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1.
J Mol Biol ; 434(8): 167406, 2022 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-34929199

RESUMO

Protein phosphorylation is a reversible, residue-specific posttranslational modification that plays a pivotal role in cell signaling, and the phosphorylation state of proteins is tightly regulated by kinases and phosphatases. Malfunction of this regulation is often associated with human diseases, and therefore elucidation of the function and regulation of this posttranslational modification is important. Genetic code expansion, which allows for site-specific introduction of noncanonical amino acids directly into target proteins in response to a non-sense codon is a powerful method for preparing homogeneously phosphorylated proteins both in Escherichia coli and mammalian cells and therefore is useful for studying protein phosphorylation. Herein, we summarize recent developments in the application of genetic code expansion for protein phosphorylation studies.


Assuntos
Código Genético , Engenharia Metabólica , Fosfoproteínas , Processamento de Proteína Pós-Traducional , Aminoacil-tRNA Sintetases/genética , Animais , Escherichia coli/genética , Escherichia coli/metabolismo , Humanos , Mamíferos/genética , Engenharia Metabólica/métodos , Fosfoproteínas/genética , Monoéster Fosfórico Hidrolases/genética , Fosforilação/genética , Proteínas Quinases/genética , Processamento de Proteína Pós-Traducional/genética , RNA de Transferência/metabolismo
2.
Chembiochem ; 22(20): 2914-2917, 2021 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-34487417

RESUMO

Supramolecular chemistry for targeting proteins is of great interest for the development of novel approaches to recognize, isolate and control proteins. Taking advantage of chemical biology approaches, such as genetic-code expansion and enzyme-mediated ligation, guest recognition elements can be built into proteins of interest, allowing supramolecular control of protein function and regulation. In this viewpoint article, we will discuss the methods, applications, limitations, and future perspectives of supramolecular chemistry for targeting proteins in a site-specific manner.


Assuntos
Proteínas/metabolismo , Substâncias Macromoleculares/química , Substâncias Macromoleculares/metabolismo , Estrutura Molecular , Proteínas/química
3.
Catheter Cardiovasc Interv ; 97 Suppl 2: 1009-1015, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33689212

RESUMO

OBJECTIVE: The present study compared 10-year clinical outcomes between transradial access (TRA) and transfemoral access (TFA) for left main (LM) percutaneous coronary intervention (PCI). BACKGROUND: There are limited data regarding the long-term safety and efficacy of TRA for LM PCI. METHODS: This retrospective study evaluated consecutive patients who underwent unprotected LM PCI between January 2004 and December 2008 at Fu Wai Hospital. The exclusion criteria were age of less than 18 years and presentation with acute myocardial infarction. The primary endpoint was major adverse cardiac or cerebrovascular events (MACCE), which was defined as a composite of all-cause death, myocardial infarction, stroke, and any revascularization at the 10-year follow-up. RESULTS: Among 913 eligible patients, TRA was used for 417 patients (45.7%) and TFA was used for 496 patients (54.3%). The 30-day clinical outcomes were similar between the two groups. Results from the 10-year follow-up revealed that MACCE occurred in 180 patients (46.7%) from the TRA group and in 239 patients (51.2%) from the TFA group (log-rank p = .3). The TRA and TFA groups also had low and comparable cumulative rates of all-cause death (14.6% vs. 17.3%, log-rank p = .56) and cardiac death (7.9% vs. 9.1%, log-rank p = .7). CONCLUSION: The present study revealed no significant differences in long-term clinical outcomes when TRA or TFA were used for LM PCI.


Assuntos
Intervenção Coronária Percutânea , Adolescente , Artéria Femoral , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Artéria Radial , Estudos Retrospectivos , Resultado do Tratamento
4.
J Interv Cardiol ; 2021: 8829686, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33519307

RESUMO

AIMS: This study sought to report the 10-year clinical outcomes of patients who underwent unprotected left main (LM) percutaneous coronary intervention (PCI) in a large centre. METHODS AND RESULTS: A total of 913 consecutive patients who underwent unprotected LM PCI from January 2004 to December 2008 at Fu Wai Hospital were retrospectively analysed; the mean age was 60.0 ± 10.9 years, females accounted for 22% of patients, diabetes was present in 27.7% of patients, and an LM bifurcation lesion occurred in 82.9% of patients. During the median follow-up of 9.7 years, major adverse cardiac or cerebrovascular events (MACCEs) occurred in 25.6% (234) of patients, and the rates of all-cause death, myocardial infarction, and stroke were 14.9%, 11.0%, and 7.1%, respectively. Cardiac death occurred in only 7.9% of patients. The estimated event rate was 41.9% for death/myocardial infarction/any revascularization and 45.9% for death/MI/stroke/any revascularization. Definite/probable stent thrombosis occurred in 4.3% (39) of patients. According to the subgroup analysis, IVUS-guided PCI was associated with less long-term MACCEs. Further multivariate analysis identified that age and LVEF<40% were the only independent predictors for 10-year death. Age, LVEF<40%, creatinine clearance, and incomplete revascularization were independent predictors for death/MI, while a two-stent strategy, diabetes, a transradial approach, and the use of bare metal stents (BMSs) or first-generation drug-eluting stents (DESs) were not. CONCLUSIONS: Unprotected LM PCI in a large cohort of consecutive patients in a single large centre demonstrated favourable long-term outcomes up to 10 years even with the use of BMSs and first-generation of DESs.


Assuntos
Doença da Artéria Coronariana , Vasos Coronários , Efeitos Adversos de Longa Duração , Infarto do Miocárdio , Intervenção Coronária Percutânea , Stents , China/epidemiologia , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/cirurgia , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/cirurgia , Feminino , Humanos , Efeitos Adversos de Longa Duração/diagnóstico , Efeitos Adversos de Longa Duração/epidemiologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/etiologia , Avaliação de Processos e Resultados em Cuidados de Saúde , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Intervenção Coronária Percutânea/métodos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Stents/efeitos adversos , Stents/classificação , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Resultado do Tratamento
5.
Angew Chem Int Ed Engl ; 60(20): 11196-11200, 2021 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-33580548

RESUMO

Regulation of specific protein function is of great importance for both research and therapeutic development. Many small or large molecules have been developed to control specific protein function, but there is a lack of a universal approach to regulate the function of any given protein. We report a general host-guest molecular recognition approach involving modification of the protein functional surfaces with genetically encoded unnatural amino acids bearing guest side chains that can be specifically recognized by cucurbit[7]uril. Using two enzymes and a cytokine as models, we showed that the activity of proteins bearing unnatural amino acid could be turned off by host molecule binding, which blocked its functional binding surface. Protein activity can be switched back by treatment with a competitive guest molecule. Our approach provides a general tool for reversibly regulating protein function through molecular recognition and can be expected to be valuable for studying protein functions.


Assuntos
Aminoácidos/análise , Hidrocarbonetos Aromáticos com Pontes/metabolismo , Imidazóis/metabolismo , Proteínas/metabolismo , Aminoácidos/genética , Hidrocarbonetos Aromáticos com Pontes/síntese química , Hidrocarbonetos Aromáticos com Pontes/química , Imidazóis/síntese química , Imidazóis/química , Substâncias Macromoleculares/síntese química , Substâncias Macromoleculares/química , Substâncias Macromoleculares/metabolismo , Estrutura Molecular , Proteínas/química
6.
Front Bioeng Biotechnol ; 8: 569191, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33042970

RESUMO

With the advances in the field of expanded genetic code, the application of non-canonical amino acid (ncAA) is considered an effective strategy for protein engineering. However, cumbersome and complicated selection schemes limit the extensive application of this technology in Saccharomyces cerevisiae. To address this issue, a simplified selection scheme with confident results was developed and tested in this study. Based on a mutation library derived from Escherichia coli tyrosyl-tRNA synthetase (EcTyrRS), a logic gate in synthetic biology was used to optimize screening procedures. We found that an "and" gate was more suitable than an "or" gate for isolating aminoacyl-tRNA synthetase from S. cerevisiae. The successful incorporation of O-methyltyrosine (OMeY) proved the utility and efficiency of this new selection scheme. After a round of positive selection, several new OMeY-tRNA synthetase (OMeYRS) mutants were screened, and their incorporation efficiency was improved. Furthermore, we characterized the insertion of several tyrosine analogs into Herceptine Fab and discovered that OMeYRS and its mutants were polyspecific. One of these mutants showed an optimal performance to incorporate different ncAAs into recombinant proteins in S. cerevisiae; this mutant was cloned and transfected into mammalian cells, and the results proved its functionality in HEK293 cells. This study could expand the application of ncAA in S. cerevisiae to construct efficient yeast cell factories for producing natural and synthetic products.

7.
ACS Synth Biol ; 9(10): 2723-2736, 2020 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-32931698

RESUMO

Genetic code expansion (GCE) is a powerful technique for site-specific incorporation of noncanonical amino acids (ncAAs) into proteins in living cells, which is achieved through evolved aminoacyl-tRNA synthetase mutants. Stability is important for promoting enzyme evolution, and we found that many of the evolved synthetase mutants have reduced thermostabilities. In this study, we characterized two novel pyrrolysyl-tRNA synthetases (PylRSs) derived from thermophilic archaea: Methanosarcina thermophila (Mt) and Methanosarcina flavescens (Mf). Further study demonstrated that the wild-type PylRSs and several mutants were orthogonal and active in both Escherichia coli and mammalian cells and could thus be used for GCE. Compared with the commonly used M. barkeri PylRS, the wild-type thermophilic PylRSs displayed reduced GCE efficiency; however, some of the mutants, as well as some chimeras, outperformed their mesophilic counterparts in mammalian cell culture at 37 °C. Their better performance could at least partially be attributed to the fact that these thermophilic synthetases exhibit a threshold of enhanced stability against destabilizing mutations to accommodate structurally diverse substrate analogues. These were indicated by the higher melting temperatures (by 3-6 °C) and the higher expression levels that were typically observed for the MtPylRS and MfPylRS mutants relative to the Mb equivalents. Using histone H3 as an example, we demonstrated that one of the thermophilic synthetase mutants promoted the incorporation of multiple acetyl-lysine residues in mammalian cells. The enzymes developed in this study add to the PylRS toolbox and provide potentially better scaffolds for PylRS engineering and evolution, which will be necessary to meet the increasing demands for expanded substrate repertoire with better efficiency and specificity in mammalian systems.


Assuntos
Aminoacil-tRNA Sintetases/genética , Aminoacil-tRNA Sintetases/metabolismo , Código Genético , Engenharia Metabólica/métodos , Methanosarcina/enzimologia , Proteínas Mutantes/metabolismo , Temperatura de Transição , Aminoácidos/genética , Domínio Catalítico/genética , Escherichia coli/genética , Escherichia coli/metabolismo , Células HEK293 , Histonas/metabolismo , Humanos , Lisina/metabolismo , Methanosarcina/classificação , Mutação , Plasmídeos/genética , Especificidade por Substrato , Transfecção
8.
Biochemistry ; 59(1): 90-99, 2020 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-31703481

RESUMO

The Escherichia coli-derived tyrosyl-tRNA synthetase was the first enzyme engineered for genetic code expansion in a eukaryotic system but can charge only a limited set of structurally simple noncanonical amino acids. In contrast, the thermophilic Methanocaldococcus jannaschii-derived tyrosyl-tRNA synthetase mutants, used in only a prokaryotic system, can charge a surprisingly large set of structurally diverse ncAAs, due to their remarkable structural ability to tolerate mutations. Inspired by this, we characterized a new class of tyrosyl-tRNA synthetase/tRNATyr pairs from thermophilic bacterium Geobacillus stearothermophilus, which is homologous to the E. coli tyrosyl-tRNA synthetase but with better thermostability. This new pair is both orthogonal in mammalian cells and in Saccharomyces cerevisiae for genetic code expansion and can charge a diverse set of ncAAs with a comparable cellular efficiency, better specificity, and lower background, as compared to those of its E. coli homologue. This thermostable enzyme provides an alternative scaffold for synthetase library screening or evolution to genetically encode more structurally complex ncAAs in eukaryotic cells.


Assuntos
Proteínas de Bactérias/genética , Código Genético , Geobacillus stearothermophilus/enzimologia , RNA de Transferência/genética , Tirosina-tRNA Ligase/genética , Proteínas de Bactérias/química , Domínio Catalítico/genética , Escherichia coli/enzimologia , Humanos , Mutação , Estabilidade Proteica , Saccharomyces cerevisiae/genética , Especificidade por Substrato , Temperatura de Transição , Tirosina-tRNA Ligase/química
9.
J Am Chem Soc ; 140(41): 13253-13259, 2018 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-30247891

RESUMO

Protein tyrosine phosphatases (PTPs) play critical roles in cell signaling pathways, but identification of unknown PTPs for a given substrate in live cells remain technically challenging. Here, we synthesized a series of tyrosine-based irreversible PTP inhibitors and characterized by site-specific encoding on substrate proteins in cells with an expanded genetic code. By fine-tuning the chemical reactivity, we identified optimal active amino acid probes to covalently cross-link a PTP and its substrate both in vitro and in mammalian cells. Using HER2 as an example, we provide first direct evidence of HER2 Y1023 and SHP2 cross-linking in situ in living human cells. Moreover, proteomic analysis using our approach identified PTP1B as a novel phosphatase for HER2 that specifically dephosphorylated pY1221 position, which may shed light on the puzzle of PTP1B's role in HER2 positive breast cancer. This novel method provides a useful tool for dissecting tyrosine phosphoregulation in living cells.


Assuntos
Reagentes para Ligações Cruzadas/química , Inibidores Enzimáticos/química , Proteína Tirosina Fosfatase não Receptora Tipo 1/análise , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Tirosina/genética , Reagentes para Ligações Cruzadas/síntese química , Cisteína/química , Inibidores Enzimáticos/síntese química , Células HEK293 , Humanos , Fosforilação/fisiologia , Estudo de Prova de Conceito , Engenharia de Proteínas/métodos , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Proteína Tirosina Fosfatase não Receptora Tipo 1/química , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Proteína Tirosina Fosfatase não Receptora Tipo 11/antagonistas & inibidores , Proteína Tirosina Fosfatase não Receptora Tipo 11/química , Proteína Tirosina Fosfatase não Receptora Tipo 11/metabolismo , Proteômica/métodos , Receptor ErbB-2/química , Tirosina/análogos & derivados , Tirosina/síntese química
10.
Chin Med J (Engl) ; 128(6): 733-9, 2015 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-25758264

RESUMO

BACKGROUND: Whether final kissing balloon (FKB) dilatation after one-stent implantation at left-main (LM) bifurcation site remains unclear. Therefore, this large sample and long-term follow-up study comparatively assessed the impact of FKB in patients with unprotected LM disease treated with one-stent strategy. METHODS: Total 1528 consecutive patients underwent LM percutaneous coronary intervention in one center from January 2004 to December 2010 were enrolled; among them, 790 patients treated with one drug-eluting stent crossover LM to left anterior descending (LAD) with FKB (n = 230) or no FKB (n = 560) were comparatively analyzed. Primary outcome was the rate of major adverse cardiovascular events, defined as a composite of death, myocardial infarction (MI) and target vessel revascularization (TVR). RESULTS: Overall, The prevalence of true bifurcation lesions, which included Medina classification (1,1,1), (1,0,1), or (0,1,1), was similar between-groups (non-FKB: 37.0% vs. FKB: 39.6%, P = 0.49). At mean 4 years follow-up, rates of major adverse cardiovascular events (non-FKB: 10.0% vs. FKB: 7.8%, P = 0.33), death, MI and TVR were not significantly different between-groups. In multivariate propensity-matched regression analysis, FKB was not an independent predictor of adverse outcomes. CONCLUSIONS: For patients treated with one-stent crossover LM to LAD, clinical outcomes appear similar between FKB and non-FKB strategy.


Assuntos
Angioplastia Coronária com Balão/métodos , Stents Farmacológicos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
11.
Zhonghua Xin Xue Guan Bing Za Zhi ; 42(5): 406-12, 2014 May.
Artigo em Chinês | MEDLINE | ID: mdl-25042920

RESUMO

OBJECTIVE: The clinical features of patients with mediastinal and/or neck hematoma after transradial cardiac catheterization were reviewed and analyzed to help the clinicians to recognize this complication, and try their best to avoid the complication and treat the complication properly. METHODS: A total of 8 patients with mediastinal and/or neck hematoma after right transradial cardiac catheterization in Fuwai hospital from January 1, 2005 to the end of 2012 were included in this study. Among these 8 patients, 1 patient underwent coronary angiography, 7 patients underwent percutaneous coronary intervention and drug eluting stents were successfully implanted in 6 patients. The clinical data of these patients were analyzed retrospectively. RESULTS: Super slide hydrophilic guild-wire was used in all patients. These patients felt chest pain, dyspnea and neck pain and neck or throat tightness after the procedure. CT scan was performed in all 8 patients and reviewed mediastinal hematoma, 4 patients complicated with neck hematoma, and suspicious laceration on the right subclavian artery or branch of innominate artery were found in 2 patients. Post procedure hemoglobin decrease was evidenced in all 8 patients. Anti-platelet therapy was discontinued until discharge in 2 patients, dual anti-platelet drugs were transiently discontinued or underwent dosage reduction in 4 patients, protamine was administered in 2 patients to neutralize heparin. Blood transfusion was not required, there was no stent thrombosis, and surgery was not indicated for all 8 patients. No complication was reported during follow up. CONCLUSIONS: Mediastinal and/or neck hematoma is a rare complication post transradial catheterization approach. This complication is caused by super slide guild-wire or catheter's injury of small vessels near the aortic arch or subclavian artery, especially with rough manipulation. Neck and mediastinal CT scan should be performed as early as possible for patients with suspect hematoma and prognosis is usually fine with suitable therapy.


Assuntos
Cateterismo Cardíaco/efeitos adversos , Hematoma/etiologia , Doenças do Mediastino/etiologia , Artéria Radial , Idoso , Cateterismo Cardíaco/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pescoço/patologia , Estudos Retrospectivos
12.
J Interv Cardiol ; 27(2): 108-16, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24588842

RESUMO

OBJECTIVES: The aim of the present study was to evaluate the safety, feasibility, procedural, and long-term outcomes by the transradial (TR) approach as compared to transfemoral (TF) approach in patients with triple vessel coronary artery disease undergoing one-stage percutaneous coronary intervention. BACKGROUND: The feasibility, safety, and efficacy between the TR and TF approach for coronary interventional treatment have been compared in some complex situations including AMI and unprotected left main disease. However, in terms of triple vessel disease (3VD) intervention, there has been no comparison regarding procedural and long-term outcomes between the TR and TF approach. METHODS: A total of 4,974 consecutive patients (TR n = 3,856, TF n = 1,118), who were diagnosed with 3VD without LM disease and underwent one-stage percutaneous revascularization, were enrolled in the study. Procedural results and clinical outcomes were obtained through database and follow-up. We used the propensity score matching method and obtained 930 pairs of patients with comparable baseline data in order to compare the procedural and long-term outcome between TR and TF groups. In the study cohort, risk reduction of all the clinical outcomes were evaluated with Cox's proportional-hazards models. Cumulative incidences concerning safety and efficacy of the cohort were estimated by the Kaplan-Meier method and a comparison was made utilizing the log-rank test. RESULTS: After propensity score matching, the baseline clinical and angiographic characteristics were similar between the 2 groups. Regarding procedural results, no significant differences were observed between the 2 groups, with the exception of a decreased hospital stay (TR 7.49 ± 4.46 days vs. TF 8.63 ± 6.23 days, P < 0.0001) and fewer bleedings (TR 1.0% vs. TF 2.9, P = 0.003) in the TRI group. After an average 21-month follow-up, the all-cause mortality (TR 1.7% vs. TF 4.2%, P = 0.0014; HR 0.44, 0.25-0.79) was significantly lower with TRI patients. Other clinical outcomes were comparable between the 2 groups. CONCLUSIONS: As compared to TFI, TRI for 3VD intervention is feasible, safe, and associated with similar procedural success, shorter hospitalization, reduced bleeding, lower incidence of death, and comparable long-term efficacy.


Assuntos
Doença da Artéria Coronariana/cirurgia , Intervenção Coronária Percutânea/métodos , Feminino , Artéria Femoral , Humanos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Artéria Radial , Resultado do Tratamento
13.
Chin Med J (Engl) ; 126(13): 2409-13, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23823809

RESUMO

BACKGROUND: Currently available evidence suggests that outcomes are less favorable when left main (LM) bifurcation lesions are treated with 2-stent techniques compared with a single-stent technique. We aimed to evaluate the long-term outcomes of the 2-stent techniques for treating unprotected LM bifurcation lesions in Chinese patients. METHODS: We enrolled 301 consecutive patients treated with drug-eluting stents (DES) implantation using 2-stent techniques for unprotected LM bifurcation lesions (MEDINA 1, 1, 1, 70.5%). The 2-stent techniques included crush technique, V stenting, T stenting, and Culottes stenting. After stenting, both vessels were redilated at a high pressure before final kissing balloon (FKB). Clinical and angiographic data were analyzed. The primary endpoints were major adverse cardiac events (MACE), which included death, myocardial infarction, and target lesion revascularization. RESULTS: Immediate procedural success was obtained in all cases with a FKB success rate of 95.3%. Follow-up data were available for all patients. The overall incidence of angiographic in-stent restenosis (ISR) rate was 20.3% and most ISRs were of the focal type. During long-term follow-up (mean duration, (54 ± 22) months), the cumulative incidence of MACE was 11.0%, with 8 (2.7%) deaths, 7 (2.3%) myocardial infarctions, and 18 (6.0%) repeated lesion revascularization. MACEs in high SYNTAX score terciles were significantly higher compared with those in low and intermediate SYNTAX score terciles (P = 0.001). CONCLUSIONS: Although percutaneous coronary intervention (PCI) with 2-stent technique for unprotected LM bifurcation lesions was accompanied with a slightly high incidence of ISR, the long-term clinical follow-up is acceptable. Technical modifications and stent innovations may further improve both the angiographic and clinical outcomes for patients with LM bifurcation disease treated by PCI.


Assuntos
Doença da Artéria Coronariana/terapia , Stents Farmacológicos , Intervenção Coronária Percutânea/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença da Artéria Coronariana/mortalidade , Reestenose Coronária/epidemiologia , Stents Farmacológicos/efeitos adversos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
14.
Chin Med J (Engl) ; 126(9): 1612-7, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23652038

RESUMO

BACKGROUND: Though drug-eluting stent (DES) almost solved a problem of restenosis, safety issues related to stent thrombosis are still the major concern of DES. We hypothesized that hybrid stent implantation may decrease the use of DES, probably improving the long-term safety but not affecting efficacy adversely when treating multilesion coronary artery disease in the DES era. METHODS: From April 2004 to October 2006, 848 patients with multilesion disease underwent hybrid stent implantation. During the same period 5647 patients with multilesion coronary heart disease were treated by exclusive DES implantation in Fu Wai Hospital. According to propensity score matching, we chose 823 pairs of patients with multileison coronary artery disease for inclusion into our study. We obtained the 24-month clinical outcome including death, myocardial infarction (MI), thrombosis, target lesion revascularization (TLR), target vessel revascularization (TVR), and major adverse cardiac events (MACE, the composite of death, MI, and TVR). We used Cox's proportional-hazard models to assess relative risks of all the outcome measures after propensity match. RESULTS: At 24 months, patients in the hybrid stent implantation group showed a significantly higher risk of TLR (8.39% vs. 3.28%, HR 2.38, 95%CI: 1.50 - 3.70), TVR (11.07% vs. 6.32%, HR 1.61, 95%CI: 1.15 - 2.27) and MACE (13.75% vs. 8.75%, HR 1.37, 95%CI: 1.02 - 1.85). No significant difference was apparent in terms of mortality (1.22% vs. 1.70%, HR 0.55, 95%CI: 0.24 - 1.25), MI (1.95% vs. 2.31%, HR 0.73, 95%CI: 0.37 - 1.42), or thrombosis (definite + probable) (0.73% vs. 1.58%, HR 0.40, 95%CI: 0.15 - 1.05). CONCLUSIONS: In patients with multilesion coronary artery disease, the exclusive DES implantation was associated with significantly lower risks of TLR, TVR and MACE, and the hybrid stent implantation did not result in any significant improvements regarding safety issues. Prospective studies are needed to confirm our results.


Assuntos
Doença da Artéria Coronariana/terapia , Stents Farmacológicos , Intervenção Coronária Percutânea , Idoso , Stents Farmacológicos/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
15.
Chin Med J (Engl) ; 126(4): 609-14, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23422176

RESUMO

BACKGROUND: Patients with multivessel coronary artery disease and depressed left ventricular ejection fraction (LVEF) represent a high risk group of patients for coronary revascularization. There are limited data on percutaneous coronary intervention treatment in this population. METHODS: Among a cohort of 4335 patients with three-vessel disease with or without left main disease undergoing percutaneous coronary intervention, 191 patients had LVEF < 40% (low ejection fraction (EF)) and 4144 patients had LVEF ≥ 40%. In-hospital and long-term outcomes were examined according to LVEF. RESULTS: The estimated two-year rates of major adverse cardiac events, cardiac death, and myocardial infarction were significantly higher in the low EF group (19.64% vs. 8.73%, Log-rank test: P < 0.01; 10.30% vs. 1.33%, Log-rank test: P < 0.01, and 10.32% vs. 2.28%, Log-rank test: P < 0.01 respectively), but there was no difference in the rates of target vessel revascularization (6.18% vs. 6.11%, Log-rank test: P = 0.96). Using the Cox proportional hazard models, LVEF < 40% was a significant risk factor for cardiac death, myocardial infarction, and major adverse cardiac events (OR (95%CI): 4.779 (2.369 - 9.637), 2.673 (1.353 - 5.282), and 1.827 (1.187 - 2.813) respectively), but was not a statistically significant risk factor for target vessel revascularization (OR (95%CI): 1.094 (0.558 - 2.147)). CONCLUSION: Among patients undergoing percutaneous coronary intervention for multivessel coronary artery disease, left ventricular dysfunction remains associated with further risk of cardiac death in-hospital and during long-term follow-up.


Assuntos
Angioplastia Coronária com Balão , Doença das Coronárias/fisiopatologia , Doença das Coronárias/terapia , Função Ventricular Esquerda/fisiologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
16.
Chin Med J (Engl) ; 125(23): 4221-5, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23217390

RESUMO

BACKGROUND: Among patients with advanced multivessel coronary disease, left ventricular (LV) function is widely variable, and clinical and angiographic correlates of ventricular dysfunction remain to be defined. METHODS: Among 73 339 patients undergoing diagnostic cardiac catheterization at a single center in China, patients with left ventriculographic assessment were identified with three-vessel coronary disease with or without left main involvement. Clinical and angiographic characteristics were examined among patients with normal or varying extent of LV dysfunction, and predictors of LV impairment (ejection fraction (EF): < 25%, 25% - 40% or > 40%) were determined. RESULTS: Among 11 950 patients identified with three-vessel coronary disease, the sample distribution of LVEF was > 40%, n = 10 776; 25% - 40%, n = 948; < 25%, n = 226. Patients with reduced LV function (< 40%) more commonly were male and had a history of myocardial infarction (MI), diabetes or unstable angina. Hypertension was more frequent in those with LVEF ≥ 40%. In a multivariate Logistic regression analysis, prior MI (odds ratio (OR), 3.37; 95% confidence interval (CI), 2.96 - 3.84) was most predictive of LVEF < 40%, followed by male gender, diabetes, and presentation with unstable angina. For LVEF < 25%, only prior MI was identified as a significant correlate of severe LV dysfunction (OR 4.06, 95%CI 3.06 - 5.39). Following exclusion of patients with previous MI (n = 7416), male gender and diabetes were predictive of LVEF < 40%, yet presentation with unstable angina was the only factor significantly associated with LVEF < 25%. CONCLUSION: Among individuals identified with three-vessel coronary disease with or without left main involvement, previous MI was the most significant risk factor of LV dysfunction.


Assuntos
Doença das Coronárias/patologia , Disfunção Ventricular Esquerda/patologia , Idoso , Angiografia Coronária , Doença das Coronárias/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Disfunção Ventricular Esquerda/fisiopatologia
17.
Chin Med J (Engl) ; 125(19): 3398-403, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23044295

RESUMO

BACKGROUND: Restenosis of bare-metal stents (BMS) and drug-eluting stents (DES) has been increasingly treated with sirolimus-eluting stents (SES), but the long-term outcomes are unknown. METHODS: In our study, 388 consecutive patients (144 DES restenosis and 244 BMS restenosis) with 400 lesions (147 DES restenosis and 253 BMS restenosis) treated with SES were included. The rates of target lesion revascularization (TLR) and major adverse cardiac events (MACE) at 42 months were analyzed. RESULTS: At the mean follow-up of 42 months, the rates of death (3.5% vs. 3.3%, P = 1.000) and myocardial infarction (2.8% vs. 1.2%, P = 0.431) in the DES group and BMS group were comparable. Compared with the BMS group, ischemia-driven TLR occurred with a higher frequency in the DES group (18.8% vs. 10.7%, P = 0.024). This translated into an increased rate of MACE in the DES group (22.2% vs. 14.0%, P = 0.034). Stent thrombosis occurred with a similar frequency in both groups (2.8% vs. 1.6%, P = 0.475). Multivariate analysis showed that DES restenosis (OR = 1.907, 95%CI 1.108 - 3.285, P = 0.020) and smoking (OR = 2.069; 95%CI 1.188 - 3.605; P = 0.010) were independent predictors of MACE. CONCLUSIONS: Although SES implantation appears to be safe and effective, it was associated with higher TLR recurrence for DES than BMS restenosis.


Assuntos
Reestenose Coronária/induzido quimicamente , Reestenose Coronária/terapia , Stents Farmacológicos/efeitos adversos , Sirolimo/uso terapêutico , Stents/efeitos adversos , Idoso , Angiografia Coronária , Reestenose Coronária/diagnóstico por imagem , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade
18.
Chin Med J (Engl) ; 124(18): 2879-82, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22040496

RESUMO

BACKGROUND: Surgical aortic valve replacement is the standard treatment for patients with severe aortic stenosis, but some registries have indicated that 30% to 60% of these patients are not treated surgically, usually due to advanced age and/or comorbidities. This single center study in China investigated the current treatment status in the patients with severe aortic stenosis and evaluated the long term clinical outcome in advanced age patients whether or not undergoing aortic valve replacement. METHODS: Clinical data of 867 consecutive patients with severe aortic stenosis between January 2000 and December 2006 were retrospectively analyzed. The patients ≥ 65 years old were followed up by telephone or information from medical records. The primary end-point was all-cause mortality. RESULTS: The patients' average age was (52 ± 19) years (range, 1 - 91 years), and 34% were women. The percentages of the patients aged < 15 years, between 15 and 34 years, between 35 and 54 years, between 55 and 64 years, between 65 and 74 years, and ≥ 75 years who underwent surgical aortic valve replacement were 82.3%, 87.2%, 88.8%, 78.2%, 65.3% and 22.2% respectively. In the patients (n = 256) ≥ 65 years old, 43.4% had New York Heart Association class III and IV symptoms, 39.1% had hypertension, 33.2% had coronary heart disease, and 3.1% had stroke. In the patients not undergoing aortic valve replacement, 1.6% had renal insufficiency, 4.7% had chronic obstructive pulmonary disease, 2.0% had critical hematopathy, and 0.4% had mammary cancer. A total of 186 (72.7%) patients finished the follow-up, and the average duration of the follow-up was (60 ± 26) months. In the patients between 65 and 74 years old, the total deaths and cardiac deaths in the patients undergoing aortic valve replacement decreased significantly compared with those with conservative treatment (10.3% vs. 53.7%, P < 0.001 and 6.3% vs. 50.7%, P < 0.001). Similarly, in the patients ≥ 75 years old, there was a significant difference between patients who had surgery and those who had conservative treatment in the total deaths and cardiac deaths (21.4% vs. 63.3%, P = 0.007 and 14.3% vs. 46.9%, P = 0.033). The total deaths in the patients aged between 65 and 74 years were significantly fewer compared with = 75 years old patients (25.4% vs. 54.0%, P < 0.001). Cox regression revealed that aortic valve replacement was the only independent predictor of mortality (HR 0.183; 95% CI, 0.101 - 0.332, P < 0.001). CONCLUSIONS: This single centre study showed that surgical aortic valve replacement was still the standard treatment for the patients with severe aortic stenosis and had a satisfying prognosis. However, the high risk patients with advanced age and comorbidities usually selected conservative treatment and had an unfavorable prognosis.


Assuntos
Estenose da Valva Aórtica/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , China , Feminino , Implante de Prótese de Valva Cardíaca/efeitos adversos , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
19.
Chin Med J (Engl) ; 124(19): 3022-9, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22040548

RESUMO

BACKGROUND: Although the role of C-reactive protein (CRP) in predicting rapid progression of atherosclerotic lesions has been intensively studied in unstable coronary artery disease, the data from patients with stable angina (SA) are largely absent. The present study evaluated a middle-size patient cohort who underwent percutaneous coronary intervention (PCI) with stent implantation and follow-up coronary angiography (CAG) and tested the hypothesis that increased plasma level of high-sensitive CRP would indicate rapid progression of de novo non-target coronary artery lesions in Chinese patients with SA. METHODS: The study population comprised of 311 consecutive patients with chronic SA who underwent coronary stent implantation on initial admission and angiographic follow-up ((8.5 ± 1.2) months). Rapid angiographic progression of non-target lesion was angiographically assessed and the patients were classified into two groups according to whether the progression existed or not. The relation of plasma CRP levels to the progression of atherosclerosis was investigated. RESULTS: Baseline demographic, clinical, and angiographic data were similar in patients with and without progression. Rapid angiographic progression of non-target lesions occurred in 136 patients (43.7%) at follow-up: 77 had a ≥ 10% diameter reduction of pre-existing stenosis ≥ 50%, 26 had a ≥ 30% diameter reduction of a pre-existing stenosis < 50%, 64 developed a new lesion ≥ 30% in a previously normal segment, and 4 had progression of a lesion to total occlusion. Progression of non-target lesions was not associated with target lesion restenosis formation. High-sensitive CRP levels were markedly higher in progression patients than in non-progression ones (1.60 (0.80 - 3.46) mg/L vs. 0.96 (0.55 - 1.87) mg/L, P < 0.001). Multivariate regression analysis showed that plasma CRP independently predicted rapid angiographic progression of non-target lesions (P = 0.001). High-sensitive CRP levels above 1.32 mg/L (the cutoff value) were associated with a 3.5-fold increase in the risk of developing rapid atherosclerotic progression (OR = 3.497, 95%CI 2.045 - 5.980). CONCLUSION: The data confirmed and extended previous studies that plasma CRP might independently predict non-target lesion progression in patients with SA after stent implantation.


Assuntos
Angina Pectoris/terapia , Proteína C-Reativa/análise , Doença da Artéria Coronariana/patologia , Stents , Angiografia Coronária , Doença da Artéria Coronariana/sangue , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
20.
Zhonghua Xin Xue Guan Bing Za Zhi ; 39(7): 617-20, 2011 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-22088240

RESUMO

OBJECTIVE: To investigate the impact of cytochrome P450 (CYP) 2C19 681G > A polymorphism on long-term prognosis of clopidogrel-treated Chinese patients after percutaneous coronary intervention (PCI). METHODS: Between January 1, 2009 and August 31,2009, 267 patients with coronary heart disease who received PCI and treated with clopidogrel for 12 months were enrolled. CYP2C19 * 2 was detected by MALDI-TOF MS and patients were grouped into CYP2C19 * 1/ * 1 (n = 130) and CYP2C19 * 2 carriers group (n = 137). Follow-up was 12 months. The primary endpoint was angina recurrence, urgent coronary revascularization, acute myocardial infarction, stent thrombosis, death and the combined end points. RESULTS: Baseline data were similar between two groups (P > 0.05). Urgent coronary revascularization and the combined end points occurred more frequently in CYP2C19 * 2 carriers than in CYP2C19 * 1/* 1 patients (7.3% vs. 1.5% and 8.0% vs. 2.3% respectively, all P < 0.05). But incidence of angina recurrence, acute myocardial infarction, stent thrombosis and death was similar between two groups (all P > 0.05). Hazard risk of 1 year cumulative survival of CYP2C19 * 2 carriers group was significantly higher than CYP2C19 * 1/ * 1 group after PCI ( HR = 3.59, 95% CI: 1.02 - 12.87, P < 0.05). CONCLUSION: CYP2C19 681G > A polymorphism is a determinant of prognosis in coronary heart disease patients receiving chronic clopidogrel treatment after PCI.


Assuntos
Hidrocarboneto de Aril Hidroxilases/genética , Doença das Coronárias/tratamento farmacológico , Inibidores da Agregação Plaquetária/uso terapêutico , Ticlopidina/análogos & derivados , Idoso , Angioplastia Coronária com Balão , Clopidogrel , Doença das Coronárias/diagnóstico , Doença das Coronárias/genética , Citocromo P-450 CYP2C19 , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Prognóstico , Ticlopidina/uso terapêutico
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