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Integrin β5 subunit regulates hyperglycemia-induced vascular endothelial cell apoptosis through FoxO1-mediated macroautophagy

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Chinese Medical Journal 2024年第5期137卷 565-576页

作者： Xuze Lin Sizhuang Huang Side Gao Jinxing Liu Jiong Tang Mengyue Yu Department of cardiology Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Science and Peking Union Medical CollegeBeijing 100037China Department of cardiology Fuwai Yunnan Cardiovascular HospitalKunmingYunnan 650000China

Background:Hyperglycemia frequently induces apoptosis in endothelial cells and ultimately contributes to microvascular dysfunction in patients with diabetes mellitus(DM).Previous research reported that the expression of integrins as well as their ligands was elevated in the diseased vessels of DM patients.However,the association between integrins and hyperglycemia-induced cell death is still unclear.This research was designed to investigate the role played by integrin subunit β5(ITGB5)in hyperglycemia-induced endothelial cell apoptosis.Methods:We used leptin receptor knockout(Lepr-KO)(db/db)mice as spontaneous diabetes animal model.Selective deletion of ITGB5 in endothelial cell was achieved by injecting vascular targeted adeno-associated virus via tail vein.Besides,we also applied small interfering RNA in vitro to study the mechanism of ITGB5 in regulating high glucose-induced cell apoptosis.Results:ITGB5 and its ligand,fibronectin,were both upregulated after exposure to high glucose in vivo and in vitro.ITGB5 knockdown alleviated hyperglycemia-induced vascular endothelial cell apoptosis and microvascular rarefaction in vivo.In vitro analysis revealed that knockdown of either ITGB5 or fibronectin ameliorated high glucose-induced apoptosis in human umbilical vascular endothelial cells(HUVECs).In addition,knockdown of ITGB5 inhibited fibronectin-induced HUVEC apoptosis,which indicated that the fibronectin-ITGB5 interaction participated in high glucose-induced endothelial cell apoptosis.By using RNA-sequencing technology and bioinformatic analysis,we identified Forkhead Box Protein O1(FoxO1)as an important downstream target regulated by ITGB5.Moreover,we demonstrated that the excessive macroautophagy induced by high glucose can contribute to HUVEC apoptosis,which was regulated by the ITGB5-FoxO1 axis.Conclusion:The study revealed that high glucose-induced endothelial cell apoptosis was positively regulated by ITGB5,which suggested that ITGB5 could potentially be used to predict and treat DM-related vascular complic

关键词： Endothelial cell apoptosis Integrin Autophagy Diabetes

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The prognostic value of collateral circulation in coronary chronic total occlusion underwent percutaneous coronary intervention

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Journal of Geriatric cardiology 2024年第2期21卷 232-241页

作者： Xiao-Ying HU Wei-Xian YANG Chang-Dong GUAN Li-Hua XIE Ke-Fei DOU Yong-Jian WU Jin-Qing YUAN Jie QIAN Yue-Jin YANG Shu-Bin QIAO Lei SONG Department of cardiology Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina National Clinical research center for cardiovascular Diseases BeijingChina Catheterization Laboratories Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

BACKGROUND The prognostic value of coronary collateral circulation(CC)in patients undergoing chronic total occlusion(CTO)percutaneous coronary intervention(PCI)is underdetermined.The purpose of the study was to assess the prognostic value of current two CC grading systems and their association with long-term outcomes in patients with CTO underwent PCI.METHODS We consecutively enrolled patients with single-vessel CTO underwent PCI between January 2010 and December2013.All patients were categorized into well-developed or poor-developed collaterals group according to angiographic Werner's CC(grade 2 vs.grade 0–1)or Rentrop(grade 3 vs.grade 0–2)grading system.The primary endpoint was 5-year cardiac death.RESULTS Of 2452 enrolled patients,the overall technical success rate was 74.1%.Well-developed collaterals were present in686 patients(28.0%)defined by Werner's CC grade 2,and in 1145 patients(46.7%)by Rentrop grade 3.According to Werner's CC grading system,patients with well-developed collaterals had a lower rate of 5-year cardiac death compared with those with poordeveloped collaterals(1.6%vs.3.3%,P=0.02),those with suboptimal recanalization was associated with higher rate of 5-year cardiac death compared with optimal recanalization(4.7%vs.0.8%,P=0.01)and failure patients(4.7%vs.1.6%,P=0.12).However,the similar effect was not shown in Rentrop grading system.CONCLUSIONS In patients with the single-vessel CTO underwent PCI,well-developed collaterals by Werner's CC definition were associated with lower rate of 5-year cardiac death.Werner's CC grading system had a greater prognostic value than Rentrop grading system in patients with CTO underwent PCI.

关键词： coronary collateral occlusion

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Effects of loneliness and isolation on cardiovascular diseases:a two sample Mendelian Randomization Study

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Journal of Geriatric cardiology 2024年第3期21卷 340-348页

作者： Jia-Yin CAI Xin WANG Cong-Yi ZHENG Xue CAO Zhen HU Run-Qing GU Yi-Xin TIAN Ye TIAN Lan SHAO Lin-Feng ZHANG Zeng-Wu WANG division of Prevention and Community Health National Center for Cardiovascular DiseaseNational Clinical Research Center of Cardiovascular DiseaseState Key Laboratory of Cardiovascular DiseaseFuwai HospitalPeking Union Medical College&Chinese Academy of Medical SciencesBeijingChina

BACKGROUND Loneliness and isolation are associated with multiple cardiovascular diseases(CVDs),but there is a lack of research on whether they were causally linked.We conducted a Mendelian Randomization(MR)study to explore causal relationships between loneliness and isolation and multiple CVDs.METHODS Single nucleotide polymorphisms associated with loneliness and isolation were identified from a genome-wide association study(GWAS)of 455,364 individuals of European ancestry in the IEU GWAS database.Summary data for 15 CVDs were also obtained from the IEU GWAS database.We used three MR methods including inverse variance weighting,MR-Egger,and weighted median estimation to assess the causal effect of exposure on outcomes.Cochran's Q test and MR-Egger intercept test were used to evaluate the heterogeneity and pleiotropy.RESULTS MR analysis showed that loneliness and isolation were significantly associated with essential hypertension(OR=1.07,95%CI:1.03-1.12),atherosclerotic heart disease(OR=1.04;95%CI:1.02-1.06),myocardial infarction(OR=1.02;95%CI:1-1.04)and angina(OR=1.04;95%CI=1.02-1.06).No heterogeneity and pleiotropy effects were found in this study.CONCLUSIONS Causal relationship of loneliness and isolation with CVDs were found in this study.

关键词： diseases cardiovascular angina

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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 paradigm.However,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 reported.Discovery of novel pathological cellular landscapes provides a large number of therapeutic targets.On 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 burden.Stem cell-or nanoparticle-based strategies spurred a lot of attention due to the attractive therapeutic effects and minimized adverse effects.Given the complexity of pathological changes of AS,attempts to develop an almighty medicine based on single mechanisms could be theoretically challenging.In 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 translation.The future challenges and improvements were also discussed.

关键词： atherosclerosis transdifferentiation extracellular traps efferocytosis stem cell nanoparticles

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Diagnostic performance of intravascular ultrasound-based fractional flow reserve in evaluating of intermediate left main stenosis

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Journal of Geriatric cardiology 2024年第1期21卷 34-43页

作者： Yong-Gang SUI Cheng YANG Chang-Dong GUAN Yan-Lu XU Na-Qiong WU Wei-Xian YANG Yong-Jian WU Ke-Fei DOU Yue-Jin YANG Shu-Bin QIAO Wei YU Bo XU Sheng-Xian TU Jie QIAN Department of cardiology Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Catheterization Laboratories Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Biomedical Instrument Institute School of Biomedical EngineeringShanghai Jiao Tong UniversityShanghaiChina National Clinical research center for cardiovascular Diseases BeijingChina

BACKGROUND The recently introduced ultrasonic flow ratio(UFR),is a novel fast computational method to derive fractional flow reserve(FFR)from intravascular ultrasound(IVUS)images.In the present study,we evaluate the diagnostic performance of UFR in patients with intermediate left main(LM)stenosis.METHODS This is a prospective,single center study enrolling consecutive patients with presence of intermediated LM lesions(diameter stenosis of 30%-80%by visual estimation)underwent IVUS and FFR measurement.An independent core laboratory assessed offline UFR and IVUS-derived minimal lumen area(MLA)in a blinded fashion.RESULTS Both UFR and FFR were successfully achieved in 41 LM patients(mean age,62.0±9.9 years,46.3%diabetes).An acceptable correlation between UFR and FFR was identified(r=0.688,P50%(AUC=0.66,P<0.001)and numerically higher than IVUS-derived MLA(AUC=0.82;P=0.09).Patient level diagnostic accuracy,sensitivity and specificity for UFR to identify FFR≤0.80 was 82.9%(95%CI:70.2-95.7),93.1%(95%CI:82.2-100.0),58.3%(95%CI:26.3-90.4),respectively.CONCLUSION In patients with intermediate LM diseases,UFR was proved to be associated with acceptable correlation and high accuracy with pressure wire-based FFR as standard reference.The present study supports the use of UFR for functional evaluation of intermediate LM stenosis.

关键词： stenosis flow fractional

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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 rest.The 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 countries.For instance,in Russian Federation,CHF is diagnosed in about 7%of cardiovascular patients.At 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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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 unavailable.Therefore,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 AMI.METHODS In this prospective study,a total of 933 consecutive old patients with AMI admitted to FuWai hospital(Beijing,China)were enrolled.On admission,ABG,SHR,and GG were assessed and all participants were classified according to their quartiles.Kaplan-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 follow-up.RESULTS During an average of 1954 patient-years of follow-up,a total of 250 cardiovascular deaths were recorded.Kaplan-Meier analyses showed the lowest CVM in quartile 1 of ABG and in quartile 2 of SHR and GG.After 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 CVM.Additionally,we observed similar associations of these acute glycemic parameters with 30-day CVM.CONCLUSIONS 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

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Development and validation of a model integrating clinical and coronary lesion-based functional assessment for longterm risk prediction in PCI patients

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Journal of Geriatric cardiology 2024年第1期21卷 44-63页

作者： Shao-Yu WU Rui ZHANG Sheng YUAN Zhong-Xing CAI Chang-Dong GUAN Tong-Qiang ZOU Li-Hua XIE Ke-Fei DOU State Key Laboratory of cardiovascular Disease BeijingChina Cardiometabolic Medicine center Fu Wai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Catheterization Laboratories Fu Wai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of cardiology Fu Wai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

OBJECTIVES To establish a scoring system combining the ACEF score and the quantitative blood flow ratio(QFR) to improve the long-term risk prediction of patients undergoing percutaneous coronary intervention(PCI).METHODS In this population-based cohort study, a total of 46 features, including patient clinical and coronary lesion characteristics, were assessed for analysis through machine learning models. The ACEF-QFR scoring system was developed using 1263consecutive cases of CAD patients after PCI in PANDA Ⅲ trial database. The newly developed score was then validated on the other remaining 542 patients in the cohort.RESULTS In both the Random Forest Model and the Deep Surv Model, age, renal function(creatinine), cardiac function(LVEF)and post-PCI coronary physiological index(QFR) were identified and confirmed to be significant predictive factors for 2-year adverse cardiac events. The ACEF-QFR score was constructed based on the developmental dataset and computed as age(years)/EF(%) + 1(if creatinine ≥ 2.0 mg/d L) + 1(if post-PCI QFR ≤ 0.92). The performance of the ACEF-QFR scoring system was preliminarily evaluated in the developmental dataset, and then further explored in the validation dataset. The ACEF-QFR score showed superior discrimination(C-statistic = 0.651;95% CI: 0.611-0.691, P < 0.05 versus post-PCI physiological index and other commonly used risk scores) and excellent calibration(Hosmer–Lemeshow χ^(2)= 7.070;P = 0.529) for predicting 2-year patient-oriented composite endpoint(POCE). The good prognostic value of the ACEF-QFR score was further validated by multivariable Cox regression and Kaplan–Meier analysis(adjusted HR = 1.89;95% CI: 1.18–3.04;log-rank P < 0.01) after stratified the patients into high-risk group and low-risk group.CONCLUSIONS An improved scoring system combining clinical and coronary lesion-based functional variables(ACEF-QFR)was developed, and its ability for prognostic prediction in patients with PCI was further validated to be significantly better than the post-PCI physiological

关键词： patients coronary prediction

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Oral anti-coagulants use in Chinese hospitalized patients with atrial fibrillation

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Chinese Medical Journal 2024年第2期137卷 172-180页

作者： Jing Lin Deyong Long Chenxi Jiang Caihua Sang Ribo Tang Songnan Li Wei Wang Xueyuan Guo Man Ning Zhaoqing Sun Na Yang Yongchen Hao Jun Liu Jing Liu Xin Du Louise Morgan Gregg C.Fonarow Sidney C.Smith Jr Gregory Y.H.Lip Dong Zhao Jianzeng Dong Changsheng Ma On behalf of CCC-AF investigators Department of cardiology Beijing Anzhen HospitalCapital Medical UniversityBeijing 100029China National Clinical research center for cardiovascular Diseases Beijing 100029 China Department of Epidemiology Beijing Anzhen HospitalCapital Medical UniversityBeijing Institute of HeartLung and Blood Vessel DiseasesBeijing 100029China International Quality Improvement Department American Heart AssociationDallasTX 07076USA division of cardiology Geffen School of Medicine at University of CaliforniaLos Angeles CA 90024USA division of cardiology University of North CarolinaChapel HillNC 27599USA Department of cardiology Liverpool Centre for Cardiovascular ScienceUniversity of Liverpool and Liverpool Heart&Chest HospitalLiverpool L143PEUK Department of Clinical Medicine Aalborg UniversityAalborg 9000Denmark 不详

Background:Oral anti-coagulants(OAC)are the intervention for the prevention of stroke,which consistently improve clinical outcomes and survival among patients with atrial fibrillation(AF).The main purpose of this study is to identify problems in OAC utilization among hospitalized patients with AF in China.Methods:Using data from the Improving Care for cardiovascular Disease in China-Atrial Fibrillation(CCC-AF)registry,guideline-recommended OAC use in eligible patients was assessed.Results:A total of 52,530 patients with non-valvular AF were enrolled from February 2015 to December 2019,of whom 38,203 were at a high risk of stroke,9717 were at a moderate risk,and 4610 were at a low risk.On admission,only 20.0%(6075/30,420)of patients with a diagnosed AF and a high risk of stroke were taking OAC.The use of pre-hospital OAC on admission was associated with a lower risk of new-onset ischemic stroke/transient ischemic attack among the diagnosed AF population(adjusted odds ratio:0.54,95%confidence interval:0.43-0.68;P70%of AF patients were at a high risk of stroke.Although poor performance on guideline-recommended OAC use was found in this study,over time the CCC-AF project has made progress in stroke prevention in the Chinese AF population.Registration:ClinicalTrials.gov,NCT02309398.

关键词： Atrial fibrillation Oral anti-coagulants OAC Stroke prevention Contraindication

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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 status.METHODS We selected 5,308 participants with AMI from the prospective,nationwide,multicenter CAMI registry,of which 2,081 were diabetic and 3,227 were nondiabetic.Patients 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,respectively.The primary endpoint was in-hospital mortality.RESULTS 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,respectively.Compared 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 changed.Further-more,FPG as a continuous variable was positively associated with in-hospital mortality in single-variable and multivariable models regardless of diabetic status.Adding FPG to the original model showed a significant improvement in C-statistic and net reclassification in diabetic and nondiabetic cohorts.CONCLUSIONS 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 diabetes.FPG might be useful to stratify patients with AMI.

关键词： patients fasting infarction

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