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1.
Nat Commun ; 14(1): 6832, 2023 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-37884553

RESUMO

Increasing evidence shows the African lineage Zika virus (ZIKV) displays a more severe neurovirulence compared to the Asian ZIKV. However, viral determinants and the underlying mechanisms of enhanced virulence phenotype remain largely unknown. Herein, we identify a panel of amino acid substitutions that are unique to the African lineage of ZIKVs compared to the Asian lineage by phylogenetic analysis and sequence alignment. We then utilize reverse genetic technology to generate recombinant ZIKVs incorporating these lineage-specific substitutions based on an infectious cDNA clone of Asian ZIKV. Through in vitro characterization, we discover a mutant virus with a lysine to arginine substitution at position 101 of capsid (C) protein (termed K101R) displays a larger plaque phenotype, and replicates more efficiently in various cell lines. Moreover, K101R replicates more efficiently in mouse brains and induces stronger inflammatory responses than the wild type (WT) virus in neonatal mice. Finally, a combined analysis reveals the K101R substitution promotes the production of mature C protein without affecting its binding to viral RNA. Our study identifies the role of K101R substitution in the C protein in contributing to the enhanced virulent phenotype of the African lineage ZIKV, which expands our understanding of the complexity of ZIKV proteins.


Assuntos
Infecção por Zika virus , Zika virus , Animais , Camundongos , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/metabolismo , Substituição de Aminoácidos , Filogenia , Replicação Viral/genética
2.
BMC Cardiovasc Disord ; 23(1): 326, 2023 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-37369992

RESUMO

AIM: To evaluate the expression profile of long non-coding RNAs (lncRNAs) in calcific aortic valve disease (CAVD) and explore their potential mechanism of action. METHODS: The gene expression profiles (GSE153555, GSE148219, GSE199718) were downloaded from the Gene Expression Omnibus (GEO) database and FastQC was run for quality control checks. After filtering and classifying candidate lncRNAs by differentially expressed genes (DEGs) and weighted co-expression networks (WGCNA) in GSE153555, we predicted the potential cis- or trans-regulatory target genes of differentially expressed lncRNAs (DELs) by using FEELnc and established the competitive endogenous RNA (ceRNA) network by miRanda, more over functional enrichment was analyzed using the ClusterProfiler package in R Bioconductor. The hub cis- or trans-regulatory genes were verified in GSE148219 and GSE199718 respectively. RESULTS: There were 340 up-regulated lncRNAs identified in AS group compared with the control group (|log2Fold Change| ≥ 1.0 and Padj ≤ 0.05), and 460 down-regulated lncRNAs. Based on target gene prediction and co-expression network construction, twelve Long non-coding RNAs (CDKN2B-AS1, AC244453.2, APCDD1L-DT, SLC12A5-AS1, TGFB3, AC243829.4, MIR4435-2HG, FAM225A, BHLHE40-AS1, LINC01614, AL356417.2, LINC01150) were identified as the hub cis- or trans-regulatory genes in the pathogenesis of CAVD which were validated in GSE148219 and GSE19971. Additionally, we found that MIR4435-2HG was the top hub trans-acting lncRNA which also plays a crucial role by ceRNA pattern. CONCLUSION: LncRNAs may play an important role in CAVD and may provide a new perspective on the pathogenesis, diagnosis, and treatment of this disease. Further studies are required to illuminate the underlying mechanisms and provide potential therapeutic targets.


Assuntos
Valvopatia Aórtica , MicroRNAs , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Redes Reguladoras de Genes , Transcriptoma , MicroRNAs/genética
3.
J Virol ; 97(3): e0180122, 2023 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-36840584

RESUMO

The Zika virus (ZIKV) represents an important global health threat due to its unusual association with congenital Zika syndrome. ZIKV strains are phylogenetically grouped into the African and Asian lineages. However, the viral determinants underlying the phenotypic differences between the lineages remain unknown. Here, multiple sequence alignment revealed a highly conserved residue at position 21 of the premembrane (prM) protein, which is glutamic acid and lysine in the Asian and African lineages, respectively. Using reverse genetics, we generated a recombinant virus carrying an E21K mutation based on the genomic backbone of the Asian lineage strain FSS13025 (termed E21K). The E21K mutation significantly increased viral replication in multiple neural cell lines with a higher ratio of M to prM production. Animal studies showed E21K exhibited increased neurovirulence in suckling mice, leading to more severe defects in mouse brains by causing more neural cell death and destruction of hippocampus integrity. Moreover, the E21K substitution enhanced neuroinvasiveness in interferon alpha/beta (IFN-α/ß) receptor knockout mice, as indicated by the increased mortality, and enhanced replication in mouse brains. The global transcriptional analysis showed E21K infection profoundly altered neuron development networks and induced stronger antiviral immune response than wild type (WT) in both neural cells and mouse brains. More importantly, the reverse K21E mutation based on the genomic backbone of the African strain MR766 caused less mouse neurovirulence. Overall, our findings support the 21st residue of prM functions as a determinant for neurovirulence and neuroinvasiveness of the African lineage of ZIKV. IMPORTANCE The suspected link of Zika virus (ZIKV) to birth defects led the World Health Organization to declare ZIKV a Public Health Emergency of International Concern. ZIKV has been identified to have two dominant phylogenetic lineages, African and Asian. Significant differences exist between the two lineages in terms of neurovirulence and neuroinvasiveness in mice. However, the viral determinants underlying the phenotypic differences are still unknown. Here, combining reverse genetics, animal studies, and global transcriptional analysis, we provide evidence that a single E21K mutation of prM confers to the Asian lineage strain FSS130125 significantly enhanced replication in neural cell lines and more neurovirulent and neuroinvasiveness phenotypes in mice. Our findings support that the highly conserved residue at position 21 of prM functions as a determinant of neurovirulence and neuroinvasiveness of the African lineage of ZIKV in mice.


Assuntos
Infecção por Zika virus , Zika virus , Animais , Camundongos , Filogenia , Replicação Viral , Linhagem Celular
4.
J Clin Med ; 12(3)2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36769804

RESUMO

INTRODUCTION: Chronic severe aortic regurgitation (AR) has a poor long-term prognosis, especially among old-age patients. Considering their advancing age, the surgical approach of aortic valve replacement may not always be the best alternative modality of treatment in such patients. Therefore, this study's primary goal was to provide an initial summary of the medium- and short-term clinical effectiveness of transcatheter aortic valve replacement (TAVR) guided by accurate multi-detector computed tomography (MDCT) measurements in patients with severe and chronic AR, especially in elderly patients. METHODS: The study enrolled retrospectively and prospectively patients diagnosed with severe AR who eventually underwent TAVR procedure from January 2019 to September 2022 at Fuwai cardiovascular Hospital, Beijing. Baseline information, MDCT measurements, anatomical classification, perioperative, and 1-year follow-up outcomes were collected and analyzed. Based on a novel anatomical categorization and dual anchoring theory, patients were divided into four categories according to the level of anchoring area. Type 1, 2, and 3 patients (with at least two anchoring regions) will receive TAVR with a transcatheter heart valve (THV), but Type 4 patients (with zero or one anchoring location) will be deemed unsuitable for TAVR and will instead receive medical care (retrospectively enrolled patients who already underwent TAVR are an exception). RESULTS: The mean age of the 37 patients with severe chronic AR was 73.1 ± 8.7 years, and 23 patients (62.2%) were male. The American Association of Thoracic Surgeons' score was 8.6 ± 2.1%. The MDCT anatomical classification included 17 cases of type 1 (45.9%), 3 cases of type 2 (8.1%), 13 cases of type 3 (35.1%), and 4 cases of Type 4 (10.8%). The VitaFlow valve (MicroPort, Shanghai, China) was implanted in 19 patients (51.3%), while the Venus A valve (Venus MedTech, Hangzhou, China) was implanted in 18 patients (48.6%). Immediate TAVR procedural and device success rates were 86.5% and 67.6%, respectively, while eight cases (21.6%) required THV-in-THV implantation, and nine cases (24.3%) required permanent pacemaker implantation. Univariate regression analysis revealed that the major factors affecting TAVR device failure were sinotubular junction diameter, THV type, and MDCT anatomical classification (p < 0.05). Compared with the baseline, the left ventricular ejection fraction gradually increased, while the left ventricular end-diastolic diameter remained small, and the N-terminal-pro hormone B-type natriuretic peptide level significantly decreased within one year. CONCLUSION: According to the results of our study, TAVR with a self-expanding THV is safe and feasible for patients with chronic severe AR, particularly for those who meet the criteria for the appropriate MDCT anatomical classification with intact dual aortic anchors, and it has a significant clinical effect for at least a year.

5.
J Med Virol ; 95(2): e28451, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36594413

RESUMO

Zika virus (ZIKV) is a mosquito-borne RNA virus that belongs to the Flaviviridae family. While flavivirus replication is known to occur in the cytoplasm, a significant portion of the viral capsid protein localizes to the nucleus during infection. However, the role of the nuclear capsid is less clear. Herein, we demonstrated SERTA domain containing 3 (SERTAD3) as an antiviral interferon stimulatory gene product had an antiviral ability to ZIKV but not JEV. Mechanistically, we found that SERTAD3 interacted with the capsid protein of ZIKV in the nucleolus and reduced capsid protein abundance through proteasomal degradation. Furthermore, an eight amino acid peptide of SERTAD3 was identified as the minimum motif that binds with ZIKV capsid protein. Remarkably, the eight amino acids synthetic peptide from SERTAD3 significantly prevented ZIKV infection in culture and pregnant mouse models. Taken together, these findings not only reveal the function of SERTAD3 in promoting proteasomal degradation of a specific viral protein but also provide a promising host-targeted therapeutic strategy against ZIKV infection.


Assuntos
Infecção por Zika virus , Zika virus , Animais , Feminino , Camundongos , Gravidez , Antivirais/uso terapêutico , Proteínas do Capsídeo/metabolismo , Replicação Viral , Zika virus/genética
6.
Echocardiography ; 39(12): 1571-1580, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36376261

RESUMO

BACKGROUND: The success of transcatheter aortic valve replacement (TAVR) in native aortic regurgitation (AR) is limited by the absence of calcified anchoring structures. We sought to evaluate transfemoral TAVR in patients with native AR using a novel aortic root imaging classification. METHODS: From March to November 2021, 81 patients with severe AR were prospectively enrolled in 2 cardiac centers in China. All were evaluated using multidetector computed tomography (MDCT) and classified into 4 anatomic types in reference to transcatheter heart valve (THV) anchoring: Type 1: anchoring at the left ventricular outflow tract (LVOT), annulus, and ascending aorta (AA); Type 2: anchoring at the annulus and AA; Type 3: anchoring at the annulus and LVOT; and Type 4: anchoring at only 1 level or none at all. Based on the dual-anchoring strategy, patients with Types 1-3 were considered TAVR candidates. Procedural and 30-day outcomes were assessed according to Valve Academic Research Consortium-3 definitions. RESULTS: TAVR was performed in 32 (39.5%) patients (71.9 ± 8.0 years of age, 71.9% were male) using 2 self-expanding THVs. Types 1, 2, and 3 comprised 13 (40.6%), 11 (34.4%), and 8 (25.0%) cases, respectively. The procedural and device success rates were 100% and 93.8%, respectively, with 2 THV migration. Eight patients (25.0%) required a permanent pacemaker, and 2 (6.3%) developed moderate paravalvular leaks. No deaths or other major complications occurred during the study. CONCLUSIONS: The novel anatomic classification and dual-anchoring strategy were associated with a high procedural success rate with favorable short-term safety and clinical outcomes.


Assuntos
Insuficiência da Valva Aórtica , Substituição da Valva Aórtica Transcateter , Humanos , Masculino , Idoso , Feminino , Insuficiência da Valva Aórtica/diagnóstico por imagem , Insuficiência da Valva Aórtica/cirurgia , China
7.
BMC Cardiovasc Disord ; 22(1): 445, 2022 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-36243693

RESUMO

BACKGROUND: Success rate of transcatheter aortic valve replacement (TAVR) in aortic regurgitation (AR) patients is relatively low on account of the absence of calcified anchoring structures. Morphological classification and corresponding TAVR strategies for AR are lacking yet. METHODS: The AURORA study is a prospective, multicenter, single-arm cohort study to evaluate the safety and efficacy of transfemoral TAVR for severe AR in patients with high or prohibitive risk for surgery. Patients who are ≥ 65 years and diagnosed with severe pure AR as defined by the Echocardiographic Core Laboratory will be consecutively enrolled for further multidetector computed tomography (MDCT) scanning and multiplanar analyses. Based on a new anatomical classification and dual anchoring theory, patients will be classified into 4 types according to the level of the anchoring area. Types 1, 2 and 3 (at least 2 anchoring areas) will undergo the TAVR procedure with a domestic Chinese self-expanding valve (VitaFlow Valve, MicroPort, Shanghai, China), whereas type 4 (0 or 1 anchoring area) patients will be considered unsuitable for TAVR and will receive medical treatment. Our goal is to recruit 100 patients to account for 10% missing data or loss of patients to follow-up. Procedural, 30-day, 6-month and 12-month outcomes will be assessed according to Valve Academic Research Consortium-3 criteria. DISCUSSION: The AURORA study will establish a new AR anatomical classification based on dual anchoring theory through MDCT multiplanar measurement and assess the safety and efficacy of TAVR guided by this new classification and strategy in AR patients. TRIAL REGISTRATION: This Study was registered at Chinses Clinical Trial Registry. The registration number: ChiCTR2200055415; The date of registration: 9, January 2022; The URL of the registration: http://www.chictr.org.cn/showproj.aspx?proj=141209 .


Assuntos
Insuficiência da Valva Aórtica , Estenose da Valva Aórtica , Próteses Valvulares Cardíacas , Substituição da Valva Aórtica Transcateter , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Insuficiência da Valva Aórtica/diagnóstico por imagem , Insuficiência da Valva Aórtica/etiologia , Insuficiência da Valva Aórtica/cirurgia , Estenose da Valva Aórtica/cirurgia , China , Estudos de Coortes , Humanos , Estudos Prospectivos , Desenho de Prótese , Fatores de Risco , Substituição da Valva Aórtica Transcateter/efeitos adversos , Resultado do Tratamento
8.
Chin J Integr Med ; 27(6): 455-460, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33433847

RESUMO

OBJECTIVE: To explore the effectiveness of Danhong Injection () on improving microcirculatory injury after percutaneous coronary intervention (PCI) in patients with coronary heart disease (CHD). METHODS: A randomized controlled trial was conducted and 90 patients were enrolled. A random sequence was generated using statistical analysis software. Patients with microcirculatory injuries after PCI were randomly divided into 3 groups for treatment (30 subjects in each group): Danhong Injection group: after PCI, Danghong Injections were given with intravenous administration with 40 mL twice a day for a week; statins intensive group: after PCI, atorvastatin calcium tablets were given oral medication with 80 mg once, and then atorvastatin 40 mg daily for 1 week; the control group: after PCI, atorvastatin calcium tablets were given oral medication with 10-20 mg daily for 1 week. The index of microcirculation resistance (IMR) was used to assess microcirculatory injury during PCI. The IMR of the target vessel was reexamined after 1 week of drug treatment. RESULTS: After one week's drug treatment, IMR was significantly decreased in both statins intensive group and Danhong Injection group compared with the control group (P<0.01), but no difference was found between statins intensive group and Danhong injection group (14.03 ± 2.54 vs. 16.03 ± 5.72 U, P=0.080). CONCLUSIONS: The efficacy of Danhong Injection is non-inferior to statin. Early use of Danhong Injection after PCI can effectively improve coronary microcirculation injury after PCI.


Assuntos
Doença das Coronárias , Intervenção Coronária Percutânea , Medicamentos de Ervas Chinesas , Humanos , Microcirculação , Resultado do Tratamento
9.
Biosci Rep ; 40(9)2020 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-32893848

RESUMO

BACKGROUND: Galectin-3 may predict mortality for patients with aortic stenosis (AS) after transcatheter aortic valve replacement (TAVR). However, the results were inconsistent. We aimed to evaluate the association between baseline galectin and mortality after TAVR in a meta-analysis. METHODS: Related follow-up studies were obtained by systematic search of PubMed, Cochrane's Library, and Embase databases. Both the fixed- and the random-effect models were used for the meta-analysis. Subgroup analyses were performed to evaluate the influences of study characteristics on the outcome. RESULTS: Five prospective cohort studies with 854 patients were included, with a follow-up period between 1 and 1.9 years. Patients with higher baseline circulating galectin-3 had an increased risk of all-cause mortality after TAVR (random-effects model: risk ratio [RR]: 1.63, 95% confidence interval [CI]: 1.19-2.23, P=0.002; fixed-effects model: RR: 1.62, 95% CI: 1.19-2.20, P=0.002; I2 = 4%). Adjustment of estimated glomerular filtration rate (RR: 1.73, P=0.02) or B-type natriuretic peptide (BNP) or N-terminal pro-BNP (RR: 1.83, P=0.02) did not significantly affect the result. A trend of stronger association between higher baseline circulating galectin-3 and increased risk of all-cause mortality after TAVR was observed in studies with an enzyme-linked fluorescent assay (ELFA) (RR: 3.04, P=0.003) compared with those with an enzyme-linked immunosorbent assay (ELISA) (RR: 1.42, P=0.04; P for subgroup difference =0.06). CONCLUSION: Higher circulating galectin-3 before the procedure may predict all-cause mortality of AS patients after TAVR.


Assuntos
Estenose da Valva Aórtica/cirurgia , Galectinas/sangue , Substituição da Valva Aórtica Transcateter , Estenose da Valva Aórtica/sangue , Estenose da Valva Aórtica/mortalidade , Proteínas Sanguíneas , Causas de Morte , Humanos , Período Pós-Operatório , Período Pré-Operatório , Medição de Risco/métodos , Fatores de Risco , Índice de Gravidade de Doença , Resultado do Tratamento
10.
J Geriatr Cardiol ; 17(12): 766-774, 2020 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-33424944

RESUMO

BACKGROUND: The effective orifice area (EOA) is utilized to characterize the hemodynamic performance of the transcatheter heart valve (THV). However, there is no consensus on EOA measurement of self-expanding THV. We aimed to compare two echocardiographic methods for EOA measurement following transcatheter self-expanding aortic valve implantation. METHODS: EOA was calculated according to the continuity equation. Two methods were constructed. In Method 1 and Method 2, the left ventricular outflow tract diameter (LVOTd) was measured at the entry of the prosthesis (from trailing-to-leading edge) and proximal to the prosthetic valve leaflets (from trailing-to- leading edge), respectively. The velocity-time integral (VTI) of the LVOT (VTILVOT) was recorded by pulsed-wave Doppler (PW) from apical windows. The region of the PW sampling should match that of the LVOTd measurement with precise localization. The mean transvalvular pressure gradient (MG) and VTI of THV was measured by Continuous wave Doppler. RESULTS: A total of 113 consecutive patients were recruited. The mean age was 77.2 ± 5.5 years, and 72 patients (63.7%) were male. EOA1 with the use of Method 1 was larger than EOA2 (1.56 ± 0.39 cm2 vs. 1.48 ± 0.41 cm2, P = 0.001). MG correlated better with the indexed EOA1 (EOAI1) (r = -0.701, P < 0.001) than EOAI2 (r = -0.645, P < 0.001). According to EOAI (EOAI ≤ 0.65 cm2/m2, respectively), the proportion of sever prosthesis-patient mismatch with the use of EOA1 was lower than EOA2 (12.4% vs. 21.2%, P < 0.05). Compared with EOA2, EOA1 had lower interobserver and intra-observer variability (intra: 0.5% ± 17% vs. 3.8% ± 22%, P < 0.001; inter: 1.0% ± 9% vs. 3.5% ± 11%, P < 0.001). CONCLUSIONS: For transcatheter self-expanding valve EOA measurement, LVOTd should be measured in the entry of the prosthesis stent (from trailing-to-leading edge), and VTILVOT should match that of the LVOTd measurement with precise localization.

11.
J Cardiovasc Pharmacol ; 65(1): 47-53, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25329748

RESUMO

BACKGROUND: Reduced expression of sarcoplasmic reticulum calcium-transporting ATPase isoform 2a (SERCA2a) has been shown to play a significant role in the cardiac dysfunction of obese animal models. It was reported recently that SUMOylation enhances the stability and activity of SERCA2a. We hypothesized that SERCA2a-SUMOylation might be involved in obesity-mediated reduction of SERCA2a. METHOD AND RESULTS: Trimetazidine (TMZ), the drug that inhibits fatty acid oxidation, was used in diet-induced obese (DIO) rats and palmitic acid (PA)-treated cardiomyocytes. The intensity of SERCA2a-SUMOylation and proteins involved in SERCA2a-SUMOylation were investigated in vivo and in vitro. DIO rats presented cardiac dysfunction, which was alleviated by TMZ treatment. Reductions of SERCA2a protein and the intensity of SERCA2a-SUMOylation were observed in DIO rats and PA-treated cardiomyocytes. These reductions were partially restored by TMZ. However, TMZ itself did not alter the intensity of SERCA2a-SUMOylation in control cardiomyocytes. The variations of protein and messenger RNA levels of Ubiquitin carrier protein 9 are in accordance with the intensity of SERCA2a-SUMOylation. Whereas the other proteins involved in SERCA2a-SUMOylation were not changed by DIO and PA. CONCLUSIONS: TMZ alleviates the DIO- and PA-induced reductions of SERCA2a-SUMOylation. Ubiquitin carrier protein 9 is involved in the reductions.


Assuntos
Obesidade/fisiopatologia , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Trimetazidina/farmacologia , Enzimas de Conjugação de Ubiquitina/genética , Animais , Modelos Animais de Doenças , Masculino , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Ácido Palmítico/farmacologia , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/genética , Sumoilação/efeitos dos fármacos
13.
Eur J Heart Fail ; 11(10): 911-21, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19789393

RESUMO

AIMS: The mechanism by which diabetes mellitus exacerbates myocardial injury and the incidence of heart failure after acute myocardial infarction (AMI), remains unclear. We studied the severity of cardiac dysfunction and time-dependent gene expression in a hyperglycaemic rat model with AMI. METHODS AND RESULTS: The diabetic model was produced by injection of streptozotocin in Sprague-Dawley rats. Ten weeks after induction of diabetes, AMI was induced by ligation of the left anterior descending coronary artery. Cardiac function and left ventricular (LV) dimensions were evaluated using two-dimensional echocardiography. Structural changes were assessed by histological examination. Gene expression profile was documented by using affymetrix genechip U230 2.0 array and real time-PCR. During 56 days post-AMI, lower survival rates, worse LV function, more severe fibrosis, and larger LV diameters were identified in diabetic rats compared with non-diabetic rats. A total 1221 genes involved in processes, such as glucose metabolism, fatty acid metabolism, extracellular matrix, and apoptosis, were found to be differentially expressed between diabetic and non-diabetic rats, of these 770 were up-regulated and 451 down-regulated. Up-regulation of the genes was found 1-2 weeks earlier in diabetic rats than in non-diabetic rats. CONCLUSION: The present data suggest that hyperglycaemia up-regulates remodelling-related genes, which may be responsible for the worse outcomes in diabetics than in non-diabetics after AMI.


Assuntos
Actinas/genética , Diabetes Mellitus Experimental/complicações , Infarto do Miocárdio/genética , Infarto do Miocárdio/patologia , Miosinas/genética , Remodelação Ventricular/genética , Actinas/metabolismo , Animais , Diabetes Mellitus Experimental/induzido quimicamente , Modelos Animais de Doenças , Progressão da Doença , Regulação para Baixo , Ecocardiografia Doppler , Fibrose/genética , Fibrose/mortalidade , Fibrose/patologia , Regulação da Expressão Gênica , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Análise em Microsséries , Microscopia Eletrônica de Transmissão , Contração Miocárdica/fisiologia , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/fisiopatologia , Miosinas/metabolismo , Probabilidade , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Estreptozocina , Análise de Sobrevida , Regulação para Cima , Remodelação Ventricular/fisiologia
14.
Chin Med J (Engl) ; 122(14): 1610-4, 2009 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-19719959

RESUMO

BACKGROUND: ST-elevated acute myocardial infarction (STEAMI) happening in the first month post percutaneous coronary intervention (PCI) is almost related to acute thrombosis or subacute thrombosis in-stents. This study aimed to investigate the possible causes of myocardial infarction one month later. METHODS: Patients who had a history of successful PCI, and received coronary angiography or re-PCI due to STEAMI were included in this study. The AMI-related lesions and previous angiographic findings such as the number of lesions, the degree of the stenosis, the type of stents and acute results of last PCI were recorded. If the AMI-related lesion was localized in-stents or at the edge of stents (distance apart from the edge < or = 5 mm), it was defined to be late thrombosis; otherwise as a new-lesion induced AMI. RESULTS: One hundred and ninety-two patients aged 40 - 79 years were included in this study. New lesions, as the cause of STEAMI, were found in 144 patients (Group A, 75%), and late thrombosis in 48 patients (Group B, 25%). Almost all newly built thromboses were found at the sites of previous insignificant lesions (diameter stenosis < 50%). There was a significant difference in the average time from previous PCI to AMI ((30.1 +/- 12.4) vs (20.3 +/- 11.9) months) between the two groups. Diabetes mellitus (DM) and drug-eluting stent (DES) utilization were associated with markedly higher morbidity of late thrombosis in adjusted Logistic regression (hazard ratio (HR) 3.4, 95% confidence interval (CI) 1.1 - 10.9 and 5.3, 95% CI 1.1 - 26.5). CONCLUSIONS: STEAMIs happening 1 month after PCI are more likely to develop from previous insignificant lesion rupture than from late thrombosis in-stents. Moreover, DM and DES are associated with the high incidence of late thrombosis, which may indicate that intensive antiplatelet therapy should be considered in patients with diabetes.


Assuntos
Angioplastia Coronária com Balão/efeitos adversos , Trombose Coronária/etiologia , Stents Farmacológicos/efeitos adversos , Infarto do Miocárdio/etiologia , Adulto , Idoso , Angiografia Coronária , Trombose Coronária/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/patologia
15.
Zhonghua Nei Ke Za Zhi ; 48(10): 814-7, 2009 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-20079220

RESUMO

OBJECTIVE: To study the possible causes of ST-elevated acute myocardial infarction (STEAMI) occurring one month after percutaneous coronary intervention (PCI). METHODS: One hundred and ninety two patients aged from 40 - 79 years who had a successful previous PCI and also received primary PCI due to STEAMI in this hospitalization were included in this study. The AMI-related lesions and previous angiographic findings such as the number of lesions, the degree of the stenosis, the type of stents and the acute results of last PCI, etc. were recorded in detail. If the AMI-related lesion was localized in-stents or at the edge of stents (distance from the edge < or = 5 mm), it was defined as late thrombosis, otherwise it was regarded as an AMI induced by new-lesion. RESULTS: New lesions, as the cause of STEAMI, were found in 144 cases (Group A, 75%), and late thrombosis in 48 patients (Group B, 25%). There was a significant difference in the average time from previous PCI to AMI (30.1 +/- 12.4 vs. 20.3 +/- 11.9 months) between the two groups. Diabetes mellitus (DM) and drug-eluting stents (DES) utilization were associated with markedly higher morbidity of late thrombosis in adjusted logistic regression analysis [hazard ratio (HR) 3.387, 95% CI 1.053 - 10.898 and HR 5.311, 95%CI 1.066 - 26.464]. CONCLUSIONS: STEAMI occurred 1 month after PCI are more likely to be developed from previous insignificant lesions than from late thrombosis in stents. Moreover, DM and DES are associated with a high incidence of late thrombosis, which may indicate that intensive antiplatelet therapy should be considered in diabetic patients receiving PCI.


Assuntos
Angioplastia Coronária com Balão , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/terapia , Idoso , Stents Farmacológicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva
16.
Zhonghua Xin Xue Guan Bing Za Zhi ; 37(12): 1093-6, 2009 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-20193180

RESUMO

OBJECTIVE: The aim of this study was to assess the long-term clinical outcome of patients with diabetes mellitus and chronic total occlusion (CTO) underwent drug-eluting stents (DES) implantation. METHODS: Data of 143 consecutive eligible patients from January, 2006 to May, 2007 were retrospectively analyzed. The endpoint of the study was the major adverse cardiac events (MACE), including death, myocardial infarction, target lesion revascularization. The patients were divided into two groups, event group and non-event group, according to the result of follow-up. RESULTS: Long-term follow-up was finished in 139 (97.2%) patients. Mean follow-up duration was (19.8 + or - 5.1) months. MACE rate was 10.5% during follow-up: 3 deaths, 1 myocardial infarction and 11 repeated target lesion revascularization with PCI. Compared with the non-event group, the percentage of residual lesion [(17.7 + or - 1.8)% vs. (15.4 + or - 5.0)%, P = 0.001] was significantly higher in the event group, however, the final minimal luminal diameter [(2.14 + or - 0.22)% vs. (2.89 + or - 0.37)%, P = 0.004] was lower. Cox regression analysis showed that final luminal diameter (OR: 0.097, 95%CI: 0.013 - 0.694, P = 0.020) was the only dependent predictor at follow-up. CONCLUSION: Final minimal luminal diameter is an independent predictor of MACE during follow-up for patients with diabetes and CTO underwent DES implantation.


Assuntos
Oclusão Coronária/terapia , Angiopatias Diabéticas/terapia , Stents Farmacológicos , Adulto , Idoso , Idoso de 80 Anos ou mais , Implante de Prótese Vascular , Doença Crônica , Oclusão Coronária/complicações , Oclusão Coronária/diagnóstico , Angiopatias Diabéticas/diagnóstico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Resultado do Tratamento
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