scholarly journals Moxibustion Improves Chronic Heart Failure by Inhibiting Autophagy and Inflammation via Upregulation of mTOR Expression

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Qingling Li ◽  
Wei Wang ◽  
Qiang Ma ◽  
Ran Xia ◽  
Bing Gao ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Cardiac Function ◽  
Heart Function ◽  
Interventricular Septum ◽  
Left Ventricular ◽  
Enzyme Linked Immunosorbent Assay ◽  
Myocardial Inflammation ◽  
Protective Effects ◽  
Inflammatory Reactions

How moxibustion improves chronic heart failure is extremely complex and still unclear. This study aimed to explore whether moxibustion inhibits autophagy and reduces inflammation by regulating mTOR expression to induce myocardial protective effects and alleviate symptoms associated with chronic heart failure. Echocardiography was used to detect cardiac function and cardiac structure of rats, including heart rate (HR), left atrium diameter (LA), left ventricular diameter (LV), left ventricular posterior wall (LVPW), interventricular septum (IVS), ejection fraction (EF), and fractional shortening (FS). BNP and NT-pro BNP levels were measured by enzyme-linked immunosorbent assay (ELISA). Autophagy-associated protein (ATG) genes and mTOR were detected by PCR. The expression of mTOR and phosphorylated-mTOR was detected through western blotting of proteins from myocardial tissue samples. The left ventricular inflammatory response was detected by immunohistochemistry and included ICAM-1, VCAM-1, MMP-2, and MMP-9 expression. The relationship between autophagy and inflammation was analyzed by correlation analysis. The results from echocardiography and ELISA showed that moxibustion could significantly improve heart function and structure. Western blot and PCR results showed that moxibustion treatment elevated mTOR expression. Further, moxibustion could inhibit autophagy and regulate the expression of key autophagy-related genes, including Vps34, ATG3, ATG5, ATG7, ATG12, and ATG13. By contrast, rapamycin could partially reduce the effects of moxibustion. Immunohistochemistry results indicated that moxibustion could reduce myocardial inflammation. Moreover, there was a positive correlation between autophagy and inflammation. Moxibustion can protect cardiac function in rats with heart failure, possibly inhibiting excessive autophagy of cardiomyocytes and reducing inflammatory reactions through the elevation of mTOR expression.

scholarly journals CHARACTERISTICS OF CLINICAL CURRENT AND STRUCTURAL-FUNCTIONAL STATE OF LEFT VENTRICULAR IN DECOMPENSATION OF CHRONIC HEART FAILURE IN PATIENTS WITH ISCHEMIC CHRONIC HEART FAILURE WITH SYSTOLIC DYSFUNCTION AND INFLAMMATION OF THE MYOCARDIUM

2018 ◽  
Vol 33 (2) ◽  
pp. 26-34
Author(s):  
E. V. Kruchinkina ◽  
T. R. Ryabova ◽  
Yu. V. Rogovskaya ◽  
R. E. Batalov ◽  
V. V. Ryabov
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Functional State ◽  
Clinical Course ◽  
Systolic Dysfunction ◽  
Interventricular Septum ◽  
Myocardial Revascularization ◽  
Left Ventricular ◽  
Volume Index ◽  
Myocardial Inflammation

The aimwas to study the clinical course of CHF decompensation and the structural and functional state of the left ventricle in patients with ischemic CHF with systolic dysfunction and myocardial inflammation.Material and Methods.This study is open, non-randomized, prospective, registered on the ClinicalTrials.gov website, identification number: NCT02649517. The analysis included 25 patients (84% men, LVEF 29.17±9.4%) with ADHF of ischemic etiology. The average age of the patients was 60.12±9.3 years. All the patients underwent an echocardiography including 2D-speckle tracking technique to assess LV deformation. All patients underwent invasive coronary angiography to exclude the progression of coronary atherosclerosis, as a cause of CHC decompensation. An endomyocardial biopsy was performed to diagnose the presence of myocardial inflammation. We performed a comparative analysis of clinical, laboratory, instrumental indicators depending on the fact of diagnosis of inflammation in the myocardium.Results.There were no specific features of the clinical course of decompensation of ischemic CHF with systolic LV dysfunction depending on the inflammation in the myocardial tissue. However, in patients with inflammation, aortocoronary bypass surgery was more often performed (p=0.00650). In addition, in patients with inflammation, there was a decrease in apical rotation (p=0.0313), its systolic velocity (p=0.0157 with decompensation of CHF. A year later, improvement in LV biomechanics, but a continuing decrease in the absolute modulus of global longitudinal LV deformation (p=0.0431) after the anti-inflammatory treatment. Also a year later, in both groups there was an increase in the LV end-diastolic volume index (p=0.0180 and p=0.0280, respectively), a decrease in the interventricular septum of the LV (p=0.0491) in the group with inflammation, and an increase in the myocardial mass index of the LV (p=0.04995) in patients with inflammation.Conclusion.Decreased apical LV rotation and its systolic velocity in patients with ischemic CHF and LV systolic dysfunction, in view of the lack of clinical improvement after optimal myocardial revascularization, may be an additional criterion of concomitant inflammation in the myocardium. Among patients with ischemic CHF and LV systolic dysfunction, more pronounced cardiac remodeling, manifested by LV dilatation and thinning of LV wall, was observed in the group with inflammation.

scholarly journals Shenlijia Attenuates Doxorubicin-Induced Chronic Heart Failure by Inhibiting Cardiac Fibrosis

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Xutao Sun ◽  
Yunjia Song ◽  
Ying Xie ◽  
Jieru Han ◽  
Fei Chen ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Cardiac Function ◽  
Molecular Mechanisms ◽  
Cardiac Fibrosis ◽  
Heart Function ◽  
Left Ventricular ◽  
Protein Chip ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction

Application of the anticancer drug doxorubicin (DOX) is restricted due to its adverse, cardiotoxic side effects, which ultimately result in heart failure. Moreover, there are a limited number of chemical agents for the clinical prevention of DOX-induced cardiotoxicity. Based on the theories of traditional Chinese medicine (TCM) on chronic heart failure (CHF), Shenlijia (SLJ), a new TCM compound, has been developed to fulfill multiple functions, including improving cardiac function and inhibiting cardiac fibrosis. In the present study, the protective effects and molecular mechanisms of SLJ on DOX-induced CHF rats were investigated. The CHF rat model was induced by intraperitoneal injection of DOX for six weeks with the cumulative dose of 15 mg/kg. All rats were then randomly divided into the control, CHF, CHF + SLJ (3.0 g/kg per day), and CHF + captopril (3.8 mg/kg per day) groups and treated for further four weeks. Echocardiography and the assessment of hemodynamic parameters were performed to evaluate heart function. A protein chip was applied to identify proteins with diagnostic values that were differentially expressed following SLJ treatment. The data from these investigations showed that SLJ treatment significantly improved cardiac function by increasing the left ventricular ejection fraction, improving the hemodynamic index, and inhibiting interstitial fibrosis. Protein chip analysis revealed that SLJ upregulated MCP-1, MDC, neuropilin-2, TGF-β3, thrombospondin, TIE-2, EG-VEGF/PK1, and TIMP-1/2/3 expressions and downregulated that of MMP-13. In addition, immunohistochemistry and western blot results further confirmed that SLJ promoted TIMP-1/2/3 and inhibited MMP-13 expression. The results of the present study suggest that SLJ was effective against DOX-induced CHF rats and is related to the improvement of heart function and ultrastructure and the inhibition of myocardial fibrosis.

scholarly journals Plasma IL-37 Elevated in Patients with Chronic Heart Failure and Predicted Major Adverse Cardiac Events: A 1-Year Follow-Up Study

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Xiling Shou ◽  
Jing Lin ◽  
Cui Xie ◽  
Yi Wang ◽  
Chaofeng Sun
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Cox Regression ◽  
Left Ventricular ◽  
Major Adverse Cardiac Events ◽  
Left Ventricular Ejection ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cardiac Events ◽  
Cox Regression Analysis ◽  
Adverse Cardiac Events

A great number of basic and clinical studies have demonstrated that inflammatory cytokines play an important role in the development and progression of chronic heart failure (CHF). However, there is limited information about the role of novel cytokine interleukin-37 (IL-37) in heart failure. We measured plasma IL-37 levels by enzyme-linked immunosorbent assay (ELISA) in 158 patients with chronic heart failure and 30 control subjects. Our results showed that plasma IL-37 levels were significantly elevated in patients with CHF compared with healthy controls (143.73 ± 26.83 pg/ml versus 45.2 ± 11.56 pg/ml,P<0.001). Furthermore, plasma IL-37 levels were positively correlated with hs-CRP, hs-TnT, and NT-proBNP and negatively correlated with left ventricular ejection function (LVEF). 11 patients died of cardiovascular cause, and 27 HF patients were rehospitalized for worsening HF within 12 months. Multivariate Cox regression analysis showed that plasma IL-37 is an independent predictor of major adverse cardiac events (MACE). Furthermore, CHF patients with >99 pg/ml plasma IL-37 had significantly higher incidences of MACE within 12 months. Our data suggest that plasma IL-37 may play a role in the pathogenesis of CHF and may be a novel predictor of poor prognosis in HF patients.

scholarly journals Qiliqiangxin Attenuates Cardiac Remodeling via Inhibition of TGF-β1/Smad3 and NF-κB Signaling Pathways in a Rat Model of Myocardial Infarction

2018 ◽  
Vol 45 (5) ◽  
pp. 1797-1806 ◽  
Author(s):  
Anbang Han ◽  
Yingdong Lu ◽  
Qi Zheng ◽  
Jian Zhang ◽  
YiZhou Zhao ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Cardiac Function ◽  
Signaling Pathways ◽  
Rat Model ◽  
Cardiac Remodeling ◽  
Left Ventricular ◽  
Protective Effects ◽  
Tnf Α ◽  
Tgf Β1

Background/Aims: Qiliqiangxin (QL), a traditional Chinese medicine, has been demonstrated to be effective and safe for the treatment of chronic heart failure. Left ventricular (LV) remodeling causes depressed cardiac performance and is an independent determinant of morbidity and mortality after myocardial infarction (MI). Our previous studies have shown that QL exhibits cardiac protective effects against heart failure after MI. The objective of this study was to explore the effects of QL on myocardial fibrosis in rats with MI and to investigate the underlying mechanism of these effects. Methods: A rat model of acute myocardial infarction was induced by ligating the left anterior descending coronary artery. The rats were treated with QL (1.0 g/kg/day) for 4 weeks after surgery. Echocardiography and histology examination were performed to evaluate heart function and fibrosis, respectively. Protein levels of transforming growth factor-β1 (TGF-β1), phosphorylated Smad3 (p-Smad3), phosphorylated Smad7 (p-Smad7), collagen I (Col- I), alpha smooth muscle actin (a-SMA), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), nuclear factor κB (NF-κB), and phosphorylated inhibitor of kappa B alpha (p-IκBα) were measured by western blot analysis. Results: QL treatment ameliorated adverse cardiac remodeling 8 weeks after AMI, including better preservation of cardiac function, decreased inflammation, and reduced fibrosis. In addition, QL treatment reduced Col-I, a-SMA, TGF-β1, and p-Smad3 expression levels but increased p-Smad7 levels in postmyocardial infarct rat hearts. QL administration also reduced the elevated levels of cardiac inflammation mediators, such as TNF-α and IL-6, as well as NF-κB and p-IκBα expression. Conclusions: QL therapy exerted protective effects against cardiac remodeling potentially by inhibiting TGF-β1/Smad3 and NF-κB signaling pathways, thereby preserving cardiac function, as well as reducing myocardial inflammation and fibrosis.

Abstract 519: Talin is Required for Normal Adult Heart Function

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Yoshitake Cho ◽  
Ruixia Li ◽  
Ana M Manso ◽  
Robert S Ross
Keyword(s):  
Heart Failure ◽  
Cardiac Function ◽  
Cardiac Dysfunction ◽  
Cardiac Development ◽  
Heart Function ◽  
Left Ventricular ◽  
Mass Spectrometry Analysis ◽  
Adult Heart ◽  
Spectrometry Analysis ◽  
Functional Changes

Talin (Tln) is a component of muscle costameres that links integrins to other components of the cellular cytoskeleton and plays an important role in maintaining the cellular integrity of cardiac myocytes (CM). There are two talin genes, Tln1 and Tln2, expressed in the heart. Tln1 is ubiquitously expressed, and Tln2 is dominantly expressed in CM. In our previous study, we show that the global deletion of Tln2 in mice (T2KO) caused no structural or functional changes in the heart, presumably because CM Tln1 became up-regulated. However, we found that mice lacking both CM Tln1 and Tln2 exhibit cardiac dysfunction by 4 weeks (w) of age with 100% mortality by 6 months (m), showing Tln plays an essential role in cardiac development and in maintaining cardiac function. In this study, we produced a tamoxifen (Tamo)-inducible mouse model in which Tln1 could be explicitly reduced in the adult CM (T1icKO), and then generate T1icKO:T2KO (T1/2dKO), so that the function of Tln could be assessed in the postnatal heart. T2KO and Tln1/2dKO mice were injected with Tamo at 8w. Echocardiograms were performed to evaluate cardiac function up to 8w post-Tamo injection. While T2KO mice showed normal cardiac function, T1/2dKO exhibited a gradual decrease in function post-Tamo injection. At 8w post-Tamo injection, T1/2dKO mice showed cardiac hypertrophy, fibrosis, and heart failure. To understand the mechanism by which deletion CM talin leads to cardiac dysfunction, left ventricular tissue protein lysates from T2KO and T1/2dKO mice at 4w post-Tamo when cardiac function (echo) and structure were preserved in dKO. The protein lysates were subjected to quantitative mass spectrometry analysis. We found there are 1,100 proteins differentially expressed in T2KO and T1/2dKO hearts. Pathway analysis was performed, and the results showed that proteins involved in vesicle transport, protein folding, and innate immunity are most up-regulated in the T1/2dKO heart. Taken together, our results show that Tln is required for maintaining proper cardiac function in the adult heart. The deletion of Tln in CM results in the up-regulation of multiple intracellular pathways, and we are currently studying the role of each pathway in the pathogenesis of heart failure induced by CM Tln deletion.

Effects of molsidomine on left ventricular dimensions and cardiac function in patients with chronic heart failure

1985 ◽  
Vol 109 (3) ◽  
pp. 691-693 ◽  
Author(s):  
Guy M. Berkenboom ◽  
John C. Sobolski ◽  
Pol P. Vandermoten ◽  
Eric E. Stoupel ◽  
Serge G. Degre
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Cardiac Function ◽  
Left Ventricular ◽  
Left Ventricular Dimensions ◽  
Ventricular Dimensions

scholarly journals Renal denervation improves cardiac function in rats with chronic heart failure: Effects on expression of β-adrenoceptors

2016 ◽  
Vol 311 (2) ◽  
pp. H337-H346 ◽  
Author(s):  
Hong Zheng ◽  
Xuefei Liu ◽  
Neeru M. Sharma ◽  
Kaushik P. Patel
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Left Ventricle ◽  
Cardiac Function ◽  
Renal Denervation ◽  
Diastolic Pressure ◽  
Left Ventricular ◽  
Sprague Dawley ◽  
Cardiac Damage ◽  
Sprague Dawley Rats

Chronic activation of the sympathetic drive contributes to cardiac remodeling and dysfunction during chronic heart failure (HF). The present study was undertaken to assess whether renal denervation (RDN) would abrogate the sympathoexcitation in HF and ameliorate the adrenergic dysfunction and cardiac damage. Ligation of the left coronary artery was used to induce HF in Sprague-Dawley rats. Four weeks after surgery, RDN was performed, 1 wk before the final measurements. At the end of the protocol, cardiac function was assessed by measuring ventricular hemodynamics. Rats with HF had an average infarct area >30% of the left ventricle and left ventricular end-diastolic pressure (LVEDP) >20 mmHg. β1- and β2-adrenoceptor proteins in the left ventricle were reduced by 37 and 49%, respectively, in the rats with HF. RDN lowered elevated levels of urinary excretion of norepinephrine and brain natriuretic peptide levels in the hearts of rats with HF. RDN also decreased LVEDP to 10 mmHg and improved basal dP/d t to within the normal range in rats with HF. RDN blunted loss of β1-adrenoceptor (by 47%) and β2-adrenoceptor (by 100%) protein expression and improved isoproterenol (0.5 μg/kg)-induced increase in +dP/d t (by 71%) and −dP/d t (by 62%) in rats with HF. RDN also attenuated the increase in collagen 1 expression in the left ventricles of rats with HF. These findings demonstrate that RDN initiated in chronic HF condition improves cardiac function mediated by adrenergic agonist and blunts β-adrenoceptor expression loss, providing mechanistic insights for RDN-induced improvements in cardiac function in the HF condition.

scholarly journals Endothelial Microvascular Dysfunction and Its Relationship with Haptoglobin Levels in Patients with Different Phenotypes of Chronic Heart Failure

2021 ◽  
Vol 17 (5) ◽  
pp. 674-682
Author(s):  
V. I. Podzolkov ◽  
N. A. Dragomiretskaya ◽  
I. G. Beliaev ◽  
Ju. S. Kucherova ◽  
A. V. Kazadaeva
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Ejection Fraction ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Enzyme Linked Immunosorbent Assay ◽  
Frequency Range ◽  
Ventricular Ejection Fraction ◽  
Doppler Flowmetry ◽  
Haptoglobin Level

Aim. To study the relationship between the level of haptoglobin and the main indicators of microcirculation (MC) in patients with different phenotypes of chronic heart failure (CHF).Materials and methods. Patients with different phenotypes of functional class II-IV chronic heart failure according to NYHA (n=80) underwent a general clinical examination, determination of the serum haptoglobin level by enzyme-linked immunosorbent assay, as well as an assessment of the MC state on the medial surface of the upper third of the leg by laser Doppler flowmetry (LDF).Results. Patients with CHF included patients with preserved left ventricular ejection fraction (HFpEF; n=27, intermediate ejection fraction (HFmrEF; n=25) and reduced ejection fraction (HFrEF; n=28). The median value of haptoglobin in the HFpEF group was 1387.6 [ 747.5; 1946.9] mg/l, in the HFmrEF group was 1583.4 [818.9; 2201.4] mg/l, in the HFrEF group was 968.5 [509.5; 1324.4] mg/l. Correlation analysis revealed statistically significant relationships between haptoglobin and the amplitudes of the endothelial frequency range (Ae) in the groups of HFmrEF (r=-0.628, 95% confidence interval [CI] -0.256; -0.825, p=0.003) and HFrEF (r=-0.503, 95% CI -0.089; -0.803, p=0.02). A negative relationship between the haptoglobin level and Kv and σ was revealed, as well as a formula for calculating the value of haptoglobin was obtained, which is predicted on the basis of the amplitude index of the endothelial frequency range: [haptoglobin]=1787-(4053×Ae).Conclusion. The multifactorial effect of haptoglobin is realized in the central and peripheral mechanisms of MC regulation. Low values of haptoglobin in blood plasma should be considered as a potential marker for the development of complications and used in a comprehensive assessment of the state of patients with CHF. Evaluation of the diagnostic and prognostic significance of haptoglobin, especially in patients with HFmrEF, requires further study.

scholarly journals Protective Effects of Thyroid Hormone Deprivation on Progression of Maladaptive Cardiac Hypertrophy and Heart Failure

2021 ◽  
Vol 8 ◽  
Author(s):  
Helena Kerp ◽  
Georg Sebastian Hönes ◽  
Elen Tolstik ◽  
Judith Hönes-Wendland ◽  
Janina Gassen ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Hypertrophy ◽  
Cardiac Function ◽  
Heart Function ◽  
Pressure Overload ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Ventricular Pressure ◽  
Cardiovascular Morbidity And Mortality ◽  
The Impact

Purpose: Thyroid hormones (TH) play a central role for cardiac function. TH influence heart rate and cardiac contractility, and altered thyroid function is associated with increased cardiovascular morbidity and mortality. The precise role of TH in onset and progression of heart failure still requires clarification.Methods: Chronic left ventricular pressure overload was induced in mouse hearts by transverse aortic constriction (TAC). One week after TAC, alteration of TH status was induced and the impact on cardiac disease progression was studied longitudinally over 4 weeks in mice with hypo- or hyperthyroidism and was compared to euthyroid TAC controls. Serial assessment was performed for heart function (2D M-mode echocardiography), heart morphology (weight, fibrosis, and cardiomyocyte cross-sectional area), and molecular changes in heart tissues (TH target gene expression, apoptosis, and mTOR activation) at 2 and 4 weeks.Results: In diseased heart, subsequent TH restriction stopped progression of maladaptive cardiac hypertrophy and improved cardiac function. In contrast and compared to euthyroid TAC controls, increased TH availability after TAC propelled maladaptive cardiac growth and development of heart failure. This was accompanied by a rise in cardiomyocyte apoptosis and mTOR pathway activation.Conclusion: This study shows, for the first time, a protective effect of TH deprivation against progression of pathological cardiac hypertrophy and development of congestive heart failure in mice with left ventricular pressure overload. Whether this also applies to the human situation needs to be determined in clinical studies and would infer a critical re-thinking of management of TH status in patients with hypertensive heart disease.

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