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Macrophages in cardiovascular diseases:molecular mechanisms and therapeutic targets

Signal Transduction and Targeted Therapy 2024年第6期9卷 2598-2641页

作者： Runkai Chen Hongrui Zhang Botao Tang Yukun Luo Yufei Yang Xin Zhong Sifei Chen Xinjie Xu Shengkang Huang Canzhao Liu Department of Cardiology Laboratory of Heart CenterHeart CenterTranslational Medicine Research CenterZhujiang HospitalSouthern Medical University253 Industrial AvenueGuangzhou 510280China State Key Laboratory of Cardiovascular disease Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China

The immune response holds a pivotal role in cardiovascular disease *** multifunctional cells of the innate immune system,macrophages play an essential role in initial inflammatory response that occurs following cardiovascular injury,thereby inducing subsequent damage while also facilitating ***,the diverse phenotypes and phenotypic alterations of macrophages strongly associate with distinct types and severity of cardiovascular diseases,including coronary heart disease,valvular disease,myocarditis,cardiomyopathy,heart failure,atherosclerosis and aneurysm,which underscores the importance of investigating macrophage regulatory mechanisms within the context of specific ***,recent strides in single-cell sequencing technologies have revealed macrophage heterogeneity,cell–cell interactions,and downstream mechanisms of therapeutic targets at a higher resolution,which brings new perspectives into macrophage-mediated mechanisms and potential therapeutic targets in cardiovascular ***,myocardial fibrosis,a prevalent characteristic in most cardiac diseases,remains a formidable clinical challenge,necessitating a profound investigation into the impact of macrophages on myocardial fibrosis within the context of cardiac *** this review,we systematically summarize the diverse phenotypic and functional plasticity of macrophages in regulatory mechanisms of cardiovascular diseases and unprecedented insights introduced by singlecell sequencing technologies,with a focus on different causes and characteristics of diseases,especially the relationship between inflammation and fibrosis in cardiac diseases(myocardial infarction,pressure overload,myocarditis,dilated cardiomyopathy,diabetic cardiomyopathy and cardiac aging)and the relationship between inflammation and vascular injury in vascular diseases(atherosclerosis and aneurysm).Finally,we also highlight the preclinical/clinical macrophage targeting strategies and translational

关键词： diseases cardiovascular therapeutic

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Effect of Intracoronary Infusion of Bone Marrow Mononuclear Cells or Peripheral Endothelial Progenitor Cells on Myocardial Ischemia-reperfusion Injury in Mini-swine

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Chinese Medical Sciences Journal 2010年第3期25卷 176-181页

作者： Chong-jian Li Run-lin Gao Yue-jin Yang Feng-huan Hu Wei-xian Yang Shi-jie You Lai-feng Song Ying-mao Ruan Shu-bin Qiao Ji-lin Chen Jian-jun Li center of coronary heart disease Department of Pathology Fuwai Hospita Chinese Academy of Medical Sciences ＆ Peking Union Medical College Beijing 100037 China

Objective To simulate and assess the clinical effect of intracoronary infusion of bone marrow mononuclear cells or peripheral endothelial progenitor cells on myocardial reperfusion injury in mini-swine model. Methods Twenty-three mini-swine with myocardial reperfusion injury were used as designed in the study protocol. About （3.54±0.90）×10^7 bone marrow mononuclear cells （MNC group, n=9） or （1.16± 1.07）× 10^7 endothelial progenitor cells （EPC group, n=7） was infused into the affected coronary segment of the swine. The other mini-swine were infused with phosphate buffered saline as control （n=7）. Echocardio- graphy and hemodynamic studies were performed before and 4 weeks after cell infusion. Myocardium infarc- tion size was calculated. Stem cell differentiation was analyzed under a transmission electromicroscope. Results Left ventricular ejection fraction dropped by 0% in EPC group, 2% in MNC group, and 10% in the control group 4 weeks after cell infusion, respectively （P〈0.05）. The systolic parameters increased in MNC and EPC groups but decreased in the control group. However, the diastolic parameters demonstrated no significant change in the three groups （P〉0.05）. EPC decreased total infarction size more than MNC did （1.60±0.26 cm2 vs. 3.71±1.38 cm2, P〈0.05）. Undermature endothelial cells and myocytes were found under transmission electromlcroscope. Conclusions Transplantation of either MNC or EPC may be beneficial to cardiac systolic function, but might not has obvious effect on diastolic function. Intracoronary infusion of EPC might be better than MNC in controlling infarction size. Both MNC and EPC may stimulate angiogenesis, inhibit flbrogenesis, and differentiate into myocardial cells.

关键词： bone marrow mononuclear cells endothelial progenitor cells myocardialischemia-reperfusion injury

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Electrical heterogeneity of canine right ventricular transient outward potassium currents

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Chinese Medical Journal 2004年第4期117卷 528-531页

作者：杨新春周鹏李翠兰 heart center Beijing 100020 China

Background Some studies have confirmed that the right ventricular walls of most rodents, such as canines and humans, have evident transient outward potassium current (I to1) heterogeneity, and this heterogeneity is closely related to J point elevation, J wave formation, and some ventricular tachycardias such as ventricular fibrillations caused by Brugada syndrome. This study is designed to investigate transmural electrical heterogeneity of the canine right ventricle during repolarization (phase 1) from the viewpoint of 4-aminopyridine sensitive and calcium-independent I to1. Methods Adult canine single right ventricular epicardial (Epi) cells, mid-myocardial (M) cells, and endocardial (Endo) cells were enzymatically dissociated. Whole cell voltage-clamp recordings were made to compare the I to1 values of the three cell types. Results At 37℃ and using 0.2 Hz and +70 mV depolarizing test potentials, the average peak I to1 values of Epi cells and M cells averaged (4070±1720) pA and (3540±1840) pA, respectively. The activated and inactivated Epi and M cells kinetic processes were in accordance with the Boltzmann distribution. Compared with I to1 in Epi cells and M cells, the average peak I to1 in Endo cells was very low, averaged (470±130) pA. Conclusions These results suggest that there are evident differences and potent gradients in I to1 between the three cardiac cell types, especially between Epi and Endo cells. These differences are among the prominent manifestations of right ventricular electrical heterogeneity, and may form an important ionic basis and prerequisite for some malignant arrhythmias in the right ventricle, including those arising from Brugada syndrome and other diseases.

关键词： electrophysiology · heart ventricles · transient outward potassium current

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Outcomes of Self-Expanding Transcatheter Pulmonary Valves:Extended Follow-Up of a Prospective Trial

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Congenital heart disease 2023年第2期18卷 219-234页

作者： Jingnan Zhang Junyi Wan Yihang Li Yu Han Jiahua Pan Fang Fang Shiliang Jiang Xiangbin Pan Gejun Zhang Department of Structural heart disease National Center for Cardiovascular DiseaseChina&Fuwai HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingChina Department of Structural heart disease Central China Fuwai HospitalZhengzhouChina Yunnan Fuwai Cardiovascular Hospital KunmingChina Department of Radiology National Center for Cardiovascular DiseaseChina&Fuwai HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingChina

Background:The Venus-P valve was the first self-expanding valve used world-wide for transcatheter pulmonary valve replacement(TPVR)in patients with severe pulmonary regurgitation(PR).We intended to report the extended follow-up results from the prospective trial(***02590679).Methods:A total of 38 patients with severe PR(mean age 24.2±13.2)were ***-up data were obtained after implanted at 1,6,and 12 months and yearly *** frame geometry was assessed on post-implant computer tomography(CT)scanning by calculating the non-circularity[circularity ratio(minimum diameter/maximum diameter)<0.9]and under-expansion[expansion ratio(derived external valve area/nominal external valve area)<0.9).Adverse events(all-cause mortality,reintervention,valve dysfunction,stent fracture and endocarditis)were ***:All valves were implanted successfully with normal function at *** CT analysis showed underexpanded valve was detected in 22 patients(63%)and non-circular valve was seen in 16 patients(46%).During a median follow-up of 4.8 years(range 0.3-8.1),there were 1 death and 1 surgical explant,both resulting from ***-year freedom from valve dysfunction and stent fracture were 84.8%(95%CI 74.8-94.7)and 83.5%(95%CI 73.8-93.2).Endocarditis occurred in 3 patients at a median time of 7 *** fracture was more common in patients with non-circularity ***:TPVR using Venus-P valve is associated with favorable outcomes at 5 ***-circular shapes in the valve level may have a higher risk of stent fracture.

关键词： Congenital heart disease pulmonary regurgitation transcatheter pulmonary valve replacement Venus-P valve

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Evolution of heart transplant donor characteristics in the 21st century: A United States single center’s experience

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World Journal of Transplantation 2024年第3期14卷 22-29页

作者： Alexander M Spring Christiana Gjelaj Shivank Madan Snehal R Patel Omar Saeed Sandhya Murthy Yogita Rochlani Daniel B Sims Sasha Vukelic Stephen J Forest Jamil F Borgi Daniel J Goldstein Ulrich P Jorde Montefiore-Einstein center for heart and Vascular Care Montefiore Medical CenterAlbert Einstein College of MedicineBronxNY 10467United States Division of Cardiothoracic Surgery Tulane UniversityNew OrleansLA 70112United States

Despite a record setting number of heart transplants performed annually,the national donor shortage continues to plague transplant teams across the United *** we describe the barriers to adaptation of numerous“non-traditional”orthotopic heart transplant donor characteristics including donors with hepatitis C virus,those meeting criteria for donation after cardiac death,donors with coronavirus disease 19 infection,donors with the human immunodeficiency virus,and grafts with left ventricular systolic *** center’s objective was to increase our transplant volume by expanding our donor pool from“traditional”donors to these“non-traditional”*** detail how medical advances such as certain laboratory studies,pharmacologic interventions,and organ care systems have allowed our center to expand the donor pool thereby increasing transplantation volume without adverse effects on outcomes.

关键词： Orthotopic heart transplantation Hepatitis C virus COVID-19 Left ventricular systolic dysfunction Human immunodeficiency virus Donation after cardiac death

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Impact of diabetes mellitus on long-term prognosis of patients after implantation of biodegradable polymer drug eluting stent or excel stent

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China Medical Abstracts (Internal Medicine) 2018年第3期 154-155页

作者：王娟 coronary heart Dis center Fuwai HospCAMS & PUMC

Objective To evaluate the impact of diabetes melli tus on prognosis of coronary artery disease patients afte implantation of the novel biodegradable polymer drug elu ting *** PANDA III was a perspective,multi-center,"all-comer", randomized controlled *** Dec. 2013 and Sep. 2014, 2 348 patients from46 centers were enrolled. All the patients underwent per

关键词： DM Impact of diabetes mellitus on long-term prognosis of patients after implantation of biodegradable polymer drug eluting stent or excel stent

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The effect of fasting plasma glucose on in-hospital mortality after acute myocardial infarction in patients with and without diabetes:findings from a prospective,nationwide,and multicenter registry

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Journal of Geriatric Cardiology 2024年第5期21卷 523-533页

作者： Rui FU Ying-Xuan ZHU Kong-Yong CUI Jin-Gang YANG Hai-Yan XU Dong YIN Wei-Hua SONG Hong-Jian WANG Cheng-Gang ZHU Lei FENG Wei WU Kai-HongCHEN Yan-Yan ZHAO Ye LU Ke-Fei DOU Yue-Jin YANG on behalf of the CAMI Registry Investigators Cardiometabolic Medicine center Fuwai HospitalNational Center for Cardiovascular DiseasesState Key Laboratory of Cardiovascular DiseaseNational Clinical Research Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Medical Research&Biometrics center Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina coronary heart disease center Fuwai HospitalNational Center for Cardiovascular DiseasesState Key Laboratory of Cardiovascular DiseaseNational Clinical Research Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of Cardiology Guangzhou Traditional Chinese Medical College First Affiliated HospitalGuangdong ProvinceChina Department of Cardiology Longyan Hospital First HospitalFujian ProvinceChina 不详

OBJECTIVES To evaluate the predictive value of fasting plasma glucose(FPG)for in-hospital mortality in patients with acute myocardial infarction(AMI)with different glucose metabolism *** We selected 5,308 participants with AMI from the prospective,nationwide,multicenter CAMI registry,of which 2,081 were diabetic and 3,227 were *** were divided into high FPG and low FPG groups according to the optim-al cutoff values of FPG to predict in-hospital mortality for diabetic and nondiabetic cohorts,*** primary endpoint was in-hospital *** Overall,94 diabetic patients(4.5%)and 131 nondiabetic patients(4.1%)died during hospitalization,and the optimal FPG thresholds for predicting in-hospital death of the two cohorts were 13.2 mmol/L and 6.4 mmol/L,*** with individuals who had low FPG,those with high FPG were significantly associated with higher in-hospital mortality in diabet-ic cohort(10.1%vs.2.8%;odds ratio[OR]=3.862,95%confidence interval[CI]:2.542-5.869)and nondiabetic cohort(7.4%vs.1.7%;HR=4.542,95%CI:3.041-6.782).After adjusting the potential confounders,this significant association was not ***-more,FPG as a continuous variable was positively associated with in-hospital mortality in single-variable and multivariable models regardless of diabetic *** FPG to the original model showed a significant improvement in C-statistic and net reclassification in diabetic and nondiabetic *** This large-scale registry indicated that there is a strong positive association between FPG and in-hospital mor-tality in AMI patients with and without *** might be useful to stratify patients with AMI.

关键词： patients fasting infarction

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Triglyceride glucose index predicts in-hospital mortality in patients with ST-segment elevation myocardial infarction who underwent primary angiography

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Journal of Geriatric Cardiology 2023年第3期20卷 185-194页

作者： Rui FU Yan-Yan ZHAO Kong-Yong CUI Jin-Gang YANG Hai-Yan XU Dong YIN Wei-Hua SONG Hong-Jian WANG Cheng-Gang ZHU Lei FENG Zhi-Fang WANG Qing-Sheng WANG Ye LU Ke-Fei DOU Yue-Jin YANG the CAMI Registry Investigators Cardiometabolic Medicine center Department of CardiologyFuwai HospitalNational Center for Cardiovascular DiseasesState Key Laboratory of Cardiovascular DiseaseNational Clinical Research Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Medical Research&Biometrics center Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina coronary heart disease center Department of CardiologyFuwai HospitalNational Center for Cardiovascular DiseasesState Key Laboratory of Cardiovascular DiseaseNational Clinical Research Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of Cardiology Xinxiang Central Hospitalthe Fourth Clinical College of Xinxiang Medical UniversityHenan ProvinceChina Department of Cardiology Qinhuangdao First HospitalHebei ProvinceChina

OBJECTIVES To assess the correlation between triglyceride glucose(TyG)index and in-hospital mortality in patients with ST-segment elevation myocardial infarction(STEMI).METHODS A total of 2190 patients with STEMI who underwent primary angiography within 12 h from symptom onset were selected from the prospective,nationwide,multicenter CAMI *** index was calculated with the formula:Ln[fasting triglycerides(mmol/L)×fasting glucose(mmol/L)/2].Patients were divided into three groups according to the tertiles of TyG *** primary endpoint was in-hospital *** Overall,46 patients died during hospitalization,in-hospital mortality was 1.5%,2.2%,2.6%for tertile 1,tertile 2,and tertile 3,***,TyG index was not significantly correlated with in-hospital mortality in single-variable logistic regression ***,after adjusting for age and sex,TyG index was significantly associated with higher mortality when regarded as a continuous variable(adjusted OR=1.75,95%CI:1.16-2.63)or categorical variable(tertile 3 *** 1:adjus-ted OR=2.50,95%CI:1.14-5.49).Furthermore,TyG index,either as a continuous variable(adjusted OR=2.54,95%CI:1.42-4.54)or categorical variable(tertile 3 *** 1:adjusted OR=3.57,95%CI:1.24-10.29),was an independent predictor of in-hospital mortality after adjusting for multiple confounders in multivariable logistic regression *** subgroup analysis,the pro-gnostic effect of high TyG index was more significant in patients with body mass index<18.5 kg/m2(P interaction=0.006).CONCLUSIONS This study showed that TyG index was positively correlated with in-hospital mortality in STEMI patients who underwent primary angiography,especially in underweight patients.

关键词： patients mortality angiography

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His-Purkinje conduction system pacing combined with atrioventricular node ablation improves quality of life in older patients with persistent atrial fibrillation refractory to multiple ablation procedures

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Journal of Geriatric Cardiology 2023年第2期20卷 130-138页

作者： Peng QI Yi-Zhen YANG Liang SHI Yan-Jiang WANG Ying TIAN Ke-Xin YUAN Xue-Feng CHEN Shu-Ren LI Yi DANG Xing-Peng LIU heart center Beijing Chaoyang HospitalCapital Medical UniversityBeijingChina heart center Hebei General HospitalHebeiChina

BACKGROUND Recurrence of atrial fibrillation(AF)is common in patients with persistent AF even after multiple ablation ***-Purkinje conduction system pacing(HPCSP)combined with atrioventricular node ablation(AVNA)is effective in managing patients with AF and heart *** study aimed to determine whether HPCSP combined with AVNA can improve quality of life and alleviate symptoms in older patients with symptomatic persistent AF refractory to multiple ablation procedures,as well as evaluate the feasibility and safety of this *** Older patients(≥65 years)with symptomatic persistent AF refractory to at least two ablation procedures were treated with combined HPCSP and *** success rates and complications were *** parameters,European heart Rhythm Association(EHRA)scores,and Atrial Fibrillation Effect on Quality-of-Life(AFEQT)scores obtained perioperatively were compared with those recorded at the 6-month follow-up *** Thirty-one patients were enrolled;of those,only thirty patients were eventually treated with AVNA because one patient developed a complete atrioventricular block following the withdrawal of the His bundle pacing *** success rates were 100%for HPCSP(22 cases with His bundle pacing,and 9 cases with left bundle branch pacing)and 93.3%(28/30)for AVNA,*** the 6-month follow-up examination,EHRA scores improved significantly(3.00±0.73 vs.2.44±0.63,P=0.014)and AFEQT scores increased markedly(49.6±20.6 vs.70.9±14.0,P=0.001).No severe complications *** When used in older patients with symptomatic persistent AF refractory to multiple ablation procedures,HPCSP combined with AVNA significantly alleviated symptoms and improved quality of life during short-term *** therapy was proved to be safe and effective in this patient population.

关键词： patients markedly conduction

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Clinical relevance of atrial septal aneurysm and patent foramen ovale with migraine

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World Journal of Clinical Cases 2018年第15期6卷 916-921页

作者： Lu He Ge-Sheng Cheng Ya-Juan Du Yu-Shun Zhang Department of Structural heart disease Xi'an Jiaotong University Medical College First Affiliated Hospital

AIM To test the potential association between atrial septal aneurysm(ASA) and migraine in patent foramen ovale(PFO) closure patients through an observational, singlecenter, case-controlled *** We studied a total of 450 migraineurs who had rightto-left shunts and underwent PFO closure in a retrospective single-center non-randomized registry from February 2012 to October 2016 on the condition that they were aged 18-45 years old. Migraine was diagnosed according to the International Classification of Headache Disorders, 3^(rd) edition and evaluated using the Headache Impact Test-6(HIT-6). All patients underwent preoperative transesophageal echocardiography, contrast transthoracic echocardiography, and computed tomography or magnetic resonance imaging examinations, with subsequent fluoroscopy-guided PFO closure. Based on whether they have ASA or not, the patients were divided into two groups: A(PFO with ASA, n = 80) and B(PFO without ASA, n = 370). Baseline characteristics and procedural and follow-up data were reviewed. RESULTS Compared to group B, group A had an increased frequency of ischemic lesions(11.3% vs 6.2%, P = 0.038) and migraine with aura(32.5% vs 21.1%, P = 0.040). The PFO size was significantly larger in group A(P = 0.007). There was no significant difference in HIT-6 scores between the two groups before and at the oneyear follow-up after the PFO closure [61(9) vs 63(9), P = 0.227; 36(13) vs 36(10), P = 0.706].CONCLUSION Despite its small sample size, our study suggests that the prevalence of ASA in PFO with migraine patients is associated with ischemic stroke, larger PFO size, and migraine with aura.

关键词： Patent foramen ovale Migraine Atrial septal aneurysm Contrast transthoracic echocardiography Right-to-left shunt Transesophageal echocardiography

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