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Genetically predicted waist circumference and risk of atrial fibrillation

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Chinese Medical Journal 2024年第1期137卷 82-86页

作者： Wenting Wang Jiang-shan Tan Jingyang Wang Wei Xu Liting Bai Yu Jin Peng Gao Peiyao Zhang Yixuan Li Yanmin Yang Jinping Liu department of Cardiopulmonary Bypass State Key Laboratory of Cardiovascular DiseaseFuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China department of Anaesthesiology Second Affiliated HospitalHainan Medical CollegeHaikouHainan 570311China State Key Laboratory of cardiovascular disease Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China

Introduction:Observational studies have revealed an association between waist circumference(WC)and atrial fibrillation(AF).However,it is difficult to infer a causal relationship from observational studies because the observed associations could be confounded by unknown risk ***,the causal role of WC in AF is *** study was designed to investigate the causal association between WC and AF using a two-sample Mendelian randomization(MR)***:In our two-sample MR analysis,the genetic variation used as an instrumental variable for MR was acquired from a genome-wide association study(GWAS)of WC(42 single nucleotide polymorphisms with a genetic significance of P<5×10^(-8)).The data of WC(from the Genetic Investigation of ANthropometric Traits consortium,containing 232,101 participants)and the data of AF(from the European Bioinformatics Institute database,containing 55,114 AF cases and 482,295 controls)were used to assess the causal role of WC on *** different approaches(inverse variance weighted[IVW],MR-Egger,and weighted median regression)were used to ensure that our results more ***:All three MR analyses provided evidence of a positive causal association between high WC and *** WC was suggested to increase the risk of AF based on the IVW method(odds ratio[OR]=1.43,95%confidence interval[CI],1.30-1.58,P=2.51×10^(-13)).The results of MR-Egger and weighted median regression exhibited similar trends(MR-Egger OR=1.40[95%CI,1.08-1.81],P=1.61×10^(-2);weighted median OR=1.39[95%CI,1.21-1.61],P=1.62×10^(-6)).MR-Egger intercepts and funnel plots showed no directional pleiotropic effects between high WC and ***:Our findings suggest that greater WC is associated with an increased risk of *** measures to reduce WC may help prevent the occurrence of AF.

关键词： Genetically predicted Waist circumference Atrial fibrillation Mendelian randomization

Top Five Stories of the Cellular Landscape and Therapies of Atherosclerosis:Current Knowledge and Future Perspectives

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Current Medical Science 2024年第1期44卷 1-27页

作者： Qi PAN Cheng CHEN Yue-jin YANG State Key Laboratory of cardiovascular disease Department of CardiologyFuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Science and Peking Union Medical CollegeBeijing 100037China

Atherosclerosis(AS)is characterized by impairment and apoptosis of endothelial cells,continuous systemic and focal inflammation and dysfunction of vascular smooth muscle cells,which is documented as the traditional cellular ***,the mechanisms appear much more complicated than we thought since a bulk of studies on efferocytosis,transdifferentiation and novel cell death forms such as ferroptosis,pyroptosis,and extracellular trap were *** of novel pathological cellular landscapes provides a large number of therapeutic *** the other side,the unsatisfactory therapeutic effects of current treatment with lipid-lowering drugs as the cornerstone also restricts the efforts to reduce global AS *** cell-or nanoparticle-based strategies spurred a lot of attention due to the attractive therapeutic effects and minimized adverse *** the complexity of pathological changes of AS,attempts to develop an almighty medicine based on single mechanisms could be theoretically *** this review,the top stories in the cellular landscapes during the initiation and progression of AS and the therapies were summarized in an integrated perspective to facilitate efforts to develop a multi-targets strategy and fill the gap between mechanism research and clinical *** future challenges and improvements were also discussed.

关键词： atherosclerosis transdifferentiation extracellular traps efferocytosis stem cell nanoparticles

Modeling drug-induced mitochondrial toxicity with human primary cardiomyocytes

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Science China(Life Sciences) 2024年第2期67卷 301-319页

作者： Xiaoli Tang Hong Liu Rongjia Rao Yafei Huang Mengqi Dong Miaomiao Xu Shanshan Feng Xun Shi Li Wang Zengwu Wang Bingying Zhou State Key Laboratory of cardiovascular disease Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100037China department of Epidemiology Cardiovascular Institute and Fuwai HospitalChinese Academy of Medical Science&Peking Union Medical CollegeBeijing 100037China Shenzhen Key Laboratory of cardiovascular disease Fuwai Hospital Chinese Academy of Medical SciencesShenzhenShenzhen 518020China

Mitochondrial toxicity induced by therapeutic drugs is a major contributor for cardiotoxicity,posing a serious threat to pharmaceutical industries and patients’***,mitochondrial toxicity testing is not incorporated into routine cardiac safety screening *** accurately model native human cardiomyocytes,we comprehensively evaluated mitochondrial responses of adult human primary cardiomyocytes(h PCMs)to a nucleoside analog,remdesivir(RDV).Comparison of their response to human pluripotent stem cell-derived cardiomyocytes revealed that the latter utilized a mitophagy-based mitochondrial recovery response that was absent in h ***,action potential duration was elongated in h PCMs,reflecting clinical incidences of RDV-induced QT *** a screen for mitochondrial protectants,we identified mitochondrial ROS as a primary mediator of RDV-induced *** study demonstrates the utility of h PCMs in the detection of clinically relevant cardiac toxicities,and offers a framework for h PCM-based high-throughput screening of cardioprotective agents.

关键词： remdesivir mitochondrial toxicity cardiotoxicity human primary cardiomyocytes high-throughput screening

Atorvastatin, etanercept and the nephrogenic cardiac sympathetic remodeling in chronic renal failure rats

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Journal of Geriatric Cardiology 2024年第4期21卷 443-457页

作者： Jing-Yue XU Zheng-Kai XUE Ya-Ru ZHANG Xing LIU Xue ZHANG Xi YANG Tong LIU Kang-Yin CHEN Tianjin Key Laboratory of Ionic-Molecular Function of cardiovascular disease Department of CardiologyTianjin Institute of Cardiologythe Second Hospital of Tianjin Medical UniversityTianjinChina

BACKGROUND Chronic renal failure(CRF) patients are predisposed to arrhythmias, while the detailed mechanisms are unclear. We hypothesized the chronic inflammatory state of CRF patients may lead to cardiac sympathetic remodeling, increasing the incidence of ventricular arrhythmia(VA) and sudden cardiac death. And explored the role of atorvastatin and etanercept in this *** A total of 48 rats were randomly divided into sham operation group(Sham group), CRF group, CRF + atorvastatin group(CRF + statin group), and CRF + etanercept group(CRF + rhTNFR-Fcgroup). Sympathetic nerve remodeling was assessed by immunofluorescence of growth-associated protein 43(GAP-43) and tyrosine hydroxylase positive area fraction. Electrophysiological testing was performed to assess the incidence of VA by assessing the ventricular effective refractory period and ventricular fibrillation threshold. The levels of tumor necrosis factor-alpha(TNF-α) and interleukin-1beta were determined by Western blotting and enzyme-linked immunosorbent *** Echocardiogram showed that compared with the Sham group, left ventricular end-systolic diameter and ventricular weight/body weight ratio were significantly higher in the CRF group. Hematoxylin-eosin and Masson staining indicated that myocardial fibers were broken, disordered, and fibrotic in the CRF group. Western blotting, enzyme-linked immunosorbent assay,immunofluorescence and electrophysiological examination suggested that compared with the Sham group, GAP-43 and TNF-α proteins were significantly upregulated, GAP-43 and tyrosine hydroxylase positive nerve fiber area was increased, and ventricular fibrillation threshold was significantly decreased in the CRF group. The above effects were inhibited in the CRF + statin group and the CRF + *** In CRF rats, TNF-α was upregulated, cardiac sympathetic remodeling was more severe, and the nephrogenic cardiac sympathetic remodeling existed. Atorvastatin and etanercept c

关键词： remodeling cardiac inhibited

Effects of PEAR1 gene polymorphism on big endothelin-1 levels in Chinese patients with acute myocardial infarction after percutaneous coronary intervention

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World Journal of Emergency Medicine 2024年第3期15卷 229-231页

作者： Yi Yao Na Xu Xiaofang Tang Ce Zhang Sida Jia Jingjing Xu Ying Song Xueyan Zhao Runlin Gao Jinqing Yuan Center for Coronary Heart disease National Center for Cardiovascular DiseasesState Key Laboratory of Cardiovascular DiseaseFuwai HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China

Acute myocardial infarction (AMI) has been associated with poor prognosis,even after revascularization with percutaneous coronary intervention (PCI),likely due to coronary endothelial cell dysfunction and injury.^([1,2])Endothelin-1 (ET-1),a peptide that serves as a vasoconstrictor of smooth muscle cell proliferation,can reflect endothelial cell functional *** to low circulation levels and short plasma half-life time,measuring plasma ET-1 levels is *** contrast,big ET-1.

关键词： coronary percutaneous endothelin

Association of acute glycemic parameters at admission with cardiovascular mortality in the oldest old with acute myocardial infarction

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Journal of Geriatric Cardiology 2024年第3期21卷 349-358页

作者： Hui-Hui LIU Meng ZHANG Yuan-Lin GUO Cheng-Gang ZHU Na-Qiong WU Ying GAO Rui-Xia XU Jie QIAN Ke-Fei DOU Jian-Jun LI Cardiometabolic Center State Key Laboratory of Cardiovascular DiseaseFuwai HospitalNational Center for Cardiovascular DiseasesNational Clinical Research Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

OBJECTIVES Stress-related glycemic indicators,including admission blood glucose(ABG),stress-hyperglycemia ratio(SHR),and glycemic gap(GG),have been associated with worse outcomes after acute myocardial infarction(AMI).However,data regarding their prognostic value in the oldest old with AMI are ***,this study aimed to investigate the association of stress-related glycemic indicators with short-and long-term cardiovascular mortality(CVM)in the oldest old(≥80 years)with *** In this prospective study,a total of 933 consecutive old patients with AMI admitted to FuWai hospital(Beijing,China)were *** admission,ABG,SHR,and GG were assessed and all participants were classified according to their ***-Meier,restricted cubic splines(RCS),and multivariate Cox regression analyses were performed to evaluate the association between these glycemic indicators and CVM within 30 days and long-term *** During an average of 1954 patient-years of follow-up,a total of 250 cardiovascular deaths were ***-Meier analyses showed the lowest CVM in quartile 1 of ABG and in quartile 2 of SHR and *** adjusting for potential covariates,patients in quartile 4 of ABG,SHR,and GG had a respective 1.67-fold(95%CI:1.03-2.69;P=0.036),1.80-fold(95%CI:1.16-2.79;P=0.009),and 1.78-fold(95%CI:1.14-2.79;P=0.011)higher risk of long-term CVM risk compared to those in the reference groups(quartile 1 of ABG and quartile 2 of SHR and GG).Furthermore,RCS suggested a J-shaped relationship of ABG and a Ushaped association of SHR and GG with long-term ***,we observed similar associations of these acute glycemic parameters with 30-day *** Our data first indicated that SHR and GG consistently had a U-shaped association with both 30-day and longterm CVM among the oldest old with AMI,suggesting that they may be useful for risk stratification in this special population.

关键词： admitted infarction shaped

Association of stage 1 hypertension defined by the 2017 ACC/AHA guideline with cardiovascular events and mortality in Chinese adults

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Chinese Medical Journal 2024年第1期137卷 63-72页

作者： Qiannan Gao Liuxin Li Jingjing Bai Luyun Fan Jiangshan Tan Shouling Wu Jun Cai Hypertension Center Fuwai HospitalState Key Laboratory of Cardiovascular DiseaseNational Center for Cardiovascular DiseasesPeking Union Medical CollegeChinese Academy of Medical SciencesBeijing 100037China department of Cardiology Kailuan General HospitalNorth China University of Science and TechnologyTangshanHebei 063000China Emergency Center Fuwai HospitalState Key Laboratory of Cardiovascular DiseaseNational Center for Cardiovascular DiseasesPeking Union Medical CollegeChinese Academy of Medical SciencesBeijing 100037China

Background:The 2017 American College of Cardiology/American Heart Association(ACC/AHA)blood pressure(BP)guideline lowered the threshold defining hypertension to 130/80 ***,how stage 1 hypertension defined using this guideline is associated with cardiovascular events in Chinese adults remains *** study assessed the association between stage 1 hypertension defined by the 2017 ACC/AHA guideline and clinical outcomes in the Chinese ***:Participants with stage 1 hypertension(n=69,509)or normal BP(n=34,142)were followed in this study from 2006/2007 to *** 1 hypertension was defined as a systolic blood pressure of 130-139 mmHg or a diastolic blood pressure of 80-89 *** were taking antihypertensive medication or had a history of myocardial infarction(MI),stroke,or cancer at *** primary outcome was a composite of MI,stroke,and all-cause *** secondary outcomes were individual components of the primary *** proportional hazards models were used for the ***:During a median follow-up of 11.09 years,we observed 10,479 events(MI,n=995;stroke,n=3408;all-cause mortality,n=7094).After multivariable adjustment,the hazard ratios for stage 1 hypertension *** BP were 1.20(95%confidence interval[CI],1.13-1.25)for primary outcome,1.24(95%CI,1.05-1.46)for MI,1.45(95%CI,1.33-1.59)for stroke,and 1.11(95%CI,1.04-1.17)for all-cause *** hazard ratios for participants with stage 1 hypertension who were prescribed antihypertensive medications compared with those without antihypertensive treatment during the follow-up was 0.90(95%CI,0.85-0.96).Conclusions:Using the new definition,Chinese adults with untreated stage 1 hypertension are at higher risk for MI,stroke,and all-cause *** finding may help to validate the new BP classification system in China.

关键词： Hypertension cardiovascular disease All-cause mortality Cox regression analysis

ASF1A-dependent P300-mediated histone H3 lysine 18 lactylation promotes atherosclerosis by regulating EndMT

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3027-3048页

作者： Mengdie Dong Yunjia Zhang Minghong Chen Yongkang Tan Jiao Min Xian He Fuhao Liu Jiaming Gu Hong Jiang Longbin Zheng Jiajing Chen Quanwen Yin Xuesong Li Xiang Chen Yongfeng Shao Yong Ji Hongshan Chen department of cardiovascular Surgery the First Affiliated Hospital of Nanjing Medical Universityand Key Laboratory of Cardiovascular and Cerebrovascular MedicineSchool of PharmacyNational Vaccine Innovation PlatformNanjing Medical UniversityNanjing 211166China Key Laboratory of cardiovascular and Cerebrovascular Medicine School of PharmacyNanjing Medical UniversityNanjing 211166China department of Clinical Medicine Nanjing Medical University TIANYUAN Honors SchoolNanjing Medical UniversityNanjing 211166China department of Anesthesiology Sir Run Run HospitalNanjing Medical UniversityNanjing 211166China department of cardiovascular Surgery the First Affiliated Hospital of Nanjing Medical UniversityNanjing 211166China Key Laboratory of cardiovascular and Cerebrovascular Medicine Key Laboratory of Targeted Intervention of Cardiovascular DiseaseCollaborative Innovation Center for Cardiovascular Disease Translational MedicineState Key Laboratory of Reproductive MedicineSchool of Pharmacythe Affiliated Suzhou Hospital of Nanjing Medical UniversityGusu SchoolNanjing Medical UniversityNanjing 211166China National Key Laboratory of Frigid Zone cardiovascular diseases(NKLFZCD) Department of Pharmacology(State-Province Key Laboratories of Biomedicine-Pharmaceutics of China)College of PharmacyKey Laboratory of Cardiovascular Medicine Research and Key Laboratory of Myocardial IschemiaChinese Ministry of EducationNHC Key Laboratory of Cell Transplantationthe Central Laboratory of the First Affiliated HospitalHarbin Medical UniversityHarbin 150081China Key Laboratory of Targeted Intervention of cardiovascular disease Collaborative Innovation Center for Cardiovascular Disease Translational MedicineNanjing Medical UniversityNanjing 211166China department of Cardiology Huai’an First People’s Hospital Affiliated with Nanjing Medical UniversityHuai’an 223399China

Endothelial-to-mesenchymal transition(EndMT)is a key driver of *** glycolysis is increased in the endothelium of atheroprone areas,accompanied by elevated lactate *** lactylation,mediated by lactate,can regulate gene expression and participate in disease ***,whether histone lactylation is involved in atherosclerosis remains ***,we report that lipid peroxidation could lead to EndMT-induced atherosclerosis by increasing lactatedependent histone H3 lysine 18 lactylation(H3K18la)in vitro and in vivo,as well as in atherosclerotic patients’***,the histone chaperone ASF1A was first identified as a cofactor of P300,which precisely regulated the enrichment of H3K18la at the promoter of SNAI1,thereby activating SNAI1 transcription and promoting *** found that deletion of ASF1A inhibited EndMT and improved endothelial *** analysis based on Apoe^(KO)Asf1a^(ECKO) mice in the atherosclerosis model confirmed the involvement of H3K18la in atherosclerosis and found that endotheliumspecific ASF1A deficiency inhibited EndMT and alleviated atherosclerosis *** of glycolysis by pharmacologic inhibition and advanced PROTAC attenuated H3K18la,SNAI1 transcription,and EndMT-induced *** study illustrates precise crosstalk between metabolism and epigenetics via H3K18la by the P300/ASF1A molecular complex during EndMT-induced atherogenesis,which provides emerging therapies for atherosclerosis.

关键词： Histone lactylation Atherosclerosis Endothelial-tomesenchymal transition ASF1A SNAI1 Endothelial dysfunction Lactate Epigenetic

LncRNA CCRR maintains Ca^(2+)homeostasis against myocardial infarction through the FTO-SERCA2a pathway

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Science China(Life Sciences) 2024年第8期67卷 1601-1619页

作者： Hua Yang Lina Xuan Shengjie Wang Huishan Luo Xiaomeng Duan Jianjun Guo Shijia Cui Jieru Xin Junwei Hao Xiufang Li Jun Chen Feihan Sun Xiaolin Hu Siyun Li Ying Zhang Lei Jiao Baofeng Yang Lihua Sun department of Pharmacology Harbin Medical University(State Key Laboratory of Frigid Zone Cardiovascular Diseasethe State-Province Key Laboratories of Biomedicine-Pharmaceutics of ChinaKey Laboratory of Cardiovascular ResearchMinistry of EducationJoint International Research Laboratory of Cardiovascular Medicine ResearchMinistry of EducationChina)College of PharmacyHarbin Medical UniversityHarbin 150081China

Cardiac conduction regulatory RNA(CCRR)has been documented as an antiarrhythmic lncRNA in our earlier *** study aimed to evaluate the effects of CCRR on SERCA2a and the associated Ca^(2+)homeostasis in myocardial infarction(MI).Overexpression of CCRR via AAV9-mediated delivery not only partially reversed ischemia-induced contractile dysfunction but also alleviated abnormal Ca^(2+)homeostasis and reduced the heightened methylation level of SERCA2a following *** effects were also observed in CCRR overexpressing transgenic mice.A conserved sequence domain of CCRR mimicked the protective function observed with the full ***,silencing CCRR in healthy mice led to intracellular Ca^(2+)overloading of *** increased SERCA2a protein stability by upregulating FTO *** direct interaction between CCRR and FTO protein was characterized by RNA-binding protein immunoprecipitation(RIP)analysis and RNA pulldown *** of NFATc3 was identified as an upstream mechanism responsible for CCRR downregulation in *** study demonstrates that CCRR is a protective lncRNA that acts by maintaining the function of FTO,thereby reducing the m^(6)A RNA methylation level of SERCA2a,ultimately preserving calcium homeostasis for myocardial contractile function in ***,CCRR may be considered a promising therapeutic strategy with a beneficial role in cardiac pathology.

关键词： CCRR calcium homeostasis FTO myocardial infarction SERCA2a