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Targeting deubiquitinase OTUB1 protects vascular smooth muscle cells in atherosclerosis by modulating PDGFRβ

Frontiers of Medicine 2024年第3期18卷 465-483页

作者： Fei Xu Han Chen Changyi Zhou Tongtong Zang Rui Wang Shutong Shen Chaofu Li Yue Yu Zhiqiang Pei Li Shen Juying Qian Junbo Ge Department of Cardiology and Laboratory of heart valve Disease West China HospitalSichuan UniversityChengdu610041China Department of Cardiology Zhongshan HospitalFudan UniversityResearch Unit of Cardiovascular Techniques and DevicesChinese Academy of Medical SciencesShanghai200032China Shanghai Institute of Cardiovascular Diseases Shanghai200032China National Clinical Research center for Interventional Medicine&Shanghai Clinical Research center for Interventional Medicine(19MC1910300) Shanghai200032China

Atherosclerosis is a chronic artery disease that causes various types of cardiovascular *** smooth muscle cells(VSMCs),the main components of atherosclerotic plaque,switch from contractile to synthetic phenotypes during *** is crucial in regulating VSMC phenotypes in atherosclerosis,and it can be reversely regulated by ***,the specific effects of deubiquitinases on atherosclerosis have not been thoroughly *** this study,RNAi screening in human aortic smooth muscle cells was performed to explore the effects of OTU family deubiquitinases,which revealed that silencing OTUB1 inhibited PDGF-BB-stimulated VSMC phenotype *** in vivo studies using Apoe−/−mice revealed that knockdown of OTUB1 in VSMCs alleviated atherosclerosis plaque burden in the advanced stage and led to a stable plaque ***,VSMC proliferation and migration upon PDGF-BB stimulation could be inhibited by silencing OTUB1 in *** RNA-sequencing data indicated that knocking down OTUB1 influenced VSMC differentiation,adhesion,and *** spectrometry of ubiquitinated protein confirmed that proteins related to cell growth and migration were differentially ***,we found that OTUB1 recognized the K707 residue ubiquitylation of PDGFRβwith its catalytic triad,thereby reducing the K48-linked ubiquitylation of PDGFRβ.Inhibiting OTUB1 in VSMCs could promote PDGFRβdegradation via the ubiquitin–proteasome pathway,so it was beneficial in preventing VSMCs’phenotype *** findings revealed that knocking down OTUB1 ameliorated VSMCs’phenotype switch and atherosclerosis progression,indicating that OTUB1 could be a valuable translational therapeutic target in the future.

关键词： atherosclerosis vascular smooth muscle cell ubiquitylation deubiquitinase OTUB1 PDGFRβ

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Pacemaker post transcatheter aortic valve replacement:A multifactorial risk?

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World Journal of Cardiology 2024年第4期16卷 168-172页

作者： Stephane Noble Karim Bendjelid Department of Medicine Structural Heart UnitUniversity Hospital of GenevaGeneva 1211Switzerland Department of Acute Medicine Geneva University HospitalsGeneva 1211Switzerland

Pacemaker post-transcatheter aortic valve replacement is related to multifactorial *** et al brought to the body of evidence electrocardiogram and clinical ***,procedural characteristics have at least as much impact on the final need for a permanent pacemaker and potentially on the pacing *** this regard,long-term follow-up and understanding of the impact of long-term stimulation is of utmost importance.

关键词： Transcatheter aortic valve replacement Permanent pacemaker implantation Conduction abnormalities Right bundle branch block Left bundle branch block

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DNA Methylation Variation Is Identified in Monozygotic Twins Discordant for Congenital heart Diseases

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Congenital heart Disease 2024年第2期19卷 247-256页

作者： Shuliang Xia Huikang Tao Shixin Su Xinxin Chen Li Ma Jianru Li Bei Gao Xumei Liu Lei Pi Jinqing Feng Fengxiang Li Jia Li Zhiwei Zhang Guangdong Provincial People’s Hospital Southern Medical UniversityGuangzhou510100China Department of Cardiovascular Surgery Guangzhou Women and Children’s Medical CenterGuangzhou Medical UniversityGuangdong Provincial Clinical Research Center for Child HealthGuangzhou510623China Department of Pediatric Cardiology Guangdong Cardiovascular InstituteGuangdong Provincial Key Laboratory of South China Structural Heart DiseaseGuangzhou510100China Clinical Physiology Laboratory Institute of PediatricsGuangzhou Women and Children’s Medical CenterGuangzhou Medical UniversityGuangdong Provincial Key Laboratory of Research in Structural Birth Defect DiseaseGuangzhou510623China Department of Echocardiogram Guangzhou Women and Children’s Medical CenterGuangzhou Medical UniversityGuangdong Provincial Clinical Research Center for Child HealthGuangzhou510623China Department of Pediatrics Washington University School of MedicineSt.LouisMO63130USA Clinical Biological Resource Bank of Guangzhou Women and Children’s Medical center Guangzhou Medical UniversityGuangzhou510623China

Aims:Multiple genes and environmental factors are known to be involved in congenital heart disease(CHD),but epigenetic variation has received little ***(MZ)twins with CHD provide a unique model for exploring this *** order to investigate the potential role of Deoxyribonucleic Acid(DNA)methyla-tion in CHD pathogenesis,the present study examined DNA methylation variation in MZ twins discordant for CHD,especially ventricular septal defect(VSD).Methods and Results:Using genome-wide DNA methylation profiles,we identified 4004 differentially methylated regions(DMRs)in 18 MZ twin pairs discordant for CHD,and 2826 genes were *** Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis revealed a list of CHD-associated *** further investigate the role of DNA methylation in VSD,data from 7 pairs of MZ twins with VSD were *** identified 1614 DMRs corresponding to 1443 genes associated with arrhythmogenic right ventricular cardiomyopathy,cyclic guanosine monopho-sphate-protein kinase G(cGMP-PKG)signaling pathway by KEGG analysis,and cell-cell adhesion,calcium ion transmembrane transport by GO analysis.A proportion of DMR-associated genes were involved in calcium signaling *** methylation changes of calcium signaling genes might be related to VSD ***:CHD is associated with differential DNA methylation in MZ *** may be etiologically linked to DNA methylation,and methylation of calcium signaling genes may be involved in the development of VSD.

关键词： Congenital heart disease monozygotic twins methylation modification epigenetics

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In vitro bench testing using patient-specific 3D models for percutaneous pulmonary valve implantation with Venus P-valve

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Chinese Medical Journal 2024年第8期137卷 990-996页

作者： Yu Han Zehua Shao Zirui Sun Yan Han Hongdang Xu Shubo Song Xiangbin Pan Peter P.T.de Jaegere Taibing Fan Gejun Zhang Department of Structure heart Disease Central China Fuwai Hospital of Zhengzhou UniversityZhengzhouHenan 451460China Children’s heart center Central China Fuwai Hospital of Zhengzhou UniversityZhengzhouHenan 451460China Department of Anesthesiology Central China Fuwai Hospital of Zhengzhou UniversityZhengzhouHenan 451460China Department of Structure heart Disease Fuwai Hospital Chinese Academy of Medical SciencesBeijing 100037China Department of Cardiology Erasmus MCRotterdam 3015 GDNetherlands

Background:Due to the wide variety of morphology,size,and dynamics,selecting an optimal valve size and location poses great difficulty in percutaneous pulmonary valve implantation(PPVI).This study aimed to report our experience with in vitro bench testing using patient-specific three-dimensional(3D)-printed models for planning PPVI with the Venus ***:Patient-specific 3D soft models were generated using PolyJet printing with a compliant synthetic material in 15 patients scheduled to undergo PPVI between July 2018 and July 2020 in Central China Fuwai Hospital of Zhengzhou ***:3D model bench testing altered treatment strategy in all patients(100%).One patient was referred for surgery because testing revealed that even the largest Venus P-valve would not anchor *** the remaining 14 patients,valve size and/or implantation location was altered to avoid valve migration and/or compression coronary *** four patients,it was decided to change the point anchoring because of inverted cone-shaped right ventricular outflow tract(RVOT)(n=2)or risk of compression coronary artery(n=2).Concerning sizing,we found that an oversize of 2-5 mm *** of the valve was dictated by the flaring of the in-and outflow portion in the pulmonary *** was successful in all 14 patients(absence of valve migration,no coronary compression,and none-to-mild residual pulmonary regurgitation[PR]).The diameter of the Venus P-valve in the 3D simulation group was significantly smaller than that of the conventional planning group(36[2]vs.32[4],Z=-3.77,Pvalve to the degree recommended by the balloon-sizing technique,as 2-5 mm sufficed.

关键词： heart valve prosthesis implantation Percutaneous pulmonary valve intervention Pulmonary regurgitation bench testing 3D printing Venus P-valve

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First-in-human Results of the Novel Transcatheter Mitral valve Repair System for Severe Mitral Regurgitation

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Cardiology Discovery 2024年第2期4卷 148-159页

作者： Zhi-Nan Lu Yutong Ke Yingnan Bian Jing He Wenhui Wu Xinmin Liu Yang Li Ran Liu Taiyang Luo Xunan Guo Guangyuan Song Interventional center of vavular heart Disease Beijing Anzhen HospitalCapital Medical UniversityBeijing 100029China Echocardiography Department Bejing Anzhen HospitalCapital Medical UniversityBeijing 100029China Research and Development Department Enlight MedicalShanghai 201209China

Objective:To evaluate the feasibility,safety,and effectiveness of a novel edge-to-edge mitral valve repair system(the NovoClasp system)in patients with severe mitral ***:In this prospective,single-arm,first-in-human study conducted at Beijing Anzhen Hospital,data were collected from patients undergoing transcatheter edge-to-edge repair using the NovoClasp *** study candidates were patients exhibiting a mitral regurgitation severity of 3+or more and were at high-risk or contraindicated for surgical *** success and device success according to the Mitral valve Academic Research Consortium definitions were used as primary *** safety and efficacy outcomes were prospectively assessed at device implantation,discharge,and 30 d,6 months,and 12 months ***:Between October 1,2021,and January 31,2022,11 patients were treated for moderate-to-severe(grade 3+)or severe(grade 4+)mitral regurgitation using the NovoClasp *** patients had a baseline New York heart Association functional class oflll-lIV,with 7/11 exhibiting complex mitral valve *** patients achieved the primary endpoints of technical and device success,with a post-operative 30-d mitral regurgitation grade reduction to 2+or lower,which was maintained at 12 *** patient had minor bleeding and hematoma at the access site before discharge,and 2 patients were readmitted due to fast atrial fibrillation within 12 months *** additional cases of death,adverse cerebral or cardiovascular events,or device-related complications was observed during the ***:This study suggested the potential feasibility and safety of the NovoClasp system,showing a promising technical and device success rate,along with a decrease in mitral regurgitation severity.A further pivotal study is needed to assess the procedural and long-term outcomes.

关键词： Mitral valve insufficiency Transcatheter edge-to-edge repair Feasibility Safety

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Recent progress in functional modification and crosslinking of bioprosthetic heart valves

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Regenerative Biomaterials 2024年第1期3卷 1-16页

作者： Cheng Zheng Li Yang Yunbing Wang National Engineering Research center for Biomaterials Sichuan UniversityChengdu 610064China

Valvular heart disease(VHD),clinically manifested as stenosis and regurgitation of native heart valve,is one of the most prevalent cardiovascular diseases with high *** valve replacement surgery has been recognized as golden standard for the treatment of *** to the clinical application of transcatheter heart valve replacement technic and the excellent hemodynamic performance of bioprosthetic heart valves(BHVs),implantation of BHVs has been increasing over recent years and gradually became the preferred choice for the treatment of ***,BHVs might fail within 10-15 years due to structural valvular degeneration(SVD),which was greatly associated with drawbacks of glutaraldehyde crosslinked BHVs,including cytotoxicity,calcification,component degradation,mechanical failure,thrombosis and immune *** prolong the service life of BHVs,much effort has been devoted to overcoming the drawbacks of BHVs and reducing the risk of *** this review,we summarized and analyzed the research and progress on:(i)modification strategies based on glutaraldehyde crosslinked BHVs and(ii)nonglutaraldehyde crosslinking strategies for BHVs.

关键词： bioprosthetic heart valves modification crosslinking anticalcification antithrombosis

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Strategy and technique for surgical treatment of Ebstein’s anomaly

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Chinese Medical Journal 2024年第10期137卷 1218-1224页

作者： Qingyu Wu Xiaoya Zhang Mingkui Zhang Hongyin Li Dongya Zhang Lianyi Wang Qingfeng Wu Cardiac center Division of Cardiac SurgeryThe First Hospital of Tsinghua UniversityBeijing 100016China

Background:Ebstein’s anomaly(EA)is a rare and complex congenital heart anomaly,and the effect of surgical treatment is not *** study aims to introduce our experience in management strategies,surgical techniques,and operative indications for patients with Ebstein’s ***:A retrospective study of 258 operations was performed in 253 patients by the same cardiac surgeon in The First Hospital of Tsinghua University between March 2004 and January 2020.32 patients had previously received cardiac surgery in other *** clinical data including diagnosis,operative indications,techniques,pathological changes,and survival rates were collected and ***:Anatomical correction was performed in 203(78.7%)operations,1½ventricle repair in 38(14.7%)operations,tricuspid valve repair only in four operations(1.6%),tricuspid valve replacement in ten(3.9%),total cavopulmonary connection(TCPC)in two(0.8%),and Glenn operation in one operation(0.4%).Reoperation was performed in five patients(2.0%)during *** them,tricuspid valve replacement was performed in one patient,1½ventricle repair in two patients,and tricuspid valve annulus reinforcement in two *** patients died with an early mortality rate of 2.0%.Complete atrioventricular conduction block was complicated in one patient(0.4%).A total of 244 patients was followed up(four in the 253 patients lost)with a duration of 3.0-168.0(87.6±38.4)*** function of 244 patients improved significantly with mean New York heart Association(NYHA)functional class recovery from 3.5 to *** mean grade of tricuspid valve regurgitation improved from 3.6 to *** late deaths(1.2%)*** survival rates at five and ten years after surgery were 98.6%and 98.2%,*** was performed in five patients(2.0%)during the follow-up ***:Based on our management strategies and operative principles and techniques,anatomical correction of EA is capable of achiev

关键词： Ebstein’s anomaly Anatomical repair Surgical treatment Long-term result

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Trans-Frame Aortic Regurgitation of New-Generation Aortic Bioprosthesis

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World Journal of Cardiovascular Surgery 2024年第4期14卷 41-44页

作者： Michael Timothy Simpson Kasmir Ramo Vinayak Bapat Andrea Miltiades Isaac George Division of Cardiothoracic Surgery New York-Presbyterian Hospital Columbia University Medical Center New York USA Division of Cardiothoracic Anesthesia New York-Presbyterian Hospital Columbia University Irving Medical Center New York USA Division of Cardiothoracic Surgery Abbott Northwestern Hospital Minneapolis Heart Institute Minneapolis USA

A widely used aortic valve bioprosthesis is susceptible to regurgitation between the sewing ring and the frame of the valve due to its relatively thin fabric coverage. In some cases this leak has been shown to resolve with administration of protamine, however, tension on this area from annular sutures placed in an asymmetric bicuspid valve annulus may exacerbate the defect.

关键词： Aortic valve Replacement Bicuspid Aortic valve Paravalvular Leak

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Relationship between mitochondrial respiratory dysfunction of blood mononuclear cells and heart failure severity

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Journal of Geriatric Cardiology 2024年第1期21卷 130-134页

作者： Viacheslav A.Korepanov Tariel A.Atabekov Tatiana Yu.Rebrova Roman E.Batalov Sergey A.Afanasiev Cardiology Research Institute Tomsk National Research Medical CenterRussian Academy of SciencesTomskRussia

Chronic heart failure(CHF)is a clinical syndrome manifested by reduced pumping ability of the heart,increased pressure in heart chambers in both physical activity and at *** symptoms of this syndrome are dyspnea,undue fatigability,peripheral edema,which follow structural and functional changes of the myocardium.[1]The growing incidence of CHF,especially among elderly people,is an urgent problem for medicine in the vast majority of industrialized *** instance,in Russian Federation,CHF is diagnosed in about 7%of cardiovascular *** the same time,this indicator varies from 0.3%in young people(20-29 years old)to 70%in the older age group.[2,3].

关键词： severity instance pumping

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Anatomical morphology of the aortic valve in Chinese aortic stenosis patients and clinical results after downsize strategy of transcatheter aortic valve replacement

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Chinese Medical Journal 2022年第24期135卷 2968-2975页

作者： Guannan Niu Walid Ben Ali Moyang Wang Hasan Jilaihawi Haitong Zhang Qian Zhang Yunqing Ye Xinmin Liu Jing Yao Qinghao Zhao Yubin Wang Zheng Zhou Lizhi Zhang Xinshuang Ren Yunqiang An Bin Lu Thomas Modine Yongjian Wu Guangyuan Song Department of Cardiology Fuwai HospitalNational Center for Cardiovascular DiseaseChinese Academy of Medical Science and Peking Union Medical CollegeBeijing 100037China structural heart Intervention Program Department of SurgeryMontreal Heart InstituteMontreal H1T 1C8QuebecCanada heart valve center NYU Langone HealthNew YorkNY 10016USA Interventional center of Valvular heart Disease Anzhen Hospital Affiliate of Capital University of Medical SciencesBeijing 100029China Eagles Corelab. YingKe Medical(Beijing)Co.LtdBeijing 100160China Department of Radiology Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China Service Médico-Chirurgical:Valvulopathies-Chirurgie Cardiaque-Cardiologie Interventionelle Structurelle Hôpital Cardiologique de Haut LévèqueCHU BordeauxBordeaux 33000France

Background:The study aimed to describe the aortic valve morphology in Chinese patients underwent transcatheter aortic valve replacement(TAVR)for symptomatic severe aortic stenosis(AS),and the impact of sizing strategies and related procedural ***:Patients with severe AS who underwent TAVR were consecutively enrolled from 2012 to *** anatomy and morphology of the aortic root were assessed."Downsize"strategy was preformed when patients had complex *** clinical outcomes of patients who performed downsize strategy were compared with those received annular sizing *** primary outcome was device success rate,and secondary outcomes included valve Academic Research Consortium-3 clinical outcomes variables based on 1-year ***:A total of 293 patients were *** them,95 patients(32.4%)had bicuspid aortic *** calcium volume(Hounsfield Unit-850)of aortic root was 449.90(243.15-782.15)*** is distributed mostly on the leaflet *** strategy was performed in 204 patients(69.6%).Compared with the patients who performed annular sizing strategy,those received downsize strategy achieved a similar device success rate(82.0%[73]vs.83.3%[170],P=0.79).Aortic valve gradients(downsize strategy group *** sizing group,11.28 mmHg vs.11.88 mmHg,P=0.64)and percentages of patients with moderate or severe paravalvular regurgitation 2.0%(4/204)vs.4.5%(4/89),P=0.21were similar in the two groups at 30 days after *** echocardiographic results were sustainable for one ***:Chinese TAVR patients have more prevalent bicuspid morphology and large calcium volume of aortic *** is distributed mostly on the leaflet *** with annular sizing strategy,downsize strategy provided a non-inferior device success rate and transcatheter heart valve hemodynamic performance in self-expanding TAVR procedure.

关键词： Aortic stenosis China Sizing strategy Transcatheter aortic valve replacement Aortic valve Morphology

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