically with heart failure and an associated AV (atrioventricular) valve regurgitation is common. Several features of the advanced disease called as “burnt-out” stage of endomyocardial fibrosis (EMF) are not fully understood. Background of these case studies described the clinical presentation, echocardiographic features and management of this late stage of the disease.

Paeoniflorin Attenuates Myocardial Fibrosis in Isoprenaline-induced Chronic Heart F ailure Rats via Inhibiting P38 MA PK Pathway

Paconiflorin(Pae)is a monoterpenoid glycoside compound and has many biological activitics,such as immunosuppression,anti-inflammation and anti-cell proliferation.However,the effects and mechanisms of Pae on chronic heart failure(CHF)remain unclear.This study was conducted to assess the effects and mechanisms of Pae on myocardial fibrosis in isoprenaline(Iso)-induced CHF rats.Pae(20 mgkg)was intragastrically administrated to CHF rats for 6 weeks.Cardiac structure and function were assessed.The protein and mRNA levels of transforming growth factorβ1(TGF-β1)and p38 were detected.C ompared to Iso group,Pae could alleviate myocardial fbrosis and improve cardiac function in CHF rats.The levels of collagen volume fraction(13.75%+3.77%vs.30.97%+4.22%,P<0.001)and perivascular collagen volume area(14.32%+2.50%v8.28.31%+3.16%,P<0.001)were significantly reduced in Pae group as compared with those in Iso group.The expression of TGF-BI protein(0.30+0.07 vs.0.66+0.07,P<0.05)and mRNA(3.51+0.44 vs.7.58+0.58,P<0.05)decreased significantly in Pac group as compared with that in Iso group.The expression of p38 protein(0.36+0.12 vs.0.81+0.38,P<0.05)and mRNA(3.84+0.05 vs.4.40+0.17,P<0.05)also decreased markedly in Pae group as compared with that in Iso group.Pae could attenuate myocardial fibrosis and improve cardiac function in CHF rats by down-regulating the p38 MAPK signaling pathway.

Taurine Inhibits Myocardial Fibrosis via PKC-ERK1/2 Signaling Pathways

Previous studies have demonstrated the important role of taurine in inhibiting proliferation of myofibrob lasts（myoFb） and myocardial fibrosis. However, the underlying mechanisms are unclear. The present study was de signed to shed light on this issue through exploring the signal pathways via in vitro experiments. Angiotension II （AngII） treatment significantly increased myoFb proliferation and the levels of collagens I and III（P〈0.05）, whereas taurine, PKCα（PKC： protein kinase C） specific inhibitor L-threo-dihydro-sphingosine（D4681）, ERK1/2 inhibitor （PD98095） abrogated myoFb proliferation and collagen levels（P〈0.05, P〈0.01, respectively）, and increased the G0/G1 phase rate and decreased S phase rate. Immunocytochemistry, confocal fluorescence staining and image analy sis showed that taurine could inhibit the translocation and expression of p-PKCαin membrane, and then inhibit nuc lear translocation and expression of p-ERK1/2. These results have statistically significant differences compared with those of AngII group（P〈0.01）. Western blot results also show that taurine could inhibit the protein expression of p-PKCα and p-ERK1/2. We used p-PKCα specific inhibitor D4681 in order to elucidate the relationship between p-PKCα and p-ERK1/2 in signal transduction pathways. Finally, the results show that the protein expression of p-ERK1/2 and nuclear translocation were suppressed in D4681 group.

The Detectability for the Myocardial Fibrosis by Tagging Imaging on Cardiovascular Magnetic Resonance

Purpose: Myocardial fibrosis causes cardiac dysfunction, arrhythmias, and sudden death. Tagging imaging on cardiovascular MR can measure the intra-myocardial motion from the dynamic deformation of lines superimposed on the myocardium. The purpose of this study was to evaluate the detectability of myocardial fibrosis using tagging imaging and to compare this with conventional cine imaging. Materials and Methods: We reviewed 4 normal control (NML) subjects, 4 patients with myocarditis (MYO), and 4 patients with old myocardial infarction (ICM). We measured circumferential strain (Ecc) from tagging imaging, and regional wall thickening (rWT) from cine imaging. Fibrosis was determined from a late gadolinium enhancement (LGE) image. We evaluate diagnostic performance by comparing values of the area under curve (AUC) using ROC analysis. Results: Mean values of Ecc and rWT decreased in the area of LGE both in MYO and ICM patients. AUC values of Ecc and rWT in all subjects were 0.98 and 0.84, respectively (p < 0.0001). These values in MYO patients were 0.95 and 0.72 (p = 0.007), respectively, and 0.99 and 0.75, respectively, in ICM patients (p = 0.0008). Conclusions: Both Ecc and rWT decreased in the area with fibrosis in the patients with MYO and ICM. Tagging imaging showed better detectability of myocardial fibrosis than did cine imaging.

Protective effects of Ginseng mixture on myocardial fibrosis in rats

Objective:To explore the protective effects of ginseng mixture on myocardial fibrosis(MF)in rats.Methods:A total of 60 Wistar rats were randomly divided into control group without modeling operation,and another 4 groups using subcutaneous injections of isopropyl adrenaline for 10 d to set up the MF model:model group with saline lavage treatment after modeling,captopril group with captopril lavage,ginseng mixture group A and group B with low and high dose mixture treatment respectively.After treatment for 14 d,abdominal aorta and myocardial tissue were extracted to observe the pathological morphological changes and heart weight index in each group.Results:The left ventricular weight and heart heavy index of captopril group and group B were significantly lower than that of model group and group A(P<0.05);Model group and group A showed a higher hydroxyproline(Hyp)content in myocardial tissue than the control group and lower catalase(CAT)activity than Gontrol group(P<0.05);captopril group and group B showed a lower Hyp content and higher CAT activity compared with group A and model group(P<0.05),a significantly lower level of serum glutathione peroxidase(GSH-PX)and CAT and a higher level of serum creatine kinase,lactate dehydrogenase and H_2O_2 in model group and group A were observed compared with the control group(P<0.05).A higher level of GSH-PX and CAT and a lower level of creatine kinase,lactate dehydrogenase and H_2O_2 in captopril group and group B were observed compared with group A and model group(P<0.05);and histopathological examination showed that in captopril group and group B,secretion of collagen fiber was significantly inhibited and myocardial injury was significantly lighter than that of model group.Conclusions:Ginseng mixture plays a protective effect on myocardium by inhibiting antioxidant process of MF.

Effect of Sodium Ferulate on Myocardial Ischemia Fibrosis Induced by Isoproterenol

We examined whether the powerful sodium ferulate（SF） could improve myocardial ischemia fibrosis degree and gain the information of myocardial energy metabolism via experimental model of myocardial ischemia fibrosis. The model of myocardial ischemia fibrosis was made for the wistar rats induced with 15 mg/kg isoproterenol（Iso） subcutaneous injection. In experiment l, Iso effective model drug of myocardial ischemia fibrosis at present was administrated to the rats with myocardial ischemia fibrosis and 2, 4, 6, 12, 24, 48 and 72 h, 7 and 21 d later, the changes of adenosine content in rat myocardial tissue and hydroxyproline in blood serum were compared. In experiment 2, SF was administrated to the rats with myocardial ischemia fibrosis and 21 d later, the effect of SF on benazepril as reference drug curing myocardial ischemia fibrosis was evaluated by measuring the changes of adenosine in rat myocardial tissue and hydroxyproline content in blood serum. In the model group, there was a remarkable increase in hydroxyproline content and a decrease in adenosine content of myocardial tissue in experiment 1; there was a remarkable decrease in hydroxyproline in blood serum and a increase in adenosine content in myocardial tissue, which were recovered gradually to control in experiment 2（P〈0.05）. The results of experiment 1 show that with the increasing of pathological change degree, the rat adenosine content reduced gradually and arrived at the lowest value three weeks later（P〈0.05）; the hydroxyproline content was obviously higher compared with that of control group（P〈0.05）. The results of experiment 2 show that rat adenosine content in myocardial tissue and hydroxyproline content in blood serum were recovered gradually to normal level after injection SF. The effect of SF against myocardial ischemia fibrosis in preventive group is better than that of improving the myocardial ischemia fibrosis drug. Meanwhile, hinting HPLC is a good method to measure the adenosine content.

Effects of Ligustrazine on Myocardial Fibrosis in Rats with Pressure Overload

Objective: To investigate the effects of ligustrazine (Li) on myocardial fibrosis in rats with pressure overload. Methods: Pressure overload rat models were established by constricting the abdominal a-orta. Sixty-three SD rats were divided into 3 groups: Sham operated group (SOG, n = 21), operated group (OG, n = 21) and operated combined with ligustrazine group (OG+Li, n = 21). Each group was randomly assigned to seven time points: The 1st, 2nd, 4th, 7th, 14th, 21st and 30th day after operation. Three rats were included in each time point. Serial sections of cardiac tissues were examined and the morphological or morphometric analysis of the SOG, OG and OG+Li done by histopathological and computer image analyzer technique. Results: (1) It showed that there were reactive fibrosis (from the 4th day on after operation) and reparative fibrosis (from the 21st day on after operation) in the OG, while myocardial fibrosis in the OG+Li was alleviated. Though reactive fibrosis (from the 21st day on after operation) was shown, reparative fibrosis wasn't seen. (2) Perivascular collagen area (PVCA) in the OG (2. 09±0. 45) was significantly higher than SOG (0. 83±0.06) from the 1st day on after operation and then steadily increased, while in the OG+Li (1.16±0.06), it was significantly lower than OG at the same time; collagen volume fraction (CVF) in the OG (3.08±0. 56) significantly increased compared with the SOG (2. 78±0. 64) from the 2nd day on after operation and showed a trend of rapid ascending from the 21st day on after operation; and in the OG + Li (4.69±0.85), it was significantly decreased compared with the OG (7.56±0.88) from the 21st day on after operation, with all P<0.05. Conclusion: Ligustrazine could alleviate and postpone the accumulation of myocardial collagen and has protective effects on the heart.

Comparison Study on Different Quantification Methods of Diffuse Myocardial Fibrosis of Dilated Cardiomyopathy Using Myocardial T1 Value

Purpose: The purpose is to compare several quantification methods and clarify which quantification method is reliable to estimate diffuse myocardial fibrosis with cardiac MRI in patients with dilated cardiomyopathy (DCM) using myocardial T1 value. Methods and Results: Delayed enhancement imaging was performed in 52 patients with DCM and 10 control subjects to identify fibrosis using an inversion time scout sequence. The mean contrast-enhanced myocardial (M) T1 values of the pre and post contrast-enhanced myocardial and left ventricular lumen (L) of control and dilated cardiomyopathy cases were compared. The calculated post M T1 value, pre M T1 value-post M T1 value, and (pre M TI value-post M T1 value)/(pre L T1 value-post L T1 value) were significantly different between the patient group and the control group (344.5 ± 31.6 vs. 390.4 ± 19.3 msec, 239.9 ± 64.2 msec vs. 134.0 ± 28.9 msec, and 0.50 ± 0.11 vs. 0.30 ± 0.60, respectively). (Pre M T1 value-post M T1 value)/(pre L T1 value-post L T1 value) was significantly the most related to the left ventricular ejection fraction (r = 0.66, p Conclusion: (Pre M T1 value-post M T1 value)/(pre L T1 value-post L T1 value) was the most reliable quantification method to estimate the severity of DCM.

Association of electrocardiographic markers with myocardial fibrosis as assessed by cardiac magnetic resonance in different clinical settings

BACKGROUND Cardiac magnetic resonance(CMR)is a unique tool for non-invasive tissue characterization,especially for identifying fibrosis.AIM To present the existing data regarding the association of electrocardiographic(ECG)markers with myocardial fibrosis identified by CMR-late gadolinium enhancement(LGE).METHODS A systematic search was performed for identifying the relevant studies in Medline and Cochrane databases through February 2021.In addition,we conducted a relevant search by Reference Citation Analysis(RCA)(https://www.referencecitationanalysis.com).RESULTS A total of 32 studies were included.In hypertrophic cardiomyopathy(HCM),fragmented QRS(fQRS)is related to the presence and extent of myocardial fibrosis.fQRS and abnormal Q waves are associated with LGE in ischemic cardiomyopathy patients,while fQRS has also been related to fibrosis in myocarditis.Selvester score,abnormal Q waves,and notched QRS have also been associated with LGE.Repolarization abnormalities as reflected by increased Tp-Te,negative Twaves,and higher QT dispersion are related to myocardial fibrosis in HCM patients.In patients with Duchenne muscular dystrophy,a significant correlation between fQRS and the amount of myocardial fibrosis as assessed by LGE-CMR was observed.In atrial fibrillation patients,advanced inter-atrial block is defined as P-wave duration≥120 ms,and biphasic morphology in inferior leads is related to left atrial fibrosis.CONCLUSION Myocardial fibrosis,a reliable marker of prognosis in a broad spectrum of cardiovascular diseases,can be easily understood with an easily applicable ECG.However,more data is needed on a specific disease basis to study the association of ECG markers and myocardial fibrosis as depicted by CMR.

Study on key genes and pathways of myocardial fibrosis and prediction of effective traditional Chinese medicine

Objectives:Bioinformatics was applied to screen the key genes of Myocardial fibrosis,explore its pathogenesis and predict the potential traditional Chinese medicines for the treatment of Myocardial fibrosis.Methods:Based on raw data of gene chip GSE59437 from gene expression database(GEO),myocardial tissue samples from 3 control mice and 3 mice treated with angiotensin II-induced myocardial fibrosis were included.Using R language processing data and screening of gene express significant differences(DEG),use a database of DAVID and the R language finish Gene Ontology(GO)annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment for differences gene,using the STRING database structure protein protein interactions(PPI)networks,using Cytoscape software visualization and use the MCODE plug-in screening key function modules in the network.Coremine Medical database was used to map the key genes,construct the gene-Chinese medicine network,and screen the traditional Chinese medicines for the treatment of myocardial fibrosis.Results:208 DEGs were screened,94 of which were up-regulated and 114 were down-regulated.DEGs is mainly involved in a variety of biological processes such as extracellular matrix remodeling,collagen fiber deposition and lipid metabolism disorders.KEGG pathway enrichment involves Platelet activation,Oxytocin signaling pathway,Insulin secretion,ECM-receptor interaction,GnRH signaling pathway,TNF signaling pathway and other signaling pathways.Key modules of PPI network including:CTGF,TIMP1,SPP1,SERPINE1,COL3A1,POSTN and FOS.The potential traditional Chinese medicines for the treatment of myocardial fibrosis are Astragalus membranaceus(Fisch.),Lepidium apetalum Willd and Salvia miltiorrhiza Bge.Conclusion:Myocardial fibrosis is a complex pathological process,and the genes related to the imbalance of extracellular matrix synthesis and degradation and excessive deposition of collagen fibers play an important role in this process.This study provides a scientific reference for further exploring the pathogenesis of myocardial fibrosis,looking for therapeutic targets and potential therapeutic traditional Chinese medicines.

Study on gene regulation mechanism of Qiliqiangxin capsule on myocardial fibrosis in myocardial infarction rats

Objective:To investigate the effect and possible mechanism of Qiliqiangxin capsule on myocardial fibrosis in rats with myocardial infarction(MI).Methods:The rat model of myocardial infarction was established by ligation of anterior descending branch of left coronary artery.The rats were randomly divided into model group,Qiliqiangxin capsule group,captopril group after operation.Rats that without ligation were set as parallel control group,namely,the sham group.Cardiac pathology was observed by hematoxylin eosin(HE)staining after 4 weeks of treatment.Masson staining was used to observe myocardial fibrosis and calculate collagen volume fraction(CVF).The miR-133a and expression levels of transforming growth factor β1(TGF-β1),Smad 2,Smad 3,type Ⅰ collagen(col-Ⅰ),type Ⅲ collagen(col-Ⅲ)mRNA were examined by Real-time PCR.Results:Compared with the sham group,myocardial cells in model group were disordered,CVF was significantly increased(P<0.01),the expression levels of col-Ⅰ,col-ⅢmRNA were increased(P<0.01);besides,the expression level of miR-133a was significantly decreased(P<0.01),the expression levels of TGF-β1,Smad 2 and Smad 3 mRNA were increased(P<0.05,P<0.01).Compared with the model group,the arrangement of myocardial cells in Qiliqiangxin capsule group and captopril group were orderly and CVF was significantly decreased(P<0.05);the expression level of miR-133a was increased(P<0.05,P<0.01);the expression levels of TGF-β1,Smad 2 and Smad 3 mRNA were significantly decreased(P<0.01).Conclusion:Qiliqiangxin capsule can improve myocardial infarction rat myocardial tissue fibrosis,its mechanism may be in related with the regulation on miR-133a/TGF-β1/Smads signal pathway at the genetic level.

Effect of adjuvant Shenqi injection therapy on cardiac function and myocardial fibrosis in patients with refractory heart failure

Objective: To explore the effect of adjuvant Shenqi injection therapy on cardiac function and myocardial fibrosis in patients with refractory heart failure. Methods: Patients with refractory heart failure who were treated in People's Hospital Affiliated to Hubei University of Medicine between December 2014 and August 2016 were reviewed and divided into the control group (n=50) who received routine western medicine treatment and the observation group (n=41) who received Shenqi injection-assisted routine western medicine treatment. The differences in serum levels of cardiac function-related indexes and myocardial fibrosis-related indexes were compared between two groups of patients before and after treatment. Results: Before treatment, the differences in serum levels of cardiac function-related indexes and myocardial fibrosis-related indexes were not statistically significant between the two groups of patients. After 1 month and 3 months of treatment, serum cardiac function-related indexes NT-proBNP, Copeptin, GDF-15 and OPN levels of observation group were lower than those of control group;serum myocardial fibrosis-related indexes TGF-β1, CTGF, PⅠCP, CⅠTP and PⅢNP levels were lower than those of control group whereas APN levels were higher than that of control group. Conclusion: Routine western medicine treatment combined with adjuvant Shenqi injection therapy can effectively optimize the cardiac function and inhibit the myocardial fibrosis process in patients with refractory heart failure.

Correlation of serum miR-148b expression with myocardial injury and myocardial fibrosis in patients with myocardial infarction

Objective:To study the correlation of serum miR-148b expression with myocardial injury and myocardial fibrosis in patients with myocardial infarction.Methods:A total of 130 patients who were diagnosed with acute myocardial infarction and 100 healthy subjects who received physical examination in Hanzhong Central Hospital between March 2013 and October 2016 were selected and enrolled in AMI group and control group respectively. Serum was collected, fluorescent quantitative PCR kit was used to detect miR-148b expression, and enzyme-linked immunosorbent assay kit was used to detect the contents of myocardial injury markers and myocardial fibrosis markers.Results:Serum miR-148b expression as well as CK-MB, cTnT, H-FABP, PICP, PIIINP, CTX-I, TGF-β1 and GDF-15 levels in AMI group was significantly higher than those in control group;serum CK-MB, cTnT, H-FABP, PICP, PIIINP, CTX-I, TGF-β1 and GDF-15 levels in AMI patients with high miR-148b expression were significantly higher than those in AMI patients with low miR-148b expression.Conclusion: Highly expressed miR-148b in serum of patients with myocardial infarction can promote myocardial injury and myocardial fibrosis.

Tropical Coronary Artery Disease and Arrhythmogenic Potentials—The Changing Pattern towards Endomyocardial Fibrosis—An Analysis

Aim: To analyse the increasing burden of coronary artery disease (CAD) in tropical and subtropical belts of the Equator since it remains blurred and carries a grim prognosis. Introduction: Endomyocardial fibrosis [EMF] is a tropical febrile disorder, confined to peculiar and limited geographical areas. Plaque buildup in endocardium and coronary arteries, causing ischemic injury and arrhythmic episodes, is a vanishing mystery in its pathogenesis and emphasizing alternative routes for understanding and treatment of this enigmatic disease. Case Report: 15 cases in various age groups were reported with potential complications of coronary artery disease and arrhythmias, associated with endocardial lesions, the characteristic feature of endomyocardial fibrosis. Conclusion: The narrowing of coronary arteries as a result of thickening of the walls, spasm, inflammation, plaques and its rupture produce ischemic episodes which can occur slowly or suddenly in a devastating pattern with arrhythmogenic potentials. The important steps to prevent and decrease the risk of CAD is to reduce the chance of getting this disorder by epidemiological measures with an advice of blood thinning medications such as small daily dose aspirin, antibiotics in susceptible individuals and revascularization in established myocardial infarction.