Journal of Cardiovascular Translational Research
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2025
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IF 2.5
Hou Xiaolu,Hu Guoling,Wang Heling,Yang Ying,Sun Qi,Bai Xiuping
Heart failure (HF) is a clinical syndrome caused by structural or functional abnormalities in heart. Egr2 has been reported to be protective for multiple diseases, but its effect on HF remains unknown. The present study intended to investigate the potential role of Egr2 in HF and its possible downstream effectors. High Egr2 expression in heart was observed in HF mice. Egr2 knockdown alleviated cardiac damage and function in HF mice. Egr2 knockdown inhibited myocardial inflammation and apoptosis both in vivo and in vitro. Egr2 inhibited Acot1 transcription expression via directly binding to its promoter. Acot1 overexpression reduced Lipopolysaccharide (LPS)-induced cardiomyocyte inflammation and apoptosis. Functional rescue experiments revealed that Acot1 reversed the effects of Egr2 on LPS-induced cell apoptosis and inflammation. Overall, Egr2 knockdown might ameliorate HF by inhibiting inflammation and apoptosis in cardiomyocytes by targeting Acot1. This study might provide evidence to better understand the molecular mechanisms of HF pathogenesis. Graphical Egr2 knockdown might ameliorate HF by inhibiting inflammation and apoptosis in cardiomyocytes, possibly through Acot1.
研究领域:
心血管生物学
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分子医学
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DOI
PubMed
高影响因子
International Heart Journal
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2025
·Vol. 66
·期 1
·114-125
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IF 1.3
Aike Fei,Li Li,Yanfei Liu,Zhe Lv,Jing Jin
Oxidative stress and cardiomyocyte apoptosis are hallmarks of heart failure (HF) development. Plant homeodomain finger protein 8 (PHF8) is a histone demethylase downregulated in failing human hearts. Nevertheless, the potential role of PHF8 in HF remains unclear. Therefore, this study aimed to explore the biological action and molecular mechanism of PHF8 in HF.
A rat model of left anterior descending coronary artery (LAD) ligation-induced HF and a cardiomyocyte
model of oxygen-glucose deprivation/reperfusion (OGD/R) were developed after gain- or loss-of-function experiments in rats and cardiomyocytes, respectively. Heart function indexes, such as left ventricular end-diastolic
diameter, left ventricular end-systolic diameter, left ventricular ejection fraction, and left ventricular fractional
shortening, were detected. Changes in myocardial tissues were examined by pathological staining. Cardiomyocyte apoptosis and oxidative stress markers, such as malondialdehyde, reactive oxygen species, superoxide dismutase, and catalase, were examined. The relationship between PHF8 and forkhead box A2 (FOXA2) was analyzed by luciferase and chromatin immunoprecipitation-quantitative polymerase chain reaction assays.
PHF8 was downregulated in LAD-ligated rats and OGD/R-exposed cardiomyocytes. Following PHF8
upregulation, pathological changes in myocardial tissues and heart dysfunction were improved in LAD-ligated
rats. Importantly, cardiomyocyte apoptosis and oxidative stress were diminished in vivo and in vitro upon PHF8
upregulation. Mechanistically, PHF8 increased FOXA2 expression in a histone demethylase-dependent manner.
FOXA2 silencing abrogated the protective effect of PHF8 upregulation on cardiomyocytes against OGD/Rinduced apoptosis and oxidative stress.
PHF8 exerts protective functions against cardiomyocyte apoptosis, oxidative stress, and heart dysfunction
in HF, in correlation with FOXA2 upregulation. These results suggest that the PHF8/FOXA2 axis may be a
promising therapeutic target to prevent HF.
CAS / MDL:
研究领域:
心血管生物学
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分子医学
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表观遗传学
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DOI
PubMed
高影响因子
Heliyon
·
2024
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IF 3.4
Ruisha Li,Keyin Zhang,Zhenjun Xu,Yanrong Yu,Dongjin Wang,Kai Li,Wenxue Liu,Jun Pan
Recent studies have underscored the cardioprotective properties of liraglutide. This research explores its impact on cardiac hypertrophy and heart failure following transverse aortic constriction (TAC). We found that liraglutide administration markedly ameliorated cardiac hypertrophy, fibrosis, and function. These benefits correlated with increased ANP expression and reduced activity in the calcineurin A/NFATc3 signaling pathway. Moreover, liraglutide mitigated ER stress and cardiomyocyte apoptosis, and enhanced autophagy. Notably, the positive effects of liraglutide diminished when co-administered with A71915, an ANP inhibitor, suggesting that ANP upregulation is critical to its cardioprotective mechanism.
研究领域:
心血管病学
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分子生物学
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DOI
PubMed
高影响因子
Journal of Cardiovascular Translational Research
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2022
·Vol. 16
·期 1
·127-140
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IF 3.216
Hao Jiameng,Chang Liping,Wang Dandong,Ji Chuanyuan,Zhang Shaolan,Hou Yunlong,Wu Yiling
Heart failure with preserved ejection fraction (HFpEF) is a common public health problem associated with increased morbidity and long-term mortality. However, effective treatment for HFpEF was not discovered yet. In the present study, we aimed to decipher the effects of Periplocin on DOCA-induced heart failure rats and explore the possible underlying mechanisms. We demonstrated that Periplocin could significantly attenuate cardiac structural remodeling and improve cardiac diastolic function. Of note, Periplocin significantly inhibited the recruitment of inflammatory and immune cells and decreased the expression of serum inflammatory cytokines. Meanwhile, Periplocin had the effect of cardiac glycosides to improve cardiomyocyte contractility and calcium transient amplitude. These findings indicate that Periplocin might be a potential medicine to treat HFpEF in patients. Graphical abstract
研究领域:
心脏病学
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药理学
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炎症
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分子生物学
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
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IF 5.988
Xue Tian,Xu Chen,Qianqian Jiang,Qianbin Sun,Tiantian Liu,Yiqin Hong,Yawen Zhang,Yanyan Jiang,Mingyan Shao,Ran Yang,Chun Li,Qiyan Wang,Yong Wang
Aims: Cardiac lipotoxicity is the common consequence of lipid metabolism disorders in cardiomyocytes during development of heart failure (HF). Adenosine 5′monophosphate-activated protein kinase (AMPK) acts as an energy sensor and has a beneficial effect in reducing lipotoxicity. Notoginsenoside R1 (NGR1) is extracted from the traditional Chinese medicine Panax notoginseng (Burkill) F.H.Chen (P. notoginseng) and has definite cardioprotective effects. However, whether NGR1 can attenuate HF by mitigating lipotoxicity has not been elucidated yet. This study aimed to explore whether NGR1 plays a protective role against HF by ameliorating cardiac lipotoxicity via the AMPK pathway.
Methods: In this study, HF mice model was established by left anterior descending (LAD) ligation. palmitic acid (PA) stimulated H9C2 cell model was applied to clarify the effects and potential mechanism of NGR1 on lipotoxicity. In vivo, NGR1 (7.14 mg/kg/days) and positive drug (simvastatin: 2.9 mg/kg/days) were orally administered for 14 days. Echocardiography was applied to assess heart functions. Lipid levels were measured by Enzyme-linked immunosorbent assay (ELISA) and key proteins in the AMPK pathway were detected by western blots. In vitro, NGR1 (40 μmol/L) or Compound C (an inhibitor of AMPK, 10 μmol/L) was co-cultured with PA stimulation for 24 h in H9C2 cells. CCK-8 assay was used to detect cell viability. Key lipotoxicity-related proteins were detected by western blots and the LipidTOX™ neutral lipid stains were used to assess lipid accumulation. In addition, Apoptosis was assessed by Hoechst/PI staining.
Results: NGR1 could significantly improve the cardiac function and myocardial injury in mice with HF and up-regulate the expression of p-AMPK. Impressively, NGR1 inhibited the synthesis of diacylglycerol (DAG) and ceramide and promoted fatty acid oxidation (FAO) in vivo. Moreover, NGR1 significantly promoted expression of CPT-1A, the key enzyme in FAO pathway, and down-regulated the expression of GPAT and SPT, which were the key enzymes catalyzing production of DAG and ceramide. In vitro experiments showed that NGR1 could significantly attenuate lipid accumulation in PA-induced H9C2 cells and the Hoechst/PI staining results showed that NGR1 ameliorated lipotoxicity-induced apoptosis in PA-stimulated H9C2 cell model. Furthermore, co-treatment with inhibitor of AMPK abrogated the protective effects of NGR1. The regulative effects of NGR1 on lipid metabolism were also reversed by AMPK inhibitor.
Conclusion: NGR1 could significantly improve the heart function of mice with HF and reduce cardiac lipotoxicity. The cardio-protective effects of NGR1 are mediated by the activation of AMPK pathway.Keywords: heart failure, cardiac lipotoxicity, NGR1, AMPK, apoptosis
研究领域:
心脏病学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
Journal of Analysis and Testing
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2023
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IF 4.7
Gong Xue,Wu Jiangling,Zhang Jiajia,Jiang Zhongwei,Wang Yi,Zhang Pu
Heart failure (HF) is a clinical hallmark of cardiovascular syndrome leading to substantial morbidity, repeated hospitalization, and enormous healthcare expenditure. As elderly populations continue to increase, biomarker-guided diagnosis and treatment for age-related cardiac decline have become essential. Accumulating evidence demonstrates that N-terminal proBNP (NT-proBNP) can provide a unique window into the diagnosis and risk stratification with HF. Herein, a simple yet robust aptasensor is developed for on-site recognizing the NT-proBNP by its targeting aptamer, thus achieving the accurate diagnosis of HF. This aptasensing system is prepared by absorbing the fluorophore-labeled aptamer strand onto the graphene oxide (GO), leading to efficient quenching without possible off-site signal leakage. The aptamer strand can specifically identify target NT-proBNP molecules via a versatile conformational transformation, resulting in the desorption of the aptamer-NT-proBNP complexes from GO and re-generation fluorescence signal, thus allowing sensitive detection of NT-proBNP in 37 clinical blood samples. Taking advantage of the high specificity of aptamer-guaranteed recognitions of NT-proBNP, this aptasensor system readily achieves better diagnostic performance for HF than commercially adopted chemiluminescence immunoassay (Siemens, CLIA) in hospitals in terms of accuracy (89.2% vs 83.8%), specificity (89.5% vs 84.2%), and positive predictive value (88.9% vs 83.3%). This work provides a stable option for the diagnosis and treatment of elderly HF-related diseases in clinics.
研究领域:
医学
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生物技术
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DOI
高影响因子
BIOSENSORS & BIOELECTRONICS
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2025
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IF 10.5
Tao Jing,Yaolei Zhang,Zhongtao Li,Xinyu Tao,Xiong Xiong,Chaoming Xie,Weili Deng,Feng Lin,Hongyu Sun,Shuxin Qu
Monitoring cardiac rhythm is crucial for diagnosis of heart failure. However, the deficient sensitivity of polyvinylidene fluoride (PVDF) sensors impede their application in monitoring of cardiac rhythm due to the limited piezoelectricity. Here, doping of CoFe 2 O 4 and aligning fibers were jointly adopted to enhance the piezoelectricity of PVDF, attributed to the transformation of α-PVDF to β-PVDF from 51.54 to 82.36 % confirmed by FTIR and First Principles simulation. Then the higher sensitivity piezoelectric sensors were developed based on aligned PVDF/CoFe 2 O 4 accompanying with the superior frequency characteristics, rapid response, endurance stability, permeability and self-cleaning capabilities, compared to that of random PVDF/CoFe 2 O 4 and PVDF sensors, which were 17.28, 13.40 and 2.16 mV kPa −1 , respectively. Thus, the sensitivity of PVDF/CoFe 2 O 4 sensors was sufficient to distinguish the variations of cardiac rhythm or arrhythmia of the established and verified heart failure rat model, including amplitude, cycle and frequency. The notable characteristic of an evolving heart failure was the significantly decreased amplitude initially, followed by a dramatic drop in the cycles of cardiac impulse. Hence, this non-invasive method is promise in providing valuable warning signs for predicting heart failure based on aligned PVDF/CoFe 2 O 4 sensors, as well as in the prevention its occurrence.
研究领域:
生物医学工程
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心血管疾病
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2021
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IF 5.811
Li Sinai,Liu Hongxu,Li Yue,Qin Xiaomei,Li Mengjie,Shang Juju,Xing Wenlong,Gong Yanbing,Liu Weihong,Zhou Mingxue
Background: Heart failure (HF) is the end stage of ischemic cardiovascular diseases; nonetheless, safe and effective therapeutic agents for HF are still lacking, and their discovery remains challenging. Our previous studies demonstrated that Shen-Yuan-Dan Capsule (SYDC), a hospital preparation of traditional Chinese herbal, effectively protected ischemic injury in cardiovascular diseases. However, its therapeutic effects and possible mechanisms on HF remain unclear.Methods: A zebrafish HF model treated with verapamil was developed to assess the therapeutic effect of SYDC on HF zebrafish. Zebrafish were administered with SYDC and digoxin (positive control) by direct soaking. After drug treatment, zebrafish were randomly assigned to the visual observation and image acquisition using a Zebralab Blood Flow System. The reactive oxygen species (ROS), MDA, and SOD levels were determined by fluorescence signal detection, TBA, and WST-8 methods. RT-PCR determined the mRNA expressions of Caspase-3, Caspase-1, Bcl-2, Bax, IL-1β, NF-κB, and TNF-α.Results: SYDC significantly inhibited the levels of heart dilatation and venous congestion and markedly increased the levels of cardiac output, blood flow dynamics, and heart rates in HF zebrafish (p < 0.05, p < 0.01, and p < 0.001). Moreover, SYDC also significantly decreased the levels of MDA and ROS and increased the level of SOD in HF zebrafish. The RT-PCR results revealed that SYDC decreased the expression of Caspase-1, Caspase-3, Bax, IL-1β, NF-κB, and TNF-α but increased the expression of Bcl-2 in HF zebrafish (p < 0.05, p < 0.01, and p < 0.001).Conclusions: SYDC improved the heart function in verapamil-induced HF zebrafish and alleviated inflammation and apoptosis by inhibiting the ROS-mediated NF-κB pathway.
研究领域:
心血管药理学
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中药研究
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分子生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2025
·Vol. 26
·期 1
·312
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IF 4.9
Rui Zhang,Siyuan Peng,Xuejuan Zhang,Zhengwei Huang,Xin Pan
Objective: The objective of this study was to explore the possibility of treating heart failure in rats by delivering mRNA of 24-dehydrocholesterol reductase (DHCR24) into the body through lipid nanoparticles (LNPs). Methods: We established a heart failure rat model using doxorubicin. The experiment was divided into blank, model, mRNA stock solution cardiac injection, mRNA stock solution intravenous injection, LNP-mRNA stock solution cardiac injection, and LNP-mRNA stock solution intravenous injection groups. We directly injected DHCR24-mRNA or LNP-DHCR24-mRNA into the myocardium in three regions through an insulin needle passing through the intercostal space under the guidance of B-ultrasound. We recorded the mortality rate, body weight, 6-min walk test return times, and organ weight of rats after administration and detected the cardiac structure and function using B-ultrasound and transmission electron microscopy (TEM). Additionally, we tested for HE staining; PRDX2, Sirt3, and TRX1 protein expression; and IL-1 β, IL-10, VEGF, NT proBNP, and BNP cytokine concentrations. Results: Compared with the model group, the administration of DHCR24-mRNA significantly reduced mortality; decreased weight loss, the ratio of heart to tibia length, and spleen weight; and improved rat motility. The administration of DHCR24-mRNA can postpone the pathological morphological alterations of myocardial cells and reduce inflammatory infiltration. In terms of biochemistry, the administration of DHCR24-mRNA can increase the expression of the PRDX2, Sirt3, and TRX1 proteins; increase the concentrations of IL-10 and VEGF; and reduce the concentrations of IL-1β, NT proBNP, and BNP. The administration of DHCR24-mRNA can also delay the process of heart failure. The delivery and therapeutic effect of DHCR24-mRNA encapsulated in LNPs were better when compared to the other groups. Conclusions: DHCR24-mRNA encapsulated in LNPs can be effectively administered to rats with heart failure and exhibits some curative effects.
研究领域:
心血管病学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Journal of Genetics and Genomics
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2025
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IF 7.1
Wuming Qin,Xiaobo Yang,Lu Zhang,Linghui Cao,Shi Ouyang,Dafeng Yang,Yangzhao Zhou,Anji Chen,Tao Liao,Xinyu Zhu,Yuting Liu,Wei Tang,Tongtong Ma,Yiyue Tang,Yonghe Ding,Yun Deng
LIM zinc finger domain containing 1 (LIMS1), an evolutionally conserved LIM domain adaptor protein, is implicated in diverse pathologies, including cancer and neurological disorders. However, its roles in cardiac diseases and the underlying mechanisms remain unclear. Here, we explore the functions and mechanisms of LIMS1 in cardiac remodeling and heart failure. We identify the elevated LIMS1 expression in patients with dilated cardiomyopathy (DCM) and murine cardiomyocytes, suggesting that LIMS1 dysregulation contributes to cardiac pathology. Using CRISPR/Cas9 technology, we generate a zebrafish model of lims1 loss-of-function mutant, which exhibits severe cardiac chamber remodeling, systolic dysfunction, and premature mortality, demonstrating the essential role of lims1 in maintaining cardiac integrity. Transcriptomic profiling reveals the activation of the gp130/Jak1/Stat3 signaling in the lims1 -deficient hearts. Strikingly, pharmacological inhibition of Stat3 or c-Fos partially rescues cardiomyopathy phenotypes. Our findings reveal the underlying mechanism of lims1 deficiency-caused heart failure through gp130/Jak1/Stat3 hyperactivation, offering insights into cardiac remodeling and potential therapeutic strategies.
研究领域:
心血管病学
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分子生物学
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遗传学
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DOI
PubMed
高影响因子
Frontiers in Cell and Developmental Biology
·
2021
·
IF 6.684
Ye Shiju,Su Lan,Shan Peiren,Ye Bozhi,Wu Shengjie,Liang Guang,Huang Weijian
Background and Purpose: The profibrotic and proinflammatory effects induced by doxorubicin (DOX) are key processes in the development of serious heart damage. Lack of effective drugs and the unclear mechanisms of its side effects limit the clinical treatment of DOX-induced cardiac injury. This study aimed to explore the protective role of LCZ696 and the potential mechanism of Toll-like receptor 2 (TLR2) in doxorubicin-induced cardiac failure.Experimental Approach: DOX (5 mg/kg/week, three times) was used to establish a chronic cardiomyopathy mouse model. Heart function tests, pathology examinations and molecular biology analyses were used to explore the effects of LCZ696 and TLR2 deficiency in vivo and in vitro. Computational docking was applied to predict the key residues for protein-ligand interaction.Key Results: The EF% declined, and the LVIDd, pro-fibrosis marker levels and NF-κB related inflammatory response increased in the chronic cardiomyopathy group induced by DOX. LCZ696 treatment and TLR2 deficiency reversed these heart damage in vivo. In H9C2 cells, pre-treatment with LCZ696 and TLR2 knockdown suppressed the DOX-induced high expression of profibrotic and proinflammatory markers. Moreover, DOX notably increased the TLR2-MyD88 interaction in vivo and in vitro, which was inhibited by LCZ696. Finally, we demonstrated the direct interaction between DOX and TLR2 via hydrogen bonds on Pro-681 and Glu-727 and Pro-681 and Ser-704 may be the key residues by which LCZ696 affects the interaction between DOX and TLR2.Conclusion and Implications: LCZ696 prevents DOX-induced cardiac dilation failure, fibrosis and inflammation by reducing the formation of TLR2-MyD88 complexes. LZC696 may be a potential effective drug to treat DOX-induced heart failure.
研究领域:
药理学
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心脏病学
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分子生物学
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DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2025
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IF 6.3
Risheng Zhao,Min Zhang,Gege Yang,Wei Liu,Hui Yu,Shuang Yan,Ting Ren,Linxin Zhang,Mengyang Wang,Haiming Sun
Hypertensive heart failure pathogenesis involves angiotensin II (Ang II)-mediated mechanisms through both hemodynamic overload and direct cellular signaling pathways. This study investigates the therapeutic potential of Portulaca oleracea L. (POL) extract and its active constituent Oleracein E (OE) in attenuating Ang II-induced pathological cardiac remodeling and subsequent heart failure progression. An experimental model of hypertensive heart failure was established in C57BL/6 mice through continuous subcutaneous infusion of Ang II for 4 weeks, with Oleracein E (OE) intervention administered during the final 2 weeks of the protocol. To elucidate the molecular mechanisms underlying OE's cardioprotective effects, we employed an integrated approach combining RNA sequencing analysis, molecular docking simulations, and target validation through drug affinity response target stability (DARTS) and cellular thermal shift assay (CETSA) techniques. The experimental results demonstrated that both POL extract and its active component OE exerted significant cardioprotective effects against Ang II-induced cardiac dysfunction in murine models, primarily through attenuation of pathological cardiac hypertrophy and suppression of inflammatory responses. Transcriptomic profiling via RNA sequencing identified the MAPK signaling pathway as a critical mediator of these protective effects. Subsequent transcription factor analysis revealed STAT2 as a key regulatory component in this pathway. Importantly, OE treatment effectively mitigated inflammatory responses in both in vivo cardiac tissues and in vitro cultured cardiomyocytes by specifically inhibiting the Ang II-activated MAPKs/STAT2 signaling cascade. Genetic ablation experiments further confirmed the essential role of this pathway, as the anti-inflammatory efficacy of OE was completely abolished in cardiomyocytes with MAPKs or STAT2 deficiency. Molecular interaction studies employing in silico docking simulations combined with experimental validation through DARTS and CETSA techniques provided direct evidence of physical binding between OE and the STAT2 protein. Our findings demonstrate that Oleracein E (OE) confers cardioprotection against Ang II-induced myocardial injury through a novel mechanism involving STAT2 targeting and subsequent suppression of MAPK signaling-mediated inflammatory cascades. These results not only elucidate a previously unrecognized pharmacological pathway but also suggest that OE and its derivatives hold significant therapeutic promise for the clinical management of hypertensive heart failure, potentially offering a targeted approach to modulate pathological cardiac remodeling.
研究领域:
药理学
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心血管病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
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