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1.
Circ J ; 87(2): 336-344, 2023 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-36216562

RESUMO

BACKGROUND: The optimal heart rate (HR) and optimal dose of ß-blockers (BBs) in patients with coronary artery disease (CAD) have been unclear. We sought to clarify the relationships among HR, BB dose, and prognosis in patients with CAD using a multimodal data acquisition system.Methods and Results: We evaluated the data for 8,744 CAD patients who underwent cardiac catheterization from 6 university hospitals and the National Cerebral and Cardiovascular Center and who were registered using the Clinical Deep Data Accumulation System. Patients were divided into quartile groups based on their HR at discharge: Q1 (HR <60 beats/min), Q2 (HR 60-66 beats/min), Q3 (HR 67-74 beats/min), and Q4 (HR ≥75 beats/min). Among patients with acute coronary syndrome (ACS) and patients with chronic coronary syndrome (CCS), those in Q4 (HR ≥75 beats/min) had a significantly greater incidence of major adverse cardiac and cerebral events (MACCE) compared with those in Q1 (ACS patients: hazard ratio 1.65, P=0.001; CCS patients: hazard ratio 1.45, P=0.019). Regarding the use of BBs (n=4,964), low-dose administration was significantly associated with MACCE in the ACS group (hazard ratio 1.41, P=0.012), but not in patients with CCS after adjustment for covariates. CONCLUSIONS: HR ≥75 beats/min was associated with worse outcomes in patients with CCS or ACS.


Assuntos
Síndrome Coronariana Aguda , Doença da Artéria Coronariana , Humanos , Doença da Artéria Coronariana/tratamento farmacológico , Frequência Cardíaca/fisiologia , Prognóstico , Antagonistas Adrenérgicos beta/efeitos adversos
2.
Circ J ; 87(6): 775-782, 2023 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-36709982

RESUMO

BACKGROUND: Several studies have reported some sex differences in patients with coronary artery diseases. However, the results regarding long-term outcomes in patients with chronic coronary syndrome (CCS) are inconsistent. Therefore, the present study investigated sex differences in long-term outcomes in patients with CCS after percutaneous coronary intervention (PCI).Methods and Results: This was a retrospective, multicenter cohort study. We enrolled patients with CCS who underwent PCI between April 2013 and March 2019 using the Clinical Deep Data Accumulation System (CLIDAS) database. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, or hospitalization for heart failure. In all, 5,555 patients with CCS after PCI were included in the analysis (4,354 (78.4%) men, 1,201 (21.6%) women). The median follow-up duration was 917 days (interquartile range 312-1,508 days). The incidence of MACE was not significantly different between the 2 groups (hazard ratio [HR] 1.20; 95% confidential interval [CI] 0.97-1.47; log-rank P=0.087). After performing multivariable Cox regression analyses on 4 different models, there were still no differences in the incidence of MACE between women and men. CONCLUSIONS: There were no significant sex differences in MACE in patients with CCS who underwent PCI and underwent multidisciplinary treatments.


Assuntos
Doença das Coronárias , Intervenção Coronária Percutânea , Feminino , Humanos , Masculino , Estudos de Coortes , População do Leste Asiático , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Estudos Retrospectivos , Fatores Sexuais , Doença das Coronárias/epidemiologia
3.
Pediatr Int ; 65(1): e15658, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37804040

RESUMO

BACKGROUND: Several studies have demonstrated the efficacy of prednisolone and cyclosporine as initial combination treatments for the prevention of coronary artery abnormalities (CAA) in patients with Kawasaki disease. However, whether prednisolone or cyclosporine results in superior clinical outcomes is unknown. Thus, this study aimed to compare the outcomes of these two treatments. METHODS: Using the Japanese Diagnosis Procedure Combination database, we identified patients with Kawasaki disease who had received prednisolone or cyclosporine in addition to initial intravenous immunoglobulin treatment between April 2014 and March 2021. The primary outcome was the proportion of CAA; secondary outcomes included intravenous immunoglobulin resistance, medical costs, and length of hospital stay. Propensity score matching was conducted to compare outcomes between the two groups. RESULTS: We identified 6288 patients with Kawasaki disease who had received prednisolone (n = 6147) or cyclosporine (n = 141) as an initial treatment in combination with intravenous immunoglobulin. Four-to-one propensity score-matched analysis demonstrated no significant difference in the proportion of CAA (0.7% vs. 2.8%; p = 0.098), intravenous immunoglobulin resistance, or medical costs between the treatment groups. The length of hospital stay was significantly longer in the prednisolone group (14 vs. 11 days, p < 0.001). CONCLUSIONS: Prednisolone and cyclosporine used in the initial combination treatment for Kawasaki disease showed similar clinical outcomes regarding the risk of CAA, intravenous immunoglobulin resistance, and medical costs, whereas the length of hospital stay was longer in the prednisolone group than in the cyclosporine group.


Assuntos
Doença da Artéria Coronariana , Síndrome de Linfonodos Mucocutâneos , Humanos , Lactente , Prednisolona/uso terapêutico , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Imunoglobulinas Intravenosas/uso terapêutico , Ciclosporina/uso terapêutico , Quimioterapia Combinada , Estudos Retrospectivos
4.
Dev Dyn ; 2022 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-36038963

RESUMO

BACKGROUND: The somatopleure serves as the primordium of the amnion, an extraembryonic membrane surrounding the embryo. Recently, we have reported that amniogenic somatopleural cells (ASCs) not only form the amnion but also migrate into the embryo and differentiate into cardiomyocytes and vascular endothelial cells. However, detailed differentiation processes and final distributions of these intra-embryonic ASCs (hereafter referred to as iASCs) remain largely unknown. RESULTS: By quail-chick chimera analysis, we here show that iASCs differentiate into various cell types including cardiomyocytes, smooth muscle cells, cardiac interstitial cells, and vascular endothelial cells. In the pharyngeal region, they distribute selectively into the thyroid gland and differentiate into vascular endothelial cells to form intra-thyroid vasculature. Explant culture experiments indicated sequential requirement of fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) signaling for endothelial differentiation of iASCs. Single-cell transcriptome analysis further revealed heterogeneity and the presence of hemangioblast-like cell population within ASCs, with a switch from FGF to VEGF receptor gene expression. CONCLUSION: The present study demonstrates novel roles of ASCss especially in heart and thyroid development. It will provide a novel clue for understanding the cardiovascular development of amniotes from embryological and evolutionary perspectives.

5.
Circ J ; 86(9): 1444-1454, 2022 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-35871575

RESUMO

BACKGROUND: Elevated levels of triglyceride (TG) and non-high-density lipoprotein cholesterol (non-HDL-C) are regarded as a residual lipid risk in low-density lipoprotein cholesterol (LDL-C)-lowering therapy. This study investigated the association between lipid risk stratified by TG and non-HDL-C and the prognosis of patients with coronary artery disease (CAD), and the association between stratified lipid risk and flow-mediated dilatation (FMD) index.Methods and Results: The 624 CAD patients enrolled in flow-mediated dilation (FMD)-J study A were divided into 4 groups: low-risk group (n=413) with TG <150 mg/dL and non-HDL-C <170 mg/dL; hyper-TG group (n=180) with TG ≥150 mg/dL and non-HDL-C <170 mg/dL; hyper-non-HDL group (n=12) with TG <150 mg/dL and non-HDL-C ≥170 mg/dL; and high-risk group (n=19) with TG ≥150 mg/dL and non-HDL-C ≥170 mg/dL. Comparison of the groups showed the cumulative incidence of a 3-point major adverse cardiovascular event (MACE) was different and highest in the high-risk group in all the patients (P=0.009), and in patients with a FMD index ≥7.0% (P=0.021), but not in those with a FMD index <7.0%. Multivariable regression analysis showed that high lipid risk (P=0.019) and FMD <7.0% (P=0.040) were independently correlated with the incidence of a 3-point MACE. CONCLUSIONS: Novel stratification of lipid risk, simply using TG and non-HDL-C levels, combined with FMD measurement, is useful for predicting cardiovascular outcomes in patients with CAD.


Assuntos
Doença da Artéria Coronariana , Colesterol , HDL-Colesterol , LDL-Colesterol , Doença da Artéria Coronariana/diagnóstico por imagem , Dilatação , Humanos , Lipoproteínas , Prognóstico , Fatores de Risco , Triglicerídeos
6.
J Am Soc Nephrol ; 32(7): 1599-1615, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33875568

RESUMO

BACKGROUND: The sympathetic nervous system regulates immune cell dynamics. However, the detailed role of sympathetic signaling in inflammatory diseases is still unclear because it varies according to the disease situation and responsible cell types. This study focused on identifying the functions of sympathetic signaling in macrophages in LPS-induced sepsis and renal ischemia-reperfusion injury (IRI). METHODS: We performed RNA sequencing of mouse macrophage cell lines to identify the critical gene that mediates the anti-inflammatory effect of ß2-adrenergic receptor (Adrb2) signaling. We also examined the effects of salbutamol (a selective Adrb2 agonist) in LPS-induced systemic inflammation and renal IRI. Macrophage-specific Adrb2 conditional knockout (cKO) mice and the adoptive transfer of salbutamol-treated macrophages were used to assess the involvement of macrophage Adrb2 signaling. RESULTS: In vitro, activation of Adrb2 signaling in macrophages induced the expression of T cell Ig and mucin domain 3 (Tim3), which contributes to anti-inflammatory phenotypic alterations. In vivo, salbutamol administration blocked LPS-induced systemic inflammation and protected against renal IRI; this protection was mitigated in macrophage-specific Adrb2 cKO mice. The adoptive transfer of salbutamol-treated macrophages also protected against renal IRI. Single-cell RNA sequencing revealed that this protection was associated with the accumulation of Tim3-expressing macrophages in the renal tissue. CONCLUSIONS: The activation of Adrb2 signaling in macrophages induces anti-inflammatory phenotypic alterations partially via the induction of Tim3 expression, which blocks LPS-induced systemic inflammation and protects against renal IRI.

7.
Kidney Int ; 95(3): 563-576, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30670317

RESUMO

The cholinergic anti-inflammatory pathway (CAP) links the nervous and immune systems and modulates innate and adaptive immunity. Activation of the CAP by vagus nerve stimulation exerts protective effects in a wide variety of clinical disorders including rheumatoid arthritis and Crohn's disease, and in murine models of acute kidney injury including ischemia/reperfusion injury (IRI). The canonical CAP pathway involves activation of splenic alpha7-nicotinic acetylcholine receptor (α7nAChR)-positive macrophages by splenic ß2-adrenergic receptor-positive CD4+ T cells. Here we demonstrate that ultrasound or vagus nerve stimulation also activated α7nAChR-positive peritoneal macrophages, and that adoptive transfer of these activated peritoneal macrophages reduced IRI in recipient mice. The protective effect required α7nAChR, and did not occur in splenectomized mice or in mice lacking T and B cells, suggesting a bidirectional interaction between α7nAChR-positive peritoneal macrophages and other immune cells including ß2-adrenergic receptor-positive CD4+ T cells. We also found that expression of hairy and enhancer of split-1 (Hes1), a basic helix-loop-helix DNA-binding protein, is induced in peritoneal macrophages by ultrasound or vagus nerve stimulation. Adoptive transfer of Hes1-overexpressing peritoneal macrophages reduced kidney IRI. Our data suggest that Hes1 is downstream of α7nAChR and is important to fully activate the CAP. Taken together, these results suggest that peritoneal macrophages play a previously unrecognized role in mediating the protective effect of CAP activation in kidney injury, and that Hes1 is a new candidate pharmacological target to activate the CAP.


Assuntos
Injúria Renal Aguda/imunologia , Macrófagos Peritoneais/imunologia , Traumatismo por Reperfusão/imunologia , Fatores de Transcrição HES-1/metabolismo , Receptor Nicotínico de Acetilcolina alfa7/metabolismo , Injúria Renal Aguda/patologia , Injúria Renal Aguda/terapia , Transferência Adotiva , Animais , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/efeitos da radiação , Linfócitos T CD4-Positivos/transplante , Modelos Animais de Doenças , Técnicas de Silenciamento de Genes , Humanos , Ativação de Macrófagos , Macrófagos Peritoneais/metabolismo , Macrófagos Peritoneais/transplante , Masculino , Camundongos , Neuroimunomodulação/efeitos da radiação , Células RAW 264.7 , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/terapia , Fatores de Transcrição HES-1/genética , Fatores de Transcrição HES-1/imunologia , Terapia por Ultrassom , Regulação para Cima/efeitos da radiação , Estimulação do Nervo Vago , Receptor Nicotínico de Acetilcolina alfa7/imunologia
8.
Circ J ; 83(5): 1064-1071, 2019 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-30918221

RESUMO

BACKGROUND: Circulating triglyceride (TG) levels are a current focus as a residual risk for cardiovascular (CV) events. We evaluated the relationship between circulating TG levels and future CV events in patients with coronary artery disease (CAD) who were treated with conventional therapy. Methods and Results: We analyzed data for 652 patients who were enrolled in the FMD-J Study A. We investigated the associations between serum TG levels and first major CV events (death from CV cause, nonfatal acute coronary syndrome (ACS), nonfatal stroke, and CAD) for a 3-year follow-up period. Patients were divided into 4 groups based on serum TG level: low-normal (<100 mg/dL), high-normal (100-149 mg/dL), borderline hypertriglyceridemia (150-199 mg/dL), and moderate hypertriglyceridemia (≥200 mg/dL). During a median follow-up period of 46.6 months, 14 patients died (9 from CV causes), 16 had nonfatal ACS, 6 had nonfatal stroke, and 54 had CAD. The Kaplan-Meier curves for first major CV event among the 4 groups were significantly different (P=0.04). After adjustment for various confounders, serum TG level ≥100 mg/dL were significantly associated with an increased risk of first major CV events compared with serum TG level <100 mg/dL. CONCLUSIONS: Serum TG level may be a surrogate marker for predicting CV events in patients with CAD.


Assuntos
Síndrome Coronariana Aguda , Doença da Artéria Coronariana , Acidente Vascular Cerebral , Triglicerídeos/sangue , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/etiologia , Síndrome Coronariana Aguda/mortalidade , Idoso , Biomarcadores/sangue , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/mortalidade , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Risco , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/mortalidade , Taxa de Sobrevida
9.
Int Heart J ; 60(2): 264-270, 2019 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-30799376

RESUMO

The utilization of electronic medical records and multimodal medical data is an ideal approach to build a real-time and precision registry type study with a smaller effort and cost, which may fill a gap between evidence-based medicine and the real-world clinical practice. The Japan Ischemic heart disease Multimodal Prospective data Acquisition for preCision Treatment (J-IMPACT) project aimed to build an clinical data registry system that electronically collects not only medical records, but also multimodal data, including coronary angiography and percutaneous coronary intervention (PCI) report, in standardized data formats for clinical studies.The J-IMPACT system comprises the standardized structured medical information exchange (SS-MIX), coronary angiography and intervention reporting system (CAIRS), and multi-purpose clinical data repository system (MCDRS) interconnected within the institutional network. In order to prove the concept, we acquired multimodal medical data of 6 consecutive cases that underwent PCI through the J-IMPACT system in a single center. Data items regarding patient background, laboratory data, prescriptions, and PCI/cardiac catheterization report were correctly acquired through the J-IMPACT system, and the accuracy of the multimodal data of the 4 categories was 100% in all 6 cases.The application of J-IMPACT system to clinical studies not only fills the gaps between randomized clinical trials and real-world medicine, but may also provide real-time big data that reinforces precision treatment for each patient.


Assuntos
Angiografia Coronária/estatística & dados numéricos , Confiabilidade dos Dados , Sistemas Computadorizados de Registros Médicos , Isquemia Miocárdica , Intervenção Coronária Percutânea/estatística & dados numéricos , Idoso , Medicina Baseada em Evidências/métodos , Feminino , Humanos , Japão/epidemiologia , Masculino , Sistemas Computadorizados de Registros Médicos/organização & administração , Sistemas Computadorizados de Registros Médicos/normas , Pessoa de Meia-Idade , Isquemia Miocárdica/epidemiologia , Isquemia Miocárdica/terapia , Estudos Prospectivos , Melhoria de Qualidade , Sistema de Registros/estatística & dados numéricos , Resultado do Tratamento
10.
Circ J ; 81(12): 1911-1918, 2017 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-28690284

RESUMO

BACKGROUND: Waist circumference (WC), waist-to-height ratio (WHtR) and body mass index (BMI) are known as easy anthropometric markers of abnormal obesity and screening tools for predicting cardiovascular outcomes, but which indices are best is unclear. We therefore investigated the superiority and association between each index and low flow-mediated dilatation (FMD) as a surrogate marker for cardiovascular outcomes in patients with morbidity in a large Japanese prospective cohort.Methods and Results:A total of 1,645 Japanese patients who had coronary artery disease and hypertension or diabetes mellitus were enrolled, and 1,087 of them were analyzed. The high-WHtR group (≥0.5) showed greater morbidity and increased inflammation in association with atherosclerosis compared with the low-WHtR group. High WHtR and advanced age were identified as predictors of low FMD (odds ratio (OR) 1.39, 95% confidence interval (CI) 1.02-1.88, P=0.037 and OR 1.55, 95% CI 1.19-2.01, P=0.001, respectively). However, WC was not associated with that risk in either sex (male: OR 1.37, 95% CI 0.97-1.93, P=0.076; female: OR 1.08, 95% CI 0.68-1.73, P=0.74), and no association was evident between high BMI and low FMD (OR 0.92, 95% CI 0.71-1.19, P=0.54). CONCLUSIONS: WHtR offers a superior predictor of decreased FMD than other anthropometric indices, and progression of arteriosclerosis might be detected more sensitively. Further study is needed to investigate the relationship between cardiovascular mortality and WHtR.


Assuntos
Endotélio/fisiopatologia , Razão Cintura-Estatura , Idoso , Povo Asiático , Aterosclerose/diagnóstico , Dilatação , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Morbidade , Estudos Prospectivos
11.
Lipids Health Dis ; 16(1): 122, 2017 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-28646901

RESUMO

BACKGROUND: Lowering cholesterol levels decreases the risk of atherosclerotic diseases. Effective ways to stably reduce LDL-C level are warranted in type 2 diabetic patients, a high-risk population for CVD, with various anti-diabetic therapeutic background. The RESEARCH study focuses on LDL-C reduction in this population along with modifications of the lipid profiles. We evaluated long-term ezetimibe add-on therapy in T2DM patients with hypercholesterolemia. METHODS: In a randomized, multicenter, open-label, prospective study, a total of 109 T2DM patients not attaining LDL-C target value despite first-line dose statin (10 mg of atorvastatin or 1 mg of pitavastatin) therapy in Japan were recruited. We investigated the difference in cholesterol lowering effect between ezetimibe (10 mg) add-on statin (EAT) group and double-dose statin (DST) group. Changes of parameters related to atherosclerotic event risks were assessed. RESULTS: The reduction of LDL-C was larger in the EAT group (28.3%) than in the DST group (9.2%) at 52 weeks as well as the primary endpoint of 12 weeks. EAT achieved significant lower levels of TC and apo B, respectively. Both treatments attained significant reduction in sd-LDL-C or hsCRP on this long-term basis. Notably, sd-LDL-C in EAT reduced as low as 36.1 ± 14.9 mg/dl to reach near the threshold (35.0 mg/dl) for atherosclerosis with significantly higher achievement rate (55.6%) than DST treatment. Simultaneously, hsCRP reduction by EAT attained as low value as 0.52 ± 0.43 mg/l. CONCLUSIONS: In the present 52-week long-term period, ezetimibe add-on therapy showed a robust advantage in lowering LDL-C and in attaining target LDL-C values compared with the doubling of statin dose. Moreover, it's meaningful that sd-LDL, powerfully atherogenic lipoprotein, exhibited prominent decrease consistently prominently by ezetimibe add-on therapy. DM patients with hypercholesterolemia are at high risk for CAD, and adding ezetimibe onto usual-dose statin treatment in Japan has been suggested as the first-line therapy for those DM patients who failed to attain the target LDL-C value (UMIN000002593).


Assuntos
Anticolesterolemiantes/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Ezetimiba/uso terapêutico , LDL-Colesterol/sangue , Diabetes Mellitus Tipo 2/sangue , Método Duplo-Cego , Feminino , Humanos , Masculino , Estudos Prospectivos
12.
Dev Biol ; 402(2): 162-74, 2015 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-25889273

RESUMO

Most gnathostomata craniofacial structures derive from pharyngeal arches (PAs), which are colonized by cranial neural crest cells (CNCCs). The anteroposterior and dorsoventral identities of CNCCs are defined by the combinatorial expression of Hox and Dlx genes. The mechanisms associating characteristic Hox/Dlx expression patterns with the topology and morphology of PAs derivatives are only partially known; a better knowledge of these processes might lead to new concepts on the origin of taxon-specific craniofacial morphologies and of certain craniofacial malformations. Here we show that ectopic expression of Hoxa2 in Hox-negative CNCCs results in distinct phenotypes in different CNCC subpopulations. Namely, while ectopic Hoxa2 expression is sufficient for the morphological and molecular transformation of the first PA (PA1) CNCC derivatives into the second PA (PA2)-like structures, this same genetic alteration does not provoke the transformation of derivatives of other CNCC subpopulations, but severely impairs their development. Ectopic Hoxa2 expression results in the transformation of the proximal Meckel's cartilage and of the malleus, two ventral PA1 CNCCs derivatives, into a supernumerary styloid process (SP), a PA2-derived mammalian-specific skeletal structure. These results, together with experiments to inactivate and ectopically activate the Edn1-Dlx5/6 pathway, indicate a dorsoventral PA2 (hyomandibular/ceratohyal) boundary passing through the middle of the SP. The present findings suggest context-dependent function of Hoxa2 in CNCC regional specification and morphogenesis, and provide novel insights into the evolution of taxa-specific patterning of PA-derived structures.


Assuntos
Região Branquial/embriologia , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Proteínas de Homeodomínio/metabolismo , Morfogênese/fisiologia , Crista Neural/metabolismo , Azul Alciano , Animais , Antraquinonas , Região Branquial/metabolismo , Primers do DNA/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento/genética , Hibridização In Situ , Camundongos , Camundongos Mutantes , Morfogênese/genética , Crista Neural/embriologia , Reação em Cadeia da Polimerase em Tempo Real
13.
EMBO J ; 31(23): 4404-14, 2012 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-23103767

RESUMO

Tumour necrosis factor alpha (TNFα) is a potent cytokine that signals through nuclear factor kappa B (NFκB) to activate a subset of human genes. It is usually assumed that this involves RNA polymerases transcribing responsive genes wherever they might be in the nucleus. Using primary human endothelial cells, variants of chromosome conformation capture (including 4C and chromatin interaction analysis with paired-end tag sequencing), and fluorescence in situ hybridization to detect single nascent transcripts, we show that TNFα induces responsive genes to congregate in discrete 'NFκB factories'. Some factories further specialize in transcribing responsive genes encoding micro-RNAs that target downregulated mRNAs. We expect all signalling pathways to contain this extra leg, where responding genes are transcribed in analogous specialized factories.


Assuntos
Regulação da Expressão Gênica , MicroRNAs/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Cromossomos/ultraestrutura , Citocinas/biossíntese , Citoplasma/metabolismo , RNA Polimerases Dirigidas por DNA/metabolismo , Células Endoteliais/citologia , Humanos , Hibridização In Situ , Hibridização in Situ Fluorescente , N-Acetilglucosaminiltransferases/metabolismo , NF-kappa B/metabolismo , Conformação Proteica , Proteínas Repressoras/metabolismo , Transdução de Sinais , Proteínas Smad/metabolismo , Fatores de Tempo , Transcrição Gênica , Fator de Crescimento Transformador beta/metabolismo
14.
EMBO J ; 30(13): 2582-95, 2011 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-21666600

RESUMO

GATA2 is well recognized as a key transcription factor and regulator of cell-type specificity and differentiation. Here, we carried out comparative chromatin immunoprecipitation with comprehensive sequencing (ChIP-seq) to determine genome-wide occupancy of GATA2 in endothelial cells and erythroids, and compared the occupancy to the respective gene expression profile in each cell type. Although GATA2 was commonly expressed in both cell types, different GATA2 bindings and distinct cell-specific gene expressions were observed. By using the ChIP-seq with epigenetic histone modifications and chromatin conformation capture assays; we elucidated the mechanistic regulation of endothelial-specific GATA2-mediated endomucin gene expression, that was regulated by the endothelial-specific chromatin loop with a GATA2-associated distal enhancer and core promoter. Knockdown of endomucin markedly attenuated endothelial cell growth, migration and tube formation. Moreover, abrogation of GATA2 in endothelium demonstrated not only a reduction of endothelial-specific markers, but also induction of mesenchymal transition promoting gene expression. Our findings provide new insights into the correlation of endothelial-expressed GATA2 binding, epigenetic modification, and the determination of endothelial cell specificity.


Assuntos
Endotélio Vascular/metabolismo , Epigênese Genética/fisiologia , Fator de Transcrição GATA2/metabolismo , Sialoglicoproteínas/genética , Animais , Sequência de Bases , Células COS , Células Cultivadas , Chlorocebus aethiops , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Endotélio Vascular/efeitos dos fármacos , Fator de Transcrição GATA2/genética , Fator de Transcrição GATA2/fisiologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Técnicas de Silenciamento de Genes , Humanos , Células K562 , Análise em Microsséries , Modelos Biológicos , Especificidade de Órgãos/efeitos dos fármacos , Especificidade de Órgãos/genética , Ligação Proteica/genética , Ligação Proteica/fisiologia , RNA Interferente Pequeno/farmacologia , Sialoglicoproteínas/metabolismo
15.
Circ J ; 78(4): 962-6, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24476843

RESUMO

BACKGROUND: Right atrial pressure (RAP) is commonly estimated using inferior vena cava (IVC) diameter and its respirophasic variations. Although a guideline has been provided for estimation of RAP due to variation in IVC dimensions based on studies in Western subjects, echocardiographic values in Asian subjects are unknown. METHODS AND RESULTS: We studied 369 patients who underwent IVC ultrasound within 24h of right heart catheterization (RHC). The maximum and minimum IVC diameter during a respiratory cycle and the percent collapse after a sniff test were measured. These IVC parameters were compared with mean RAP measured on RHC. Receiver operating characteristic curves were generated for each IVC parameter to determine the optimal cut-off to detect RAP >10mmHg. The IVC maximum diameter cut-off for detecting RAP >10mmHg was 19mm (sensitivity, 75%; specificity, 78%) and the percent collapse cut-off was 30% (sensitivity, 75%; specificity, 83%). Both cut-offs were smaller than those previously reported in patients from Western countries. When the cut-off values from the existing guideline were applied to the present cohort, the sensitivity and specificity for normal RAP (0-5mmHg) were 38.6% and 74.2%, respectively, and 60.0% and 92.0% for elevated RAP (>10mmHg). CONCLUSIONS: The optimal IVC maximum diameter and percent collapse cut-offs to detect elevated RAP were smaller in Asian subjects than in a previously reported Western cohort.


Assuntos
Povo Asiático , Função Atrial/fisiologia , Pressão na Veia Porta/fisiologia , Veia Cava Superior/fisiologia , Adulto , Idoso , Feminino , Átrios do Coração/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Ultrassonografia , Veia Cava Superior/diagnóstico por imagem
16.
Circ J ; 78(10): 2483-91, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25143319

RESUMO

BACKGROUND: Indications of implantable cardioverter-defibrillator (ICD) for patients with an old myocardial infarction (OMI) and left ventricular dysfunction (LVD) were expanded in Western countries after the results of MADIT II. However, the prognosis of OMI patients with LVD and the merits of prophylactic implantation of ICD, based on evidence in Japan, have not yet been clarified. This subanalysis of the Japanese Coronary Artery Disease (JCAD) Study focused on MADIT II-compatible patients to clarify the prognosis of OMI patients with LVD in Japan. METHODS AND RESULTS: Consecutive 6,868 OMI patients were prospectively followed up for 3 years or until clinical events occurred. 291 patients had left ventricular ejection fraction (LVEF) ≤30%. Clinical events, congestive heart failure, cardiopulmonary arrest on arrival and vascular events were significantly more frequent in patients with LVEF ≤30% than in those with better LVEF. In the LVEF ≤30% group, cardiopulmonary arrest on arrival comprised 33% of all-cause deaths, and the survival curves at 2 years of the LVEF ≤30% group were almost compatible with those of the MADIT II ICD group. CONCLUSIONS: In this subanalysis, LVD was less frequent than in Western countries. The annual death rate in JCAD was better than for the MADIT II ICD group. The prophylactic use of ICD seemed to be less effective than in Western countries but still expected to be useful for OMI patients with LVD in Japan.


Assuntos
Desfibriladores Implantáveis , Infarto do Miocárdio , Revascularização Miocárdica , Disfunção Ventricular Esquerda , Idoso , Doença da Artéria Coronariana , Intervalo Livre de Doença , Seguimentos , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/cirurgia , Volume Sistólico , Taxa de Sobrevida , Disfunção Ventricular Esquerda/complicações , Disfunção Ventricular Esquerda/mortalidade , Disfunção Ventricular Esquerda/cirurgia
17.
Hypertens Res ; 47(3): 685-699, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37907600

RESUMO

Recent years have witnessed significant transformations in cardiovascular medicine, driven by the rapid evolution of artificial intelligence (AI). This scoping review was conducted to capture the breadth of AI applications within cardiovascular science. Employing a structured approach, we sourced relevant articles from PubMed, with an emphasis on journals encompassing general cardiology and digital medicine. We applied filters to highlight cardiovascular articles published in journals focusing on general internal medicine, cardiology and digital medicine, thereby identifying the prevailing trends in the field. Following a comprehensive full-text screening, a total of 140 studies were identified. Over the preceding 5 years, cardiovascular medicine's interplay with AI has seen an over tenfold augmentation. This expansive growth encompasses multiple cardiovascular subspecialties, including but not limited to, general cardiology, ischemic heart disease, heart failure, and arrhythmia. Deep learning emerged as the predominant methodology. The majority of AI endeavors in this domain have been channeled toward enhancing diagnostic and prognostic capabilities, utilizing resources such as hospital datasets, electrocardiograms, and echocardiography. A significant uptrend was observed in AI's application for omics data analysis. However, a clear gap persists in AI's full-scale integration into the clinical decision-making framework. AI, particularly deep learning, has demonstrated robust applications across cardiovascular subspecialties, indicating its transformative potential in this field. As we continue on this trajectory, ensuring the alignment of technological progress with medical ethics becomes crucial. The abundant digital health data today further accentuates the need for meticulous systematic reviews, tailoring them to each cardiovascular subspecialty.


Assuntos
Cardiologia , Fármacos Cardiovasculares , Insuficiência Cardíaca , Humanos , Inteligência Artificial , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Eletrocardiografia
18.
Int J Gynaecol Obstet ; 166(3): 1323-1329, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38634271

RESUMO

OBJECTIVE: The study aimed to investigate treatment options for older women with pelvic organ prolapse (POP) and postoperative outcomes based on their long-term care (LTC) status. METHODS: We used the medical and LTC insurance claims databases of Tochigi Prefecture in Japan, covering 2014 to 2019. We included women 65 years and older with POP and evaluated their care status and treatment, excluding women with an observation period <6 months. Among women with a postsurgical interval ≥6 months, we compared care level changes and deaths within 6 months and complications within 1 month postoperatively between those with and without LTC using Fisher exact test. RESULTS: We identified 3406 eligible women. Of the 447 women with LTC and 2959 women without LTC, 16 (3.6%) and 415 (14.0%), respectively, underwent surgery. Among 393 women with a postsurgical interval ≥6 months, 19 (4.8%) required LTC at surgery. Two of the 19 women with LTC (10.5%) and eight of 374 women without LTC (2.1%) experienced worsening care-needs level. No deaths were recorded. Urinary tract infection (UTI) was significantly more frequent in women with LTC than in women without LTC (36.8% vs 8.6%). Other complications were rare in both groups. CONCLUSION: The proportion of patients who underwent surgery for POP was lower in women with LTC than in women without LTC. Postoperative UTI was common and 11% had a worsening care-needs level postoperatively, whereas other complications were infrequent. Further detailed studies would contribute to providing optimal treatment to enhance patients' quality of life.


Assuntos
Assistência de Longa Duração , Prolapso de Órgão Pélvico , Complicações Pós-Operatórias , Humanos , Feminino , Prolapso de Órgão Pélvico/cirurgia , Idoso , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Japão , Idoso de 80 Anos ou mais , Resultado do Tratamento , Procedimentos Cirúrgicos em Ginecologia/estatística & dados numéricos , Procedimentos Cirúrgicos em Ginecologia/métodos , Procedimentos Cirúrgicos em Ginecologia/efeitos adversos
19.
Int J Cardiol Heart Vasc ; 53: 101430, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39228973

RESUMO

Background: Limited data exist on the prognostic value of changes in pulse pressure (PP, the difference between systolic and diastolic blood pressure) during hospitalization for patients with coronary artery disease who have undergone percutaneous coronary intervention (PCI). Methods: In the Clinical Deep Data Accumulation System (CLIDAS), we studied 8,708 patients who underwent PCI. We aimed to examine the association between discharge PP and cardiovascular outcomes. PP was measured before PCI and at discharge. Patients were divided into five groups (quintiles) based on the change in PPQ1 (-18.0 ± 9.9 mmHg), Q2 (-3.8 ± 2.6), Q3 (reference; 3.7 ± 2.0), Q4 (11.3 ± 2.6), and Q5 (27.5 ± 11.2). We then analyzed the relationship between PP change and outcomes. Results: The mean patient age was 70 ± 11 years, with 6,851 (78 %) men and 3,786 (43 %) having acute coronary syndrome. U-shaped relationships were observed for the incidence rates of major adverse cardiac or cerebrovascular events (MACCE, a composite endpoint of cardiovascular death, myocardial infarction, and stroke), revascularization, and hospitalization for heart failure (HF). After adjusting for confounding factors, higher PP at discharge was associated with an increased risk of MACCE (adjusted hazard ratio 1.41; 95 %CI, 1.06-1.87 in Q5 [73.9 ± 9.3 mmHg]). Evaluating PP change revealed a U-shaped association with MACCE (1.50; 1.11-2.02 in Q1 and 1.47; 0.98-2.20 in Q5). Additionally, Q5 had a higher risk for hospitalization for HF (1.37; 1.00-1.88). Conclusions: Our findings demonstrate a U-shaped association between changes in PP and cardiovascular outcomes. This data suggests the significance of blood pressure control during hospitalization for patients who have undergone PCI.

20.
Hypertens Res ; 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39300294

RESUMO

The Japanese Society of Hypertension have established a blood pressure (BP) target of 130/80 mmHg for patients with coronary artery disease (CAD). We evaluated the data of 8793 CAD patients in the Clinical Deep Data Accumulation System database who underwent cardiac catheterization at six university hospitals and the National Cerebral and Cardiovascular Center (average age 70 ± 11 years, 78% male, 43% with acute coronary syndrome [ACS]). Patients were divided into two groups based on whether or not they achieved the guideline-recommended BP of <130/80 mmHg. We analyzed the relationship between BP classification and major adverse cardiac and cerebral event (MACCE) separately in two groups: those with ACS and those with chronic coronary syndrome (CCS). During an average follow-up period of 33 months, 710 MACCEs occurred. A BP below 130/80 mmHg was associated with fewer MACCEs in both the overall (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.70-1.00, p = 0.048) and the ACS group (HR 0.67, 95%CI 0.51-0.88, p = 0.003). In particular, stroke events were also lower among those with a BP below 130/80 mmHg in both the overall (HR 0.69, 95%CI 0.53-0.90, p = 0.006) and ACS groups (HR 0.44, 95%CI 0.30-0.67, p < 0.001). In conclusion, the achievement of BP guidelines was associated with improved outcomes in CAD patients, particularly in reducing stroke risk among those with ACS.

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