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1.
Methods Mol Biol ; 2206: 57-66, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32754811

RESUMO

The construction of vascular networks is essential for developing functional organ/tissue constructs in terms of oxygen and nutrient supply. Although recent advances in microfluidic techniques have allowed for the construction of microvascular networks using microfluidic devices, their structures cannot be maintained for extended periods of time due to a lack of perivascular cells. To construct long-lasting microvascular networks, it is important that perivascular cells are present to provide structural support to vessels, because in vivo microvessels are covered by perivascular cells and stabilized. Here, we describe a microfluidic cell culture platform for the construction of microvascular networks with supportive perivascular cells. Our results showed that microvascular networks covered by pericyte-like perivascular cells formed in a microfluidic device and their structures were maintained for at least 3 weeks in vitro.

2.
Free Radic Biol Med ; 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33096250

RESUMO

Superoxide dismutase 1 (Sod1) plays pivotal roles in antioxidation via accelerating the conversion of superoxide anion radicals into hydrogen peroxide, thus inhibiting the subsequent radical chain reactions. While Sod1 deficient cells inevitably undergo death in culture conditions, Sod1-knockout (KO) mice show relatively mild phenotypes and live approximately two years. We hypothesized that the presence of abundant levels of ascorbic acid (AsA), which is naturally produced in mice, contributes to the elimination of reactive oxygen species (ROS) in Sod1-KO mice. To verify this hypothesis, we employed mice with a genetic ablation of aldehyde reductase (Akr1a), an enzyme that is involved in the biosynthesis of AsA, and established double knockout (DKO) mice that lack both Sod1 and Akr1a. Supplementation of AsA (1.5 mg/ml in drinking water) was required for the DKO mice to breed, and, upon terminating the AsA supplementation, they died within approximately two weeks regardless of age or gender. We explored the etiology of the death from pathophysiological standpoints in principal organs of the mice. Marked changes were observed in the lungs in the form of macroscopic damage after the AsA withdrawal. Histological and immunological analyses of the lungs indicated oxidative damage of tissue and activated immune responses. Thus, preferential oxidative injury that occurred in pulmonary tissues appeared to be primary cause of the death in the mice. These collective results suggest that the pivotal function of AsA in coping with ROS in vivo, is largely in pulmonary tissues that are exposed to a hyperoxygenic microenvironment.

3.
Heart Vessels ; 2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32926229

RESUMO

Aortic aneurysm is an increasingly important public health problem with high morbidity and mortality. It is associated with coronary artery disease (CAD), which is a comorbidity of high incidence that is reported to worsen perioperative complications and long-term clinical outcomes in patients with an aortic aneurysm. Patients with significant coronary artery stenosis may require coronary revascularization and/or optimal medical therapy in the perioperative period of aneurysm surgery. However, the prognostic impact of non-significant coronary artery stenosis not indicated for coronary revascularization on clinical outcomes of patients with aortic aneurysms remains unclear. We performed coronary angiography on 239 consecutive patients with thoracic and abdominal aortic aneurysms before endovascular aortic repair or surgical repair. The patients were divided into the following 3 groups according to the severity of stenosis of major coronary arteries: non-CAD group (with < 25% stenosis), non-significant CAD group (with ≥ 25% but < 75% stenosis), and significant CAD group (with ≥ 75% stenosis). CAD was diagnosed in 133 (56%) patients consisting of 48 (20%) patients with non-significant CAD and 85 (36%) patients with significant CAD. Thirty-nine major adverse cardiovascular and cerebrovascular events (MACCEs) occurred in a median follow-up period of 723 days. Kaplan-Meier analysis revealed that the risk of MACCEs was higher in the significant and non-significant CAD groups than in the non-CAD group. Multivariate Cox proportional hazard regression analysis showed that the risk of MACCEs was equally high in the non-significant CAD and significant CAD groups compared to that in the non-CAD group after adjustment for confounding factors. CAD is significantly associated with poor outcomes in patients with aortic aneurysms, irrespective of the significance of CAD.

4.
Sci Rep ; 10(1): 14281, 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32868835

RESUMO

Despite advances in medicine, aortic diseases (ADs) such as aortic dissection and aortic aneurysm rupture remain fatal with extremely high mortality rates. Owing to the relatively low prevalence of AD, the risk of AD-related death has not yet been elucidated. The aim of the present study was to examine whether hyperuricemia is a risk factor for AD-related mortality in the general population. We used a nationwide database of 474,725 subjects (age 40-75 years) who participated in the annual "Specific Health Check and Guidance in Japan" between 2008 and 2013. There were 115 deaths from aortic dissection and aortic aneurysm rupture during the follow-up period of 1,803,955 person-years. Kaplan-Meier analysis revealed that subjects with hyperuricemia had a higher rate of AD-related death than those without hyperuricemia. Multivariate Cox proportional hazard regression analysis demonstrated that hyperuricemia was an independent risk factor for AD-related death in the general population. The net reclassification index was improved by addition of hyperuricemia to the baseline model. This is the first report to demonstrate that hyperuricemia is a risk factor for AD-related death, indicating that hyperuricemia could be a crucial risk for AD-related death in the general population.

5.
Diabetes Ther ; 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32968947

RESUMO

INTRODUCTION: Type 2 diabetes (T2DM) is associated with cardiovascular death, including sudden cardiac death due to arrhythmias. Patients with an implantable cardioverter-defibrillator (ICD) are also at high risk of developing a clinically significant ventricular arrhythmia. It has been reported that sodium-glucose cotransporter 2 (SGLT2) inhibitors can reduce cardiovascular deaths; however, the physiological mechanisms of this remain unclear. It is, however, well known that SGLT2 inhibitors increase blood ketone bodies, which have been suggested to have sympatho-suppressive effects. Empagliflozin (EMPA) is an SGLT2 inhibitor. The current clinical trial titled "Placebo-controlled, double-blind study of empagliflozin (EMPA) and implantable cardioverter-defibrillator (EMPA-ICD) in patients with type 2 diabetes (T2DM)" was designed to investigate the antiarrhythmic effects of EMPA. METHODS: The EMPA-ICD study is a prospective, multicenter, placebo-controlled, double-blind, randomized, investigator-initiated clinical trial currently in progress. A total of 210 patients with T2DM (hemoglobin A1c 6.5-10.0%) will be randomized (1:1) to receive once-daily placebo or EMPA, 10 mg, for 24 weeks. The primary endpoint is the number of clinically significant ventricular arrhythmias for 24 weeks before and 24 weeks after study drug administration, as documented by the ICD. The secondary endpoints of the study are the change from baseline concentrations in blood ketone and catecholamine 24 weeks after drug treatment. CONCLUSION: The EMPA-ICD study is the first clinical trial to assess the effect of an SGLT2 inhibitor on clinically significant ventricular arrhythmias in patients with T2DM and an ICD. TRIAL REGISTRATION: Unique trial number, jRCTs031180120 ( https://jrct.niph.go.jp/latest-detail/jRCTs031180120 ).

6.
PLoS One ; 15(8): e0237601, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32817643

RESUMO

BACKGROUND: Plasma volume status (PVS), a marker of plasma volume expansion and contraction, is gaining attention in the field of cardiovascular disease because of its role in the prevention and of the management of heart failure. However, it remains undetermined whether an abnormal PVS is a risk for all-cause and cardiovascular mortality in the general population. METHODS AND RESULTS: We used a nationwide database of 230,882 subjects (age 40-75 years) who participated in the annual "Specific Health Check and Guidance in Japan" check-up between 2008 and 2011. There were 586 cardiovascular deaths, 2,552 non-cardiovascular deaths, and 3,138 all-cause deaths during the follow-up period of four years. Abnormally high and low PVS were identified from the results of 80% of all subjects (high and low PVS ≥ 7 and < -13.3, respectively). Multivariate Cox proportional hazard regression analysis demonstrated that high PVS was an independent risk factor for all-cause, cardiovascular and non-cardiovascular deaths. Although low PVS was a positive risk factor for cardiovascular deaths as well, it was a negative risk factor for non-cardiovascular deaths. The addition of PVS to cardiovascular risk factors significantly improved the C-statistic, net reclassification, and integrated discrimination indexes. CONCLUSIONS: This is the first prospective report to reveal the impact of PVS on all-cause and cardiovascular mortality. PVS could be an additional risk factor for all-cause and cardiovascular mortality in the general population.


Assuntos
Biomarcadores/sangue , Doenças Cardiovasculares/mortalidade , Mortalidade/tendências , Volume Plasmático , Adulto , Idoso , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/fisiopatologia , Causas de Morte , Bases de Dados Factuais , Feminino , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Taxa de Sobrevida , Fatores de Tempo
7.
Biofabrication ; 12(4): 045008, 2020 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-32644945

RESUMO

Vascular networks consist of hierarchical structures of various diameters and are necessary for efficient blood distribution. Recent advances in vascular tissue engineering and bioprinting have allowed us to construct large vessels, such as arteries, small vessels, such as capillaries and microvessels, and intermediate-scale vessels, such as arterioles, individually. However, little is known about the control of vessel diameters between small vessels and intermediate-scale vessels. Here, we focus on vascular remodeling, which creates lasting structural changes in the vessel wall in response to hemodynamic stimuli, to regulate vessel diameters in vitro. The purpose of this study is to control the vessel diameter at an intermediate scale by inducing outward remodeling of microvessels in vitro. Human umbilical vein endothelial cells and mesenchymal stem cells were cocultured in a microfluidic device to construct microvessels, which were then perfused with a culture medium to induce outward vascular remodeling. We successfully constructed vessels with diameters of 40-150 µm in perfusion culture, whereas vessels with diameters of <20 µm were maintained in static culture. We also revealed that the in vitro vascular remodeling was mediated by NO pathways and MMP-9. These findings provide insight into the regulation of diameters of tissue-engineered blood vessels. This is an important step toward the construction of hierarchical vascular networks within biofabricated three-dimensional systems.

8.
Sci Rep ; 10(1): 10345, 2020 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-32587339

RESUMO

Pulmonary arterial hypertension (PAH) is a progressive fatal disease caused by pulmonary arterial remodeling. Midkine regulates cell proliferation and migration, and it is induced by hypoxia, but its roles in pulmonary arterial remodeling remain unclear. Serum midkine levels were significantly increased in PAH patients compared with control patients. Midkine expression was increased in lungs and sera of hypoxia-induced PAH mice. Hypoxia-induced pulmonary arterial remodeling and right ventricular hypertrophy were attenuated in midkine-knockout mice. Midkine-induced proliferation and migration of pulmonary arterial smooth muscle cells (PASMC) and epidermal growth factor receptor (EGFR) signaling were significantly increased under hypoxia, which also induced cell-surface translocation of nucleolin. Nucleolin siRNA treatment suppressed midkine-induced EGFR activation in vitro, and nucleolin inhibitor AS1411 suppressed proliferation and migration of PASMC induced by midkine. Furthermore, AS1411 significantly prevented the development of PAH in Sugen hypoxia rat model. Midkine plays a crucial role in PAH development through interaction with surface nucleolin. These data define a role for midkine in PAH development and suggest midkine-nucleolin-EGFR axis as a novel therapeutic target for PAH.

9.
Endosc Ultrasound ; 9(3): 187-192, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32584314

RESUMO

Objectives: The aim of this study is to estimate the cutoff length for stereomicroscopically visible white core (SVWC) required for the pathological diagnosis of subepithelial lesions (SELs) from samples obtained using a novel 22-G Franseen biopsy needle and determine the sensitivity using the SVWC cutoff length. Patients and Methods: Thirty patients with SELs requiring pathological diagnoses were included. EUS-guided fine-needle biopsies (EUS-FNBs) were performed using a novel 22G Franseen biopsy needle. SVWC cutoff lengths were measured using sample isolation processing by stereomicroscopy (SIPS). The utility of the calculated SVWC cutoff lengths was measured. Results: The procedural success and SVWC sampling rates were both 100%. The median SVWC length was 14.5 mm. Pathological examinations identified 16 patients with gastrointestinal stromal tumors, 7 with schwannomas, 6 with leiomyomas, and 1 with an ectopic pancreas. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for diagnosing malignancy using EUS-FNB were all 100%. The final diagnostic accuracy was 100%. Regarding the final diagnosis, based on the receiver operating characteristic curves calculated using the SVWC length, the area under the curve was 0.958 (95% confidence interval: 0.897-1.020, P < 0.001) and the cutoff length was 4 mm. The sensitivity of the new SVWC cutoff length was 98.7%. Conclusions: Diagnostic results of EUS-FNBs using a novel 22-G Franseen biopsy needle were significantly better with SVWC cutoff lengths ≥4 mm. Performing the SIPS procedure with a cutoff value of 4 mm as an index may be especially useful for successful pathological diagnosis of SELs at institutions where rapid on-site evaluation cannot be performed.

10.
Allergol Int ; 2020 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-32444304

RESUMO

BACKGROUND: The deterioration of pulmonary function, such as FEV1-decline, is strongly associated with poor prognosis in patients with chronic obstructive pulmonary disease (COPD). However, few investigations shed light on useful biomarkers for predicting the decline of pulmonary function. We evaluated whether thymus and activation-regulated chemokine (TARC), a Th2 inflammation marker, could predict rapid FEV1-decline in COPD patients. METHODS: We recruited 161 patients with stable COPD and performed pulmonary function test once every six months. At the time of registration, blood tests, including serum levels of TARC were performed. We assessed the correlation between changes in parameters of pulmonary function tests and serum levels of TARC. The rapid-decline in pulmonary function was determined using 25th percentile of change in FEV1 or FEV1 percent predicted (%FEV1) per year. RESULTS: In the FEV1-rapid-decline group, the frequency of exacerbations, the degree of emphysema, and serum levels of TARC was higher than in the non-rapid-decline group. When using %FEV1 as a classifier instead of FEV1, age, the frequency of exacerbations, the degree of emphysema and serum levels of TARC in the rapid-decline group was significantly greater than those in the non-rapid-decline group. In univariate logistic regression analysis, TARC was the significant predictive factor for rapid-decline group. In multivariate analysis adjusted for emphysema, serum levels of TARC are independently significant predicting factors for the rapid-decline group. CONCLUSIONS: TARC is an independent predictive biomarker for the rapid-decline in FEV1. Measuring serum TARC levels may help the management of COPD patients by predicting the risk of FEV1 decline.

11.
ESC Heart Fail ; 7(4): 1735-1743, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32432414

RESUMO

AIMS: Reactive oxygen species are reportedly involved in the mechanism underlying heart failure with preserved ejection fraction (HFpEF); however, the disease pathophysiology remains poorly understood. Xanthine oxidoreductase (XOR), the rate-limiting enzyme of purine metabolism, plays an important role in uric acid production and generates reactive oxygen species. However, the impact of plasma XOR activity on the clinical outcomes of patients with HFpEF remains unclear. The aim of this study was to investigate whether plasma XOR activity is associated with major adverse cardiovascular events (MACEs) in patients with HFpEF. METHODS AND RESULTS: The plasma XOR activity was measured in 257 patients with HFpEF, who were then divided into three groups according to the activity levels: low XOR group (<33 pmol/h/mL, n = 45), normal XOR group (33-120 pmol/h/mL, n = 160), and high XOR group (>120 pmol/h/mL, n = 52). During the median follow-up period of 809 days, there were 74 MACEs. Kaplan-Meier analysis revealed that the high XOR group was at the highest risk for MACEs. Multivariate analysis by Cox's proportional hazard regression approach showed that high XOR activity was significantly associated with MACEs, after adjustment for confounding factors. The patients were also divided into four groups according to the absence/presence of high XOR activity and/or hyperuricaemia. According to the multivariate Cox regression analysis, high XOR activity was associated with MACEs, regardless of the hyperuricaemia status. CONCLUSIONS: Elevated plasma XOR activity is significantly associated with adverse clinical outcomes in patients with HFpEF.

12.
Sci Rep ; 10(1): 5570, 2020 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-32221372

RESUMO

Chronic kidney disease (CKD) and chronic obstructive pulmonary disease (COPD) are known risk factors for mortality. In this study, we examined the overlap of CKD and airflow limitation (AFL) that characterises COPD and its effect on 10-year mortality in a community-based population. This study included 1,233 health check-up participants (mean age, 63.7 years; 46.7% men). We defined serum creatinine-based CKD (CKDcr) and serum cystatin C-based CKD (CKDcys) as glomerular filtration rate <60 mL/min/1.73 m2, estimated using serum creatinine or cystatin C, and/or dipstick proteinuria ≥1+. AFL was defined as forced expiratory volume in 1 s to forced vital capacity ratio <70% on spirometry. Compared with subjects without AFL, those with AFL showed a significantly higher prevalence of CKDcys but not of CKDcr. Cox proportional hazard analysis adjusted for confounders showed that the hazard ratio (95% confidence interval) for all-cause mortality was 1.45 (0.77-2.63) in subjects with CKDcys alone, 1.29 (0.60-2.54) in those with AFL alone, and 2.94 (1.33-6.12) in those with both CKDcys and AFL, with subjects without both AFL and CKD as the reference. This study showed that AFL and CKDcys are strongly associated and that their overlap is a significant risk factor for mortality in community-based populations.

13.
PLoS One ; 15(2): e0226053, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32040481

RESUMO

Hypertension is a major public health problem among the aging population worldwide. It causes cardiac remodeling, including hypertrophy and interstitial fibrosis, which leads to development of hypertensive heart disease (HHD). Although microRNA-21 (miR-21) is associated with fibrogenesis in multiple organs, its contribution to cardiac remodeling in hypertension is poorly understood. Circulating miR-21 level was higher in patients with HHD than that in the control subjects. It also positively correlated with serum myocardial fibrotic markers. MiR-21 expression levels were significantly upregulated in the mice hearts after angiotensin II (Ang II) infusion or transverse aortic constriction (TAC) compared with control mice. Expression level of programmed cell death 4 (PDCD4), a main target of miR-21, was significantly decreased in Ang II infused mice and TAC mice compared with control mice. Expression levels of transcriptional activator protein 1 (AP-1) and transforming growth factor-ß1 (TGF-ß1), which were downstream targets of PDCD4, were increased in Ang II infused mice and TAC mice compared with control mice. In vitro, mirVana-miR-21-specific inhibitor attenuated Ang II-induced PDCD4 downregulation and contributed to subsequent deactivation of AP-1/TGF-ß1 signaling pathway in neonatal rat cardiomyocytes. Thus, suppression of miR-21 prevents hypertrophic stimulation-induced cardiac remodeling by regulating PDCD4, AP-1, and TGF-ß1 signaling pathway.


Assuntos
Cardiomegalia/etiologia , Hipertensão/complicações , MicroRNAs/genética , Miocárdio/metabolismo , Idoso , Angiotensina II/farmacologia , Animais , Animais Recém-Nascidos , Proteínas Reguladoras de Apoptose/metabolismo , Cardiomegalia/sangue , Cardiomegalia/patologia , Modelos Animais de Doenças , Feminino , Fibrose , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Miocárdio/patologia , Miócitos Cardíacos/metabolismo , Proteínas de Ligação a RNA/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição AP-1/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
14.
Heart Vessels ; 35(2): 187-196, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31332507

RESUMO

Kidney dysfunction (KD) is closely associated with poor clinical outcome in patients with heart failure (HF). KD is classified as intrinsic and pre-renal KD. However, the impact of each KD on the clinical outcome in patients with HF has not yet been fully elucidated. We measured the urinary to serum creatinine (UC/SC) ratio, a marker for intrinsic and pre-renal KD, in 1009 consecutive patients with HF at admission. There were 314 cardio-renal events including HF and advanced end-stage renal dysfunction during the median follow-up period of 1154 days. There were 63 (6%) patients with intrinsic KD (UC/SC ratio < 20), 118 (12%) patients with intermediate KD (UC/SC ratio 20-40), 607 (60%) patients with pre-renal KD (UC/SC ratio > 40), and 221 (22%) patients with no KD. Multivariate Cox's proportional hazard regression analysis demonstrated that intrinsic and intermediate KDs were significantly associated with poor clinical outcome. The prediction model for cardio-renal events was significantly improved by the addition of UC/SC ratio to the confounding risk factors. Subgroup analysis in patients with HF with severely reduced glomerular filtration rates showed that the prevalence rates of intrinsic, intermediate, and pre-renal KDs were 23%, 30%, and 47%, respectively. The cardio-renal event rate was the highest in the intrinsic KD group compared with that in the other groups. Intrinsic KD was closely associated with extremely poor clinical outcome in patients with HF. The UC/SC ratio could provide important clinical information for the treatment and management of KD in patients with HF.

15.
Cardiovasc Res ; 116(5): 983-994, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31393559

RESUMO

AIMS: Calcific aortic valve stenosis (CAVS) is the most common valvular heart disease and is increased with elderly population. However, effective drug therapy has not been established yet. This study aimed to investigate the role of microRNAs (miRs) in the development of CAVS. METHODS AND RESULTS: We measured the expression of 10 miRs, which were reportedly involved in calcification by using human aortic valve tissue from patients who underwent aortic valve replacement with CAVS or aortic regurgitation (AR) and porcine aortic valve interstitial cells (AVICs) after treatment with osteogenic induction medium. We investigated whether a specific miR-inhibitor can suppress aortic valve calcification in wire injury CAVS mice model. Expression of miR-23a, miR-34a, miR-34c, miR-133a, miR-146a, and miR-155 was increased, and expression of miR-27a and miR-204 was decreased in valve tissues from CAVS compared with those from AR. Expression of Notch1 was decreased, and expression of Runt-related transcription factor 2 (Runx2) was increased in patients with CAVS compared with those with AR. We selected miR-34a among increased miRs in porcine AVICs after osteogenic treatment, which was consistent with results from patients with CAVS. MiR-34a increased calcium deposition in AVICs compared with miR-control. Notch1 expression was decreased, and Runx2 expression was increased in miR-34a transfected AVICs compared with that in miR-control. Conversely, inhibition of miR-34a significantly attenuated these calcification signals in AVICs compared with miR-control. RNA pull-down assay revealed that miR-34a directly targeted Notch1 expression by binding to Notch1 mRNA 3' untranslated region. In wire injury CAVS mice, locked nucleic acid miR-34a inhibitor suppressed aortic velocity, calcium deposition of aortic valves, and cardiac hypertrophy, which were involved in decreased Runx2 and increased Notch1 expressions. CONCLUSION: miR-34a plays an important role in the development of CAVS via Notch1-Runx2 signalling pathway. Inhibition of miR-34a may be the therapeutic target for CAVS.

16.
Heart Vessels ; 35(2): 207-213, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31327031

RESUMO

The precise physiological changes associated with the use of left ventricular assist device (LVAD) are not well characterized. We examined the impact of changes in hemodynamic state using LVAD on endothelial function. We measured flow-mediated vasodilation (FMD) to evaluate endothelial vasodilator function of the brachial artery in 53 patients (dilated cardiomyopathy: 39, ischemic cardiomyopathy: 4, and others: 10) with an implanted LVAD (DuraHeart, EVAHEART, or HeartMate II). We found that FMD value in the HeartMateII LVAD group (9.3% ± 2.9%) was significantly higher than those in the other two groups (EVAHEART: 6.7% ± 2.8% and DuraHeart: 6.2% ± 4.0%). Other factors that affected the FMD value were age (r = - 0.31, p = 0.026), Brinkman index (r = - 0.30, p = 0.029); however, aortic opening, aortic regurgitation, and other hemodynamic parameters such as cardiac index or pulmonary capillary wedge pressure did not correlate with FMD. Multivariate analyses revealed that the difference among the LVAD models most significantly affected the FMD values after adjusting for age and smoking status (t = 2.6, p = 0.014). Event free survival rate of death and cerebral infarction was not significantly different according to the value of FMD. The difference among the LVAD groups most significantly affected the state of endothelial function and it had more impact than other clinical factors.

17.
Am J Respir Cell Mol Biol ; 62(5): 588-597, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31726018

RESUMO

Smoking is a major risk factor for chronic obstructive pulmonary disease (COPD). Smoking susceptibility is important for the onset and development of COPD. We previously reported an association between serum iron concentrations and pulmonary function in male smokers. However, the mechanism governing smoking susceptibility in relation to iron deficiency is unclear; this study aimed to elucidate this mechanism. C57BL/6 male mice were fed an iron-deficient or normal diet and then exposed to cigarette smoke. BAL, histological analysis, and pulmonary function tests were performed after cigarette smoke exposure. Human alveolar type II epithelial A549 cells were treated with an iron chelator. Subsequently, A549 cells were exposed to cigarette smoke extract. In mice exposed to cigarette smoke for 2 weeks, the concentration of alveolar macrophages in the BAL fluid recovered from iron-deficient mice was significantly higher than that in normal diet mice. IL-6 and MCP-1 (monocyte chemotactic protein 1) concentrations in the BAL fluid increased significantly from baseline in iron-deficient mice, but not in normal diet mice. In mice exposed to cigarette smoke for 8 weeks, the pathological mean linear intercepts, physiological total lung capacity, and functional residual capacity in the lungs of iron-deficient mice were significantly greater than in normal diet mice. Phosphorylation of NF-κB was enhanced in the lungs of iron-deficient mice exposed to cigarette smoke and in the iron-chelating A549 cells exposed to cigarette smoke extract. Iron deficiency exaggerated cigarette smoke-induced pulmonary inflammation, suggesting that it may accelerate COPD development.

18.
J Epidemiol ; 30(4): 188-193, 2020 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-30956258

RESUMO

BACKGROUND: Positive and negative psychological factors are associated with mortality and cardiovascular disease. This study prospectively investigated associations of daily frequency of laughter with mortality and cardiovascular disease in a community-based population. METHODS: This study included 17,152 subjects ≥40 years old who participated in an annual health check in Yamagata Prefecture. Self-reported daily frequency of laughter was grouped into three categories (≥1/week; ≥1/month but <1/week; <1/month). Associations of daily frequency of laughter with increase in all-cause mortality and cardiovascular disease incidence were determined using Cox proportional hazards modeling. RESULTS: During follow-up (median, 5.4 years), 257 subjects died and 138 subjects experienced cardiovascular events. Kaplan-Meier analysis revealed that all-cause mortality and cardiovascular disease incidence were significantly higher among subjects with a low frequency of laughter (log-rank P < 0.01). Cox proportional hazard model analysis adjusted for age, gender, hypertension, smoking, and alcohol drinking status showed that risk of all-cause mortality was significantly higher in subjects who laughed <1/month than in subjects who laughed ≥1/week (hazard ratio [HR] 1.95; 95% confidence interval [CI], 1.16-3.09). Similarly, risk of cardiovascular events was higher in subjects who laughed ≥1/month but <1/week than in subjects who laughed ≥1/week (HR 1.62; 95% CI, 1.07-2.40). CONCLUSION: Daily frequency of laughter represents an independent risk factor for all-cause mortality and cardiovascular disease in a Japanese general population.

19.
Intern Med ; 59(1): 37-44, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31511483

RESUMO

Objective To evaluate the effect of endovascular therapy (EVT) on the central blood pressure (CBP) and augmentation index (AIx) in patients with peripheral artery disease (PAD). Methods The CBP and AIx were assessed by radial applanation tonometry the day before and the day after EVT. We compared the differences in the therapeutic effects between the stenotic and occlusive lesions and between the iliac and superficial femoral artery (SFA) lesions. Patients We enrolled 60 consecutive patients with PAD who underwent EVT for de novo lesions. Results Both the CBP and AIx were significantly decreased after EVT (125±22 mmHg to 112±22 mmHg; p=0.002 and 84%±16% to 73%±15%; p<0.001, respectively). The effects of EVT on the CBP and AIx were equivalent, regardless of whether the target lesion was the stenotic lesion or the occlusive lesion. There were no significant differences between the iliac and SFA lesions in the effects of EVT on the CBP and AIx. Conclusion EVT improved the CBP and AIx in patients with PAD, regardless of the morphology or site of the lesions.


Assuntos
Pressão Sanguínea , Procedimentos Endovasculares , Artéria Femoral/cirurgia , Artéria Ilíaca/cirurgia , Doença Arterial Periférica/cirurgia , Idoso , Idoso de 80 Anos ou mais , Determinação da Pressão Arterial , Constrição Patológica , Feminino , Hemodinâmica , Humanos , Masculino , Manometria , Pessoa de Meia-Idade , Artéria Radial , Resultado do Tratamento
20.
EXCLI J ; 18: 1062-1070, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31839762

RESUMO

When examining patients with acute inflammatory respiratory diseases, it is difficult to distinguish between infectious pneumonia and interstitial pneumonia and predict patient prognosis at the beginning of treatment. In this study, we assessed whether endothelial selectin (E-selectin) predicts the outcome of patients with acute inflammatory respiratory diseases. We measured E-selectin serum levels in 101 patients who were admitted to our respiratory care unit between January 2013 and December 2013 because of acute inflammatory respiratory diseases that were eventually diagnosed as interstitial pneumonia (n = 38) and lower respiratory tract infection (n = 63). Seven of these patients (n = 101) died. The pneumonia severity score was significantly higher and the oxygen saturation of arterial blood measured by pulse oximeter (SpO2)/fraction of inspiratory oxygen (FiO2) was significantly lower in the deceased patients than in the surviving patients. There were significantly fewer peripheral lymphocytes and significantly higher E-selectin serum levels in the deceased patients than in the surviving patients. In the multiple logistic regression analysis, the E-selectin serum levels and SpO2/FiO2 ratio were independent predictive factors of prognosis. The risk of death during acute respiratory disease was determined using a receiver operating characteristic (ROC) curve analysis. The area under the curve (AUC) was 0.871 as calculated from the ES, and the cutoff value was 6453.04 pg/ml, with a sensitivity of 1.00 and a specificity of 0.72 (p = 0.0027). E-selectin may be a useful biomarker for predicting the prognosis of patients with acute inflammatory respiratory diseases.

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