Heart failure(HF)is a highly morbid syndrome that seriously affects the physical and mental health of patients and generates an enormous socio-economic burden.In addition to cardiac myocyte oxidative stress and apopto...Heart failure(HF)is a highly morbid syndrome that seriously affects the physical and mental health of patients and generates an enormous socio-economic burden.In addition to cardiac myocyte oxidative stress and apoptosis,which are considered mechanisms for the development of HF,alterations in cardiac energy metabolism and pathological autophagy also contribute to cardiac abnormalities and ultimately HF.Silent information regulator 1(Sirt1)and adenosine monophosphate-activated protein kinase(AMPK)are nicotinamide adenine dinucleotide(NAD+)-dependent deacetylases and phosphorylated kinases,respectively.They play similar roles in regulating some pathological processes of the heart through regulating targets such as peroxisome proliferator-activated receptorγcoactivator 1α(PGC-1α),protein 38 mitogen-activated protein kinase(p38 MAPK),peroxisome proliferator-activated receptors(PPARs),and mammalian target of rapamycin(mTOR).We summarized the synergistic effects of Sirt1 and AMPK in the heart,and listed the traditional Chinese medicine(TCM)that exhibit cardioprotective properties by modulating the Sirt1/AMPK pathway,to provide a basis for the development of Sirt1/AMPK activators or inhibitors for the treatment of HF and other cardiovascular diseases(CVDs).展开更多
Background:The aim of this study is to investigate the mechanism of action underlying the therapeutic effects of the national patent Chinese medicine compound“Qiangxinhuoli prescription(QXHLF)”on chronic heart failu...Background:The aim of this study is to investigate the mechanism of action underlying the therapeutic effects of the national patent Chinese medicine compound“Qiangxinhuoli prescription(QXHLF)”on chronic heart failure(CHF).Methods:In vitro,the H_(9)C_(2) cell model was induced by ANGII,and cell proliferation and related protein expression were detected by Cell Counting Kit-8 and Western blot.In vivo,A rat model of CHF was prepared by ligation of the left anterior descending coronary artery.The effects of QXHLF on cardiac function in CHF rats were evaluated by cardiac index,hemodynamic changes,enzyme-linked immunosorbent assay,hematoxylin-eosin staining,immunohistochemistry,Western blot and RT-PCR.The expression of pro-apoptotic factors and anti-apoptotic factors,as well as TGFβ1,p-p38,TAK 1 mRNA,and protein,were detected.Results:In vitro,QXHLF has a significant inhibitory effect on the proliferation of H_(9)C_(2) cells.QXHLF can reduce the expression levels of TAK 1,TGFβ1,p-p38,Caspase3 and BAX proteins in H_(9)C_(2) cells,and increase the expression level of BCL_(2) protein.In vivo,QXHLF has the potential to increase left ventricular systolic pressure,m aximum rate of change in left ventricular pressure while decreasing left ventricular end diastolic pressure,and inhibiting the serum levels of brain natriuretic peptide.Moreover,QXHLF exhibits significant improvements in the pathological alterations of myocardial cells and fibers in CHF rats,leading to enhanced myocardial tissue morphology and notable advantages in combating myocardial fibrosis.QXHLF can reduce the levels of BAX and Caspase3 and up-regulate the expression of BCL_(2),thereby inhibiting cardiomyocyte apoptosis.Furthermore,QXHLF demonstrates inhibitory effects on the mRNA and protein expression levels of TGFβ_(1),TAK_(1),and p-p38 in the heart tissue of the CHF rat model.Conclusion:These findings indicate that QXHLF has a therapeutic effect on CHF by inhibiting the p38-MAPK signaling pathway,reducing myocardial fibrosis,preventing apoptosis,inhibiting cell proliferation,and restoring myocardial injury.展开更多
Therapy with glucagon-like peptide 1(GLP1)receptor agonists has raised great interest for its beneficial cardiovascular effects in preventing atherosclerosis and heart failure-related outcomes.However,while evidence a...Therapy with glucagon-like peptide 1(GLP1)receptor agonists has raised great interest for its beneficial cardiovascular effects in preventing atherosclerosis and heart failure-related outcomes.However,while evidence about atherosclerosis consistently suggests a cardioprotective potential with class effect,controversies remain on its impact on heart failure.GLP1 receptor agonists appear to prevent hospitalization for new-onset heart failure and reduce symptoms in heart failure with preserved ejection fraction(as demonstrated by the recent STEP-HFpEF Trial).Still,GLP1 agonism has resulted in neutral or even harmful effects in patients with established heart failure with reduced ejection fraction(the LIVE trial).GLP1 receptor agonists benefit the cardiovascular system indirectly through their marked metabolic effects(improved weight management,glycemic control,blood pressure,systemic and tissue inflammation),while direct effects on the heart have been questioned.Nonetheless,weight loss alone achieved through GLP1 receptor agonists has failed in improving left ventricular functions.Tirzepatide is a dual agonist of GLP1 and glucose-dependent insulinotropic polypeptide,representing an innovative treatment option in diabetes with a major impact on weight loss and promising cardiovascular benefits.Whether this class of therapies is going to change the history of heart failure is an ongoing debate.展开更多
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 tre...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.展开更多
Chronic heart failure(HF)is a clinical syndrome with high morbidity and mor-tality worldwide.Cardiac rehabilitation(CR)is a medically supervised program designed to maintain or improve cardiovascular health of people ...Chronic heart failure(HF)is a clinical syndrome with high morbidity and mor-tality worldwide.Cardiac rehabilitation(CR)is a medically supervised program designed to maintain or improve cardiovascular health of people living with HF,recommended by both American and European guidelines.A CR program con-sists of a multispecialty group including physicians,nurses,physiotherapists,trainers,nutritionists,and psychologists with the common purpose of improving functional capacity and quality of life of chronic HF patients.Physical activity,lifestyle,and psychological support are core components of a successful CR program.CR has been shown to be beneficial in all ejection fraction categories in HF and most patients,who are stable under medication,are capable of participating.An individualized exercise prescription should be developed on the basis of a baseline evaluation in all patients.The main modalities of exercise training are aerobic exercise and muscle strength training of different intensity and frequency.It is important to set the appropriate clinical outcomes from the beginning,in order to assess the effectiveness of a CR program.There are still significant limitations that prevent patients from participating in these programs and need to be solved.A significant limitation is the generally low quality of research in CR and the presence of negative trials,such as the rehabilitation after myocardial infarction trial,where comprehensive rehabilitation following myocardial infraction had no important effect on mortality,morbidity,risk factors,or health-related quality of life or activity.In the present editorial,we present all the updated knowledge and recommendations in CR programs.展开更多
Introduction: Type 1 cardiorenal syndrome (CRS 1) is characterized by acute impairment of cardiac function leading to acute renal dysfunction. CRS1 is present in 25% of patients admitted for heart failure. The objecti...Introduction: Type 1 cardiorenal syndrome (CRS 1) is characterized by acute impairment of cardiac function leading to acute renal dysfunction. CRS1 is present in 25% of patients admitted for heart failure. The objective of our study is to analyze the epidemiological, clinical, therapeutic profile and the risk and prognostic factors of these patients. Materials and Methods: We identified 120 patients with cardiorenal syndrome (CRS) over a one-year period to determine the prevalence and risk factors for developing CRS 1. We analyzed the clinical, biological, and evolutionary profiles of patients with CRS 1 and determined the risk factors for the occurrence of acute kidney injury (AKI) as well as the mortality factors in these patients. Résultats: The average age of our patients with CRS1 is 58 ± 9 years, with a sex ratio of 1.4. The average eGFR of our patients is 35 ± 6.5 ml/min/1.73m2. Diabetes was found in 17% of our patients and hypertension in 14%. The etiology of cardiac impairment is predominantly acute coronary syndrome (ACS), followed by rhythm disorders. Renally, all our patients have acute kidney injury (AKI), with 86% having functional acute renal failure and 14% having acute tubular necrosis. Therapeutically, 50% of our patients are on diuretics, 42% receive beta-blocker treatment, and RAAS blockers are used in 29% of cases. Renal replacement therapy (RRT) sessions were required in 13.8% of cases. In univariate analysis, male gender, tachyarrhythmia, and hypertension are associated with the early onset of acute kidney injury (AKI). The use of diuretics, anemia, and low left ventricular ejection fraction (LVEF) are linked to a higher risk of developing CRS 1 (p = 0.021, p = 0.037, p = 0.010 respectively). In multivariate analysis, advanced age is significantly associated with increased mortality risk in CRS 1 patients (p = 0.030), while beta-blocker use is considered a protective factor (p = 0.014). Conclusion: Our study identifies several key factors associated with outcomes in type 1 CRS. Male gender, tachyarrhythmia, and hypertension are linked to early-onset AKI. The use of diuretics and the presence of anemia increase the risk of developing CRS1. Advanced age is significantly associated with higher mortality rates. Conversely, the use of beta-blockers appears to be protective in this patient population. .展开更多
Heart failure represents the end point of a variety of cardiovascular diseases.It is a growing health burden and a leading cause of death worldwide.To date,limited treatment options exist for the treatment of heart fa...Heart failure represents the end point of a variety of cardiovascular diseases.It is a growing health burden and a leading cause of death worldwide.To date,limited treatment options exist for the treatment of heart failure,but exercise has been well-established as one of the few safe and effective interventions,leading to improved outcomes in patients.However,a lack of patient adherence remains a significant barrier in the implementation of exercise-based therapy for the treatment of heart failure.The insulin-like growth factor 1(IGF1)phosphoinositide 3-kinase(PI3K)pathway has been recognized as perhaps the most critical pathway for mediating exercisedinduced heart growth and protection.Here,we discuss how modulating activity of the IGF1PI3K pathway may be a valuable approach for the development of therapies that mimic the protective effects of exercise on the heart.We outline some of the promising approaches being investigated that utilize PI3K-based therapy for the treatment of heart failure.We discuss the implications for cardiac pathology and cardiotoxicity that arise in a setting of reduced PI3K activity.Finally,we discuss the use of animal models of cardiac health and disease,and genetic mice with increased or decreased cardiac PI3K activity for the discovery of novel drug targets and biomarkers of cardiovascular disease.展开更多
Background Myocardial infarction （MI） has likely contributed to the increased prevalence of heart failure （HF）. As a result of re- duced cardiac function, splanchnic blood flow decreases, causing ischemia in villi...Background Myocardial infarction （MI） has likely contributed to the increased prevalence of heart failure （HF）. As a result of re- duced cardiac function, splanchnic blood flow decreases, causing ischemia in villi and damage to the intestinal barrier. The induction of heme oxygenase-1 （HO-1） could prevent, or lessen the effects of stress and inflammation. Thus, the effect and mechanism thereof of HO-1 on the intestines of rats with HF was investigated. Methods Male Wistar rats with heart failure through ligation of the left coronary artery were identified with an left ventricular ejection fraction of 〈 45% through echocardiography and then divided into various experimental groups based on the type of peritoneal injection they received [MI： saline; MI ＋ Cobalt protoporphyrin （CoPP）： CoPP solution; and MI ＋ Tin mesoporphyrin IX dichloride （SnMP）： SnMP solution]. The control group was comprised of rats without coronary ligation. Echocardiogra- phy was performed before ligation for a baseline and eight weeks after ligation in order to evaluate the cardiac function of the rats. The bac- terial translocation （BT） incidence, mesenteric microcirculation, amount of endotoxins in the vein serum, ileum levels of HO- 1, carbon oxide （CO）, nitric oxide （NO）, intedeuldn （IL）-10, turnour necrosis factor-et （TNF-ct）, and the ileum morphology were determined eight weeks after the operation. Results The rats receiving MI ＋ CoPP injections exhibited a recovery in cardiac function, an amelioration of mesenteric microcirculation and change in morphology, a lower BT incidence, a reduction in serum and ileac NO and TNF-ct levels, and an elevation in ileac HO-1, CO, and interleukin-10 （[L-10） levels compared to the MI group （P 〈 0.05）. The rats that received the MI ＋ SnMP injections exhibited results inverse to the MI （P 〈 0.05） group. Conclusions HO-1 exerted a protective effect on the intestines of rats with HF by inhibiting the inflammation and amelioration of microcirculation through the CO pathway. This protective effect could be independent from the recovery of cardiac function.展开更多
Objective We performed experiments using Neuregulin-1β （NRG-1β） treatment to determine a mechanism for the protective role derived from its beneficial effects by remodeling gap junctions （GJs） during heart failu...Objective We performed experiments using Neuregulin-1β （NRG-1β） treatment to determine a mechanism for the protective role derived from its beneficial effects by remodeling gap junctions （GJs） during heart failure （HF）. Methods Rat models of I-IF were established by aortocaval fistula. Forty-eight rats were divided randomly into the HF （HF, n = 16）, NRG-1β trealanent （NRG, n = 16）, and sham operation （S, n = 16） group. The rats in the NRG group were administered NRG-1β （10 μg/kg per day） for 7 days via the tail vein, whereas the other groups were injected with the same doses of saline, Twelve weeks after operation, Connexin 43 （Cx43） expression in single myocytes obtained from the left ventricle was determined by immunocytochemistry. Total protein was extracted from frozen left ventricular tissues for immunoblotting assay, and the ultrastmcture of myocytes was observed by transmission electron microscopy. Results Compared with the HF group, the cardiac fimction of rats in the NRG group was markedly improved, irregular distribution and deceased Cx43 expression were relieved. The ultrastmcture of myocytes was seriously damaged in HF rats, and NRG-1β reduced these pathological damages. Conclusions Short-term NRG-1β treatment can rescue pump failure in experimental models of volume overload-induced HF, which is related to the recovery of GJs structure and the improvement of Cx43 expression.展开更多
Aldosterone mediates many of the physiological and pathophysiological/cardio-toxic effects of angiotensin II(Ang II). Its synthesis and secretion from the zona glomerulosa cells of the adrenal cortex, elevated in chro...Aldosterone mediates many of the physiological and pathophysiological/cardio-toxic effects of angiotensin II(Ang II). Its synthesis and secretion from the zona glomerulosa cells of the adrenal cortex, elevated in chronic heart failure(HF), is induced by Ang II type 1 receptors(AT1Rs). The AT1R is a G protein-coupled receptor, mainly coupling to Gq/11 proteins. However, it can also signal through β-arrestin-1(βarr1) or-2(βarr2), both of which mediate G protein-independent signaling. Over the past decade, a second, Gq/11 proteinindependent but βarr1-dependent signaling pathway emanating from the adrenocortical AT1R and leading to aldosterone production has become appreciated. Thus, it became apparent that AT1R antagonists that block both pathways equally well are warranted for fully effective aldosterone suppression in HF. This spurred the comparison of all of the currently marketed angiotensin receptor blockers(ARBs, AT1R antagonists or sartans) at blocking activation of the two signaling modes(G protein-, and βarr1-dependent) at the Ang IIactivated AT1R and hence, at suppression of aldosterone in vitro and in vivo. Although all agents are very potent inhibitors of G protein activation at the AT1R, candesartan and valsartan were uncovered to be the most potent ARBs at blocking βarr activation by Ang II and at suppressing aldosterone in vitro and in vivo in post-myocardial infarction HF animals. In contrast, irbesartan and losartan are virtually G protein-"biased" blockers at the human AT1R, with very low efficacy for βarr inhibition and aldosterone suppression. Therefore, candesartan and valsartan(and other, structurally similar compounds) may be the most preferred ARB agents for HF pharmacotherapy, as well as for treatment of other conditions characterized by elevated aldosterone.展开更多
Compared to antiarrhythmic drugs, implantable cardioverter defibrillator （ICD） leads to a more significant im- provement in preventing ventricular arrhythmia in heart failure patients. However, an important question...Compared to antiarrhythmic drugs, implantable cardioverter defibrillator （ICD） leads to a more significant im- provement in preventing ventricular arrhythmia in heart failure patients. However, an important question has been raised that how to select appropriate patients for ICD therapy. 1-123 metaiodobenzylguanidine （MIBG） planar and SPECT imaging have shown great potentials to predict ventricular arrhythmia in heart failure patients by as- sessing the abnormalities of the sympathetic nervous system. Clinical trials demonstrated that several parameters measured from 1-123 MIBG planar and SPECT imaging, such as heart-to-mediastinum ratio, washout rate, defect score, and innervation/perfusion mismatch, predicted ventricular arrhythmias in heart failure patients. This paper introduces the current practice of ICD therapy and reviews the technical background of 1-123 MIBG planar and SPECT imaging and their clinical data in predicting ventricular arrhythmia.展开更多
目的探讨肿瘤坏死因子诱导蛋白3相互作用蛋白1(TNFAIP3-interacting protein 1,TNIP1)基因单核苷酸多态性及其mRNA表达水平与老年慢性心力衰竭患者肺部感染的相关性。方法选择2019年10月至2022年10月于上海建工医院重症医学科就诊的130...目的探讨肿瘤坏死因子诱导蛋白3相互作用蛋白1(TNFAIP3-interacting protein 1,TNIP1)基因单核苷酸多态性及其mRNA表达水平与老年慢性心力衰竭患者肺部感染的相关性。方法选择2019年10月至2022年10月于上海建工医院重症医学科就诊的130例老年慢性心力衰竭患者作为研究对象,根据是否于院内发生肺部感染分为感染组(32例)和未感染组(98例)。对TNIP1基因的两个SNP位点rs6889239(T>C)、rs17728338(A>G)进行基因分型,并检测外周血TNIP1基因的mRNA表达水平。结果TNIP1基因rs6889239位点在感染组和非感染组之间的基因型分布以及等位基因频率的差异均无统计学意义(P>0.05);两组的rs17728338位点AA、AG、GG基因型分布比较差异有统计学意义(P<0.05),且感染组等位基因G的频率显著高于未感染组(P<0.05)。相较于未感染组,感染组患者的外周血TNIP1基因mRNA表达水平显著增加,差异有统计学意义(P<0.001)。受试者工作特征(Receiver operating characteristic,ROC)曲线分析结果显示外周血TNIP1基因表达水平预测慢性心力衰竭患者发生肺部感染的灵敏度和特异度分别为71.9%和95.9%。感染组和非感染组TNIP1基因rs6889239位点不同基因型患者的外周血TNIP1基因的表达水平比较差异均无统计学意义(P>0.05),而rs17728338位点不同基因型患者的外周血TNIP1基因表达水平比较差异有统计学意义(P<0.05)。结论TNIP1基因rs17728338表达水平与老年慢性心力衰竭患者发生肺部感染有关。展开更多
基金supported by the Natural Science Foundation of China(Grant No.:82130113)the“Xinglin Scholars”Research Promotion Program of Chengdu University of Traditional Chinese Medicine(Program No.:ZDZX2022005)+1 种基金the China Postdoctoral Science Foundation(Grant No.:2021MD703800)the Science Foundation for Youths of Science&Technology Department of Sichuan Province(Grant No.:2022NSFSC1449).
文摘Heart failure(HF)is a highly morbid syndrome that seriously affects the physical and mental health of patients and generates an enormous socio-economic burden.In addition to cardiac myocyte oxidative stress and apoptosis,which are considered mechanisms for the development of HF,alterations in cardiac energy metabolism and pathological autophagy also contribute to cardiac abnormalities and ultimately HF.Silent information regulator 1(Sirt1)and adenosine monophosphate-activated protein kinase(AMPK)are nicotinamide adenine dinucleotide(NAD+)-dependent deacetylases and phosphorylated kinases,respectively.They play similar roles in regulating some pathological processes of the heart through regulating targets such as peroxisome proliferator-activated receptorγcoactivator 1α(PGC-1α),protein 38 mitogen-activated protein kinase(p38 MAPK),peroxisome proliferator-activated receptors(PPARs),and mammalian target of rapamycin(mTOR).We summarized the synergistic effects of Sirt1 and AMPK in the heart,and listed the traditional Chinese medicine(TCM)that exhibit cardioprotective properties by modulating the Sirt1/AMPK pathway,to provide a basis for the development of Sirt1/AMPK activators or inhibitors for the treatment of HF and other cardiovascular diseases(CVDs).
基金the Science and Technology Research Project of the Education Department of Jilin Province(No.JJKH20220862KJ)the Jilin Province higher education teaching reform research topic(No.20224BRFI7U003M)National Natural Science Foundation of China(No.82074324).
文摘Background:The aim of this study is to investigate the mechanism of action underlying the therapeutic effects of the national patent Chinese medicine compound“Qiangxinhuoli prescription(QXHLF)”on chronic heart failure(CHF).Methods:In vitro,the H_(9)C_(2) cell model was induced by ANGII,and cell proliferation and related protein expression were detected by Cell Counting Kit-8 and Western blot.In vivo,A rat model of CHF was prepared by ligation of the left anterior descending coronary artery.The effects of QXHLF on cardiac function in CHF rats were evaluated by cardiac index,hemodynamic changes,enzyme-linked immunosorbent assay,hematoxylin-eosin staining,immunohistochemistry,Western blot and RT-PCR.The expression of pro-apoptotic factors and anti-apoptotic factors,as well as TGFβ1,p-p38,TAK 1 mRNA,and protein,were detected.Results:In vitro,QXHLF has a significant inhibitory effect on the proliferation of H_(9)C_(2) cells.QXHLF can reduce the expression levels of TAK 1,TGFβ1,p-p38,Caspase3 and BAX proteins in H_(9)C_(2) cells,and increase the expression level of BCL_(2) protein.In vivo,QXHLF has the potential to increase left ventricular systolic pressure,m aximum rate of change in left ventricular pressure while decreasing left ventricular end diastolic pressure,and inhibiting the serum levels of brain natriuretic peptide.Moreover,QXHLF exhibits significant improvements in the pathological alterations of myocardial cells and fibers in CHF rats,leading to enhanced myocardial tissue morphology and notable advantages in combating myocardial fibrosis.QXHLF can reduce the levels of BAX and Caspase3 and up-regulate the expression of BCL_(2),thereby inhibiting cardiomyocyte apoptosis.Furthermore,QXHLF demonstrates inhibitory effects on the mRNA and protein expression levels of TGFβ_(1),TAK_(1),and p-p38 in the heart tissue of the CHF rat model.Conclusion:These findings indicate that QXHLF has a therapeutic effect on CHF by inhibiting the p38-MAPK signaling pathway,reducing myocardial fibrosis,preventing apoptosis,inhibiting cell proliferation,and restoring myocardial injury.
文摘Therapy with glucagon-like peptide 1(GLP1)receptor agonists has raised great interest for its beneficial cardiovascular effects in preventing atherosclerosis and heart failure-related outcomes.However,while evidence about atherosclerosis consistently suggests a cardioprotective potential with class effect,controversies remain on its impact on heart failure.GLP1 receptor agonists appear to prevent hospitalization for new-onset heart failure and reduce symptoms in heart failure with preserved ejection fraction(as demonstrated by the recent STEP-HFpEF Trial).Still,GLP1 agonism has resulted in neutral or even harmful effects in patients with established heart failure with reduced ejection fraction(the LIVE trial).GLP1 receptor agonists benefit the cardiovascular system indirectly through their marked metabolic effects(improved weight management,glycemic control,blood pressure,systemic and tissue inflammation),while direct effects on the heart have been questioned.Nonetheless,weight loss alone achieved through GLP1 receptor agonists has failed in improving left ventricular functions.Tirzepatide is a dual agonist of GLP1 and glucose-dependent insulinotropic polypeptide,representing an innovative treatment option in diabetes with a major impact on weight loss and promising cardiovascular benefits.Whether this class of therapies is going to change the history of heart failure is an ongoing debate.
基金the China’s National Key Research and Development Program Projects(No.2022YFC3500500 and No.2022YFC3500502).
文摘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.
文摘Chronic heart failure(HF)is a clinical syndrome with high morbidity and mor-tality worldwide.Cardiac rehabilitation(CR)is a medically supervised program designed to maintain or improve cardiovascular health of people living with HF,recommended by both American and European guidelines.A CR program con-sists of a multispecialty group including physicians,nurses,physiotherapists,trainers,nutritionists,and psychologists with the common purpose of improving functional capacity and quality of life of chronic HF patients.Physical activity,lifestyle,and psychological support are core components of a successful CR program.CR has been shown to be beneficial in all ejection fraction categories in HF and most patients,who are stable under medication,are capable of participating.An individualized exercise prescription should be developed on the basis of a baseline evaluation in all patients.The main modalities of exercise training are aerobic exercise and muscle strength training of different intensity and frequency.It is important to set the appropriate clinical outcomes from the beginning,in order to assess the effectiveness of a CR program.There are still significant limitations that prevent patients from participating in these programs and need to be solved.A significant limitation is the generally low quality of research in CR and the presence of negative trials,such as the rehabilitation after myocardial infarction trial,where comprehensive rehabilitation following myocardial infraction had no important effect on mortality,morbidity,risk factors,or health-related quality of life or activity.In the present editorial,we present all the updated knowledge and recommendations in CR programs.
文摘Introduction: Type 1 cardiorenal syndrome (CRS 1) is characterized by acute impairment of cardiac function leading to acute renal dysfunction. CRS1 is present in 25% of patients admitted for heart failure. The objective of our study is to analyze the epidemiological, clinical, therapeutic profile and the risk and prognostic factors of these patients. Materials and Methods: We identified 120 patients with cardiorenal syndrome (CRS) over a one-year period to determine the prevalence and risk factors for developing CRS 1. We analyzed the clinical, biological, and evolutionary profiles of patients with CRS 1 and determined the risk factors for the occurrence of acute kidney injury (AKI) as well as the mortality factors in these patients. Résultats: The average age of our patients with CRS1 is 58 ± 9 years, with a sex ratio of 1.4. The average eGFR of our patients is 35 ± 6.5 ml/min/1.73m2. Diabetes was found in 17% of our patients and hypertension in 14%. The etiology of cardiac impairment is predominantly acute coronary syndrome (ACS), followed by rhythm disorders. Renally, all our patients have acute kidney injury (AKI), with 86% having functional acute renal failure and 14% having acute tubular necrosis. Therapeutically, 50% of our patients are on diuretics, 42% receive beta-blocker treatment, and RAAS blockers are used in 29% of cases. Renal replacement therapy (RRT) sessions were required in 13.8% of cases. In univariate analysis, male gender, tachyarrhythmia, and hypertension are associated with the early onset of acute kidney injury (AKI). The use of diuretics, anemia, and low left ventricular ejection fraction (LVEF) are linked to a higher risk of developing CRS 1 (p = 0.021, p = 0.037, p = 0.010 respectively). In multivariate analysis, advanced age is significantly associated with increased mortality risk in CRS 1 patients (p = 0.030), while beta-blocker use is considered a protective factor (p = 0.014). Conclusion: Our study identifies several key factors associated with outcomes in type 1 CRS. Male gender, tachyarrhythmia, and hypertension are linked to early-onset AKI. The use of diuretics and the presence of anemia increase the risk of developing CRS1. Advanced age is significantly associated with higher mortality rates. Conversely, the use of beta-blockers appears to be protective in this patient population. .
基金All authors are supported by the Victorian Government’s Operational Infrastructure Support ProgramSBS is supported by a joint Baker Heart and Diabetes Institute-La Trobe University doctoral scholarshipRM is supported by a National Health and Medical Research Council Senior Research Fellowship(Grant No.1078985).
文摘Heart failure represents the end point of a variety of cardiovascular diseases.It is a growing health burden and a leading cause of death worldwide.To date,limited treatment options exist for the treatment of heart failure,but exercise has been well-established as one of the few safe and effective interventions,leading to improved outcomes in patients.However,a lack of patient adherence remains a significant barrier in the implementation of exercise-based therapy for the treatment of heart failure.The insulin-like growth factor 1(IGF1)phosphoinositide 3-kinase(PI3K)pathway has been recognized as perhaps the most critical pathway for mediating exercisedinduced heart growth and protection.Here,we discuss how modulating activity of the IGF1PI3K pathway may be a valuable approach for the development of therapies that mimic the protective effects of exercise on the heart.We outline some of the promising approaches being investigated that utilize PI3K-based therapy for the treatment of heart failure.We discuss the implications for cardiac pathology and cardiotoxicity that arise in a setting of reduced PI3K activity.Finally,we discuss the use of animal models of cardiac health and disease,and genetic mice with increased or decreased cardiac PI3K activity for the discovery of novel drug targets and biomarkers of cardiovascular disease.
文摘Background Myocardial infarction （MI） has likely contributed to the increased prevalence of heart failure （HF）. As a result of re- duced cardiac function, splanchnic blood flow decreases, causing ischemia in villi and damage to the intestinal barrier. The induction of heme oxygenase-1 （HO-1） could prevent, or lessen the effects of stress and inflammation. Thus, the effect and mechanism thereof of HO-1 on the intestines of rats with HF was investigated. Methods Male Wistar rats with heart failure through ligation of the left coronary artery were identified with an left ventricular ejection fraction of 〈 45% through echocardiography and then divided into various experimental groups based on the type of peritoneal injection they received [MI： saline; MI ＋ Cobalt protoporphyrin （CoPP）： CoPP solution; and MI ＋ Tin mesoporphyrin IX dichloride （SnMP）： SnMP solution]. The control group was comprised of rats without coronary ligation. Echocardiogra- phy was performed before ligation for a baseline and eight weeks after ligation in order to evaluate the cardiac function of the rats. The bac- terial translocation （BT） incidence, mesenteric microcirculation, amount of endotoxins in the vein serum, ileum levels of HO- 1, carbon oxide （CO）, nitric oxide （NO）, intedeuldn （IL）-10, turnour necrosis factor-et （TNF-ct）, and the ileum morphology were determined eight weeks after the operation. Results The rats receiving MI ＋ CoPP injections exhibited a recovery in cardiac function, an amelioration of mesenteric microcirculation and change in morphology, a lower BT incidence, a reduction in serum and ileac NO and TNF-ct levels, and an elevation in ileac HO-1, CO, and interleukin-10 （[L-10） levels compared to the MI group （P 〈 0.05）. The rats that received the MI ＋ SnMP injections exhibited results inverse to the MI （P 〈 0.05） group. Conclusions HO-1 exerted a protective effect on the intestines of rats with HF by inhibiting the inflammation and amelioration of microcirculation through the CO pathway. This protective effect could be independent from the recovery of cardiac function.
基金This research was supported by the Key Program，the National Natural Science Foundation of China
文摘Objective We performed experiments using Neuregulin-1β （NRG-1β） treatment to determine a mechanism for the protective role derived from its beneficial effects by remodeling gap junctions （GJs） during heart failure （HF）. Methods Rat models of I-IF were established by aortocaval fistula. Forty-eight rats were divided randomly into the HF （HF, n = 16）, NRG-1β trealanent （NRG, n = 16）, and sham operation （S, n = 16） group. The rats in the NRG group were administered NRG-1β （10 μg/kg per day） for 7 days via the tail vein, whereas the other groups were injected with the same doses of saline, Twelve weeks after operation, Connexin 43 （Cx43） expression in single myocytes obtained from the left ventricle was determined by immunocytochemistry. Total protein was extracted from frozen left ventricular tissues for immunoblotting assay, and the ultrastmcture of myocytes was observed by transmission electron microscopy. Results Compared with the HF group, the cardiac fimction of rats in the NRG group was markedly improved, irregular distribution and deceased Cx43 expression were relieved. The ultrastmcture of myocytes was seriously damaged in HF rats, and NRG-1β reduced these pathological damages. Conclusions Short-term NRG-1β treatment can rescue pump failure in experimental models of volume overload-induced HF, which is related to the recovery of GJs structure and the improvement of Cx43 expression.
文摘Aldosterone mediates many of the physiological and pathophysiological/cardio-toxic effects of angiotensin II(Ang II). Its synthesis and secretion from the zona glomerulosa cells of the adrenal cortex, elevated in chronic heart failure(HF), is induced by Ang II type 1 receptors(AT1Rs). The AT1R is a G protein-coupled receptor, mainly coupling to Gq/11 proteins. However, it can also signal through β-arrestin-1(βarr1) or-2(βarr2), both of which mediate G protein-independent signaling. Over the past decade, a second, Gq/11 proteinindependent but βarr1-dependent signaling pathway emanating from the adrenocortical AT1R and leading to aldosterone production has become appreciated. Thus, it became apparent that AT1R antagonists that block both pathways equally well are warranted for fully effective aldosterone suppression in HF. This spurred the comparison of all of the currently marketed angiotensin receptor blockers(ARBs, AT1R antagonists or sartans) at blocking activation of the two signaling modes(G protein-, and βarr1-dependent) at the Ang IIactivated AT1R and hence, at suppression of aldosterone in vitro and in vivo. Although all agents are very potent inhibitors of G protein activation at the AT1R, candesartan and valsartan were uncovered to be the most potent ARBs at blocking βarr activation by Ang II and at suppressing aldosterone in vitro and in vivo in post-myocardial infarction HF animals. In contrast, irbesartan and losartan are virtually G protein-"biased" blockers at the human AT1R, with very low efficacy for βarr inhibition and aldosterone suppression. Therefore, candesartan and valsartan(and other, structurally similar compounds) may be the most preferred ARB agents for HF pharmacotherapy, as well as for treatment of other conditions characterized by elevated aldosterone.
文摘Compared to antiarrhythmic drugs, implantable cardioverter defibrillator （ICD） leads to a more significant im- provement in preventing ventricular arrhythmia in heart failure patients. However, an important question has been raised that how to select appropriate patients for ICD therapy. 1-123 metaiodobenzylguanidine （MIBG） planar and SPECT imaging have shown great potentials to predict ventricular arrhythmia in heart failure patients by as- sessing the abnormalities of the sympathetic nervous system. Clinical trials demonstrated that several parameters measured from 1-123 MIBG planar and SPECT imaging, such as heart-to-mediastinum ratio, washout rate, defect score, and innervation/perfusion mismatch, predicted ventricular arrhythmias in heart failure patients. This paper introduces the current practice of ICD therapy and reviews the technical background of 1-123 MIBG planar and SPECT imaging and their clinical data in predicting ventricular arrhythmia.
文摘目的探讨肿瘤坏死因子诱导蛋白3相互作用蛋白1(TNFAIP3-interacting protein 1,TNIP1)基因单核苷酸多态性及其mRNA表达水平与老年慢性心力衰竭患者肺部感染的相关性。方法选择2019年10月至2022年10月于上海建工医院重症医学科就诊的130例老年慢性心力衰竭患者作为研究对象,根据是否于院内发生肺部感染分为感染组(32例)和未感染组(98例)。对TNIP1基因的两个SNP位点rs6889239(T>C)、rs17728338(A>G)进行基因分型,并检测外周血TNIP1基因的mRNA表达水平。结果TNIP1基因rs6889239位点在感染组和非感染组之间的基因型分布以及等位基因频率的差异均无统计学意义(P>0.05);两组的rs17728338位点AA、AG、GG基因型分布比较差异有统计学意义(P<0.05),且感染组等位基因G的频率显著高于未感染组(P<0.05)。相较于未感染组,感染组患者的外周血TNIP1基因mRNA表达水平显著增加,差异有统计学意义(P<0.001)。受试者工作特征(Receiver operating characteristic,ROC)曲线分析结果显示外周血TNIP1基因表达水平预测慢性心力衰竭患者发生肺部感染的灵敏度和特异度分别为71.9%和95.9%。感染组和非感染组TNIP1基因rs6889239位点不同基因型患者的外周血TNIP1基因的表达水平比较差异均无统计学意义(P>0.05),而rs17728338位点不同基因型患者的外周血TNIP1基因表达水平比较差异有统计学意义(P<0.05)。结论TNIP1基因rs17728338表达水平与老年慢性心力衰竭患者发生肺部感染有关。
