11 results on '"Rifeng Gao"'
Search Results
2. Alda-1 treatment promotes the therapeutic effect of mitochondrial transplantation for myocardial ischemia-reperfusion injury☆
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Aijun Sun, Hang Chen, Hao Jiang, Heng Yang, Yongchao Zhao, Yunzeng Zou, Xiaolei Sun, Jin Liu, Wenjia Li, Jingjing Hu, Rifeng Gao, Zhen Dong, and Junbo Ge
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media_common.quotation_subject ,ALDH2 activation ,0206 medical engineering ,Biomedical Engineering ,Aldehyde dehydrogenase ,Infarction ,02 engineering and technology ,Mitochondrion ,Pharmacology ,Article ,Biomaterials ,medicine ,lcsh:TA401-492 ,Internalization ,lcsh:QH301-705.5 ,Mitochondrial transfer ,ALDH2 ,media_common ,biology ,business.industry ,Activator (genetics) ,Ischemia-reperfusion ,021001 nanoscience & nanotechnology ,medicine.disease ,020601 biomedical engineering ,Transplantation ,lcsh:Biology (General) ,Myocardial injury ,biology.protein ,lcsh:Materials of engineering and construction. Mechanics of materials ,0210 nano-technology ,business ,Reperfusion injury ,Biotechnology - Abstract
Mitochondrial damage is a critical driver in myocardial ischemia-reperfusion (I/R) injury and can be alleviated via the mitochondrial transplantation. The efficiency of mitochondrial transplantation is determined by mitochondrial vitality. Because aldehyde dehydrogenase 2 (ALDH2) has a key role in regulating mitochondrial homeostasis, we aimed to investigate its potential therapeutic effects on mitochondrial transplantation via the use of ALDH2 activator, Alda-1. Our present study demonstrated that time-dependent internalization of exogenous mitochondria by cardiomyocytes along with ATP production were significantly increased in response to mitochondrial transplantation. Furthermore, Alda-1 treatment remarkably promoted the oxygen consumption rate and baseline mechanical function of cardiomyocytes caused by mitochondrial transplantation. Mitochondrial transplantation inhibited cardiomyocyte apoptosis induced by the hypoxia-reoxygenation exposure, independent of Alda-1 treatment. However, promotion of the mechanical function of cardiomyocytes exposed to hypoxia-reoxygenation treatment was only observed after mitochondrial Alda-1 treatment and transplantation. By using a myocardial I/R mouse model, our results revealed that transplantation of Alda-1-treated mitochondria into mouse myocardial tissues limited the infarction size after I/R injury, which was at least in part due to increased mitochondrial potential-mediated fusion. In conclusion, ALDH2 activation in mitochondrial transplantation shows great potential for the treatment of myocardial I/R injury., Graphical abstract Image 1, Highlights • Internalization of exogenous mitochondria in cardiomyocytes occurrs in a time-dependent manner. • Mitochondrial Alda1 treatment and transplantation enhances the respiration-mediated mechanical function of cardiomyocytes. • Transplantation of Alda1 treated mitochondria ameliorates I/R injury in mice. • The cardioprotective role of ALDH2-activated mitochondrial transplantation is promoted by mitochondrial fusion.
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- 2021
3. Surgical Treatment of Coronary Pseudoaneurysm: A Case Report and Literature Review
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Jin Li, Rifeng Gao, Yanhua Tang, Fei Lu, Juesheng Yan, Haiyan Xiang, and Juxiang Li
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Male ,medicine.medical_specialty ,Coronary pseudoaneurysm ,Coronary Angiography ,Asymptomatic ,Lesion ,Pseudoaneurysm ,Imaging, Three-Dimensional ,Aneurysm ,medicine ,Humans ,cardiovascular diseases ,Cardiac Surgical Procedures ,Aged ,medicine.diagnostic_test ,business.industry ,Coronary Aneurysm ,General Medicine ,medicine.disease ,Coronary Vessels ,medicine.anatomical_structure ,Angiography ,cardiovascular system ,Surgery ,Radiology ,medicine.symptom ,Tomography, X-Ray Computed ,Cardiology and Cardiovascular Medicine ,Complication ,business ,Aneurysm, False ,Artery - Abstract
A coronary pseudoaneurysm is a rare complication of chest trauma. In this report, we describe the case of a 65-year-old man with a mediastinal lesion. On admission, he complained of chest tightness and dry cough, and a pseudoaneurysm was confirmed in the left anterior descending branch of the coronary artery on chest computerized tomography, angiography, and coronary angiography. The patient had experienced chest trauma 5 years previously. With the help of extracorporeal bypass surgery, the pseudoaneurysm was resected under direct observation. The patient recovered well after surgery. Traumatic coronary artery pseudoaneurysms usually are asymptomatic and often misdiagnosed. Preoperative coronary angiography is a crucial diagnostic used for deciding appropriate surgical management.
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- 2020
4. The proteasome activator REGγ accelerates cardiac hypertrophy by declining PP2Acα–SOD2 pathway
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Robb E. Moses, Xiaotao Li, Rifeng Gao, Wenlong Yang, Junbo Ge, Aijun Sun, Yifan Xie, Zheng Dong, and Yang Gao
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0301 basic medicine ,Proteasome Endopeptidase Complex ,Primary Cell Culture ,SOD2 ,Cardiomegaly ,030204 cardiovascular system & hematology ,medicine.disease_cause ,Autoantigens ,Article ,Muscle hypertrophy ,Rats, Sprague-Dawley ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Ubiquitin ,medicine ,Animals ,Humans ,Myocytes, Cardiac ,Molecular Biology ,chemistry.chemical_classification ,Mice, Knockout ,Reactive oxygen species ,biology ,Proteasome ,Activator (genetics) ,Chemistry ,Cell Biology ,Angiotensin II ,Cell biology ,Rats ,Mice, Inbred C57BL ,Oxidative Stress ,030104 developmental biology ,HEK293 Cells ,Animals, Newborn ,biology.protein ,cardiovascular system ,Cardiomyopathies ,Reactive Oxygen Species ,Oxidative stress - Abstract
Pathological cardiac hypertrophy eventually leads to heart failure without adequate treatment. REGγ is emerging as 11S proteasome activator of 20S proteasome to promote the degradation of cellular proteins in a ubiquitin- and ATP-independent manner. Here, we found that REGγ was significantly upregulated in the transverse aortic constriction (TAC)-induced hypertrophic hearts and angiotensin II (Ang II)-treated cardiomyocytes. REGγ deficiency ameliorated pressure overload-induced cardiac hypertrophy were associated with inhibition of cardiac reactive oxygen species (ROS) accumulation and suppression of protein phosphatase 2A catalytic subunit α (PP2Acα) decay. Mechanistically, REGγ interacted with and targeted PP2Acα for degradation directly, thereby leading to increase of phosphorylation levels and nuclear export of Forkhead box protein O (FoxO) 3a and subsequent of SOD2 decline, ROS accumulation, and cardiac hypertrophy. Introducing exogenous PP2Acα or SOD2 to human cardiomyocytes significantly rescued the REGγ-mediated ROS accumulation of Ang II stimulation in vitro. Furthermore, treatment with superoxide dismutase mimetic, MnTBAP prevented cardiac ROS production and hypertrophy features that REGγ caused in vivo, thereby establishing a REGγ–PP2Acα–FoxO3a–SOD2 pathway in cardiac oxidative stress and hypertrophy, indicates modulating the REGγ-proteasome activity may be a potential therapeutic approach in cardiac hypertrophy-associated disorders.
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- 2020
5. Acetaldehyde dehydrogenase 2 deficiency exacerbates cardiac fibrosis by promoting mobilization and homing of bone marrow fibroblast progenitor cells
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Zhiwei Qiu, Xiao Li, Daile Jia, Yufan Li, Rongle Liu, Rifeng Gao, Zeng Wang, Ji'e Yang, Huairui Shi, Kai Hu, Aijun Sun, Junbo Ge, Xiaolei Sun, Peng Wang, Zhen Dong, Xinyu Weng, and Shuqi Zhang
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Male ,0301 basic medicine ,Receptors, CXCR4 ,medicine.medical_specialty ,Cardiac fibrosis ,Bone Marrow Cells ,Constriction, Pathologic ,030204 cardiovascular system & hematology ,Models, Biological ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Animals ,Progenitor cell ,Molecular Biology ,Cell Proliferation ,ALDH2 ,Mice, Knockout ,Pressure overload ,business.industry ,Aldehyde Dehydrogenase, Mitochondrial ,Myocardium ,Stem Cells ,Cell Polarity ,Fibroblasts ,medicine.disease ,Fibrosis ,Chemokine CXCL12 ,Mice, Inbred C57BL ,Transplantation ,Oxidative Stress ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,Animals, Newborn ,Heart failure ,Bone marrow ,Cardiology and Cardiovascular Medicine ,business ,Signal Transduction ,Homing (hematopoietic) - Abstract
Cardiac fibrosis is a common feature of various cardiovascular diseases. Previous studies showed that acetaldehyde dehydrogenase 2 (ALDH2) deficiency exacerbated pressure overload-induced heart failure. However, the role and mechanisms of cardiac fibrosis in this process remain largely unknown. This study aimed to investigate the effect of ALDH2 deficiency on cardiac fibrosis in transverse aortic constriction (TAC) induced pressure overload model in mice. Echocardiography and histological analysis revealed cardiac dysfunction and enhanced cardiac fibrosis in TAC-operated animals; ALDH2 deficiency further aggravated these changes. ALDH2 chimeric mice were generated by bone marrow (BM) transplantation of WT mice into the lethally irradiated ALDH2KO mice. The proportion of circulating fibroblast progenitor cells (FPCs) and ROS level in BM after TAC were significantly higher in ALDH2KO mice than in ALDH2 chimeric mice. Furthermore, FPCs were isolated and cultured for in vitro mechanistic studies. The results showed that the stem cell-derived factor 1 (SDF-1)/C-X-C chemokine receptor 4 (CXCR4) axis played a major role in the recruitment of FPCs. In conclusion, our research reveals that increased bone marrow FPCs mobilization and myocardial homing contribute to the enhanced cardiac fibrosis and dysfunction induced by TAC in ALDH2 KO mice via exacerbating accumulation of ROS in BM and myocardial SDF-1 expression.
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- 2019
6. GSDMD-Mediated Cardiomyocyte Pyroptosis Promotes Myocardial I/R Injury
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Rifeng Gao, Aijun Sun, Huairui Shi, Junbo Ge, Zeng Wang, Xiaolei Sun, Shuqi Zhang, Yang Gao, Zhen Dong, Feng Zhang, Ji'e Yang, Xiao Li, Kai Hu, and Leilei Ma
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0301 basic medicine ,Male ,Programmed cell death ,Necrosis ,Physiology ,Inflammation ,Myocardial Reperfusion Injury ,030204 cardiovascular system & hematology ,medicine.disease_cause ,03 medical and health sciences ,Mice ,0302 clinical medicine ,medicine ,Pyroptosis ,Animals ,Humans ,Myocytes, Cardiac ,Caspase ,Cells, Cultured ,Aged ,biology ,Myosin Heavy Chains ,business.industry ,I r injury ,Interleukin-18 ,Intracellular Signaling Peptides and Proteins ,Middle Aged ,Phosphate-Binding Proteins ,Pathophysiology ,Caspases, Initiator ,Cell Hypoxia ,Mice, Inbred C57BL ,030104 developmental biology ,biology.protein ,Cancer research ,ST Elevation Myocardial Infarction ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Oxidative stress - Abstract
Rationale: Pyroptosis is a morphologically and mechanistically distinct form of cell death and is characterized by GSDMD (gasdermin D) or GSDME (gasdermin E)-mediated necrosis with excessive inflammatory factor release. Cardiomyocyte necrosis and inflammation play key roles in the pathophysiology of myocardial ischemia/reperfusion (I/R) injury. However, whether cardiomyocytes undergo pyroptosis and the underlying mechanism in myocardial I/R injury remain unclear. Objective: We aimed to investigate the role of pyroptosis in myocardial I/R injury. Methods and Results: In vivo and in vitro experiments were used to investigate pyroptosis of cardiomyocyte and the associated mechanisms during I/R injury. Wild-type, Myh6-Cre, and cardiomyocyte-specific GSDMD-deficient male mice were subjected to I/R. Human peripheral blood samples were collected from patients with acute ST-segment–elevation myocardial infarction or control patients at 0, 1, and 24 hours after percutaneous coronary intervention in our department. The serum levels of GSDMD were measured by ELISA. Hypoxia/reoxygenation induced cardiomyocyte pyroptosis and the release of mature IL (interleukin)-18 but not IL-1β, which mechanistically resulted from GSDMD cleavage by caspase-11 in cardiomyocytes. Furthermore, GSDMD gene deletion blocked hypoxia/reoxygenation-induced cardiomyocyte pyroptosis and IL-18 release. GSDMD and its pyroptosis-inducing N-terminal fragment were upregulated in myocardial tissues after I/R injury. Immunofluorescence analysis showed that GSDMD was mainly localized in cardiomyocytes. GSDMD deficiency in cardiomyocytes significantly reduced the I/R-induced myocardial infarct size. Moreover, increased GSDMD serum levels were detected in patients exhibiting I/R injury 1 hour after percutaneous coronary intervention for ST-segment–elevation myocardial infarction. Conclusions: Our results show that GSDMD-mediated cardiomyocyte pyroptosis is a key event during myocardial I/R injury and that the caspase-11/GSDMD pathway may be essential to this process. Additionally, GSDMD inhibition significantly reduces cardiomyocyte pyroptosis and I/R-induced myocardial injury.
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- 2021
7. A Hybrid Procedure Combining Mini-Thoracotomy with Interventional Endocardial Lead Implantation for Cardiac Resynchronization Therapy in Patients with Chronic Congestive Heart Failure: A Report of Four Cases
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Juxiang Li, Fei Lu, Haiyan Xiang, Juesheng Yang, Yanhua Tang, Rifeng Gao, and Jin Li
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Cardiac function curve ,medicine.medical_specialty ,Chronic congestive heart failure ,medicine.medical_treatment ,Heart Ventricles ,Cardiac resynchronization therapy ,Hemodynamics ,Cardiac Resynchronization Therapy ,Internal medicine ,medicine ,Humans ,Minimally Invasive Surgical Procedures ,In patient ,Aged ,Heart Failure ,business.industry ,General Medicine ,Endocardial lead ,Middle Aged ,Mini thoracotomy ,Prognosis ,Electrodes, Implanted ,medicine.anatomical_structure ,Treatment Outcome ,Thoracotomy ,Cardiology ,Surgery ,Female ,Intercostal space ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background: We describe the application and effectiveness of transthoracic electrode implantation for epicardial left ventricular pacing in cardiac resynchronization therapy (CRT) for patients with chronic congestive heart failure. Methods: We assessed four patients with chronic congestive heart failure for whom implantation of endocardial electrodes was contraindicated. The epicardial electrodes were implanted via a mini-thoracotomy in the fourth or fifth left intercostal space. We analyzed the surgical implantation technique and the short-term effectiveness of the procedure. Results: The epicardial electrodes successfully were implanted in all four patients. The patients’ hemodynamic status, cardiac function, and symptoms significantly improved. Patients I, II, III, and IV were discharged from the hospital on the 8, 11, 4, and 7 days, respectively, after the operation. Follow up lasted for 12 months. None of the patients presented with electrode fractures or surgical wound infections, and the pacing threshold and electrode impedance were normal. In one case, phrenic nerve stimulation occurred due to the low placement position of the electrode. When the electrode was moved slightly inward and upward, the sacral nerve stimulation sign disappeared, and no other complications were noted. One patient developed capsule infection, and the presence of an ectopic pacemaker was noted; therefore, a pacemaker replacement procedure was required. Conclusion: In CRT, the implantation of a left ventricular epicardial electrode through a left-sided small incision is safe, feasible, and effective. This hybrid surgery combining interventional and cardiac techniques can maximize the curative effect of CRT.
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- 2019
8. A Hybride Procedure Combining Mini-Thoracotomy with Interventional Endocardial Lead Implantation for Cardiac Resynchronization Therapy in Patients with Chronic Congestive Heart Failure: A Report of 4 Cases
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Juxiang Li, Haiyan Xiang, Fei Lu, Juesheng Yang, Yanhua Tang, Rifeng Gao, and Ji Li
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medicine.medical_specialty ,Chronic congestive heart failure ,business.industry ,medicine.medical_treatment ,Cardiac resynchronization therapy ,General Medicine ,030204 cardiovascular system & hematology ,Endocardial lead ,medicine.disease ,Mini thoracotomy ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Internal medicine ,Heart failure ,medicine ,Cardiology ,In patient ,030212 general & internal medicine ,Intercostal space ,business ,Biomedical sciences - Abstract
Chronic heart failure, also known as chronic congestive heart failure, is a commonly seen clinical syndrome.
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- 2019
9. Exosomes derived from M1 macrophages aggravate neointimal hyperplasia following carotid artery injuries in mice through miR-222/CDKN1B/CDKN1C pathway
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Zeng Wang, Aijun Sun, Rongle Liu, Junbo Ge, Xinyu Weng, Kai Hu, Hongtao Shi, Rifeng Gao, Xiao Li, Yunzeng Zou, Hong Zhu, and Huan Zhao
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0301 basic medicine ,Neointima ,Cancer Research ,Vascular smooth muscle ,Myocytes, Smooth Muscle ,Immunology ,Cyclin-dependent kinase inhibitor 1C ,030204 cardiovascular system & hematology ,Exosomes ,Benzylidene Compounds ,Article ,Mice ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Restenosis ,Cell Movement ,medicine ,Animals ,lcsh:QH573-671 ,3' Untranslated Regions ,Cyclin-Dependent Kinase Inhibitor p57 ,Cell Proliferation ,Neointimal hyperplasia ,Aniline Compounds ,Hyperplasia ,Carotid artery disease ,lcsh:Cytology ,business.industry ,Macrophages ,Antagomirs ,Cell Biology ,Cyclin-Dependent Kinase Inhibitor 1B ,medicine.disease ,Microvesicles ,Cell invasion ,MicroRNAs ,RAW 264.7 Cells ,030104 developmental biology ,cardiovascular system ,Cancer research ,CDKN1B ,Carotid Artery Injuries ,business ,Cyclin-Dependent Kinase Inhibitor p27 ,Signal Transduction - Abstract
The role of M1 macrophages (M1M)-derived exosomes in the progression of neointimal hyperplasia remains unclear now. Using a transwell co-culture system, we demonstrated that M1M contributed to functional change of vascular smooth muscle cell (VSMC). We further stimulated VSMCs with exosomes isolated from M1M. Our results demonstrated that these exosomes could be taken up by VSMCs through macropinocytosis. Using a microRNA array assay, we identified that miR-222 originated from M1M-derived exosomes triggered the functional changes of VSMCs. In addition, we confirmed that miR-222 played a key role in promoting VSMCs proliferation and migration by targeting Cyclin Dependent Kinase Inhibitor 1B (CDKN1B) and Cyclin Dependent Kinase Inhibitor 1C (CDKN1C) in vitro. In vivo, M1M-derived exosomes significantly aggravated neointima formation following carotid artery ligation injury and wire injury and these effects were partly abolished by miR-222 inhibitor 2′OMe-miR-222. Our findings thus suggest that exosomes derived from M1M could aggravate neointimal hyperplasia through delivering miR-222 into VSMCs. Future studies are warranted to validate if the post-injury vascular neointimal hyperplasia and restenosis could be attenuated by inhibiting miR-222.
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- 2019
10. The selective NLRP3-inflammasome inhibitor MCC950 reduces myocardial fibrosis and improves cardiac remodeling in a mouse model of myocardial infarction
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Juesheng Yang, Yanhua Tang, Lei Xu, Suchi Chang, Huairui Shi, Haiyan Xiang, Xiao Li, Heng Yang, Rifeng Gao, Chunyu Lv, and Yang Gao
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0301 basic medicine ,Cardiac function curve ,Male ,medicine.medical_specialty ,Cardiotonic Agents ,Inflammasomes ,Immunology ,Interleukin-1beta ,Anti-Inflammatory Agents ,Myocardial Infarction ,Heterocyclic Compounds, 4 or More Rings ,03 medical and health sciences ,0302 clinical medicine ,Left coronary artery ,Fibrosis ,Internal medicine ,medicine.artery ,NLR Family, Pyrin Domain-Containing 3 Protein ,medicine ,Immunology and Allergy ,Animals ,Myocardial infarction ,Sulfones ,Furans ,Pharmacology ,Sulfonamides ,Ventricular Remodeling ,business.industry ,Myocardium ,Inflammasome ,Fibroblasts ,medicine.disease ,In vitro ,Mice, Inbred C57BL ,Disease Models, Animal ,030104 developmental biology ,Indenes ,030220 oncology & carcinogenesis ,Cardiology ,Myocardial fibrosis ,business ,Ligation ,medicine.drug - Abstract
Early inflammatory responses after myocardial infarction (MI) are likely to increase myocardial fibrosis and subsequent cardiac remodeling. MCC950, a specific NLRP3 inhibitor, was previously found to effectively inhibit the release of inflammatory factors IL-18 and IL-1β. In this study, we evaluated the effect of MCC950, as a potential new treatment strategy for MI, on myocardial fibrosis and cardiac remodeling using an experimental mouse model.Male C57BL/6 mice were subjected to left coronary artery ligation to induce MI and then treated with MCC950 (10 mg/kg) or PBS for 14 days. After 30 days, echocardiography was performed to assess cardiac function and myocardial fibrosis was evaluated using HE- and Masson's Trichrome-stained sections. Myocardial expression of inflammatory factors and fibrosis markers was analyzed by western blotting, immunofluorescence, ELISA, and real-time quantitative PCR.The ejection fraction in the 10 mg/kg group (40.7 ± 4.2%; N = 6, p = 0.0029) was statistically preserved compared to that in the control group (14.0 ± 4.4%). Myocardial fibrosis was also reduced in MCC950-treated animals (MCC950, 23.2 ± 3.0 vs PBS, 36.2 ± 3.7; p 0.05). Moreover, myocardial NLRP3, cleaved IL-1β, and IL-18 levels were reduced in MCC950-treated animals. HE and molecular examination revealed decreases in inflammatory cell infiltration and inflammatory factor expression in the heart. In vitro, MCC950 inhibited NLRP3, reduced caspase-1 activity, and further downregulated IL-1β and IL-18.MCC950, as a specific NLRP3 inhibitor, can alleviate fibrosis and improve cardiac function in a mouse model by suppressing early inflammatory responses post-MI.
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- 2018
11. The covalent NLRP3-inflammasome inhibitor Oridonin relieves myocardial infarction induced myocardial fibrosis and cardiac remodeling in mice
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Hong-Zhang Chen, Yanhua Tang, Juesheng Yang, Xiaolei Sun, Wei Luo, Rifeng Gao, Xiao Li, Chunyu Lv, Yi-Qing Yang, Haiyan Xiang, Heng Yang, and Yang Gao
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Male ,0301 basic medicine ,Inflammasomes ,Neutrophils ,Interleukin-1beta ,Anti-Inflammatory Agents ,Myocardial Infarction ,Pharmacology ,Ventricular Function, Left ,0302 clinical medicine ,Immunology and Allergy ,Medicine ,Myocytes, Cardiac ,Sulfones ,Myocardial infarction ,Cells, Cultured ,Receptors, Interleukin-18 ,Sulfonamides ,Ejection fraction ,Ventricular Remodeling ,Interleukin ,Indenes ,Neutrophil Infiltration ,030220 oncology & carcinogenesis ,Thiazolidines ,Diterpenes, Kaurane ,Signal Transduction ,Cardiac function curve ,Immunology ,Heterocyclic Compounds, 4 or More Rings ,03 medical and health sciences ,Left coronary artery ,medicine.artery ,NLR Family, Pyrin Domain-Containing 3 Protein ,Animals ,Furans ,business.industry ,Macrophages ,Therapeutic effect ,Thiones ,Stroke Volume ,medicine.disease ,Fibrosis ,Mice, Inbred C57BL ,Disease Models, Animal ,030104 developmental biology ,Myocardial fibrosis ,Ligation ,business - Abstract
Background Myocardial infarction (MI) triggers a strong inflammatory response that is associated with myocardial fibrosis and cardiac remodeling. Interleukin (IL)-1β and IL-18 are key players in this response and are controlled by NLRP3-inflammatory bodies. Oridonin is a newly reported NLRP3 inhibitor with strong anti-inflammatory activity. We hypothesized that the covalent NLRP3 inhibitor Oridonin could reduce IL-1β and IL-18 expression and ameliorate myocardial fibrosis after myocardial infarction in mice, improve poor heart remodeling, and preserve heart function. Methods Male C57BL/6 mice were subjected to left coronary artery ligation to induce MI and then treated with Oridonin (1, 3, or 6 mg/kg), MCC950 (10 mg/kg), CY-09 (5 mg/kg) or saline three times a week for two weeks. Four weeks after MI, cardiac function and myocardial fibrosis were assessed. In addition, myocardial expressions of inflammatory factors and fibrotic markers were analyzed by western blot, immunofluorescence, enzyme-linked immunosorbent assay, and quantitative real-time polymerase chain reaction. Results Oridonin treatment preserved left ventricular ejection fraction and fractional shortening, and markedly limited the myocardial infarct size in treated mice. The myocardial fibrosis was lower in the 1 mg/kg group (15.98 ± 1.64)%, 3 mg/kg group (17.39 ± 2.45)%, and 6 mg/kg group (16.76 ± 3.06)% compared to the control group (23.38 ± 1.65)%. Moreover, similar with the results of Oridonin, MCC950 and CY-09 also preserved cardiac function and reduced myocardial fibrosis. The expression levels of NLRP3, IL-1β and IL-18 were decreased in the Oridonin treatment group compared to non-treated group. In addition, myocardial macrophage and neutrophil influxes were attenuated in the Oridonin treated group. Conclusions The covalent NLRP3-inflammasome inhibitor Oridonin reduces myocardial fibrosis and preserves cardiac function in a mouse MI model, which indicates potential therapeutic effect of Oridonin on acute MI patients.
- Published
- 2021
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