Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 21
Filtrar
1.
Heliyon ; 10(13): e33785, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39044992

RESUMO

Background and aims: Postoperative atrial fibrillation (POAF) is a frequent complication following cardiac surgery and is associated with adverse clinical outcomes. Our study aimed at determining the clinical and echocardiographic predictors of POAF in patients with cardiac surgery and management of this group of patients may improve their outcome. Methods: We prospectively enrolled patients from the department of cardiovascular surgery in the Second Hospital of Tianjin Medical University from October 23, 2020 to October 30, 2022, without a history of atrial fibrillation. Cox regression was used to identify significant predictors of POAF. Results: A total of 217 patients (79 [36.41 %] were female, 63.96 ± 12.32 years) were included. 88 (40.55 %) patients met the criteria for POAF. Cox regression showed that preoperative left atrial diameter (LAD) (HR: 1.040, 95 % CI 1.008-1.073, p = 0.013) and postoperative QRS/LVEDD (HR: 0.398, 95 % CI 0.193-0.824, p = 0.013) and E/e' (HR: 1.029, 95 % CI 1.002-1.057,p = 0.033) were predictors of POAF. Conclusion: Preoperative LAD and postoperative QRS/LVEDD and E/e' were predictors of POAF in patients undergoing cardiac surgery. Trial registration site: http://www.chictr.org.cn. Registration number: ChiCTR2200063344.

2.
J Orthop Translat ; 47: 39-49, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39007037

RESUMO

Sclerostin emerges as a novel target for bone anabolic therapy in bone diseases. Osteogenesis imperfecta (OI) and X-linked hypophosphatemia (XLH) are rare bone diseases in which therapeutic potential of sclerostin inhibition cannot be ignored. In OI, genetic/pharmacologic sclerostin inhibition promoted bone formation of mice, but responses varied by genotype and age. Serum sclerostin levels were higher in young OI-I patients, while lower in adult OI-I/III/IV. It's worth investigating whether therapeutic response of OI to sclerostin inhibition could be clinically predicted by genotype and age. In XLH, preclinical/clinical data suggested factors other than identified FGF23 contributing to XLH. Higher levels of circulating sclerostin were detected in XLH. Sclerostin inhibition promoted bone formation in Hyp mice, while restored phosphate homeostasis in age-/gender-dependent manner. The role of sclerostin in regulating phosphate metabolism deserves investigation. Sclerostin/FGF23 levels of XLH patients with/without response to FGF23-antibody warrants study to develop precise sclerostin/FGF23 inhibition strategy or synergistic/additive strategy. Notably, OI patients were associated with cardiovascular abnormalities, so were XLH patients receiving conventional therapy. Targeting sclerostin loop3 promoted bone formation without cardiovascular risks. Further, blockade of sclerostin loop3-LRP4 interaction while preserving sclerostin loop2-ApoER2 interaction could be a potential precise sclerostin inhibition strategy for OI and XLH with cardiovascular safety. The Translational Potential of this Article. Preclinical data on the molecular understanding of sclerostin inhibition in OI and therapeutic efficacy in mouse models of different genotypes, as well as clinical data on serum sclerostin levels in patients with different phenotypes of OI, were reviewed and discussed. Translationally, it would facilitate to develop clinical prediction strategies (e.g. based on genotype and age, not just phenotype) for OI patients responsive to sclerostin inhibition. Both preclinical and clinical data suggested sclerostin as another factor contributing to XLH, in addition to the identified FGF23. The molecular understanding and therapeutic effects of sclerostin inhibition on both promoting bone anabolism and improving phosphate homostasis in Hyp mice were reviewed and discussed. Translationaly, it would facilitate the development of precise sclerostin/FGF23 inhibition strategy or synergistic/additive strategy for the treatment of XLH. Cardiovascular risk could not be ruled out during sclerostin inhibition treatment, especially for OI and XLH patients with cardiovascular diseases history and cardiovascular abnormalities. Studies on the role of sclerostin in inhiting bone formation and protecting cardiovascular system were reviewed and discussed. Translationaly, blockade of sclerostin loop3-LRP4 interaction while preserving sclerostin loop2-ApoER2 interaction could be a potential precise sclerostin inhibition strategy for OI and XLH with cardiovascular safety.

4.
Cell Mol Life Sci ; 81(1): 264, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38878214

RESUMO

Atrial fibrillation (AF) is the most common arrhythmia, and atrial fibrosis is a pathological hallmark of structural remodeling in AF. Prostaglandin I2 (PGI2) can prevent the process of fibrosis in various tissues via cell surface Prostaglandin I2 receptor (IP). However, the role of PGI2 in AF and atrial fibrosis remains unclear. The present study aimed to clarify the role of PGI2 in angiotensin II (Ang II)-induced AF and the underlying molecular mechanism. PGI2 content was decreased in both plasma and atrial tissue from patients with AF and mice treated with Ang II. Treatment with the PGI2 analog, iloprost, reduced Ang II-induced AF and atrial fibrosis. Iloprost prevented Ang II-induced atrial fibroblast collagen synthesis and differentiation. RNA-sequencing analysis revealed that iloprost significantly attenuated transcriptome changes in Ang II-treated atrial fibroblasts, especially mitogen-activated protein kinase (MAPK)-regulated genes. We demonstrated that iloprost elevated cAMP levels and then activated protein kinase A, resulting in a suppression of extracellular signal-regulated kinase1/2 and P38 activation, and ultimately inhibiting MAPK-dependent interleukin-6 transcription. In contrast, cardiac fibroblast-specific IP-knockdown mice had increased Ang II-induced AF inducibility and aggravated atrial fibrosis. Together, our study suggests that PGI2/IP system protects against atrial fibrosis and that PGI2 is a therapeutic target for treating AF.The prospectively registered trial was approved by the Chinese Clinical Trial Registry. The trial registration number is ChiCTR2200056733. Data of registration was 2022/02/12.


Assuntos
Angiotensina II , Fibrilação Atrial , Remodelamento Atrial , Epoprostenol , Camundongos Endogâmicos C57BL , Transdução de Sinais , Animais , Fibrilação Atrial/metabolismo , Fibrilação Atrial/patologia , Fibrilação Atrial/induzido quimicamente , Fibrilação Atrial/prevenção & controle , Camundongos , Humanos , Masculino , Transdução de Sinais/efeitos dos fármacos , Remodelamento Atrial/efeitos dos fármacos , Epoprostenol/metabolismo , Fibrose , Fibroblastos/metabolismo , Fibroblastos/efeitos dos fármacos , Fibroblastos/patologia , Átrios do Coração/metabolismo , Átrios do Coração/patologia , Átrios do Coração/efeitos dos fármacos , Iloprosta/farmacologia , Receptores de Epoprostenol/metabolismo , Receptores de Epoprostenol/genética , Feminino
5.
Int J Mol Sci ; 25(9)2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38731911

RESUMO

In drug discovery, selecting targeted molecules is crucial as the target could directly affect drug efficacy and the treatment outcomes. As a member of the CCN family, CTGF (also known as CCN2) is an essential regulator in the progression of various diseases, including fibrosis, cancer, neurological disorders, and eye diseases. Understanding the regulatory mechanisms of CTGF in different diseases may contribute to the discovery of novel drug candidates. Summarizing the CTGF-targeting and -inhibitory drugs is also beneficial for the analysis of the efficacy, applications, and limitations of these drugs in different disease models. Therefore, we reviewed the CTGF structure, the regulatory mechanisms in various diseases, and drug development in order to provide more references for future drug discovery.


Assuntos
Fator de Crescimento do Tecido Conjuntivo , Descoberta de Drogas , Humanos , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Descoberta de Drogas/métodos , Animais , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Oftalmopatias/tratamento farmacológico , Oftalmopatias/metabolismo , Fibrose , Doenças do Sistema Nervoso/tratamento farmacológico , Doenças do Sistema Nervoso/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos
7.
BMC Cardiovasc Disord ; 23(1): 405, 2023 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-37592223

RESUMO

BACKGROUND: Infectious endocarditis (IE) is a disease caused by the colonization of toxic microorganisms on the endocardium of heart valves [1]. Although much progress has been made in the diagnosis and treatment of IE, its complications, such as annular abscesses [2], still have a high mortality rate. In this case, we describe a patient with infective endocarditis complicated by occult deteriorated aortic annular abscess. CASE PRESENTATION: A 44-year-old man was admitted due to weakness of his right limbs and unclear speech for 10 h. He had recurrent fevers for 1 month before admission. Transthoracic echocardiography showed a mix-echoic vegetation attached to the bicuspid aortic valve, moderate aortic regurgitation and a possible aortic annular abscess. Blood cultures were negative and empiric antibiotic therapy was begun. The patient did not have fever again and seem to be clinically improved. However, follow-up transesophageal echocardiography revealed a large periaortic abscess led to aortic sinus pseudoaneurysm. The patient underwent mechanical prosthetic valve replacement and annulus reconstruction successfully. Perivalvular abscess may be insidious deterioration in patients who seem to be clinically improved, which requires us to pay more attention. DISCUSSION: Occult deterioration of an aortic annular abscess is rare and more attention should be paid. Re-evaluation of echocardiography is required even if the patient's symptoms improve.


Assuntos
Falso Aneurisma , Doença da Válvula Aórtica Bicúspide , Masculino , Humanos , Adulto , Abscesso/diagnóstico por imagem , Abscesso/etiologia , Abscesso/terapia , Falso Aneurisma/diagnóstico por imagem , Falso Aneurisma/etiologia , Falso Aneurisma/terapia , Catéteres , Aorta
8.
Stem Cell Res Ther ; 14(1): 188, 2023 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-37507770

RESUMO

BACKGROUND: Mesenchymal stem cells (MSCs) are widely used in a variety of tissue regeneration and clinical trials due to their multiple differentiation potency. However, it remains challenging to maintain their replicative capability during in vitro passaging while preventing their premature cellular senescence. Forkhead Box P1 (FOXP1), a FOX family transcription factor, has been revealed to regulate MSC cell fate commitment and self-renewal capacity in our previous study. METHODS: Mass spectra analysis was performed to identify acetylation sites in FOXP1 protein. Single and double knockout mice of FOXP1 and HDAC7 were generated and analyzed with bone marrow MSCs properties. Gene engineering in human embryonic stem cell (hESC)-derived MSCs was obtained to evaluate the impact of FOXP1 key modification on MSC self-renewal potency. RESULTS: FOXP1 is deacetylated and potentiated by histone deacetylase 7 (HDAC7) in MSCs. FOXP1 and HDAC7 cooperatively sustain bone marrow MSC self-renewal potency while attenuating their cellular senescence. A mutation within human FOXP1 at acetylation site (T176G) homologous to murine FOXP1 T172G profoundly augmented MSC expansion capacity during early passages. CONCLUSION: These findings reveal a heretofore unanticipated mechanism by which deacetylation of FOXP1 potentiates self-renewal of MSC and protects them from cellular senescence. Acetylation of FOXP1 residue T172 as a critical modification underlying MSC proliferative capacity. We suggest that in vivo gene editing of FOXP1 may provide a novel avenue for manipulating MSC capability during large-scale expansion in clinical trials.


Assuntos
Senescência Celular , Células-Tronco Mesenquimais , Animais , Humanos , Camundongos , Diferenciação Celular/genética , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Histona Desacetilases/genética , Células-Tronco Mesenquimais/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo
9.
J Clin Ultrasound ; 51(1): 46-50, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36173749

RESUMO

A 66-year-old woman was admitted to our hospital due to chest distress and shortness of breath during 1 week. Transthoracic echocardiography (TTE) revealed massive pericardial effusion and multiple, irregular and high-density echo "tumor-like" masses on the heart, with the largest one on the apex. However, there were no masses found by computed tomography (CT) scan, except for increased lipids around the coronary artery. We performed emergency pericardiocentesis and drainage to relieve symptoms. The positron emission tomography/CT (PET/CT) also showed several ununiformly high accumulations in pericardial cavity. However, the high-density echo "tumor-like" masses cannot be seen by TTE after pericardiocentesis, and also cannot be detected when surgery. Pericardiotomy was performed due to severe pericardial adhesion. The diagnosis of tuberculosis (TB) was confirmed by pericardiotomy and pericardial biopsy.


Assuntos
Neoplasias , Derrame Pericárdico , Pericardite Tuberculosa , Feminino , Humanos , Idoso , Pericardite Tuberculosa/complicações , Pericardite Tuberculosa/diagnóstico por imagem , Pericardite Tuberculosa/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Pericárdio/diagnóstico por imagem , Derrame Pericárdico/diagnóstico por imagem , Neoplasias/patologia
11.
Development ; 149(7)2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35297993

RESUMO

Beige adipocytes have a discrete developmental origin and possess notable plasticity in their thermogenic capacity in response to various environmental cues, but the transcriptional machinery controlling beige adipocyte development and thermogenesis remains largely unknown. By analyzing beige adipocyte-specific knockout mice, we identified a transcription factor, forkhead box P4 (FOXP4), that differentially governs beige adipocyte differentiation and activation. Depletion of Foxp4 in progenitor cells impaired beige cell early differentiation. However, we observed that ablation of Foxp4 in differentiated adipocytes profoundly potentiated their thermogenesis capacity upon cold exposure. Of note, the outcome of Foxp4 deficiency on UCP1-mediated thermogenesis was confined to beige adipocytes, rather than to brown adipocytes. Taken together, we suggest that FOXP4 primes beige adipocyte early differentiation, but attenuates their activation by potent transcriptional repression of the thermogenic program.


Assuntos
Adipócitos Bege , Adipócitos Marrons , Animais , Diferenciação Celular/genética , Regulação da Expressão Gênica , Camundongos , Termogênese/genética
12.
J Bone Miner Res ; 36(10): 2017-2026, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34131944

RESUMO

Adiponectin (AdipoQ), a hormone abundantly secreted by adipose tissues, has multiple beneficial functions, including insulin sensitization as well as lipid and glucose metabolism. It has been reported that bone controls energy metabolism through an endocrine-based mechanism. In this study, we observed that bone also acts as an important endocrine source for AdipoQ, and its capacity in osteoblasts is controlled by the forkhead box P1 (FOXP1) transcriptional factor. Deletion of the Foxp1 gene in osteoblasts led to augmentation of AdipoQ levels accompanied by fueled energy expenditure in adipose tissues. In contrast, overexpression of Foxp1 in bones impaired AdipoQ secretion and restrained energy consumption. Chromatin immunoprecipitation sequencing (ChIP-seq) analysis revealed that AdipoQ expression, which increases as a function of bone age, is directly controlled by FOXP1. Our results indicate that bones, especially aged bones, provide an important source of a set of endocrine factors, including AdipoQ, that control body metabolism. © 2021 American Society for Bone and Mineral Research (ASBMR).


Assuntos
Tecido Adiposo , Metabolismo Energético , Tecido Adiposo/metabolismo , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Regulação da Expressão Gênica , Osteoblastos/metabolismo
13.
J Cardiovasc Transl Res ; 13(2): 181-190, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31712976

RESUMO

The long-term patency rate of saphenous vein (SV) grafts is poor compared to arterial grafts. To investigate the effects of surgical preparation (distention) of SV on hydrogen sulfide (H2S) released from the endothelium, human SV segments were harvested from 43 patients during coronary artery bypass surgery (CABG). Acetylcholine (ACh) induced relaxation that was inhibited by NG-nitro-L-arginine + indomethacin and cysteine aminotransferase inhibitor aminooxyacetic acid in the normal SV. In contrast, ACh did not evoke relaxation in the distended SV (DSV). The concentration of H2S quantified by methylene blue assay in DSV was significantly lower than that in control. Transmission electron microscope and immunohistochemistry studies showed that the preparation destroyed the endothelium, smooth muscle, organelle, and vasa vasorum. We conclude that surgical preparation injures the endothelium and smooth muscle of the SV grafts and reduces H2S release from SV. These effects may contribute to the poor long-term patency of the SV graft.


Assuntos
Ponte de Artéria Coronária/efeitos adversos , Endotélio Vascular/transplante , Oclusão de Enxerto Vascular/etiologia , Sulfeto de Hidrogênio/metabolismo , Músculo Liso Vascular/transplante , Veia Safena/transplante , Coleta de Tecidos e Órgãos/efeitos adversos , Lesões do Sistema Vascular/etiologia , Idoso , Endotélio Vascular/lesões , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Feminino , Oclusão de Enxerto Vascular/metabolismo , Oclusão de Enxerto Vascular/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Liso Vascular/lesões , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/fisiopatologia , Veia Safena/lesões , Veia Safena/metabolismo , Veia Safena/fisiopatologia , Transdução de Sinais , Grau de Desobstrução Vascular , Lesões do Sistema Vascular/metabolismo , Lesões do Sistema Vascular/fisiopatologia
14.
BMC Cardiovasc Disord ; 19(1): 266, 2019 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-31775633

RESUMO

BACKGROUND: Although perioperative care during heart surgery has improved considerably, the rate of postoperative complications has remained stable. It has not been concluded how to better apply grip strength to clinical, postoperative complications. So our study aimed at researching the best way for using grip value for predicting early postoperative complications. METHODS: A total of 212 patients with mean age 63.8 ± 6.3 who underwent cardiac surgery participated in our study. We analyzed the ROC curve of grip strength, grip/weight and grip recovery with complications, found the best cutoff point. Logistic regression confirmed the association between grip strength grouping and complications. RESULTS: We found that 36 patients had 30-day complications. EuroSCORE were 2.15 ± 1.52 and 2.42 ± 1.58 between normal and complication groups, respectively. The area under the receiver-operating characteristic curve (AUC) of grip recovery take the most area (0.837, p < 0.001), and the cutoff point was 83.92%. In logistic regression, lower grip recovery has higher risk impact on 30-day complications for 25.68 times than normal group, after adjusted surgery-related factors. After regrouped characteristic information by grip recovery cutoff point, we found that percentage of the estimated 6 min walk distance (41.5 vs 48.3, p = 0.028) and hospitalization time (7.2 vs 6.1, p = 0.042) had worse trends in lower recovery group. CONCLUSIONS: Poor grip recovery may be related to higher risk of postoperative complications within 30 days after discharge in middle-aged and older people independent of surgical risk. The results of this study provide a reference for the development of rehabilitation programs in the early postoperative recovery, and may also be a prognostic indicator for postoperative high-risk groups. TRIAL REGISTRATION: Our research was registered on Research Registry website, the registry number was ChiCTR1800018465. Date: 2018/9/20. Status: Successful.


Assuntos
Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Força da Mão , Alta do Paciente , Complicações Pós-Operatórias/etiologia , Fatores Etários , Idoso , Feminino , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Período Perioperatório , Projetos Piloto , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/fisiopatologia , Estudos Prospectivos , Recuperação de Função Fisiológica , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
16.
Clin Rehabil ; 33(5): 913-922, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30722696

RESUMO

OBJECTIVE: To determine the prophylactic efficacy of short-term intensive preoperative inspiratory muscle training on the incidence of postoperative pulmonary complications in patients scheduled for cardiac surgery. DESIGN: Single-blind, randomized controlled pilot study. SETTING: TEDA International Cardiovascular Hospital, China. SUBJECTS: In total, 197 subjects aged ⩾50 years scheduled for cardiac surgery were selected. INTERVENTION: The intervention group ( n = 98) received five days of preoperative inspiratory muscle training on top of the usual care received by the patients in the control group ( n = 99). MAIN MEASURES: The primary outcome variable was the occurrence of postoperative pulmonary complications. The secondary outcome variables were inspiratory muscle strength, lung function and length of hospitalization. RESULTS: After cardiac surgery, a total of 10 (10.2%) of the 98 patients in the intervention group and 27 (27.3%) of 99 patients in the control group had postoperative pulmonary complications (risk ratio, 0.23; 95% confidence interval (CI), 0.09-0.58, P = 0.002). The study revealed that, compared with the control group, the intervention group had a significant increase in inspiratory muscle strength (by 10.48 cm H2O, P < 0.001), forced expiratory volume in the first second of expiration (FEV1) %predicted (by 3.75%, P = 0.030), forced vital capacity (FVC) %predicted (by 4.15%, P = 0.008) and maximal voluntary ventilation (MVV) %predicted (by 6.44%, P = 0.034). Length of hospital stay was 7.51 (2.83) days in the intervention group and 9.38 (3.10) days in the control group ( P = 0.039). CONCLUSION: A five-day intensive pattern of preoperative inspiratory muscle training reduced the incidence of postoperative pulmonary complications and duration of postoperative hospitalization in patients undergoing cardiac surgery.


Assuntos
Exercícios Respiratórios , Procedimentos Cirúrgicos Cardíacos , Complicações Pós-Operatórias/prevenção & controle , Cuidados Pré-Operatórios , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Força Muscular/fisiologia , Projetos Piloto , Ventilação Pulmonar/fisiologia , Método Simples-Cego , Capacidade Pulmonar Total/fisiologia
17.
Interact Cardiovasc Thorac Surg ; 28(6): 893-899, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30649484

RESUMO

OBJECTIVES: Our goal was to investigate risk factors for acute kidney injury (AKI) after coronary artery bypass grafting (CABG) and the impact of AKI on short-term outcomes. METHODS: Data on 1395 patients (1261 who had isolated CABG and 134 with other operations) who underwent non-emergent CABG from January 2013 to March 2016 were retrospectively collected from a single centre. Logistic regression was performed to analyse risk factors. Cox regression was used to analyse the impact of AKI on the postoperative 30-day death rate. A 1:1 propensity score matching was performed to balance the baseline characteristics. RESULTS: The incidence of AKI with on-pump and off-pump coronary artery bypass was 10.4% and 3.5%, respectively. With logistic regression, duration of surgery was a risk factor for AKI (stage ≥2); previous hypertension, preoperative renal function insufficiency and the presence of cardiopulmonary bypass (CPB) were risk factors for mild AKI (stage ≥1). CPB time >207.5 min could be used to predict AKI (sensitivity 79.2%, specificity 78.6%) in the combined group. After adjusting for the duration of the operation, postoperative AKI (stage ≥1) was a risk factor for 30-day death and there was no difference in the 30-day death rate between on-pump and off-pump CABG. CONCLUSIONS: The use of CPB was a risk factor for mild AKI that did not affect the 30-day death rate of CABG whereas moderate to severe AKI caused by prolonged CPB time associated with surgical complexity affected the 30-day death rate. AKI may indicate surgical injury. The decision to use the on- or off-pump technique does not affect the 30-day death rate of CABG.


Assuntos
Injúria Renal Aguda/epidemiologia , Ponte de Artéria Coronária/efeitos adversos , Doença da Artéria Coronariana/cirurgia , Complicações Pós-Operatórias/epidemiologia , Pontuação de Propensão , Injúria Renal Aguda/etiologia , China/epidemiologia , Ponte de Artéria Coronária sem Circulação Extracorpórea/efeitos adversos , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida/tendências
18.
Nitric Oxide ; 81: 21-27, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30300735

RESUMO

Homocysteine (Hcy) is an independent risk factor for endothelial dysfunction in cardiovascular diseases. We hypothesized that the eNOS transcription enhancer AVE3085 may protect the endothelial function damaged by Hcy in the human internal mammary artery (IMA). Cumulative concentration-relaxation curves to acetylcholine (-10 to -4.5 log mol/L) or sodium nitroprusside were established in IMA from patients undergoing coronary artery surgery precontracted by U46619 (-8 log mol/L) in the absence/presence of Hcy (100 µmol/L) with/without AVE3085 (30 µmol/L) in vitro in a myograph. RT-qPCR and ELISA were used to quantify the mRNA and protein levels of eNOS. Colorimetric assay method was used to detect the production of nitric oxide (NO). Maximal relaxation was significantly attenuated by Hcy in human IMA. Co-incubation with AVE3085 protected endothelium from the impairment by Hcy and increased the production of NO. Exposure to Hcy for 24 h downregulated eNOS protein expression (P < 0.05) whereas it upregulated the expression of eNOS at mRNA levels (P < 0.05). The presence of AVE3085 in addition to Hcy significantly increased the eNOS protein (P < 0.05) and slightly decreased the mRNA level. The study for the first time revealed that in the human blood vessels (IMA) the clinically-relevant high concentration of Hcy directly causes endothelial dysfunction by downregulating eNOS protein that may be reversed by AVE3085. These findings not only provide new direction for protecting endothelium during coronary artery bypass grafting and improving long-term patency of the grafts, but also provide evidence to the use of eNOS enhancer in the patients with endothelial dysfunction in various pathological conditions.


Assuntos
Benzodioxóis/farmacologia , Endotélio Vascular/fisiopatologia , Homocisteína/metabolismo , Indanos/farmacologia , Artéria Torácica Interna/efeitos dos fármacos , Óxido Nítrico Sintase Tipo III/metabolismo , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico/farmacologia , Acetilcolina/farmacologia , Acetilcisteína/farmacologia , Endotélio Vascular/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Homocisteína/farmacologia , Humanos , Artéria Torácica Interna/fisiopatologia , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/genética , Nitroprussiato/farmacologia , Técnicas de Cultura de Órgãos , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia
19.
Mol Med Rep ; 14(1): 184-94, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27176713

RESUMO

Rapid and accurate differential diagnosis of acute myocardial infarction (AMI) is crucial for timely interventions and the improvement of prognosis. However, this is difficult to achieve using current methods. Therefore, the present study aimed to evaluate the suitability of circulating microRNAs (miRNAs) as AMI biomarkers in patients with acute coronary syndrome (ACS). miRNA profiling in plasma samples from patients with AMI (n=3) and healthy controls (n=3) was performed using microarrays. Results were then validated in five patients and five healthy controls. miRNA-125b-5p and miR-30d-5p expression levels were quantified in plasma samples from 230 patients with ACS and 79 healthy controls using reverse transcription-quantitative polymerase chain reaction. Routine diagnostic parameters were assessed, including creatinine kinase MB, cardiac troponin I (cTnI) and myoglobin. A total of 33 miRNAs were differentially expressed in patients with AMI and healthy controls. Following validation based on the previously established roles for these miRNAs, six miRNAs were validated. miR­125b­5p and miR­30d­5p were selected for further investigation. Expression levels of miR­125b­5p and miR­30d­5p in plasma were higher in patients with ACS compared with the healthy controls (P<0.001). Receiver operating characteristic curve analysis revealed that the area under the curve of miR­30d­5p was higher than that of cTnI (0.915 and 0.899). miR­125b­5p (sensitivity, 0.808; specificity, 0.845) and miR­30d­5p (sensitivity, 0.855; specificity, 0.810) were suitable diagnostic predictors of AMI. Kaplan-Meier survival analysis indicated that miR-125b-5p levels were associated with 6 month cardiovascular events in patients with AMI, but not miR­30d­5p. miR-125b-5p and miR-30d-5p presented a diagnostic value for early diagnosis of AMI, and miR­30d­5p may have a higher diagnostic value than cTnI.


Assuntos
MicroRNAs/genética , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Estudos de Casos e Controles , Análise por Conglomerados , Comorbidade , Feminino , Perfilação da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , Fenótipo , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto Jovem
20.
J Cardiothorac Surg ; 7: 30, 2012 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-22490269

RESUMO

BACKGROUND: Functional tricuspid regurgitation (TR) occurs in patients with rheumatic mitral valve disease even after mitral valve surgery. The aim of this study was to analyze surgical results of TR after previous successful mitral valve surgery. METHODS: From September 1996 to September 2008, 45 patients with TR after previous mitral valve replacement underwent second operation for TR. In those, 43 patients (95.6%) had right heart failure symptoms (edema of lower extremities, ascites, hepatic congestion, etc.) and 40 patients (88.9%) had atrial fibrillation. Twenty-six patients (57.8%) were in New York Heart Association (NYHA) functional class III, and 19 (42.2%) in class IV. Previous operations included: 41 for mechanical mitral valve replacement (91.1%), 4 for bioprosthetic mitral valve replacement (8.9%), and 7 for tricuspid annuloplasty (15.6%). RESULTS: The tricuspid valves were repaired with Kay's (7 cases, 15.6%) or De Vega technique (4 cases, 8.9%). Tricuspid valve replacement was performed in 34 cases (75.6%). One patient (2.2%) died. Postoperative low cardiac output (LCO) occurred in 5 patients and treated successfully. Postoperative echocardiography showed obvious reduction of right atrium and ventricle. The anterioposterior diameter of the right ventricle decreased to 25.5 ± 7.1 mm from 33.7 ± 6.2 mm preoperatively (P < 0. 05). CONCLUSION: TR after mitral valve replacement in rheumatic heart disease is a serious clinical problem. If it occurs or progresses late after mitral valve surgery, tricuspid valve annuloplasty or replacement may be performed with satisfactory results. Due to the serious consequence of untreated TR, aggressive treatment of existing TR during mitral valve surgery is recommended.


Assuntos
Anuloplastia da Valva Cardíaca , Implante de Prótese de Valva Cardíaca , Insuficiência da Valva Mitral/cirurgia , Estenose da Valva Mitral/cirurgia , Cardiopatia Reumática/cirurgia , Insuficiência da Valva Tricúspide/cirurgia , Adulto , Idoso , China , Feminino , Seguimentos , Implante de Prótese de Valva Cardíaca/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Insuficiência da Valva Tricúspide/mortalidade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...