Frontiers in Pharmacology
·
2023
·
IF 5.6
Wang Shuai,Bai Jie,Che Yilin,Qu Weikun,Li Jing
Background: Humans with hypertensive heart disease are more likely to experience heart failure, arrhythmia, myocardial infarction, and sudden death, and it is crucial to treat this condition. Fucoidan (FO) is a natural substance derived from marine algae that has antioxidant and immunomodulatory activities. FO has also been shown to regulate apoptosis. However, whether FO can protect against cardiac hypertrophy is unknown.Methods: We investigated the effect of FO in hypertrophic models in vivo and in vitro. C57BL/6 mice were given an oral gavage of FO (300 mg/kg/day) or PBS (internal control) the day before surgery, followed by a 14-day infusion of Ang II or saline. AC-16 cells were treated with si-USP22 for 4 h and then treated with Ang II (100 nM) for 24 h. Systolic blood pressure (SBP) was recorded, echocardiography was used to assess cardiac function, and pathological changes in heart tissues were assessed by histological staining. Apoptosis levels were detected by TUNEL assays. The mRNA level of genes was assessed by qPCR. Protein expression was detected by immunoblotting.Results: Our data showed that USP22 expression was lowered in Ang II-infused animals and cells, which could promote cardiac dysfunction and remodeling. However, treatment with FO significantly upregulated the expression of USP22 and reduced the incidence of cardiac hypertrophy, fibrosis, inflammation, and oxidative responses. Additionally, FO treatment lowered p53 expression and apoptosis while increasing Sirt 1 and Bcl-2 expression.Conclusion: By reducing the level of Ang II-induced apoptosis through the regulation of USP22/Sirt 1 expression, FO treatment might improve cardiac function. According to this study, FO might be potential targeted approach for treating heart failure.
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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免疫学
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产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
·
2020
·
IF 6.793
Danting Wang,Yuhuan Zhang,Jieyi Li,Randy A. Dahlgren,Xuedong Wang,Haishan Huang,Huili Wang
Triclosan (TCS) and its two derivatives (2,4-dichlorophenol and 2,4,6-trichlorophenol) are priority pollutants that coexist in aquatic environments. Joint exposure of TCS, 2,4-dichlorophenol and 2,4,6-trichlorophenol, hereafter referred to as TCS-DT, contributes severe toxicity to aquatic organisms. There is currently a paucity of data regarding TCS-DT molecular toxicity, especially on cardiac diseases. We used zebrafish ( Danio rerio ) as a model organism, and evaluated the molecular-level cardiotoxicity induced by TCS-DT from embryonic to adult stages. TCS-DT exposure prominently led to phenotypic malformations, such as pericardial cysts, cardiac bleeding, increased SV-BA distance, decreased heart rate and reduced ejection fraction, as well as abnormal swimming behavior. Analyses of the GO and KEGG pathways revealed enrichment pathways related to cardiac development and screened for significantly down-regulated adrenaline signaling in cardiomyocytes. The cardiac marker genes ( amhc , cmlc2 , vmhc , and nkx2.5 ) were obtained through protein-protein interaction (PPI) networks, and expressed as down-regulation by WISH. After chronic exposure to TCS-DT from 30 to 90-dpf, both body mass and heart indexes prominently increased, showing myocardial hypertrophy, abnormal heart rate and histopathological injury. Heart tissue damage included disordered and ruptured myocardial fibers, broken and dissolved myofilaments, nuclear pyknosis, mitochondrial injury and inflammatory cell infiltration . Further, abnormal changes in a series of cardiac functions-related biomarkers, including superoxide dismutase, triglyceride, lactate dehydrogenase and creatinine kinase MB, provided evidence for cardiac pathological responses. These results highlight the molecular mechanisms involving TCS-DT induced cardiac toxicity, and provide theoretical data to guide prevention and treatment of pollutant-induced cardiac diseases.
研究领域:
环境毒理学
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水生生物学
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分子生物学
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心脏病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Cardiovascular Translational Research
·
2024
·
IF 2.4
Hu Guangquan,Chen Jin,Chen Min,Yang Kai,Wang Yuchen,Ma Ziyang,Bao Huangxin,Ding Xiaojie
Cardiac fibrosis following myocardial infarction (MI) seriously affects the prognosis and survival rate of patients. This study aimed to determine the effect and regulation mechanism of the dedicator of cytokinesis 2 (DOCK2) during this process. Experiments were carried out in mice in vivo, and in Ang II treated cardiac fibroblasts (CFs) in vitro. DOCK2 was increased in mouse myocardial tissues after MI and Ang II-treated CFs. In MI mice, DOCK2 silencing improved cardiac function, and ameliorated cardiac fibrosis. DOCK2 knockdown suppressed the activation of CFs and decreased the expression of α-SMA, collagen I, and collagen III. Suppression of DOCK2 mitigated Ang II induced migration of CFs. DOCK2 inhibition reduced the activity of the PI3K/Akt and Wnt/β-catenin pathways, while this change could be reversed by the pathway activators, SC79 and SKL2001. In summary, DOCK2 suppression improves cardiac dysfunction and attenuates cardiac fibrosis after MI via attenuating PI3K/Akt and Wnt/β-catenin pathways.
研究领域:
心脏病学
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分子生物学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2023
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IF 7.9
Shanshan Dai,Yunxuan Chen,Xiaoxi Fan,Jibo Han,Lingfeng Zhong,Yucong Zhang,Qingran Liu,Jiahui Lin,Weijian Huang,Lan Su,Zhouqing Huang,Bozhi Ye
Background Doxorubicin (Dox), which is an anticancer drug, has significant cardiac toxicity and side effects. Pyroptosis occurs during Dox-induced cardiotoxicity (DIC), and drug inhibition of this process is one therapeutic approach for treating DIC. Previous studies have indicated that emodin can reduce pyroptosis. However, the role of emodin in DIC and its molecular targets remain unknown. Hypothesis/Purpose We aimed to clarify the protective role of emodin in mitigating DIC, as well as the mechanisms underlying this effect. Methods The model of DIC was established via the intraperitoneal administration of Dox at a dosage of 5 mg/kg per week for a span of 4 weeks. Emodin at two different doses (10 and 20 mg/kg) or a vehicle was intragastrically administered to the mice once per day throughout the Dox treatment period. Cardiac function, myocardial injury markers, pathological morphology of the heart, level of pyroptosis and mitochondrial function were assessed. Protein microarray, biolayer interferometry and pull-down assays were used to confirm the target of emodin. Moreover, GSDMD-overexpressing plasmids were transfected into GSDMD −/− mice and HL-1 cells to further verify whether emodin suppressed GSDMD activation. Results Emodin therapy markedly enhanced cardiac function and reduced cardiomyocyte pyroptosis in mice induced by Dox. Mechanistically, emodin binds to GSDMD and inhibits the activation of GSDMD by targeting the Trp415 and Leu290 residues. Moreover, emodin was able to mitigate Dox-induced cardiac dysfunction and myocardial injury in GSDMD −/− mice overexpressing GSDMD, as shown by increased EF and FS, decreased serum levels of CK-MB, LDH and IL-1β and mitigated cell death and cell morphological disorder. Additionally, emodin treatment significantly reduced GSDMD-N expression and plasma membrane disruption in HL-1 cells overexpressing GSDMD induced by Dox. In addition, emodin reduced mitochondrial damage by alleviating Dox-induced GSDMD perforation in the mitochondrial membrane. Conclusion Emodin has the potential to attenuate DIC by directly binding to GSDMD to inhibit pyroptosis. Emodin may become a promising drug for prevention and treatment of DIC.
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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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Oxidative Medicine and Cellular Longevity
·
2014
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IF 3.363
Siying Li,Wenjuan Wang,Ting Niu,Hui Wang,Bin Li,Lei Shao,Yimu Lai,Huanjie Li,Joseph S. Janicki,Xing Li Wang,Dongqi Tang,Taixing Cui
The anticancer therapy of doxorubicin (Dox) has been limited by its acute and chronic cardiotoxicity. In addition to a causative role of oxidative stress, autophagy appears to play an important role in the regulation of Dox-induced cardiotoxicity. However, the underlying mechanisms remain unclear. Accordingly, we explored a role of nuclear factor erythroid-2 related factor 2 (Nrf2) in Dox-induced cardiomyopathy with a focus on myocardial oxidative stress and autophagic activity. In wild type (WT) mice, a single intraperitoneal injection of 25 mg/kg Dox rapidly induced cardiomyocyte necrosis and cardiac dysfunction, which were associated with oxidative stress, impaired autophagy, and accumulated polyubiquitinated protein aggregates. However, these Dox-induced adverse effects were exaggerated in Nrf2 knockout (Nrf2−/−) mice. In cultured cardiomyocytes, overexpression of Nrf2 increased the steady levels of LC3-II, ameliorated Dox-induced impairment of autophagic flux and accumulation of ubiquitinated protein aggregates, and suppressed Dox-induced cytotoxicity, whereas knockdown of Nrf2 exerted opposite effects. Moreover, the exaggerated adverse effects in Dox-intoxicated Nrf2 depleted cardiomyocytes were dramatically attenuated by forced activation of autophagy via overexpression of autophagy related gene 5 (Atg5). Thus, these results suggest that Nrf2 is likely an endogenous suppressor of Dox-induced cardiotoxicity by controlling both oxidative stress and autophagy in the heart.
研究领域:
药理学
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心脏病学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICAL RESEARCH
·
2023
·Vol. 28
·期 1
·1-12
·
IF 4.2
Jia Ji,Zhao Xing-an,Tao Si-ming,Wang Jun-wen,Zhang Rong-liang,Dai Hua-lei,Zhang Xin-jin,Han Ming-hua,Yang Bei,Li Yu,Li Jin-tao
Background Postinfarction cardiac remodeling presents a compensatory mechanism aimed at mitigating congestive heart failure. It is distinguished by progressive dilatation and hypertrophy of the ventricular chambers, fibrotic alterations, and prolonged apoptosis of cardiomyocytes. The primary objective of this study was to assess the effects of icariin on myocardial fibrosis and ventricular remodeling in rats subjected to myocardial infarction (MI).Methods Male Sprague‒Dawley (SD) rats were subjected to randomization and subsequently divided into distinct groups: the control group, the sham group (undergoing sham operation), the MI group (experiencing ligation of the left anterior descending artery), and the icariin group. Within the icariin group, rats were further categorized into three different dose groups based on the administered icariin dosage: the MI30 group (30 mg/kg/day), the MI60 group (60 mg/kg/day), and the MI120 group (120 mg/kg/day). Cardiac function evaluation was carried out using echocardiography. Histological examinations, including hematoxylin and eosin (HE) staining, Masson staining, and immunohistochemistry studies, were conducted 90 days after the occurrence of MI. Additionally, Western blotting was employed to assess TGF‐β1, p-Smad2, and p-Smad3 levels.Results The administration of icariin revealed a noteworthy enhancement in cardiac function among rats afflicted with left anterior descending coronary artery (LAD) ligation. In comparison to the icariin groups, the MI group exhibited reduced EF and FS, along with elevated LVEDD and LVESD. Furthermore, the cardiac fibrosis levels in the MI group rats exhibited a considerable increase compared to those in the icariin group. Notably, the levels of Collagen I, Collagen III, MMP2, and MMP9 were significantly higher in the MI group than in the icariin group, with evident distinctions. Moreover, the expression levels of TGF-β, IL-13, p-Smad2, and p-Smad3 were notably upregulated in the MI group compared to the icariin group.Conclusion sIn an experimental rat model of MI, the administration of icariin resulted in the amelioration of both cardiac function and remodeling processes, operating through the intricate TGF-β1/Smad signaling pathway.
研究领域:
药理学
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心脏病学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2023
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IF 10
Yanxin Zhang,Xin Li,Zhaowenbin Zhang,Huili Li,Dongmin Chen,Yiren Jiao,Chen Fan,Zhen Zeng,Jiang Chang,Yuhong Xu,Baowei Peng,Chen Yang,Yumei Que
In the pursuit of therapeutic strategies for myocardial infarction (MI), a pivotal objective lies in the concurrent restoration of blood perfusion and reduction of cardiomyocyte apoptosis. However, achieving these dual goals simultaneously presents a considerable challenge. In this study, a Zn 2 SiO 4 bioceramic capable of concurrently sustaining the release of bioactive SiO 3 2− and Zn 2+ ions, which exhibit a synergistic impact on endothelial cell angiogenesis promotion, cardiomyocyte apoptosis inhibition, and myocardial mitochondrial protection against oxygen-free radical (reactive oxygen species) induced injury is developed. Furthermore, in vivo outcomes from a murine MI model demonstrate that either systemic administration via tail vein injection of Zn 2 SiO 4 extract or local application through intramyocardial injection of a Zn 2 SiO 4 composite hydrogel promotes cardiac function and reduces cardiac fibrosis, thus aiding myocardial repair. This research is the first to elucidate the advantageous effects of dual bioactive ions in myocardial protection and may offer a novel therapeutic avenue for ischemic heart disease based on meticulously engineered bioceramics.
研究领域:
心脏病学
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生物医学工程
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材料科学
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治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
·
IF 5.6
Jiwen Fan,Meng Ren,Weiwei Chen,Haodong Wang,Yuquan He
Background Myocardial infarction (MI) triggers a strong inflammatory response mediating by NLRP3 inflammasome which is associated with cardiac fibrosis. The key players in this response are Interleukin (IL)-1 and IL-18, which are regulated by NLRP3 inflammasomes. Celastrol, a traditional Chinese medicine with strong anti-inflammatory activity, has recently reported as a cardioprotective agent. However, the mechanisms by which celastrol is cardioprotective in MI remain elusive. We hypothesized that Celastrol could reduce IL-1β and IL-18 expression and ameliorate myocardial fibrosis after myocardial infarction in rats, improve poor heart remodeling, and preserve heart function. Methods Myocardial infarction (MI) was caused by ligating the left anterior descending of male SD rats. Celastrol (1 mg/kg) or saline was administered every other day for 4 weeks. Heart function and fibrosis were assessed. Inflammatory and fibrotic markers in the myocardia were evaluated with immunohistochemistry, western blot, and ELISA. Molecular docking was employed to predict Celastrol's binding to NLRP3 protein. The effects of Celastrol on the expression of NLRP3 inflammasome and myocardial fibrosis genes were then examined in vitro . Results Celastrol maintained the left ventricular fractional shortening (FS) and ejection fraction (EF). Fibrosis was significantly reduced in animals treated with 1 mg/kg Celastrol (15.17 ± 1.82%) relative to controls (29.88 ± 4.28%). Celastrol also significantly reduced the NLRP3, IL-18, and IL-1β levels, together with macrophage and neutrophil infiltration in the myocardium. Molecular docking predicted that NLRP3 would bind tightly to Celastrol [Docking energy: −8.9 (kcal/mol)]. In vitro experiments showed reduced NLRP3 inflammasome and myocardial fibrosis-associated proteins expression in neonatal rat cardiac fibroblasts treated with Celastrol. Conclusions In post-MI rats, Celastrol, a naturally occurring active ingredient, was able to reduce myocardial fibrosis and improve cardiac function, according to our study. These effects may result from inhibiting the NLRP3 inflammasome and attenuating the early inflammatory storm after MI, suggesting that Celastrol may be useful in treating acute MI.
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
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Materials Technologies
·
2021
·Vol. 7
·期 1
·2100934
·
IF 7.848
Yunpeng Wang,Wei Liao,Jiahao Sun,Rajib Nandi,Zhongqiang Yang
Human muscles, including skeletal, smooth, and cardiac muscles, are able to perform diverse deformations and execute complex biofunctions stimulated by nerve signals. Similarly, liquid crystal elastomer (LCE), which can respond to external stimuli with large and reversible deformations, demonstrates superior advantages to mimic nature muscles to fabricate artificial muscles. Till now, LCE has been utilized to simulate deformations and related functions of skeletal and smooth muscles. However, limited by the existing fabrication strategy, employing LCE to mimic the motion of cardiac muscles and further realizing the structure-determined pumping functions, is still an open challenge. Learning from the specific spatial arrangements and synergistic actuation of cardiac muscle fibers within human heart, a simple and general strategy to construct artificial cardiac muscles with LCE fibers is proposed. In this work, LCE fibers with similar modulus and actuation behavior to muscle fibers are fabricated and spatially arranged in biological architectures as cardiac muscle fibers. As a result, artificial cardiac muscles are constructed and are able to perform simultaneous contraction and torsion motions, realizing heart-pumping functions. This general strategy should be also applicable for other smart materials to conduct challenging tasks.
研究领域:
生物材料学
·
仿生学
·
组织工程
✓ 已验证
DOI
高影响因子
ACS Nano
·
2024
·
IF 15.8
Tianyi Zhang,Sheng Yang,Yiling Ge,Lihong Yin,Yuepu Pu,Zhongze Gu,Zaozao Chen,Geyu Liang
Exposure to micro- and nanoplastics (MNPs) has been implicated in potential cardiotoxicity. However, in vitro models based on cardiomyocyte cell lines lack crucial cardiac characteristics, while interspecies differences in animal models compromise the reliability of the conclusions. In addition, current research has predominantly focused on single-time point exposures to MNPs, neglecting comparative analyses of cardiac injury across early and late stages. Moreover, there remains a large gap in understanding the susceptibility to MNPs under pathological conditions. To address these limitations, this study integrated cardiac organoids (COs) and organ-on-a-chip (OoC) technology to develop the cardiac organoid-on-a-chip (COoC), which was validated for cardiotoxicity evaluation through multiple dimensions. Based on COoC, we conducted a dynamic observation of the cardiac damage caused by short- and long-term exposure to polystyrene nanoplastics (PS-NPs). Oxidative stress, inflammation, disruption of calcium ion homeostasis, and mitochondrial dysfunction were confirmed as the potential mechanisms of PS-NP-induced cardiotoxicity and the crucial events in the early stages, while cardiac fibrosis emerged as a prominent feature in late stages. Notably, low-dose exposure exacerbated myocardial infarction symptoms under pathological states, despite no significant cardiotoxicity shown in healthy models. In conclusion, these findings further deepened our understanding of PS-NP-induced cardiotoxic effects and introduced a promising in vitro platform for assessing cardiotoxicity.
研究领域:
毒理学
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心脏病学
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生物医学工程
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纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Open Life Sciences
·
2024
·Vol. 19
·期 1
·
IF 1.7
Xiaokeya Yasen,Renaguli Aikebaier,Atiguli Maimaiti,Munire Mushajiang
Radiotherapy for treating breast cancer is associated with cardiac damage. This study aimed to investigate the role of the interleukin (IL)-33/soluble receptor ST2 (sST2) axis in radiation-induced cardiac injury. Expressions of IL-33 and sST2 were detected in breast cancer patients following radiotherapy, radiation-induced cardiac damaged mice model, and cardiomyocytes using quantitative real-time PCR (qRT-PCR) and immunohistochemical assay. Cardiac injury was evaluated through an ultrasound imaging system and hematoxylin & eosin staining. The transcriptional factor was assessed using dual-luciferase reporter assay and chromatin immunoprecipitation. The results indicated that IL-33 and sST2 were highly expressed in breast cancer patients, which further elevated post-6 months but reduced after 12 months of radiotherapy. Radiation induces cardiac dysfunction and elevated IL-33 and sST2 levels in a time-dependent manner. However, silencing of IL-33 decreased sST2 expression to alleviate radiation-induced cardiac dysfunction. The IL-33 could be transcriptional activated by TCF7L2 by binding to IL33 promoter sites, which mutation alleviated cardiomyocyte injury caused by radiation. Additionally, radiation treatment resulted in higher levels of TCF7L2, IL-33, and sST2 in cardiomyocytes, and TCF7L2 knockdown reduced IL-33 and sST2 expression. In conclusion, TCF7L2 transcriptional-activated IL-33 mediated sST2 to regulate radiation-induced cardiac damage, providing novel insights into radiotherapy-induced cardiac damage.
Graphical abstract
研究领域:
肿瘤学
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心脏病学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BMC Cardiovascular Disorders
·
2024
·Vol. 24
·期 1
·1-12
·
IF 2
Qian Kai,Song Li,Guo Jia-Min,Fu Dan,Shi Jia,Ma Yu,Ge Zi-Jie,Li Lei,Zhang Su-qin
Background Cardiovascular disease carries the highest mortality rate among diseases, and pharmacological interventions have limited efficacy. Baicalin (Bai) promotes biological metabolic processes, eliminates oxygen free radicals, and is anti-inflammatory. This study aimed to investigate the effect of Bai on the cardiac injury model induced by isoproterenol in mice.Methods and ResultIn this study, all groups except the control received intraperitoneal injections of isoproterenol (ISO) to induce a cardiac injury model, with the drug administered continuously for 14 days. hematoxylin and eosin staining and Masson’s trichrome staining revealed that Bai significantly mitigated ISO-induced pathological changes in mouse heart tissue and alleviated myocardial hypertrophy. Echocardiography assessments demonstrated that Bai preserved cardiac function in ISO-treated mice. Furthermore, our findings indicated that Bai activated the Nrf2 signaling pathway in vivo and in vitro. To delve deeper, mice were further treated with ML385 (ML) via intraperitoneal injection to inhibit the Nrf2 pathway. Results showed that ML385 blocked the cardioprotective effects of Bai in mouse heart tissue.Conclusion Bai protects against ISO-induced cardiac injury, and its mechanism is related to activating the Nrf2/HO-1 signaling pathway to regulate cardiac ferroptosis and improve cardiac remodeling.
研究领域:
心血管疾病
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药理学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）