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Nanotechnology for cardiovascular diseases

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The Innovation 2022年第2期3卷 17-37页

作者： Qinqin Hu Zheyan Fang junbo ge Hua Li Department of Cardiology Shanghai Institute of Cardiovascular DiseasesShanghai Xuhui District Central Hospital&Zhongshan-xuhui HospitalZhongshan HospitalFudan UniversityShanghai 200032China Institutes of Biomedical Sciences Fudan UniversityShanghai 200032China

Cardiovascular diseases have become the major killers in today’s world,among which coronary artery diseases(CADs)make the greatest contributions to morbidity and *** state-of-the-art technologies have increased our knowledge of the cardiovascular system,the current diagnosis and treatment modalities for CADs still have *** an emerging cross-disciplinary approach.

关键词： diseases cardiovascular diagnosis

The effects of nicotinamide adenine dinucleotide in cardiovascular diseases: Molecular mechanisms, roles and therapeutic potential

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genes & Diseases 2022年第4期9卷 959-972页

作者： Xiaokai Zhang Yang Zhang Aijun Sun junbo ge Department of Cardiology Zhongshan HospitalFudan UniversityShanghai Institute of Cardiovascular DiseasesShanghai 200032PR China Institute of Biomedical Sciences Fudan UniversityShanghai 200032PR China

Recently, cardiovascular diseases (CVDs) were identified as the leading cause of mortality, imposing a heavy burden on health care systems and the social economy. Nicotinamide adenine dinucleotide (NAD+), as a pivotal co-substrate for a range of different enzymes, is involved in many signal transduction pathways activated in CVDs. Emerging evidence has shown that NAD+ can exert remediating effects on CVDs by regulating metabolism, maintaining redox homeostasis and modulating the immune response. In fact, NAD+ might delay ageing through sirtuin and non-sirtuin pathways and thus contribute to interventions for age-related diseases such as CVDs. Considering that robust clinical studies of NAD+ are ongoing, we discuss current challenges and the future translational potential of NAD+ based on existing studies and our understanding. Despite some remaining gaps in its clinical application, NAD+ has been shown to have broad prospects and pan-effects, making it a suitable prophylactic drug for CVDs.

关键词： Ageing Cardiovascular disease Metabolism Nicotinamide adenine dinucleotide Sirtuin

Active greeting technique: a mother-and-child catheter based technique to facilitate retrograde wire externalization in recanalization of coronary chronic total occlusion

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Science Bulletin 2018年第23期63卷 1565-1569页

作者： junbo ge Lei ge Bin Zhang Xin Zhong Jianying Ma Leisheng Ru Tao Hu Juying Qian 无 Shanghai Institute of Cardiovascular Diseases Zhongshan HospitalFudan UniversityShanghai 200022China Institutes of Biomedical Sciences.Fudan University Shanghai 200032China Department of Cardiology Guangdong Cardiovascular InstituteGuangdong General Hospital Guangzhou510080China Department of Cardiology Bethune International Peace HospitalShzjiazhuang 050082China Department of Cardiology Xijing HospitalXi'an 710032China Chronic Total Occlusion Club China

Although retrograde approach has greatly improved the success rate of percutaneous coronary intervention(PCI) for coronary chronic total occlusion(CTO), retrograde wire externalization still remains challenging and time-consuming in some cases. Cases utilizing ‘‘Active Greeting Technique(AGT)", a mother-and-child catheter based technique to facilitate retrograde wire externalization, were extracted from Chronic Total Occlusion Club, China(CTOCC) database. AGT was performed by deep intubation a mother-and-child catheter(GuidezillaTMextension, 4 or 5 Fr inner catheter, and etc.) in combination with either reverse controlled antegrade or retrograde subintimal tracking(CART) technique or retrograde wire crossing technique. A total of 111 patients with 112 CTO lesions treated with this technique were retrospectively analyzed. Reverse CART technique and retrograde wire crossing technique were performed in 90.2% and 9.8% of all procedures. The utilization of GuidezillaTMextension, 4 Fr, and 5 Fr inner catheter accounted for 94.6%, 3.6%, and 1.8%, respectively. Externalization of retrograde wire was successful in all cases. No procedural complications were adjudicated to AGT. Complications independent of AGT included two target vessel perforations and two collateral perforations. No in-hospital major adverse cardiac events were found. AGT is a feasible and safe technique that facilitates retrograde wire externalization.

关键词： Percutaneous coronary intervention Chronic total occlusion Retrograde wire externalization Active greeting technique

Origin and Spread of the ALDH2 Glu504Lys Allele

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Phenomics 2021年第5期1卷 222-228页

作者： Xiaokai Zhang Aijun Sun junbo ge Department of Cardiology Zhongshan HospitalFudan UniversityShanghai Institute of Cardiovascular DiseasesShanghai 200032China Institute of Biomedical Sciences Fudan UniversityShanghai 200032China

gene polymorphism of acetaldehyde dehydrogenase 2(ALDH2),a key enzyme for alcohol metabolism in humans,can affect catalytic *** ALDH2 Glu504Lys mutant allele has a high-frequency distribution in East Asian populations and has been demonstrated to be associated with an increased risk of cardiovascular disease,stroke,and *** evidence suggests that the evolution of the ALDH2 gene has been influenced by multiple *** mutations pro-duce Glu504Lys,and genetic drift alters the frequency of this allele;additionally,environmental factors such as hepatitis B virus infection and high-elevation hypoxia affect its frequency through selective effects,ultimately resulting in a high frequency of this allele in East Asian ***,the origin,selection,and spread of the ALDH2 Glu504Lys allele are discussed,and an outlook for further research is proposed to realize a precision medical strategy based on the genetic and environmental variations in ALDH2.

关键词： Acetaldehyde dehydrogenase 2 gene Environment Precision medicine

The critical roles of m6A modification in metabolic abnormality and cardiovascular diseases

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genes & Diseases 2021年第6期8卷 746-758页

作者： Beijian Zhang Hao Jiang Zhen Dong Aijun Sun junbo ge Department of Cardiology Zhongshan HospitalFudan UniversityShanghai200032PR China Shanghai Institute of Cardiovascular Diseases Shanghai200003PR China Institutes of Biomedical Sciences Fudan UniversityShanghai200433PR China NHC Key Laboratory of Viral Heart Diseases Shanghai200032PR China Key Laboratory of Viral Heart Diseases Chinese Academy of Medical SciencesShanghai200032PR China

N6-methyladenosine(m6A)RNA methylation is an emerging area of epigenetics,which is a reversible and dynamic modification mediating by‘writers’(methylase,adding methyl groups,METTL3,METTL14,and WTAP),‘erasers’(demethylase,deleting methyl groups,FTO and ALKBH5),and‘readers’(YTHDF1-3,YTHDC1 and YTHDC2).Recent studies in human,animal models and cell levels have disclosed a critical role of m6A modification in regulating the homeostasis of metabolic processes and cardiovascular *** from these studies identify m6A as a candidate of biomarker and therapeutic target for metabolic abnormality and cardiovascular diseases(CVD).Comprehensive understanding of the complexity of m6A regulation in metabolic diseases and CVD will be helpful for us to understand the pathogenesis of *** this review,we discuss the regulatory role of m6A in metabolic abnormality and *** will emphasize the clinical relevance of m6A dysregulation in CVD.

关键词： Cardiovascular disease FTO Heart failure Metabolic syndrome METTL3 Myocardial infarction N6-methyladenosine RNA epigenetics

Clinical importance of intravascular ultrasound in coronary interventions

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Journal of geriatric Cardiology 2005年第1期2卷 61-64页

作者： junbo ge Department of Cardiology Zhongshan Hospital Fudan University China

Since the introduction of coronary angiography in 1959, 1 a new "gold standard" examination became available for the evaluation of coronary artery disease.

关键词： IVUS PTCA

Hydrogen sulfide suppresses transforming growth factor-β1-induced differentiation of human cardiac fibroblasts into myofibroblasts

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Science China(Life Sciences) 2015年第11期58卷 1126-1134页

作者： ZHANG YouEn WANG JiaNing LI Hua YUAN LiangJun WANG Lei WU Bing ge junbo Institute of Clinical Medicine and Department of Cardiology Renmin Hospital Hubei University of Medicine Shanghai Institute of Cardiovascular Diseases Zhongshan Hospital Fudan University Institutes of Biomedical Sciences Fudan University

In heart disease, transforming growth factor-β1 （TGF-β1） converts fibroblasts into myofibroblasts, which synthesize and se- crete fibrillar type I and III collagens. The purpose of the present study was to investigate how hydrogen sulfide （HzS） sup- presses TGF-~l-induced differentiation of human cardiac fibroblasts to myofibroblasts. Human cardiac fibroblasts were se- rum-starved in fibroblast medium for 16 h before exposure to TGF-β1 （10 ng mL-1） for 24 h with or without sodium hydrosul- fide （NariS, 100 μmol L-1, 30 min pretreatment） treatment. NariS, an exogenous HzS donor, potently inhibited the prolifera- tion and migration of TGF-β1-induced human cardiac fibroblasts and regulated their cell cycle progression. Furthermore, NariS treatment led to suppression of fibroblast differentiation into myofibroblasts, and reduced the levels of collagen, TGF-β1, and activated Smad3 in TGF-β1-induced human cardiac fibroblasts in vitro. We therefore conclude that H2S sup- presses TGF-β1-stimulated conversion of fibroblasts to myofibroblasts by inhibiting the TGF-β1/Smad3 signaling pathway, as well as by inhibiting the proliferation, migration, and cell cycle progression of human cardiac myofibroblasts. These effects of H2S may play significant roles in cardiac remodeling associated with heart failure.

关键词： human cardiac fibroblasts hydrogen sulfide transforming growth factor β1 myofibroblasts

Berberine alleviates myocardial diastolic dysfunction by modulating Drp1-mediated mitochondrial fission and Ca^(2+) homeostasis in a murine model of HFpEF

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Frontiers of Medicine 2023年第6期17卷 1219-1235页

作者： Miyesaier Abudureyimu Mingjie Yang Xiang Wang Xuanming Luo junbo ge Hu Peng Yingmei Zhang Jun Ren Cardiovascular Department Shanghai Xuhui Central HospitalFudan UniversityShanghai 200031China Department of Cardiology Zhongshan HospitalFudan UniversityShanghai Institute of Cardiovascular DiseasesShanghai 200032China Key Laboratory of Viral Heart Diseases National Health CommissionShanghai 200032China Key Laboratory of Viral Heart Diseases Chinese Academy of Medical SciencesShanghai 200032China National Clinical Research Center for Interventional Medicine Shanghai 200032China Department of general Surgery Shanghai Xuhui Central HospitalFudan UniversityShanghai 200031China Department of geriatrics Shanghai Tenth HospitalTongji UniversityShanghai 200072China Department of Medical Laboratory and Pathology UniversityofWashingtonSeattleWA98195USA

Heart failure with preserved ejection fraction(HFpEF)displays normal or near-normal left ventricular ejection fraction,diastolic dysfunction,cardiac hypertrophy,and poor exercise ***,an isoquinoline alkaloid,possesses cardiovascular *** male mice were assigned to chow or high-fat diet with L-NAME(“two-hit”model)for 15 *** function was assessed using echocardiography and noninvasive Doppler *** morphology,mitochondrial ultrastructure,and cardiomyocyte mechanical properties were *** analysis,autophagic flux,and intracellular Ca^(2+)were also assessed in chow and HFpEF *** results show exercise intolerance and cardiac diastolic dysfunction in“two-hit”-induced HFpEF model,in which unfavorable geometric changes such as increased cell size,interstitial fibrosis,and mitochondrial swelling occurred in the *** dysfunction was indicated by the elevated E value,mitral E/A ratio,and E/e’ratio,decreased e’value and maximal velocity of re-lengthening(-dL/dt),and prolonged re-lengthening in HFpEF *** effects of these processes were alleviated by ***,berberine ameliorated autophagic flux,alleviated Drp1 mitochondrial localization,mitochondrial Ca^(2+)overload and fragmentation,and promoted intracellular Ca^(2+)reuptake into sarcoplasmic reticulum by regulating phospholamban and ***,berberine alleviated diastolic dysfunction in“two-hit”diet-induced HFpEF model possibly because of the promotion of autophagic flux,inhibition of mitochondrial fragmentation,and cytosolic Ca^(2+)overload.

关键词： HFpEF berberine Drpl autophagy Ca^(2+)

Therapeutic silencing miR-146b-5p improves cardiac remodeling in a porcine model of myocardial infarction by modulating the wound reparative phenotype

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Protein & Cell 2021年第3期12卷 194-212页

作者： Yiteng Liao Hao Li Hao Cao Yun Dong Lei Gao Zhongmin Liu junbo ge Hongming Zhu Research Center for Translational Medicine Shanghai East HospitalTongji University School of MedicineShanghai 200120China Department of Cardiology Shanghai Tenth People's HospitalTongji University School of MedicineShanghai 200072China Department of Cardiovascular Surgery Shanghai East HospitalTongji University School of MedicineShanghai 200120China Department of Ultrasound in Medicine Shanghai East HospitalTongji University School of MedicineShanghai 200120China Department of Cardiology Shanghai Institute of Cardiovascular DiseasesZhongshan Hospital of Fudan UniversityShanghai 200032China

Fibrotic remodeling is an adverse consequence of immune response-driven phenotypic modulation of cardiac cells following myocardial infarction(Ml).MicroRNA-146b(miR-146b)is an active regulator of immunomodulation,but its function in the cardiac inflammatory cascade and its clinical implication in fibrotic remodeling following Ml remain largely ***,miR-146b-5p was found to be upregulated in the infarcted myocardium of mice and the serum of myocardial ischemia ***-and loss-of-function experiments demonstrated that miR-146b-5p was a hypoxia-induced regulator that governed the pro-fibrotic phenotype transition of cardiac *** of miR-146b-5p activated fibroblast proliferation,migration,and fibroblast-to-myofibroblast transition,impaired endothelial cell function and stress survival,and disturbed macrophage paracrine ***,the opposite effects were observed when miR-146b-5p expression was *** assays and rescue studies demonstrated that the miR-146b-5p target genes mediating the above phenotypic modulations included interleukin 1 receptor associated kinase 1(IRAKI)and carcinoembryonic antigen related cell adhesion molecule 1(CEACAM1).Local delivery of a miR-146b-5p antagomir significantly reduced fibrosis and cell death,and upregulated capillary and reparative macrophages in the infarcted myocardium to restore cardiac remodeling and function in both mouse and porcine Ml *** inhibition of miR-146b-5p may represent a novel therapeutic approach to treat cardiac fibrotic remodeling and dysfunction following Ml.

关键词： cardiac fibrosis microRNA porcine model myocardial infarction