Although sodium‒glucose cotransporter-2 (SGLT2) inhibitors have cardiorenal benefits, their efficacy in patients with type 2 diabetes mellitus (T2DM) and chronic coronary syndrome (CCS) undergoing percutaneous coronary intervention (PCI) remains underexplored. To evaluate the cardiorenal protective effects of the SGLT2 inhibitor dapagliflozin in patients with T2DM and CCS receiving PCI. This was a cross-sectional analysis of 1,430 patients from a tertiary hospital database who underwent PCI (January 1, 2018, to March 31, 2022). Cardiac outcomes (PMI/4aMI) and renal outcomes (eGFR and CI-AKI). After 1:1 propensity score matching (PSM) (176 dapagliflozin vs. 176 control), the dapagliflozin group showed significantly lower PMI/4aMI rates pre-PSM (39.78

tRNA-derived small RNAs (tsRNAs) are a newly recognized class of non-coding RNAs involved in regulating RNA processing and translational control. Pathological cardiac hypertrophy, characterized by left ventricular remodeling under chronic stress, serves as a critical precursor to severe cardiovascular pathologies including myocardial ischemia, infarction, and heart failure. Utilizing an angiotensin II (Ang II)-induced mouse cardiac hypertrophy model combined with tsRNA transcriptome profiling, we identified differentially expressed tsRNAs and investigated their functional relevance. Validation in neonatal mouse ventricular myocytes (NMVMs) revealed five upregulated tsRNAs associated with hypertrophic progression. Functional characterization showed that overexpressing tRF-Glu-CTC-013 significantly reduced cardiomyocyte hypertrophy and inhibited inflammation and fibrosis. Further luciferase reporter assays revealed that tRF-Glu-CTC-013 could bind to the 3' UTR of TAS1R3, thereby inhibiting its expression and enhancing the level of autophagy in NMVMs. Taken together, these findings suggest that tsRNAs may act as novel regulators of cardiac remodeling, with tRF-Glu-CTC-013 emerging as a promising therapeutic candidate for cardioprotection via anti-hypertrophic, anti-inflammatory, and anti-fibrotic mechanisms.

Shock wave therapy (SWT) is a new alternative therapy for patients with severe coronary artery disease that improves myocardial ischemic symptoms by delivering low-energy shock wave stimulation to ischaemic myocardium with low-energy pulsed waves. However, the specific mechanism of its protective effect is not fully understood, especially for the protective mechanism in cardiomyocytes after hypoxia/reoxygenation (H/R). We selected a rat H9c2 cardiomyocyte cell line to establish a stable H/R cardiomyocyte injury model by hypoxia/reoxygenation, and then used SWT for therapeutic intervention to explore its cardiomyocyte protective mechanisms. The results showed that SWT significantly increased cell viability and GSH levels while decreasing LDH levels, ROS levels, and MDA levels. SWT also improved mitochondrial morphology and function of cells after H/R. Meanwhile, we found that SWT could increase the expression of GPX4, xCT, and Bcl-2, while decreasing the expression of Bax and cleaved caspase-3, and inhibiting cardiomyocyte apoptosis and ferroptosis. Moreover, this protective effect of SWT on cardiomyocytes could be significantly reversed by knockdown of xCT, a key regulator protein of ferroptosis. In conclusion, our study shows that SWT can attenuate hypoxia-reoxygenation-induced myocardial injury and protect cardiomyocyte function by inhibiting H/R-induced apoptosis and ferroptosis, and this therapy may have important applications in the treatment of clinical myocardial ischemic diseases.

Doxorubicin (DOX) is an anthracycline that has excellent anticancer effects during tumor chemotherapy, but it can cause cardiotoxic effects and its clinical use has been limited. Therefore, finding new drugs or methods to prevent or reverse the cardiac damage caused by DOX therapy in cancer patients is essential. Previous studies have identified potential cardioprotective effects of Centella asiatica (C. asiatica), and madecassic acid (MA) is a pentacyclic triterpenoid derived from C. asiatica. However, the pharmacological effects of MA on the heart and tumors during tumor chemotherapy are not fully understood. The aim of this study was to investigate the pharmacological function and molecular mechanisms of MA in the heart and tumor during chemotherapy. In a DOX-induced acute heart failure mouse model and a cardiomyocyte injury model, MA reduced cardiomyocyte oxidative stress and the inflammatory response, improved mitochondrial function, and attenuated autophagic flux blockade and apoptosis. Interestingly, MA significantly increased the expression and activity of SIRT1. When SIRT1 was knocked down, the protective effect of MA on cardiomyocytes was significantly inhibited, suggesting that MA may exert cardioprotective effects through the SIRT1 pathway. Interestingly, in contrast to its cardioprotective effect, MA could synergize with DOX and significantly contribute to the anticancer chemotherapeutic effect of DOX by inhibiting proliferation, migration and invasion; promoting apoptosis; and suppressing tumor progression by inhibiting the expression of the DDX5 pathway in tumor cells. Here, we identified the pharmacological functions of the pentacyclic triterpenoid MA in ameliorating DOX-induced cardiotoxicity and enhancing the antitumor efficacy of DOX.

DEAD-box helicase 17 (DDX17) is a typical member of the DEAD-box family with transcriptional cofactor activity. Although DDX17 is abundantly expressed in the myocardium, its role in heart is not fully understood. We generated cardiomyocyte-specific Ddx17-knockout mice (Ddx17-cKO), cardiomyocyte-specific Ddx17 transgenic mice (Ddx17-Tg), and various models of cardiomyocyte injury and heart failure (HF). DDX17 is downregulated in the myocardium of mouse models of heart failure and cardiomyocyte injury. Cardiomyocyte-specific knockout of Ddx17 promotes autophagic flux blockage and cardiomyocyte apoptosis, leading to progressive cardiac dysfunction, maladaptive remodeling and progression to heart failure. Restoration of DDX17 expression in cardiomyocytes protects cardiac function under pathological conditions. Further studies showed that DDX17 can bind to the transcriptional repressor B-cell lymphoma 6 (BCL6) and inhibit the expression of dynamin-related protein 1 (DRP1). When DDX17 expression is reduced, transcriptional repression of BCL6 is attenuated, leading to increased DRP1 expression and mitochondrial fission, which in turn leads to impaired mitochondrial homeostasis and heart failure. We also investigated the correlation of DDX17 expression with cardiac function and DRP1 expression in myocardial biopsy samples from patients with heart failure. These findings suggest that DDX17 protects cardiac function by promoting mitochondrial homeostasis through the BCL6-DRP1 pathway in heart failure.

Background SGLT2 inhibitor (SGLT2i) may reduce the risk of contrast-induced acute kidney injury (CI-AKI) in patients with type 2 diabetes mellitus (T2DM) with chronic coronary syndrome (CCS) undergoing angiography. However, the evidence is still inconclusive. We aimed to conduct a real world study and systematically review to provide updated and larger-scale evidence. Study design: Ambispective Cohort Study and Meta-analysis. Setting & population: Patients with T2DM and CCS. Methods The data was obtained from December 2017 to July 2024. Propensity score techniques were applied to enhance between-group comparability. We analyzed CI-AKIESUR and CI-AKIKDIGO and conducted subgroup analyses based on the types of angiographic procedures, including percutaneous coronary interventions (PCI), coronary arteriography (CAG), and Coronary Computed Tomographic Angiography (CCTA). We retrieved similar cohort studies from the literature to perform a meta-analysis. Results from trials reporting CI-AKIESUR and/or CI-AKIKDIGO rates among patients randomized to SGLT2i versus placebo were also meta-analysed. Results A total of 2,350 patients receiving dapagliflozin and 16,251 patients did not receiving any SGLT2i were included before PSM. 2,071 SGLT2i users were matched with 2,071 control patients. The incidence of primary outcome 1 and 2 were both significant lower in SGLT2i group than in the control group, which were both confirmed before and after PSM analysis. Subgroup analysis showed that the incidence of CI-AKI in the SGLT2i group was significantly lower after either PCI, CAG or CCTA. The meta-analysis of cohort studies further confirmed this result, that is, the rate of CI-AKI occurrence after angiography in the SGLT2i group was significantly lower than in the control group regardless of which criterion for CI-AKI was used. Limitations Results may be limited by single-center nature, inevitable sample selection bias, etc. and subgroup analysis of angiography operation types was conducted. Conclusion In real-world T2DM patients, SGLT2i was associated with lower CI-AKI risk. Clinical trial registration: Chinese Clinical Trial Registry, identifier: ChiCTR2300076484

DEAD-box (DDX)5 and DDX17, which belong to the DEAD-box RNA helicase family, are nuclear and cytoplasmic shuttle proteins. These proteins are expressed in most tissues and cells and participate in the regulation of normal physiological functions; their abnormal expression is closely related to tumorigenesis and tumor progression. DDX5/DDX17 participate in almost all processes of RNA metabolism, such as the alternative splicing of mRNA, biogenesis of microRNAs (miRNAs) and ribosomes, degradation of mRNA, interaction with long noncoding RNAs (lncRNAs) and coregulation of transcriptional activity. Moreover, different posttranslational modifications, such as phosphorylation, acetylation, ubiquitination, and sumoylation, endow DDX5/DDX17 with different functions in tumorigenesis and tumor progression. Indeed, DDX5 and DDX17 also interact with multiple key tumor-promoting molecules and participate in tumorigenesis and tumor progression signaling pathways. When DDX5/DDX17 expression or their posttranslational modification is dysregulated, the normal cellular signaling network collapses, leading to many pathological states, including tumorigenesis and tumor development. This review mainly discusses the molecular structure features and biological functions of DDX5/DDX17 and their effects on tumorigenesis and tumor progression, as well as their potential clinical application for tumor treatment.

Cardiac shockwave therapy (CSWT) is a noninvasive treatment for patients with refractory angina or myo-cardial ischemia. This study aims to evaluate the potential beneficial effect and safety of CSWT in patients with severe coronary artery disease (CAD) who have undergone coronary artery bypass grafting (CABG). This was a single-arm prospective cohort study. A total of 30 patients with severe CAD who were not suit-able for coronary revascularization and who had undergone CABG were enrolled. All patients received CSWT for nine sessions. Evaluation was performed before and after CSWT, including the Canadian Cardiovascular So-ciety (CCS) classification, New York Heart Association (NYHA) classification, 6-minute walk test (6MWT), Se-attle Angina Questionnaire (SAQ) score, nitroglycerin dosage, echocardiography, myocardial perfusion imaging (MPI), and safety parameters. All patients were followed up at both 1 month and 9 months after CSWT. After treatment, CSWT significantly improved CCS classification (P < 0.05), NYHA classification (P < 0.05), nitroglycerin dosage (P < 0.001), and 6MWT (P < 0.05) at 1 month and 9 months after CSWT. SAQ score (P < 0.05) and left ventricular ejection fraction (LVEF; P = 0.037) by echocardiography significantly im-proved at 1 month after CSWT. Significant decreases in summed stress score (SSS), summed difference score (SDS), ischemic area stress, and ischemic area difference by MPI were observed at 1 month and 9 months after CSWT (P < 0.01). There were no changes in safety parameters before and after CSWT. CSWT may have a beneficial effect on improving myocardial perfusion, clinical symptoms, exertional ca-pacity, and quality of life and is a safe alternative treatment for patients with severe CAD who have undergone CABG.

Apigenin is a natural flavonoid which is widely found in vegetables and fruits. However, the mechanism of apigenin in oxidative stress-induced myocardial injury has not been fully elucidated. We established an isoproterenol (Iso)-induced myocardial injury mouse model and a hypoxia/reoxygenation (H/R)-induced H9c2 cell injury model, followed by pretreatment with apigenin to explore its protective effects. Apigenin can significantly alleviate isoproterenol-induced oxidative stress, cell apoptosis and myocardial remodeling in vivo. Apigenin pretreatment can also significantly improve cardiomyocyte morphology, decrease H/R induced oxidative stress, and attenuate cell apoptosis and inflammation in vitro. Further mechanism study revealed that apigenin treatment reversed isoprenaline and H/R-induced decrease of Sirtuin1 (SIRT1). Molecular docking results proved that apigenin can form hydrogen bond with 230 Glu, a key site of SIRT1 activation, indicating that apigenin is an agonist of SIRT1. Moreover, SIRT1 knockdown by siRNA significantly reversed the protective effect of apigenin in H/R-induced myocardial injury. In conclusion, apigenin protects cardiomyocyte function from oxidative stress-induced myocardial injury by modulating SIRT1 signaling pathway, which provides a new potential therapeutic natural compound for the clinical treatment of cardiovascular diseases.

目的 探索冠心病患者心脏体外震波治疗(cardiac shock wave therapy,CSWT)护理流程及安全性.方法 选取2016年12月至2022年8月在北京医院就诊的冠心病并行CSWT的患者.收集临床基本资料,总结护理流程的关键点.收集加拿大心绞痛(Canadian Cardiology Society,CCS)分级、西雅图量表(Seattle Angina Questionnaire,SAQ)、6分钟步行试验(6-minute walk test,6MWT)、治疗中的心电图参数和血清心肌标志物的结果.比较治疗前后生命体征、心电图参数、血清心肌标志物、SAQ和6MWT距离的变化.结果 共有105例患者最终纳入了此研究,男性79例,女性26例,平均年龄为(69.39±9.35)岁.人文关怀贯穿于治疗前后和治疗中.CSWT前后,心率、收缩压、舒张压、血氧饱和度数值变化差异有统计学意义(P<0.001),但均在正常范围内波动.肌酸激酶同工酶(creatine kinase MB type,CK-MB)在治疗前后没有变化(P=0.840),血清心肌标志物包括肌钙蛋白(troponin T,TNT)(P=0.007)和脑钠肽(brain na-triuretic peptide,BNP)(P=0.033),变化差异具有统计学意义,但其中位数均在正常范围内.治疗前后的QRS间期(P=0.236)无明显改变,心率(P<0.001)、PR间期(P<0.001)和QT间期(P<0.001)均具有显著变化,但均在正常范围.CCS分级在治疗后明显改善(2.62级vs.1.92级,P<0.001)、SAQ的5个条目均在治疗后显著改善(P<0.001)、6MWT距离在治疗后明显提高(P<0.001).结论 CSWT的护理过程中需要人文关怀.冠心病患者接受CSWT安全,CSWT可以改善患者心绞痛症状、提高活动能力及改善生活质量.

Background The clinical features of mitochondrial cardiomyopathy (MCM) are diverse. It can present as hypertrophic cardiomyopathy or dilated cardiomyopathy. The diagnosis of MCM is challenging and usually based on biopsy. Case presentation The 30-year-old man was admitted to hospital due to dyspnea for 1 month and edema of both lower extremities for 1 week. Echocardiography suggested a whole heart enlargement, a whole heart diminished function. Renal impairment and diabetes were observed. Coronary angiography showed single-vessel disease (90% stenosis in the ostium of a small marginal branch). Left ventricular endomyocardial biopsy was performed. Conclusion Myocardial histopathology demonstrated a large number of abnormal mitochondrial accumulation, so the diagnosis was considered as mitochondrial cardiomyopathy.

Objective. To investigate the protective effects and regulatory mechanism of miR-488-3p on doxorubicin-induced cardiotoxicity. Methods. The C57BL/6 mice and primary cardiomyocytes were used to construct doxorubicin-induced cardiomyocyte injury models in vivo and in vitro. The levels of miR-488-3p and its downstream target genes were analyzed by quantitative real-time PCR. Mouse cardiac function, cell survival, cellular injury-related proteins, and the apoptosis level of cardiomyocytes were analyzed by echocardiography, MTT analysis, Western blotting, and DNA laddering separately. Results. Cardiomyocyte injury caused by a variety of stimuli can lead to the reduction of miR-488-3p level, especially when stimulated with doxorubicin. Doxorubicin led to significant decrease in cardiac function, cell autophagic flux blockage, and apoptosis in vivo and in vitro. The expression of miR-488-3p's target gene, CyclinG1, increased remarkably in the doxorubicin-treated neonatal mouse cardiomyocytes. Overexpression of miR-488-3p inhibited CyclinG1 expression, increased cardiomyocyte viability, and attenuated doxorubicin-induced cardiomyocyte autophagic flux blockage and apoptosis. Conclusions. miR-488-3p is one of the important protective miRNAs in doxorubicin-induced cardiotoxicity by inhibiting the expression of CyclinG1, which provides insight into the possible clinical application of miR-488-3p/CyclinG1 as therapeutic targets in doxorubicin-induced cardiovascular diseases.

Abstract Background Clopidogrel is a widely-used antiplatelet and acts as an adenosine diphosphate receptor inhibitor. Neutropenia is a rare but serious adverse effect of clopidogrel. It is unknown whether this adverse effect has any association with impaired kidney function. Case presentation An 80-year-old male with chronic kidney disease was diagnosed with non-ST elevation myocardial infarction and underwent percutaneous coronary intervention. During hospitalization, the patient was diagnosed with contrast-induced nephropathy, treated symptomatically, and discharged with a back-to-baseline creatinine level. Two weeks later, the patient presented to the emergency department with fever and chills. Complete blood count showed leukopenia (0.84 × 103/mm3) and severe neutropenia (0.13 × 103/mm3). Blood cultures were positive for Pseudomonas aeruginosa. Clopidogrel was stopped immediately and switched into ticagrelor. Imipenem and granulocyte colony-stimulating factor were administered to the patient. The patient’s white blood cell and absolute neutrophil count were within the normal range after four days of treatment. The patient was discharged after a 10-day hospitalization, and his complete blood counts were normal during further follow-ups. Conclusions Clopidogrel was the most likely primary cause of neutropenia in our case. The incidence of clopidogrel-induced neutropenia is low and the exact mechanism is not fully explained. We provide suggestions on the management of clopidogrel-associated neutropenia, and summarize all five cases of clopidogrel-induced neutropenia in patients with impaired kidney function.

Background Previous studies proved the efficacy of cardiac shock wave therapy (CSWT) for coronary artery disease (CAD) patients who are not candidate for reperfusion therapy. Randomized control trials are limited. We try to explore the efficacy and safety of CSWT for patients with severe CAD. Methods Thirty patients with severe CAD who had obvious ischemia on myocardial perfusion imaging (MPI) were enrolled and randomly assigned to the CSWT group or the control group. They had received optimal medication treatment for at least three months. Nine sessions of shock wave therapy were conducted over 3 months. CSWT group received the real treatment, while the control group received the pseudo-treatment. Clinical symptom, imaging outcomes and safety parameters were compared between two groups. Results After treatment, regional stress score (P = .023), improvement rate (IR) of ischemic area (IA) stress (P < .001) and IR of IA difference (P < .001) were significantly favor CSWT group. The interaction of summed rest score (P < .001), summed stress score (P = .004), summed difference score (P = .036) were significantly improved in the CSWT group compared to the control group. Seattle angina questionnaire, quality of life (QOL) and the distance of six-minute walking test (6MWT) were improved in both groups without significant difference between them. Hemodynamic parameters were stable during procedure. Myocardial injury markers showed no changes in two groups. Conclusions Our study demonstrated CSWT could effectively and safely improve myocardial perfusion in patients with severe CAD. Clinical symptom, QOL and 6MWT were all improved after treatment, but no significant difference between two groups.

Heart failure is a global health problem that affects approximately 26 million people worldwide. As conventional diagnostic techniques for heart failure have been in practice with various limitations, it is necessary to develop novel diagnostic models to supplement existing methods. With advances and improvements in gene sequencing technology in recent years, more heart failure-related genes have been identified. Using existing gene expression data in the Gene Expression Omnibus (GEO) database, we screened differentially expressed genes (DEGs) of heart failure and identified six key genes (HMOX2, SERPINA3, LCN6, CSDC2, FREM1, and ZMAT1) by random forest classifier. Of these genes, CSDC2, FREM1, and ZMAT1 have never been associated with heart failure. We also successfully constructed a new diagnostic model of heart failure using an artificial neural network and verified its diagnostic efficacy in public datasets.

目的 评估高尿酸血症(hyperuricemia,HUA)与择期冠状动脉介入治疗(percutaneous coronary intervention,PCI)术后短期预后的关系.方法 回顾性分析北京医院2013年9月 ～2017年9月期间行择期PCI患者的资料.高尿酸血症诊断标准定义为血尿酸水平男性>420 umol/L(7 mg/d1),女性>357 umol/L(6 mg/d1),将患者分为高尿酸组和正常尿酸组.主要不良心脏事件(major adverse cardiac events,MACE)包括死亡,心肌梗死和靶血管再血管化治疗.收集患者住院期间资料信息,比较两组患者PCI术后院内主要不良心脏事件的差异.数据分析采用χ2检验,各变量之间的相关性采用logistic回归分析,统计结果 的显著性水平均选为0.05.结果 共纳入2654例患者,其中HUA组571人,非HUA组2083人.HUA组与非HUA组相比冠状动脉血管单支病变的比例更低,而双支病变及三支病变的比例更高(单支病变:24.3％vs.35.3％,双支病变:30.6％vs.28.0％,三支病变:45.0％vs.36.7％,P<0.001);经logistic回归分析,调整了传统冠心病危险因素后,HUA与PCI术后的主要不良心脏事件独立相关(OR=1.309,95％CI:1.066～1.607,P=0.010),其中HUA与PCI术后院内心肌梗死独立相关(OR=1.349,95％CI:1.097～1.659,P=0.005),HUA与PCI术后院内靶血管再血管化(OR=1.681,95％CI:0.562～5.022,P=0.353)及死亡(OR=0.361,95％CI:0.031～4.194,P=0.415)不独立相关.结论 HUA是择期PCI术后院内主要不良心脏事件及院内心肌梗死的独立危险因素.

Objective: To investigate the effect of the erythropoietin-activating EPO-EPOR signalling pathway on improving cardiac function in diabetic rats. Methods: The rats were randomly divided into the normal control group, the diabetes group and the diabetes + EPO intervention group, with 10 rats in each group. The diabetic rats model was established. The rats in the diabetes + EPO intervention group were given a subcutaneous injection of 1000IU/kg EPO and the normal control group and the diabetes group were given subcutaneous injections of normal saline of equal volume once a week for 12 consecutive weeks. Echocardiography was used to determine the heart to body weight ratio, left ventricular end-diastolic diameter (LVDd), ejection fraction (EF) and left ventricular end-systolic diameter (LVDs) in rats. The levels of blood lipids (glycerin trilaurate [TG]), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), blood glucose content and blood routine red blood cell (RBC) were measured by the Hitachi automatic biochemical analyser, the GOD-PAP method and the blood routine detector JHF7-3000, respectively. The expression of the glucose-regulated protein 78 (GRP78), the sarcoplasmic reticulum Ca2+-ATP enzyme (SERCA2a) and the EPOR mRNA in the left ventricular myocardium of the rats was detected by an RT-PCR assay. The expression levels of GRP78, SERCA2a and EPOR proteins were detected by a western blot assay and the immunohistochemistry method. Results: The EF and LVDD values of rats in the diabetes group were significantly lower than those of the normal control group (P<0.01), and the heart to body weight ratio was markedly higher than that of the normal control group (P<0.01). There was no statistically significant difference in LVDS between the diabetes group and the normal control group (P>0.05). The EF value of rats in the diabetes + EPO intervention group was significantly higher than that in the diabetes group, and the LVDS and LVDD values and heart to body weight ratio were remarkably lower than those in the diabetes group (P<0.01). The body weight and HDL-C levels of the rats in the diabetes group were significantly lower than those in the control group, while the levels of blood glucose, TG, TC and LDL-C were remarkably higher than those in the control group (P<0.01). There was no statistically significant difference in the RBC level between the diabetes group and the control group (P>0.05). Moreover, the weight of rats in the diabetes + EPO intervention group was significantly higher than that in the diabetes group, and there was no statistically significant difference in blood lipid, blood glucose and RBC levels compared with the diabetes group (P>0.05). The expression of GRP78 mRNA in the diabetes group was markedly higher than that in the control group (P<0.01), and the expression of the SERCA2a, EPOR mRNA in the diabetes group was significantly lower than that in the control group (P<0.01). Besides, the expression of the GRP78 mRNA in the diabetes + EPO group was significantly lower than that in the diabetes group (P<0.01), and the expression of the SERCA2a, EPOR mRNA in the diabetes group was obviously higher than that in the diabetes group (P<0.01). The expression of the GRP78 protein in the diabetes group was significantly higher than that in the control group (P<0.01), and the expression of the SERCA2a, EPOR protein in the diabetes group was remarkably lower than that in the control group (P<0.01). Moreover, the expression of the GRP78 protein in the diabetes + EPO group was significantly lower than that in the diabetes group (P<0.01), and the expression of the SERCA2a, EPO protein in the diabetes group was significantly higher than that in the diabetes group (P<0.01). Conclusion: EPO can effectively improve cardiac function in rats, which may be due to the activation of the EPO-EPOR signalling pathway by reducing the stress response of the myocardial endoplasmic reticulum, thus leading to the increased expression of the SERCA2a and EPOR protein and playing a protective role in the heart.