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Large animal models of cardiac ischemia-reperfusion injury:Where are we now?

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Zoological Research 2023年第3期44卷 591-603页

作者： Attaur Rahman Yuhao Li To-Kiu Chan Hui Zhao Yaozu Xiang Xing Chang Hao Zhou Dachun Xu Sang-Bing Ong Department of medicine and Therapeutics Faculty of MedicineThe Chinese University of Hong Kong(CUHK)Hong Kong SARChina Centre for Cardiovascular Genomics and medicine(CCGM) Lui Che Woo Institute Innovative MedicineThe Chinese University of Hong Kong(CUHK)Hong Kong SARChina College of Veterinary Sciences and Animal Husbandry Abdul Wali Khan University MardanMardanKhyber Pakhtunkhwa 23200Pakistan school of Biomedical Sciences CUHK-GIBH CAS Joint Laboratory on Stem Cell and Regenerative MedicineThe Chinese University of Hong Kong(CUHK)Hong Kong SARChina institute for Tissue Engineering and Regenerative medicine(iTERM) The Chinese University of Hong Kong(CUHK)Hong Kong SARChina SBS Core Laboratory CUHK Shenzhen Research InstituteShenzhenGuangdong 518172China Kunming institute of Zoology–The Chinese university of Hong Kong(KIZ-CUHK)Joint Laboratory of Bioresources and Molecular Research of Common Diseases Hong Kong SARChina Shanghai East Hospital Key Laboratory of Arrhythmias of the Ministry of Education of ChinaSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Guang’anmen Hospital China Academy of Chinese Medical SciencesBeijing 100053China Department of cardiology Chinese People’s Liberation Army General HospitalBeijing 100853China center for Cardiovascular Research and Alternative medicine University of Wyoming College of Health SciencesLaramieWY 82071USA Department of cardiology Shanghai Tenth People’s HospitalTongji University School of MedicineShanghai 200072China Hong Kong Hub of Paediatric Excellence(HK HOPE) Hong Kong Children’s Hospital(HKCH)Kowloon BayHong Kong SARChina CUHK Shenzhen Research institute(SZRI) ShenzhenGuangdong 518172China Neural Vascularand Metabolic Biology Thematic Research ProgramSchool of Biomedical SciencesThe Chinese University of Hong Kong(CUHK)Hong Kong SARChina

Large animal models of cardiac ischemia-reperfusion are critical for evaluation of the efficacy of cardioprotective interventions prior to clinical ***,current cardioprotective strategies/interventions formulated in preclinical cardiovascular research are often limited to small animal models,which are not transferable or reproducible in large animal models due to different factors such as:(i)complex and varied features of human ischemic cardiac disease(ICD),which are challenging to mimic in animal models,(ii)significant differences in surgical techniques applied,and(iii)differences in cardiovascular anatomy and physiology between small versus large *** article highlights the advantages and disadvantages of different large animal models of preclinical cardiac ischemic reperfusion injury(IRI),as well as the different methods used to induce and assess IRI,and the obstacles faced in using large animals for translational research in the settings of cardiac IR.

关键词： Cardiovascular disorder Ischemic cardiac disease Ischemic-reperfusion injury Large animal model Myocardial infarction Translational gap

A shared role of the myocardin-family transcriptional coactivators in cardiomyocyte maturation

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Science China(Life Sciences) 2023年第12期66卷 2939-2942页

作者： Yuxuan Guo Yangpo Cao Blake D.Jardin Neil Mazumdar Congting Guo Luzi Yang Junsen Lin Zhan Chen Qing Ma Mingming Zhao Erdan Dong William T.Pu Peking university Health Science center School of Basic Medical SciencesBeijing 100191China Peking university institute of Cardiovascular Sciences Beijing 100191China State Key Laboratory of vascular Homeostasis and Remodeling Peking UniversityBeijing100191China Beijing Key Laboratory of Cardiovascular Receptors Research Beijing 100191China Boston Children’s Hospital Department of CardiologyBoston MA 02115USA Peking university Third Hospital Department of Cardiology and Institute of Vascular MedicineBeijing 100191China Research Unit of Medical Science Research Management/Basic and Clinical Research of Metabolic Cardiovascular Diseases Chinese Academy of Medical SciencesHaihe Laboratory of Cell EcosystemBeijing 100191China National Health Commission Key Laboratory of Cardiovascular Molecular biology and Regulatory Peptides Beijing 100191China Harvard Stem Cell institute Cambridge MA 02138USA

Dear Editor,In development,after cells make a commitment to their fates,they undergo a continuous and adaptive maturation process to eventually reach their terminal *** maturity often decays during aging and *** immat... 详细信息

关键词： states eventually decay

VEGF-B prevents excessive angiogenesis by inhibiting FGF2/FGFR1 pathway

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Signal Transduction and Targeted Therapy 2023年第9期8卷 4380-4393页

作者： Chunsik Lee Rongyuan Chen Guangli Sun Xialin Liu Xianchai Lin Chang He Liying Xing Lixian Liu Lasse DJensen Anil Kumar Harald FLanger Xiangrong Ren Jianing Zhang Lijuan Huang Xiangke Yin JongKyong Kim Juanhua Zhu Guanqun Huang Jiani Li Weiwei Lu Wei Chen Juanxi Liu Jiaxin Hu Qihang Sun Weisi Lu Lekun Fang Shasha Wang Haiqing Kuang Yihan Zhang Geng Tian Jia Mi Bi-Ang Kang Masashi Narazaki Aaron Prodeus Luc Schoonjans David MOrnitz Jean Gariepy Guy Eelen Mieke Dewerchin Yunlong Yang Jing-Song Ou Antonio Mora Jin Yao Chen Zhao Yizhi Liu Peter Carmeliet Yihai Cao Xuri Li State Key Laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen University and Guangdong Provincial Key Laboratory of Ophthalmology and Visual ScienceGuangzhou 510060P.R.China Affiliated Eye Hospital of Nanjing Medical university Nanjing 210000China Department of Obstetrics and Gynecology Guangdong Provincial Key Laboratory of Major Obstetric DiseasesGuangdong Provincial Clinical Research Center for Obstetrics and GynecologyThe Third Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina Shenzhen Eye Hospital Jinan UniversityShenzhen Eye InstituteShenzhenChina Department of Health Medical and Caring SciencesDivision of Diagnostics and Specialist MedicineLinköping University58183 LinköpingSweden Department of cardiology AngiologyHaemostaseology and Medical Intensive CareUniversity Medical Centre MannheimMedical Faculty MannheimHeidelberg UniversityMannheimGermany DZHK(German Research Centre for Cardiovascular Research) partner site Mannheim/HeidelbergMannheimGermany European center for Angioscience Medical Faculty MannheimHeidelberg UniversityMannheimGermany Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease Guangdong Research Institute of GastroenterologyDepartment of Colorectal SurgeryThe Sixth Affiliated Hospital of Sun Yat-sen UniversityGuangzhouChina Eye institute Eye and ENT HospitalShanghai Medical CollegeFudan UniversityKey Laboratory of Myopia of State Health Ministry(Fudan University)and Shanghai Key Laboratory of Visual Impairment and Restoration200031 ShanghaiChina Shandong Technology Innovation center of Molecular Targeting and Intelligent Diagnosis and Treatment Binzhou Medical UniversityYantai 264003P.R.China Division of Cardiac Surgery National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular DiseasesNHC key Laboratory of Assisted Circulation(Sun Yat-sen University)The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina Department of Respiratory medicine and Clinical Imm

Although VEGF-B was discovered as a VEGF-A homolog a long time ago,the angiogenic effect of VEGF-B remains poorly understood with limited and diverse findings from different ***,drugs that inhibit VEGF-B together with other VEGF family members are being used to treat patients with various neovascular *** is therefore critical to have a better understanding of the angiogenic effect of VEGF-B and the underlying *** comprehensive in vitro and in vivo methods and models,we reveal here for the first time an unexpected and surprising function of VEGF-B as an endogenous inhibitor of angiogenesis by inhibiting the FGF2/FGFR1 pathway when the latter is abundantly ***,we unveil that VEGF-B binds to FGFR1,induces FGFR1/VEGFR1 complex formation,and suppresses FGF2-induced Erk activation,and inhibits FGF2-driven angiogenesis and tumor *** work uncovers a previously unrecognized novel function of VEGF-B in tethering the FGF2/FGFR1 *** the anti-angiogenic nature of VEGF-B under conditions of high FGF2/FGFR1 levels,caution is warranted when modulating VEGF-B activity to treat neovascular diseases.

关键词： FGFR1 FGF2 drugs

FUS-mediated HypEVs: Neuroprotective effects against ischemic stroke

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Bioactive Materials 2023年第11期29卷 196-213页

作者： Yousheng Wu Xiaoxiong Huang Zefeng Tan Jiankun Zang Min Peng Niu He Tao Zhang Hongcheng Mai Anding Xu Dan Lu Department of Neurology and Stroke center The First Affiliated Hospital of Jinan UniversityGuangzhouChina Clinical Neuroscience institute The First Affiliated Hospital of Jinan UniversityGuangzhouChina Key Lab of Guangzhou Basic and Translational Research of Pan-vascular Diseases The First Affiliated Hospital of Jinan UniversityGuangzhouChina Department of Neurology and Stroke center The Central Hospital of ShaoyangHunanChina Department of Neurology The First People’s Hospital of FoshanGuangdongChina Department of cardiology The First Affiliated Hospital of Jinan UniversityGuangzhouChina Munich Medical Research school(MMRS) Ludwig-Maximilians University MunichMunichGermany Insititute for Tissue Engineering and Regenerative medicine(iTERM) Helmholtz Zentrum MünchenNeuherbergGermany

Few studies have investigated the properties and protein composition of small extracellular vesicles (sEVs) derived from neurons under hypoxic conditions. Presently, the extent of the involvement of these plentiful sEVs in the onset and progression of ischemic stroke remains an unresolved question. Our study systematically identified the characteristics of sEVs derived from neurons under hypoxic conditions (HypEVs) by physical characterization, sEV absorption, proteomics and transcriptomics analysis. The effects of HypEVs on neurites, cell survival, and neuron structure were assessed in vitro and in vivo by neural complexity tests, magnetic resonance imaging (MRI), Golgi staining, and Western blotting of synaptic plasticity-related proteins and apoptotic proteins. Knockdown of Fused in Sarcoma (FUS) small interfering RNA (siRNA) was used to validate FUS-mediated HypEV neuroprotection and mitochondrial mRNA release. Hypoxia promoted the secretion of sEVs, and HypEVs were more easily taken up and utilized by recipient cells. The MRI results illustrated that the cerebral infarction volume was reduced by 45% with the application of HypEVs, in comparison to the non- HypEV treatment group. Mechanistically, the FUS protein is necessary for the uptake and neuroprotection of HypEVs against ischemic stroke as well as carrying a large amount of mitochondrial mRNA in HypEVs. However, FUS knockdown attenuated the neuroprotective rescue capabilities of HypEVs. Our comprehensive dataset clearly illustrates that FUS-mediated HypEVs deliver exceptional neuroprotective effects against ischemic stroke, primarily through the maintenance of neurite integrity and the reduction of mitochondria-associated apoptosis.

关键词： Hypoxia FUS Neuron-derived small extracellular vesicle Neuroprotection Mitochondrial mRNA

Cardiac rehabilitation and exercise therapy in the elderly： Should we invest in the aged？

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Journal of Geriatric cardiology 2012年第1期9卷 68-75页

作者： Arthur R Menezes Carl J Lavie Richard V Milani Ross A Arena Timothy S Church Department of Cardiovascular Diseases John Ochsner Heart and Vascular Institute Ochsner Clinical School The University of Queensland School ofMedicine 1514 Jefferson Highway New Orleans LA 70121 USA Department of Orthopaedics Physical Therapy Program and Division of Cardiology Department of Internal Medicine University of New MexicoAlbuquerque NM87131 USA Department of Preventive medicine Pennington Biomedical Research Center Louisiana State University System Baton Rouge LA 70808 USA

Coronary heart disease （CHD） is the leading cause of death worldwide and becomes increasingly prevalent among patients aged 65 years and *** patients are at a higher risk for complications and accelerated physical deconditioning after a cardiovascular event,especially compared to their younger *** last few decades were privy to multiple studies that demonstrated the beneficial effects of cardiac rehabilitation （CR） and exercise therapy on mortality,exercise capacity,psychological risk factors,inflammation,and obesity among patients with ***,a significant portion of the available data in this field pertains to younger patients.A viable explanation is that older patients are grossly underrepresented in these programs for multiple reasons starting with the patient and extending to the *** this article,we will review the benefits of CR programs among the elderly,as well as some of the barriers that hinder their participation.

关键词： Cardiac rehabilitation Exercise therapy Elderly patients Exercise capacity

Tongxinluo Improves Apolipoprotein E-Deficient Mouse Heart Function

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Chinese Medical Journal 2018年第5期131卷 544-552页

作者： Guo-Qiang Yuan Song Gao Yong-Jian Geng Yao-Ping Tang Min-Juan Zheng Harnath S Shelat Scott Collins Han-Jing Wu Yi-Ling Wu 'Department of Collateral Disease Research Institute of Integrated Traditional Chinese Medicine and Western Medicine of Hebei Shijiazhuang Hebei 050035 China Department of Cardiovascular Disease Hebei Yiling Hospital Shijiazhuang Hebei 050091 China Department of Internal medicine McGovern Medical School The University of Texas Health Science Center at Houston Houston TX 77030 USA center for Cell Signaling Institute of Molecular Medicine Houston Health Science Center The University of "IX Houston TX 77030 USA Department of Pediatric cardiology Baylor College of Medicine Houston TX 77030 USA

Background： Our previous studies have shown that Tongxinluo （TXL）, a compound Chinese medicine, can decrease myocardial ischemia-reperfusion injury, protect capillary endothelium function, and lessen cardiac ventricle reconstitution in animal models. The aim of this study was to illuminate whether TXL can improve hypercholesterolemia-impaired heart function by protecting artery endothelial function and increasing microvascular density （MVD） in heart. Furthermore, we will explore the underlying molecular mechanism of TXL cardiovascular protection. Methods： After intragastric administration of TXL （0.1 ml/10 g body weight） to C57BL/6J wild-type mice （n = 8） and ApoE-/- mice （n=8）, total cholesterol, high-density lipoprotein-cholesterol, very-low-density lipoprotein （VLDL）-cholesterol, triglyceride, and blood glucose levels in serum were measured. The parameters of heart rate （HR）, lelt ventricular diastolic end diameter, and left ventricular systolic end diameter were harvested by ultrasonic cardiogram. The left ventricular ejection fraction, stroke volume, cardiac output, and let1 ventricular fractional shortening were calculated. Meanwhile, aorta peak systolic flow velocity （PSV）, end diastolic flow velocity, and mean flow velocity （MFV） were measured. The pulsatility index （PI） and resistant index were calculated in order to evaluate the vascular elasticity and resistance. Tile endothelium-dependent vasodilatation was evaluated by relaxation of aortic rings in response to acetylcholine. Western blotting and real-time quantitative reverse transcription polymerase chain reaction were performed for protein and gene analyses of vascular endothelial growth factor （VEGF）. lnamunohistochenaical detection was perlbrmed for myocardial CD34 expression. Data in this study were compared by one-way analysis of variance between groups. A value of P 〈 0.05 was considered statistically significant. Results： Although there was no significant decrease of cholesterol level （F = 2.300

关键词： Heart Function: Microvascular Protection:Tongxinluo

Nitric oxide and geriatrics:Implications in diagnostics and treatment of the elderly

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Journal of Geriatric cardiology 2011年第4期8卷 230-242页

作者： Ashley C Torregrossa Mayank Aranke Nathan S Bryan Texas Therapeutics institute Brown Foundation Institute of Molecular MedicineUniversity of Texas Health Science Center at Houston1825 Pressler St.530CHoustonTX 77030USA The university of Texas at Austin University StationAustinTX 78712USA The university of Texas Graduate school of Biomedical Sciences 6767 Bertner Av.HoustonTX 77030USA

The nation’s aging population is growing *** 2030,the number of adults age 65 and older will nearly double to 70 *** are living longer and older adults can now live for many years with multiple chronic illnesses but with a substantial cost to health *** percent of the Medicare population has at least five chronic conditions i.e.,hypertension,diabetes,arthritis,*** in experimental models and even humans reveal that constitutive production of nitric oxide(NO)is reduced with aging and this circumstance may be relevant to a number of diseases that plague the aging *** is a multifunctional signaling molecule,intricately involved with maintaining a host of physiological processes including,but not limited to,host defense,neuronal communication and the regulation of vascular *** is one of the most important signaling molecules in our body,and loss of NO function is one of the earliest indicators or markers of *** studies provide evidence that insufficient NO production is associated with all major cardiovascular risk factors,such as hyperlipidemia,diabetes,hypertension,smoking and severity of atherosclerosis,and also has a profound predictive value for disease progression including cardiovascular and Alzheimers *** plus years after its discovery and over 13 years since a Nobel Prize was awarded for its discovery,there have been no hallmark therapeutic breakthroughs or even NO based *** will review the current state of the science surrounding NO in the etiology of a number of different diseases in the geriatric *** these observations,it can be concluded that enzymatic production of NO declines steadily with increasing age in healthy human *** strategies to diagnose and treat NO insufficiency may provide enormous benefit to the geriatric patient.

关键词： nitrite nitrate cardiovascular disease Alzheimer’s disease bloodflow circulation

Structural and temporal dynamics analysis on drug-eluting stents: History, research hotspots and emerging trends

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Bioactive Materials 2023年第5期23卷 170-186页

作者： Lili Tan Xiangxiu Wang Kungshan Yuan Tieying Yin Ruolin Du Li Shen Zhirong Zhu Suhua Yu Haijun Zhang Guixue Wang Key Laboratory of Biorheological and Technology of Ministry of Education State and Local Joint Engineering Laboratory for Vascular ImplantsModern Life Science Experiment Teaching Center at Bioengineering College of Chongqing UniversityChongqing400030China National United Engineering Laboratory for Biomedical Material Modification Shandong Rientech Medical Tech Co.LtdDezhouShandong251100China Department of cardiology Zhongshan HospitalFudan UniversityShanghai Institute of Cardiovascular DiseasesShanghaiNational Clinical Research Center for Interventional MedicineShanghai200032China Shanghai Key Lab of Chemical Assessment and Sustainability School of Chemical Science and EngineeringTongji UniversityShanghai200092China Blue Sail Pioneer Lab JW Medical SystemsJiwei Shandong264200China JinFeng Laboratory Chongqing401329China

Purpose:This review aims to explore the history,research hotspots,and emerging trends of drug-eluting stents(DES)in the last two decades from the perspective of structural and temporal ***:Publications on DES were retrieved from *** bibliometric tools including CiteSpace and HistCite were used to identify the historical features,the evolution of active topics,and emerging trends on the DES ***:In the last 20 years,the field of DES is still in the hot phase and there is a wide range of extensive scientific *** addition,active topics emerge in different periods,as evidenced by a total of 41 disciplines,511 keywords,and 1377 papers with citation *** clustering anchored five emerging research subfields,namely#0 dual antiplatelet therapy,#3 drug-coated balloon,#4 bifurcation,5#rotational atherectomy,and 6#quantitative flow *** keyword alluvial map shows that the most persistent research concepts in this field are thrombosis,restenosis,etc.,and the emerging keywords are paclitaxel eluting balloon,coated balloon,drug-eluting balloon,*** are 7 recent research subfields anchored by reference clustering,namely#2 dual antiplatelet therapy,#4 drug-coated balloon,#5 peripheral artery disease,#8 fractional flow reserve,#10 bioresorbable vascular scaffold,#13 intravascular ultrasound,#14 biodegradable ***:The findings based on the bibliometric studies provide the current status and trends in DES research and may help researchers to identify hot topics and explore new research directions in this field.

关键词： Drug-eluting stents Dual antiplatelet therapy Drug-coated balloon Bioresorbable scaffold Bibliometric

An international Delphi consensus statement on metabolic dysfunction-associated fatty liver disease and risk of chronic kidney disease

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Hepatobiliary Surgery and Nutrition 2023年第3期12卷 386-403,I0014-I0016页

作者： Dan-Qin Sun Giovanni Targher Christopher D.Byrne David C.Wheeler Vincent Wai-Sun Wong Jian-Gao Fan Herbert Tilg Wei-Jie Yuan Christoph Wanner Xin Gao Michelle T.Long Mehmet Kanbay Mindie H.Nguyen Sankar D.Navaneethan Yusuf Yilmaz Yuli Huang Rino A.Gani Pierluigi Marzuillo Jérôme Boursier Huijie Zhang Chan-Young Jung Jin Chai Luca Valenti George Papatheodoridis Giovanni Musso Yu-Jun Wong Mohamed El-Kassas Nahum Méndez-Sánchez Silvia Sookoian Michael Pavlides Ajay Duseja Adriaan G.Holleboom Junping Shi Wah-Kheong Chan Yasser Fouad Junwei Yang Sombat Treeprasertsuk Helena Cortez-Pinto Masahide Hamaguchi Manuel Romero-Gomez Mamun Al Mahtab Ponsiano Ocama Atsushi Nakajima Chunsun Dai Mohammed Eslam Lai Wei Jacob George Ming-Hua Zheng Department of Nephrology Jiangnan University Medical CenterWuxiChina Affiliated Wuxi Clinical College of Nantong university WuxiChina Section of Endocrinology Diabetes and MetabolismDepartment of MedicineAzienda Ospedaliera Universitaria Integrata VeronaVeronaItaly Southampton National institute for Health and Care Research Biomedical Research Centre University Hospital Southamptonand Southampton General HospitalUniversity of SouthamptonSouthamptonUK Department of Renal medicine University College LondonLondonUK Department of medicine and Therapeutics Chinese University of Hong KongHong KongChina center for Fatty Liver Department of GastroenterologyXin Hua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina Department of Internal medicine I GastroenterologyEndocrinology&MetabolismMedical University InnsbruckInnsbruckAustria Department of Nephrology Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Division of Nephrology Department of MedicineWürzburg University ClinicWürzburgGermany Department of Endocrinology and Metabolism Zhongshan HospitalFudan UniversityShanghaiChina Section of Gastroenterology Boston Medical CenterBoston University School of MedicineBostonMAUSA Division of Nephrology Department of Medicine(M.K.)Koc University School of MedicineIstanbulTurkey Division of Gastroenterology and Hepatology Department of MedicineStanford University Medical CenterPalo AltoCAUSA Department of Epidemiology and Population Health Stanford University Medical CenterPalo AltoCAUSA Section of Nephrology and institute of Clinical and Translational Research Baylor College of Medicineand Michael E.DeBakey VA Medical CenterHoustonTXUSA Department of Gastroenterology School of MedicineMarmara UniversityIstanbulTurkey Department of Gastroenterology School of MedicineRecep Tayyip Erdoğan UniversityRizeTurkey Department of cardiology Shunde HospitalSouthern Medical UniversityFoshanChina Division of Hepat

Background:With the rising global prevalence of fatty liver disease related to metabolic dysfunction,the association of this common liver condition with chronic kidney disease(CKD)has become increasingly *** 2020,the more inclusive term metabolic dysfunction-associated fatty liver disease(MAFLD)was proposed to replace the term non-alcoholic fatty liver disease(NAFLD).The observed association between MAFLD and CKD and our understanding that CKD can be a consequence of underlying metabolic dysfunction support the notion that individuals with MAFLD are at higher risk of having and developing CKD compared with those without ***,to date,there is no appropriate guidance on CKD in individuals with ***,there has been little attention paid to the link between MAFLD and CKD in the Nephrology *** and Results:Using a Delphi-based approach,a multidisciplinary panel of 50 international experts from 26 countries reached a consensus on some of the open research questions regarding the link between MAFLD and ***:This Delphi-based consensus statement provided guidance on the epidemiology,mechanisms,management and treatment of MAFLD and CKD,as well as the relationship between the severity of MAFLD and risk of CKD,which establish a framework for the early prevention and management of these two common and interconnected diseases.

关键词： Metabolic dysfunction-associated fatty liver disease(MAFLD) non-alcoholic fatty liver disease(NAFLD) chronic kidney disease(CKD) consensus