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1.
Cell Commun Signal ; 22(1): 438, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39261825

RESUMO

Pathological cardiac hypertrophy is the primary cause of heart failure, yet its underlying mechanisms remain incompletely understood. Transmembrane protein 100 (TMEM100) plays a role in various disorders, such as nervous system disease, pain and tumorigenesis, but its function in pathological cardiac hypertrophy is still unknown. In this study, we observed that TMEM100 is upregulated in cardiac hypertrophy. Functional investigations have shown that adeno-associated virus 9 (AAV9) mediated-TMEM100 overexpression mice attenuates transverse aortic constriction (TAC)-induced cardiac hypertrophy, including cardiomyocyte enlargement, cardiac fibrosis, and impaired heart structure and function. We subsequently demonstrated that adenoviral TMEM100 (AdTMEM100) mitigates phenylephrine (PE)-induced cardiomyocyte hypertrophy and downregulates the expression of cardiac hypertrophic markers in vitro, whereas TMEM100 knockdown exacerbates cardiomyocyte hypertrophy. The RNA sequences of the AdTMEM100 group and control group revealed that TMEM100 was involved in oxidative stress and the MAPK signaling pathway after PE stimulation. Mechanistically, we revealed that the transmembrane domain of TMEM100 (amino acids 53-75 and 85-107) directly interacts with the C-terminal region of TAK1 (amino acids 1-300) and inhibits the phosphorylation of TAK1 and its downstream molecules JNK and p38. TAK1-binding-defective TMEM100 failed to inhibit the activation of the TAK1-JNK/p38 pathway. Finally, the application of a TAK1 inhibitor (iTAK1) revealed that TAK1 is necessary for TMEM100-mediated cardiac hypertrophy. In summary, TMEM100 protects against pathological cardiac hypertrophy through the TAK1-JNK/p38 pathway and may serve as a promising target for the treatment of cardiac hypertrophy.


Assuntos
Cardiomegalia , MAP Quinase Quinase Quinases , Proteínas de Membrana , Miócitos Cardíacos , Animais , Cardiomegalia/genética , Cardiomegalia/metabolismo , Cardiomegalia/patologia , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , MAP Quinase Quinase Quinases/metabolismo , MAP Quinase Quinase Quinases/genética , Camundongos , Camundongos Endogâmicos C57BL , Masculino , Progressão da Doença , Humanos , Fenilefrina/farmacologia , Sistema de Sinalização das MAP Quinases , Estresse Oxidativo
2.
Mol Cell Biochem ; 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39264395

RESUMO

The fundamental pathophysiological mechanism in the progression of chronic heart failure following acute myocardial infarction (AMI) is ventricular remodeling, in which innate and adaptive immunity both play critical roles. Myeloid-derived suppressor cells (MDSCs) have been demonstrated to function in a range of pathological conditions, such as infections, inflammation, autoimmune diseases, and tumors. However, it is unclear how MDSCs contribute to cardiac remodeling following AMI. This study aimed to identify the function and underlying mechanism of MDSCs in controlling cardiac remodeling following AMI. Following AMI in mice, MDSCs frequencies changed dynamically, considerably increased on day 7 in blood, spleens, lymph nodes and hearts, and decreased afterwards. Consistently, mice with AMI displayed enhanced cardiac function on day 14 post-AMI, reduced infract size and higher survival rates on day 28 post-AMI following the adoptive transfer of MDSCs. Furthermore, MDSCs inhibited the inflammatory response by decreasing pro-inflammatory cytokine (TNF-α, IL-17, Cxcl-1, and Cxcl-2) expression, up-regulating anti-inflammatory cytokine (TGF-ß1, IL-10, IL-4, and IL-13) expression, reducing CD3+ T cell infiltration in the infarcted heart and enhancing M2 macrophage polarization. Mechanistically, MDSCs improved the release of anti-inflammatory factors (TGF-ß1 and IL-10) and decreased the injury of LPS-induced cardiomyocytes in vitro in a manner dependent on cell-cell contact. Importantly, blockade of IL-10 partially abolished the cardioprotective role of MDSCs. This study found that MDSCs contributed to the restoration of cardiac function and alleviation of adverse cardiac remodeling after AMI possibly by inhibiting inflammation.

3.
IUBMB Life ; 73(1): 238-251, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33331071

RESUMO

Atherosclerosis (AS) is the main cause of coronary heart disease, in which enhancer of zeste homolog 2 (EZH2) has been implied to participate in this process. Thus, this work proposed to explore the effect of EZH2 on AS from microRNA-139-5p (miR-139-5p)/signal transducer and activator of transcription 1 (STAT1) axis. EZH2, miR-139-5p, and STAT1 expression in arterial tissues of AS patients were detected. Human arterial smooth muscle cells (HASMCs) induced with oxidized low-density lipoprotein (ox-LDL) and the mice fed with high fat diet were treated with silenced EZH2 or upregulated miR-139-5p to explore their roles in proliferation and apoptosis of HASMCs, together with inflammation response and oxidative stress of mice. Chromatin immunoprecipitation experiment was applied to verify the regulatory effect of EZH2 on miR-139-5p through methylation of H3K27me3. The targeting relationship between miR-139-5p and STAT1 was verified by online website and luciferase activity assay. Reduced miR-139-5p and overexpressed EHZ2 and STAT1 were found in AS. Silenced EZH2 or elevated miR-139-5p decreased the production of cholesterol and inhibited inflammation reaction in serum of mice with AS. Silenced EZH2 or elevated miR-139-5p facilitated proliferation and restrained apoptosis of ox-LDL-treated HASMCs, and restrained oxidative stress and cell apoptosis in arterial tissues of AS mice. EZH2 regulated miR-139-5p through H3K27me3, and miR-139-5p targeted STAT1. miR-139-5p silencing antagonized the effects of EZH2 down-regulation on AS. This study manifests that down-regulated EZH2 or elevated miR-139-5p inhibits ox-LDL-induced HASMCs apoptosis, plaque formation, and inflammatory response in AS mice, which may be related to down-regulated STAT1.


Assuntos
Aterosclerose/patologia , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Proteína Potenciadora do Homólogo 2 de Zeste/fisiologia , Regulação da Expressão Gênica , MicroRNAs/genética , Fator de Transcrição STAT1/metabolismo , Animais , Apoptose , Aterosclerose/genética , Aterosclerose/metabolismo , Proliferação de Células , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Humanos , Masculino , Metilação , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Fator de Transcrição STAT1/genética
4.
J Interv Cardiol ; 2021: 2632343, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34934407

RESUMO

BACKGROUND: The revascularization of small vessels using drug-eluting stents remains challenging. The use of the drug-coated balloon is an attractive therapeutic strategy in de novo lesions in small coronary vessels, particularly in the diabetic group. This study aimed to assess the outcomes of DCB-only angioplasty in small vessel disease. METHODS: A total of 1198 patients with small vessel disease treated with DCB-only strategy were followed. Patients were divided into the diabetic and nondiabetic groups. Clinical and angiographical follow-up were organized at 12 months. The primary endpoints were target lesion failure and secondary major adverse cardiac events. RESULTS: There was a significantly higher rate of target lesion failure among diabetic patients compared to nondiabetic [17 (3.9%) vs. 11 (1.4%), P=0.006], taken separately, the rate of target lesion revascularization significantly differed between groups with a higher rate observed in the diabetic group [9 (2%) vs. 4 (0.5%), P=0.014]. Diabetes mellitus remained an independent predictor for TLF (HR: 2.712, CI: 1.254-5.864, P=0.011) and target lesion revascularization (HR: 3.698, CI: 1.112-12.298, P=0.033) after adjustment. However, no significant differences were observed between groups regarding the target vessel myocardial infarction (0.6% vs. 0.1%, P=0.110) and MACE [19 (4.4%) vs. 21 (2.7%), P=0.120]. CONCLUSION: Drug-coated balloon-only treatment achieved lower incidence rates of TLF and MACE. Diabetes is an independent predictor for target lesion failure and target lesion revascularization at one year following DCB treatment in small coronary vessels. We observed no significant differences between groups regarding MACE in one year.


Assuntos
Angioplastia Coronária com Balão , Doença da Artéria Coronariana , Diabetes Mellitus , Preparações Farmacêuticas , Angiografia Coronária , Doença da Artéria Coronariana/cirurgia , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/cirurgia , Diabetes Mellitus/epidemiologia , Humanos , Resultado do Tratamento
5.
BMC Cardiovasc Disord ; 20(1): 487, 2020 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-33213381

RESUMO

BACKGROUND: To explore potential value of guard-wire technology during percutaneous coronary intervention (PCI) in patients with ostial coronary lesions. METHODS: Patients, who underwent PCI, were collected between October 2011 and March 2017. Of the 141 patients, 63 (44.7%) have ostial lesions, and 78 (55.3%) have distal bifurcation sites. They were divided into group A (n = 71) and group B (n = 70). Group A received PCI after guard-wire technology. Group B were given balloon dilation and stent after placing guide wire through target lesion vessel. X-ray exposure time, contrast agent dosage, total PCI duration, pressure incarceration times, cases of malignant arrhythmia and cases of failed PCI of all patients were analyzed, respectively. RESULTS: The general clinical characteristics includes patients age, sex ratio, the proportion of complications, smoking ratio and left ventricular ejection fraction of both groups was not significantly different. X-ray exposure time, contrast agent dosage, PCI total time, stent positioning time, pressure infestation frequency, arrhythmia frequency and complication number of group B were higher than those of group A. There is no case of malignant arrhythmia and case of failed PCI in group A, while there were five malignant arrhythmia and four failed PCI in group B. Contrast agent dosage and cases of failed PCI increased in group B compared with group A. CONCLUSION: The guard wire technology is safer and more feasible to patients with ostial coronary lesions who underwent PCI.


Assuntos
Angioplastia Coronária com Balão/instrumentação , Cateterismo Cardíaco/instrumentação , Cateteres Cardíacos , Doença da Artéria Coronariana/terapia , Estenose Coronária/terapia , Idoso , Cateterismo Cardíaco/efeitos adversos , Doença da Artéria Coronariana/diagnóstico por imagem , Estenose Coronária/diagnóstico por imagem , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Stents , Fatores de Tempo , Resultado do Tratamento
6.
J Med Virol ; 91(3): 337-346, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30133872

RESUMO

Hemorrhagic fever with renal syndrome (HFRS) is highly endemic in China, where approximately 90% of the total human cases in the world are reported. The Hebei province, one of areas with the highest prevalence, has reported HFRS cases every year in the last two decades. This study describes the spatiotemporal patterns of HFRS in the Hebei province from 2001 to 2016, detects the high-risk spatiotemporal clusters of HFRS, and provides valuable information for planning and implementation of local preventive measures. For the purpose of the analysis, HFRS cases recorded during the sixteen years in the Hebei province were aggregated into three temporal periods (2001-2006, 2007-2012, and 2013-2016). Spatiotemporal analyses, including Global spatial autocorrelation analysis and Kulldorff's scan statistical analysis, were applied to analyze te spatiotemporal clusters of HFRS at the county level. The results revealed that the spatial extent of the HFRS epidemic in the Hebei province changed dynamically from 2001 to 2016, which indicated that a comprehensive preventative strategy should be implemented in the northeastern regions of the Hebei province in spring.


Assuntos
Febre Hemorrágica com Síndrome Renal/epidemiologia , Análise Espaço-Temporal , China/epidemiologia , Análise por Conglomerados , Sistemas de Informação Geográfica , Humanos , Incidência , Estações do Ano
7.
BMC Infect Dis ; 19(1): 765, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477045

RESUMO

BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS) is an emerging zoonotic infectious disease caused by hantaviruses which circulate worldwide. So far, it was still considered as one of serious public health problems in China. The present study aimed to reveal the stabilities and variations of hantavirus infection in Hebei province located in North China through a long-term retrospective observation. METHODS: The epidemiological data of HFRS cases from all 11 cities of Hebei province since 1981 through 2016 were collected and descriptively analyzed. The rodent densities, species compositions and virus-carrying rates of different regions were collected from six separated rodent surveillance points which set up since 2007. The molecular diversity and phylogenetic relationship of hantaviruses circulating among rodents were analyzed based on partial viral glycoprotein gene. RESULTS: HFRS cases have been reported every year in Hebei province, since the first local case was identified in 1981. The epidemic history can be artificially divided into three phases and a total of 55,507 HFRS cases with 374 deaths were reported during 1981-2016. The gender and occupational factors of susceptible population were invarible throughout, however age of that was gradually aging. The annual outbreak peak always present in spring, while the main epidemic region had gradully altered from south to northeast. Surveillance of rodents revealed that residential rodents significantly possessed higher density and virus-carring rate than field rodents. The house rat, Rattus norvegicus, was the dominant rodent species and Seoul virus S3 sub-genotype which is continued but slightly evolving perhaps to be the sole pathogen for local HFRS cases of Hebei province. CONCLUSIONS: This long-term province-wide surveillance and epidemiological analysis has revealed the stabilities and variations of hantavirus infection in North China. In order to improve current prevention and control strategies of HFRS in China, all surveillance should be continuously enhanced and variations should be paid more attentions.


Assuntos
Infecções por Hantavirus/epidemiologia , Febre Hemorrágica com Síndrome Renal/epidemiologia , Animais , China/epidemiologia , Surtos de Doenças/estatística & dados numéricos , Epidemias/estatística & dados numéricos , Genótipo , Orthohantavírus/classificação , Orthohantavírus/genética , Orthohantavírus/isolamento & purificação , Infecções por Hantavirus/virologia , Febre Hemorrágica com Síndrome Renal/virologia , Humanos , Filogenia , Dinâmica Populacional , Vigilância da População , Ratos , Estudos Retrospectivos , Roedores/virologia , Fatores de Tempo , Zoonoses/epidemiologia , Zoonoses/virologia
8.
Pak J Pharm Sci ; 27(5 Suppl): 1627-31, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25262509

RESUMO

This paper introduces the research progress related to the antioxidant activity of bamboo leaf flavonoid (EOB-f) and its pharmacological activity of heart and cerebral vessels. The paper studied what role EOB-f played in the diagnosis of heart and cerebral vessels, based on the in vitro, in vivo and animal model as well as the pharmacological research experiment. 1) The in vitro and in vivo experiments indicated that EOB-f has the function of anti-reactive-oxide species, anti-aging and anti-fatigue; 2) The research of animal model indicated that EOB-f can significantly decrease the triglyceride (TG) content in serum, significantly increase high density lipoprotein cholesterol (HDL-C) content in serum, regulate blood lipids and reduce the risk of atherosclerosis; 3) The pharmacological study showed that EOB-f has the effect to resist the whole animal anoxia, can effectively dilate coronary vessels, increase coronary flow, increase myocardial contractility, obviously improve myocardial ischemia and diminish the myocardial infarction scope, inhibit the coagulation process and reduce platelet aggregation, and has certain protective effect on cerebral ischemia. EOB-f has the potential to develop as the natural drug and functional foods for prevention of cardiovascular and cerebrovascular diseases.


Assuntos
Antioxidantes/farmacologia , Transtornos Cerebrovasculares/tratamento farmacológico , Vasos Coronários/efeitos dos fármacos , Flavonoides/farmacologia , Sasa , Animais , HDL-Colesterol/sangue , Vasos Coronários/fisiologia , Flavonoides/uso terapêutico , Hiperlipidemias/tratamento farmacológico , Masculino , Agregação Plaquetária/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
9.
Viral Immunol ; 37(4): 194-201, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38717820

RESUMO

COVID-19 is a highly infectious respiratory disease whose progression has been associated with multiple factors. From SARS-CoV-2 infection to death, biomarkers capable of predicting different disease processes are needed to help us further understand the molecular progression of COVID-19 disease. The aim is to find differentially expressed proteins that are associated with the progression of COVID-19 disease or can be potential biomarkers, and to provide a reference for further understanding of the molecular mechanisms of COVID-19 occurrence, progression, and treatment. Data-independent Acquisition (DIA) proteomics to obtain sample protein expression data, using R language screening differentially expressed proteins. Gene Ontology and Kyoto Encyclopedia for Genes and Genomes analysis was performed on differential proteins and protein-protein interaction (PPI) network was constructed to screen key proteins. A total of 47 differentially expressed proteins were obtained from COVID-19 incubation patients and healthy population (L/H), mainly enriched in platelet-related functions, and complement and coagulation cascade reaction pathways, such as platelet degranulation and platelet aggregation. A total of 42 differential proteins were obtained in clinical and latent phase patients (C/L), also mainly enriched in platelet-related functions and in complement and coagulation cascade reactions, platelet activation pathways. A total of 10 differential proteins were screened in recovery and clinical phase patients (R/C), mostly immune-related proteins. The differentially expressed proteins in different stages of COVID-19 are mostly closely associated with coagulation, and key differential proteins, such as FGA, FGB, FGG, ACTB, PFN1, VCL, SERPZNCL, APOC3, LTF, and DEFA1, have the potential to be used as early diagnostic markers.


Assuntos
COVID-19 , Biologia Computacional , Mapas de Interação de Proteínas , Proteômica , SARS-CoV-2 , Humanos , COVID-19/metabolismo , SARS-CoV-2/genética , Biomarcadores , Ontologia Genética
10.
Mitochondrial DNA B Resour ; 9(9): 1218-1222, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39291128

RESUMO

Rattus tanezumi (Niethammer, 1975) is one of the commensal rodent species in South China. With the development of transportation and climate change, R. tanezumi has gradually migrated north and become the dominant rat species for the past few years. In this study, we assembled a complete mitochondrial genome of R. tanezumi, captured from North China. The mitogenome contains 16,307 nucleotide pairs, including 13 protein-coding genes, 2 ribosomal RNA genes, and 22 transfer RNA genes, as well as one non-coding control region. Based on whole mitogenome phylogenetical analysis showed that R. tanezumi captured from North China had a close phylogenetic relationship with that from Japan and South Korea. These findings are valuable for further studies on the evolution, genetic diversity, and taxonomy of Asian commensal rodent.

11.
Zhonghua Xin Xue Guan Bing Za Zhi ; 41(2): 126-9, 2013 Feb.
Artigo em Zh | MEDLINE | ID: mdl-23710743

RESUMO

OBJECTIVE: To observe the expression and clinical implication of plasma miR-328 in patients with atrial fibrillation (AF). METHODS: Fifty-eight patients with AF (AF group: 17 paroxysmal AF, 21 persistent AF, and 20 permanent AF) and 15 healthy volunteers (Control group) were included. General clinical data and related biochemical parameters were collected. Plasma miR-328 levels were detected with quantitative real-time polymerase chain reaction (qRT-PCR) analysis. The correlation between plasma miR-328 and AF risk factors was analyzed. RESULTS: (1) Compared with the control group, the expression level of plasma miR-328 was significantly elevated in AF group (fold 7.72 ± 9.32) (P < 0.05). (2) In AF group, the expression of plasma miR-328 was significantly different in different type of AF[paroxysmal AF with (1.98 ± 0.81), persistent AF with (6.57 ± 5.82) and permanent AF with (13.47 ± 12.29)] (P < 0.05), and which was increased in proportion to the duration of AF. (3) There was a positive correlation between plasma miR-328 level and left atrial diameter in the AF group (r = 0.310, P < 0.05). CONCLUSION: miR-328 expression is significantly increased in patients with AF, which may be involved in the atrial remodeling process of AF.


Assuntos
Fibrilação Atrial/sangue , MicroRNAs/sangue , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
12.
Infect Genet Evol ; 114: 105503, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37717798

RESUMO

Seoul virus (SEOV) is a major pathogen which causes hemorrhagic fever with renal syndrome (HFRS), and is present all over the world. However, there are currently few long-term systematic studies of SEOV's phylogenetic and evolutionary mechanisms in epidemic areas. Thus, in this study, we used RT-PCR combined with NGS to obtain the genomes of six SEOV viruses from 1993, as well as 56 Hebei province-specific tissue samples from 1999 to 2022. Phylogenetic analysis showed that the SEOV samples could be divided into seven groups and showed geographic clustering. The geographic region may be the main factor affecting the genetic diversity of SEOV. We also found that SEOV was subject to strong overall purifying selection and positive selection at certain sites during evolution. Recombination events and high nucleotide substitution rates were also shown to accelerate SEOV's evolution. Evolutionary feature of the L segment is more representative of complete genome. Our detailed analysis provides a deeper understanding of the genetic diversity and evolutionary drivers of SEOV within its primary epidemic areas. It will be important to further monitor epidemiological trends and drivers of variation to help increase our understanding of the pathogenicity of SEOV infections.


Assuntos
Febre Hemorrágica com Síndrome Renal , Vírus Seoul , Humanos , Vírus Seoul/genética , Filogenia , Febre Hemorrágica com Síndrome Renal/epidemiologia , China/epidemiologia , Evolução Molecular , Variação Genética
13.
J Biomol Struct Dyn ; 41(20): 11255-11261, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-36625725

RESUMO

To measure the expression of angiotensin converting enzyme 2 (ACE2) mRNA in SARS-CoV-2 infection with different infection status and at different stages during infection, we used RT-qP CR to measure the expression of ACE2 mRNA. Measurements were analyzed by two-way repeated measures analysis of variance (RMANOVA). Expression of ACE2 mRNA was downregulated in initial stages of SARS-CoV-2 infection both in the asymptomatic infection (ASY) group and the confirmed cases (CON) group (t=-8.0845, P < 0.0001; t=-8.1904, P < 0.0001, respectively). The expression of ACE2 mRNA in the incubation period of CON group was lower compared with the intinal period of ASY group (F = 6.084, p = 0.016, partialη2 = 0.070). Relative expression of ACE2 mRNA was upregulated at the late stage of SARS-CoV-2 infection in the ASY and CON groups (F = 23.489, p = 0.000, partialη2 = 0.225; F = 46.555, p = 0.000, partialη2 = 0.365, respectively). The relative expression of ACE2 mRNA was down-regulated (mean ± SEM:0.69 ± 0.03) after inoculation with SARSCoV- 2 Spike pseudovirus, and there was a statistical difference (one-way t test, mean diffience =-0.31, 95%CI: -0.37˜-0.24, t=-8.1904, P < 0.0001). The expression of ACE2 mRNA is downregulated in the initial stage of SARS-CoV-2 infection, and then upregulated in the late stage of SARS-CoV-2 infection. The lower expression of ACE2 mRNA during the incubation period can lead to clinical symptoms. Downregulation of ACE2 mRNA was related to the interaction between SARS-CoV-2 S protein and ACE2.Communicated by Ramaswamy H. Sarma.


Assuntos
COVID-19 , Humanos , COVID-19/genética , Enzima de Conversão de Angiotensina 2/genética , SARS-CoV-2/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/metabolismo
14.
J Geriatr Cardiol ; 20(10): 716-727, 2023 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-37970224

RESUMO

BACKGROUND: Controversy exists as to the optimal treatment approach for ostial left anterior descending (LAD) or ostial left circumflex artery (LCx) lesions. Drug-coated balloons (DCB) may overcome some of the limitations of drug-eluting stents (DES). Therefore, we investigated the security and feasibility of the DCB policy in patients with ostial LAD or ostial LCx lesions, and compared it with the conventional DES-only strategy. METHODS: We retrospectively enrolled patients with de novo ostial lesions in the LAD or LCx who underwent interventional treatment. They were categorized into two groups based on their treatment approach: the DCB group and the DES group. The treatment strategies in the DCB group involved the use of either DCB-only or hybrid strategies, whereas the DES group utilized crossover or precise stenting techniques. Two-year target lesion revascularization was the primary endpoint, while the rates of major adverse cardiovascular events, cardiac death, target vessel myocardial infarction, and vessel thrombosis were the secondary endpoints. Using propensity score matching, we assembled a cohort with comparable baseline characteristics. To ensure result analysis reliability, we conducted sensitivity analyses, including interaction, and stratified analyses. RESULTS: Among the 397 eligible patients, 6.25% of patients who were planned to undergo DCB underwent DES. A total of 108 patients in each group had comparable propensity scores and were included in the analysis. Two-year target lesion revascularization occurred in 5 patients (4.90%) and 16 patients (16.33%) in the DCB group and the DES group, respectively (odds ratio = 0.264, 95% CI: 0.093-0.752, P = 0.008). Compared with the DES group, the DCB group demonstrated a lower major adverse cardiovascular events rate (7.84% vs. 19.39%, P = 0.017). However, differences with regard to cardiac death, non-periprocedural target vessel myocardial infarction, and definite or probable vessel thrombosis between the groups were non-significant. CONCLUSIONS: The utilization of the DCB approach signifies an innovative and discretionary strategy for managing isolated ostial lesions in the LAD or LCx. Nevertheless, a future randomized trial investigating the feasibility and safety of DCB compared to the DES-only strategy specifically for de novo ostial lesions in the LAD or LCx is highly warranted.

15.
Free Radic Biol Med ; 209(Pt 2): 252-264, 2023 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-37852547

RESUMO

Heart failure (HF) severely impairs human health because of its high incidence and mortality. Cardiac hypertrophy is the main cause of HF, while its underlying mechanism is not fully clear. As an E3 ubiquitin ligase, Ring finger protein 13 (RNF13) plays a crucial role in many disorders, such as liver immune, neurological disease and tumorigenesis, whereas the function of RNF13 in cardiac hypertrophy remains largely unknown. In the present study, we found that the protein expression of RNF13 is up-regulated in the transverse aortic constriction (TAC)-induced murine hypertrophic hearts and phenylephrine (PE)-induced cardiomyocyte hypertrophy. Functional investigations indicated that RNF13 global knockout mice accelerates the degree of TAC-induced cardiac hypertrophy, including cardiomyocyte enlargement, cardiac fibrosis and heart dysfunction. On the contrary, adeno-associated virus 9 (AAV9) mediated-RNF13 overexpression mice alleviated cardiac hypertrophy. Furthermore, we demonstrated that adenoviral RNF13 attenuates the PE-induced cardiomyocyte hypertrophy and down-regulates the expression of cardiac hypertrophic markers, while the opposite results were observed in the RNF13 knockdown group. The RNA-sequence of RNF13 knockout and wild type mice showed that RNF13 deficiency activates oxidative stress after TAC surgery. In terms of the mechanism, we found that RNF13 directly interacted with p62 and promoted the activation of downstream NRF2/HO-1 signaling. Finally, we proved that p62 knockdown can reverse the effect of RNF13 in cardiac hypertrophy. In conclusion, RNF13 protects against the cardiac hypertrophy via p62-NRF2 axis.


Assuntos
Insuficiência Cardíaca , Fator 2 Relacionado a NF-E2 , Animais , Camundongos , Cardiomegalia/metabolismo , Insuficiência Cardíaca/patologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Miócitos Cardíacos/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Transdução de Sinais , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
16.
Front Cardiovasc Med ; 10: 1122290, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37388642

RESUMO

Background: Coronary artery calcification (CAC) is associated with high rates of restenosis and adverse clinical events after percutaneous coronary intervention (PCI) with drug-eluting stents (DES). Objectives: The aim of this study was to evaluate the long-term clinical outcomes of drug-coated balloon (DCB)-only treatment for de novo lesions with and without CAC. Methods: Patients with de novo coronary disease treated with the DCB-only strategy were retrospectively enrolled from three centers and categorized into a CAC group and a non-CAC group. The primary endpoint was the target lesion failure (TLF) rate during the 3-year follow-up. Secondary endpoints included the occurrence of major adverse cardiac events (MACEs), target lesion revascularization (TLR), cardiac death, myocardial infarction (MI) and any revascularization. Propensity score matching (PSM) was conducted to assemble a cohort of patients with similar baseline characteristics. Results: A total of 1,263 patients with 1,392 lesions were included, and 243 patients were included in each group after PSM. Compared with the non-CAC group, the incidence rates of TLF (9.52% vs. 4.94%, odds ratio [OR]: 2.080; 95% confidence interval [CI]: 1.083-3.998, P = 0.034) and TLR (7.41% vs. 2.88%, OR: 2.642; 95% CI: 1.206-5.787, P = 0.020) in the CAC group were higher. The incidence rates of MACE (12.35% vs. 7.82%, OR: 1.665; 95% CI: 0.951-2.916, P = 0.079), cardiac death (2.06% vs. 2.06%, OR: 0.995; 95% CI: 0.288-3.436, P = 0.993), MI (1.23% vs. 0.82%, OR: 2.505; 95% CI: 0.261-8.689, P = 0.652) and any revascularization (12.76% vs. 9.67%, OR: 1.256; 95% CI: 0.747-2.111, P = 0.738) were similar between groups. Conclusions: CAC increased the incidence of TLF and TLR without a substantial increase in the risk of MACE, cardiac death, MI, or any revascularization in patients treated with DCB-only angioplasty during the 3-year follow-up.

17.
Front Cardiovasc Med ; 10: 1045859, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36937919

RESUMO

Background: Data on drug-coated balloons (DCB) for de novo coronary chronic total occlusion (CTO) are limited. We aimed to investigate the long-term outcomes of substitution of drug-eluting stents (DES) by DCB. Methods: We compared the outcomes of less DES strategy (DCB alone or combined with DES) and DES-only strategy in treating de novo coronary CTO in this prospective, observational, multicenter study. The primary endpoints were major adverse cardiovascular events (MACE), target vessel revascularization, myocardial infarction, and death during 3-year follow-up. The secondary endpoints were late lumen loss (LLL) and restenosis until 1-year after operation. Results: Of the 591 eligible patients consecutively enrolled between January 2015 and December 2019, 281 (290 lesions) were treated with DCB (DCB-only or combined with DES) and 310 (319 lesions) with DES only. In the DCB group, 147 (50.7%) lesions were treated using DCB-only, and the bailout stenting rate was relatively low (3.1%). The average stent length per lesion in the DCB group was significantly shorter compared with the DES-only group (21.5 ± 25.5 mm vs. 54.5 ± 26.0 mm, p < 0.001). A total of 112 patients in the DCB group and 71 patients in the DES-only group (38.6% vs. 22.3%, p < 0.001) completed angiographic follow-up until 1-year, and LLL was much less in the DCB group (-0.08 ± 0.65 mm vs. 0.35 ± 0.62 mm, p < 0.001). There were no significant differences in restenosis occurrence between the two groups (20.5% vs. 19.7%, p > 0.999). The Kaplan-Meier estimates of MACE at 3-year (11.8% vs. 12.0%, log-rank p = 0.688) was similar between the groups. Conclusion: Percutaneous coronary intervention with DCB is a potential "stent-less" therapy for de novo CTO lesions with satisfactory long-term clinical results compared to the DES-only approach.

18.
Front Cardiovasc Med ; 9: 1028007, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36407423

RESUMO

Aims: An increasing body of evidence suggests that drug-coated balloon (DCB) angioplasty represents a valuable option for revascularization in selected patients with coronary bifurcation disease. However, there remains a paucity of real-world observational evidence on the efficacy of DCB in left main (LM) true bifurcation lesion. We compared clinical and angiographic outcomes of hybrid [DCB + drug-eluting stent (DES)] versus DES-only strategy (provisional stenting or two-stent strategies) in de novo LM true bifurcated lesions. Methods: The primary endpoint was the 2-year composite rate of target lesion failure (TLF): cardiac death, target vessel myocardial infarction (TVMI), or clinically driven target lesion revascularization (CD-TLR). A routine 1-year angiographic follow-up was scheduled. Propensity-score matching was utilized to assemble a cohort of patients with similar baseline characteristics. Results: Among 1077 eligible patients, 199 who received DCB treatment and 398 who were assigned to DES therapy had similar propensity scores and were included in the analysis. TLF within 2 years occurred in 13 patients (7.56%) assigned to DCB group, and 52 patients (14.36%) assigned to DES group (odds ratio: 0.487; 95% confidence interval: 0.258-0.922; P = 0.025; Log-rank P = 0.024). Compared with the DES group, the DCB group resulted in a lower rate of CD-TLR (2.91% vs. 9.42%; P = 0.007). Cardiac death, TVMI, all-cause mortality, and stent thrombosis were comparable between both groups. Patients treated with DES-only were associated with a higher late lumen loss (0.42 ± 0.62 mm vs. 0.13 ± 0.42 mm, P < 0.001) compared with the DCB group at 1 year. In sensitivity analysis, the DCB group also presented a lower incidence of TLF, CD-TLR and stent thrombosis both compared to the two-stent strategy and compared to provisional stenting (Ps < 0.05). Conclusion: The 2-year results of PCI utilizing DCB for LM true bifurcation lesions are superior to employing DES alone in terms of safety and effectiveness.

19.
Front Cardiovasc Med ; 9: 935263, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36211569

RESUMO

Background: Drug-coated balloons (DCB), alone or in combination with drug-eluting stents (DES), may be used to treat diffuse coronary lesions. We aimed to explore the efficacy and safety of DCB in patients with diffuse coronary lesions. Methods: Consecutive patients with diffuse coronary lesions (lesion length > 25 mm) who underwent DCB and/or DES between January 2015 and December 2019 were included in this prospective, observational, multicenter study. The DCB group included 355 patients (360 lesions), of which 142 patients (143 lesions, 39.7%) received the DCB-only strategy and 213 patients (217 lesions, 60.3%) received the hybrid strategy (DCB combined with DES). The DES group included 672 patients (831 lesions) treated with DES alone. Target lesion revascularization (TLR) during 3-year follow-up was the primary outcome of interest. The secondary outcome was major adverse cardiac events (MACE), defined as a composite of all-cause death, non-fatal myocardial infarction, and target vessel revascularization. Results: The two groups had comparable baseline clinical and lesion characteristics. Lesion length was similar (43.52 ± 16.46 mm vs. 44.87 ± 15.80 mm, P = 0.181), but the stent length in the DCB group was significantly shorter (24.02 ± 23.62 mm vs. 51.89 ± 15.81 mm, P < 0.001). Ten lesions (2.8%) in the DCB group received bailout stents. Over 3 years of follow-up, no significant difference in TLR incidence between the groups (7.3 vs. 8.3%, log-rank P = 0.636) was observed. Incidence of MACE also did not differ significantly (11.3 vs. 13.7%, log-rank P = 0.324). No thrombosis events occurred in the DCB group, while four patients (0.6%) in the DES group experienced stent thrombosis (log-rank P = 0.193). Moreover, similar TLR and MACE rates were observed between DCB-only and hybrid strategies (TLR: 6.4 vs. 8.0%, log-rank P = 0.651; MACE: 11.4 vs. 11.2%, log-rank P = 0.884). Conclusion: Long-term outcomes show that the efficacy and safety of the DCB strategy (DCB alone or combined with DES) are similar to those of DES alone in diffuse coronary lesions. These findings suggest that this strategy is a promising alternative for select patients with diffuse coronary lesions.

20.
Am J Transl Res ; 14(9): 6256-6267, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36247262

RESUMO

BACKGROUND: Currently, there is no optimal treatment strategy for ostial left anterior descending (LAD) or ostial left circumflex artery (LCx) lesions. This study explored effectiveness and safety of drug-coated balloons (DCB) in individuals presenting with ostial LAD or LCx lesions. METHODS: A total of 137 patients with de novo ostial LAD or LCx lesions scheduled for DCB treatment were prospectively recruited into the study. After mandatory lesion preparation, DCB-only or hybrid strategy [DCB + drug-eluting stent (DES)] were performed on 120 patients (87.59%). The primary endpoint was the rate of 2-year target lesion revascularization (TLR). Rates of major adverse cardiovascular events (MACE), cardiac death, target vessel myocardial infarction (TVMI), and vessel thrombosis were explored as the secondary outcomes. Quantitative coronary angiography software was used to analyze coronary angiograms. RESULTS: Of the participants, 58 were treated with DCB-only and 62 with hybrid strategy. Relative to the DCB-only group, patients in the hybrid group had longer target lesions (15.47 ± 10.08 vs. 36.85 ± 9.46 mm, P<0.001) and higher Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery (SYNTAX) scores (23.47 ± 5.22 vs. 29.98 ± 3.18, P<0.001). During follow-up (731 ± 64 days), neither the primary endpoint (TLR) nor the secondary endpoints (including MACE, cardiac death, TVMI, and vessel thrombosis) differed statistically between the two groups (all P > 0.05). Treatment strategy (DCB-only or hybrid) was not a significant risk factor for TLR. Patients who underwent DCB-only exhibited less late lumen loss compared with the patients who underwent hybrid strategy (-0.26 ± 0.59 vs. 0.42 ± 0.47 mm, P<0.001) at 1-year angiographic follow-up. CONCLUSIONS: With regards to safety and efficacy, the strategy of DCB as a standalone therapy was similar in comparison with the hybrid strategy of DCB + DES for ostial LAD and ostial LCx lesions. This approach might be effective and technically easy in treating ostial LAD and LCx diseases.

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