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Bach1 is a known transcriptional repressor of the heme oxygenase-1 (HO-1) gene. The purpose of this study was to determine whether angiogenesis is accelerated by genetic ablation of Bach1 in a mouse ischemic hindlimb model. Hindlimb ischemia was surgically induced in wild-type (WT) mice, Bach1-deficient (Bach1-/-) mice, apolipoprotein E-deficient (ApoE-/-) mice, and Bach1/ApoE double-knockout (Bach1-/-/ApoE-/-) mice. Blood flow recovery after hindlimb ischemia showed significant improvement in Bach1-/- mice compared with that in WT mice. Bach1-/-/ApoE-/- mice showed significantly improved blood flow recovery compared with that in ApoE-/- mice to the level of that in WT mice. Migration of endothelial cells in ApoE-/- mice was significantly decreased compared with that in WT mice. Migration of endothelial cells significantly increased in Bach1-/-/ApoE-/- mice compared with that in ApoE-/- mice to the level of that in WT mice. The expression levels of HO-1, peroxisome proliferator-activated receptor γ co-activator-1α, angiopoietin 1, and fibroblast growth factor 2 in endothelial cells isolated from Bach1-/-/ApoE-/- mice were significantly higher than those in ApoE-/- mice. Oxidative stress assessed by anti-acrolein antibody staining in ischemic tissues and urinary 8-isoPGF2α excretion were significantly increased in ApoE-/- mice compared with those in WT and Bach1-/- mice. Oxidative stress was reduced in Bach1-/-/ApoE-/- mice compared with that in ApoE-/- mice. These findings suggest that genetic ablation of Bach1 plays an important role in ischemia-induced angiogenesis under the condition of increased oxidative stress. Bach1 could be a potential therapeutic target to reduce oxidative stress and potentially improve angiogenesis for patients with peripheral arterial disease.
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Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Células Endoteliais/metabolismo , Isquemia/metabolismo , Músculo Esquelético/irrigação sanguínea , Neovascularização Fisiológica , Estresse Oxidativo , Animais , Apoptose , Fatores de Transcrição de Zíper de Leucina Básica/deficiência , Fatores de Transcrição de Zíper de Leucina Básica/genética , Velocidade do Fluxo Sanguíneo , Movimento Celular , Células Cultivadas , Modelos Animais de Doenças , Células Endoteliais/patologia , Heme Oxigenase-1/metabolismo , Membro Posterior , Isquemia/genética , Isquemia/patologia , Isquemia/fisiopatologia , Masculino , Proteínas de Membrana/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Densidade Microvascular , Fluxo Sanguíneo Regional , Transdução de SinaisRESUMO
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. MethodsâandâResults: 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.
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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 SobrevidaRESUMO
PURPOSE: The purpose of this study was to evaluate acute effects of coffee with a high content of chlorogenic acids and different hydroxyhydroquinone contents on postprandial endothelial dysfunction. METHODS: This was a single-blind, randomized, placebo-controlled, crossover-within-subject clinical trial. A total of 37 patients with borderline or stage 1 hypertension were randomized to two study groups. The participants consumed a test meal with a single intake of the test coffee. Subjects in the Study 1 group were randomized to single intake of coffee with a high content of chlorogenic acids and low content of hydroxyhydroquinone or coffee with a high content of chlorogenic acids and a high content of hydroxyhydroquinone with crossover. Subjects in the Study 2 group were randomized to single intake of coffee with a high content of chlorogenic acids and low content of hydroxyhydroquinone or placebo coffee with crossover. Endothelial function assessed by flow-mediated vasodilation and plasma concentration of 8-isoprostanes were measured at baseline and at 1 and 2 h after coffee intake. RESULTS: Compared with baseline values, single intake of coffee with a high content of chlorogenic acids and low content of hydroxyhydroquinone, but not coffee with a high content of chlorogenic acids and high content of hydroxyhydroquinone or placebo coffee, significantly improved postprandial flow-mediated vasodilation and decreased circulating 8-isoprostane levels. CONCLUSIONS: These findings suggest that a single intake of coffee with a high content of chlorogenic acids and low content of hydroxyhydroquinone is effective for improving postprandial endothelial dysfunction. CLINICAL TRIAL REGISTRATION: URL for Clinical Trial: https://upload.umin.ac.jp ; Registration Number for Clinical Trial: UMIN000013283.
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Ácido Clorogênico/farmacologia , Café , Endotélio Vascular/efeitos dos fármacos , Hidroquinonas/farmacologia , Hipertensão/dietoterapia , Estudos Cross-Over , Endotélio Vascular/fisiopatologia , Feminino , Humanos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Período Pós-Prandial , Método Simples-CegoRESUMO
PURPOSE: Our previous work indicated the greater magnitude of damage to the thoracic aorta at 6 months after starting 5 Gy irradiation in descending order of exposure to X-rays in 25 fractions > acute X-rays > acute γ-rays > X-rays in 100 fractions â« chronic γ-rays, in which the limitations of the study included a lack of data for fractionated γ-ray exposure. To better understand effects of dose protraction and radiation quality, the present study examined changes after exposure to γ-rays in 25 fractions, and compared its biological effectiveness with five other irradiation regimens. MATERIALS AND METHODS: Male C57BL/6J mice received 5 Gy of 137Cs γ-rays delivered in 25 fractions spread over six weeks. At 6 months after starting irradiation, mice were subjected to echocardiography, followed by tissue sampling. The descending thoracic aorta underwent scanning electron microscopy, immunofluorescence staining and histochemical staining. The integrative analysis of multiple aortic endpoints was conducted for inter-regimen comparisons. RESULTS: Exposure to γ-rays in 25 fractions induced vascular damage (evidenced by increases in endothelial detachment and vascular endothelial cell death, decreases in endothelial waviness, CD31, endothelial nitric oxide synthase and vascular endothelial cadherin), inflammation (evidenced by increases in tumor necrosis factor α, CD68 and F4/80) and fibrosis (evidenced by increases in transforming growth factor ß1, alanine blue stain and intima-media thickness). The integrative analysis revealed biological effectiveness in descending order of exposure to X-rays in 25 fractions > acute X-rays > γ-rays in 25 fractions > acute γ-rays > X-rays in 100 fractions â« chronic γ-rays. CONCLUSIONS: The results suggest that dose protraction effects on aortic damage depend on radiation quality, and are not a simple function of dose rate and the number of fractions.
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Aorta , Espessura Intima-Media Carotídea , Camundongos , Masculino , Animais , Camundongos Endogâmicos C57BL , Doses de Radiação , Raios X , Raios gama/efeitos adversos , Relação Dose-Resposta à RadiaçãoRESUMO
BACKGROUND: The relationship between cumulative low-density lipoprotein cholesterol (LDL-C) exposure and progression of atherosclerosis remains uncertain. OBJECTIVE: The aim of this study was to determine the relationship between cumulative LDL-C level and flow-mediated vasodilation (FMD), nitroglycerine-induced vasodilation (NID) and the presence of plaque in the common carotid artery (CCA). METHODS: This was a cross-sectional study. We measured FMD in 8208 subjects, NID in 1822 subjects, and CCA plaque in 591 subjects who were not taking lipid-lowering drugs. The subjects were divided into four groups based on cumulative LDL-C exposure: <4000 mg·year/dL, 4000-4999 mg·year/dL, 5000-5999 mg·year/dL, and ≥6000 mg·year/dL. RESULTS: The odds ratio of the lower quartile of FMD in the cholesterol-year-score <4000 mg·year/dL group was significantly higher than the odds ratios in the other groups. The odds ratio of the lower quartile of NID in the <4000 mg·year/dL group was significantly higher than the odds ratios in the 5000-5999 mg·year/dL and ≥6000 mg·year/dL groups. The odds ratio of the prevalence of CCA plaque in the <4000 mg·year/dL group was significantly higher than that in the ≥6000 mg·year/dL group. CONCLUSIONS: Endothelial dysfunction occurred from cumulative LDL-C exposure of 4000 mg·year/dL, vascular smooth muscle dysfunction occurred from cumulative LDL-C exposure of 5000 mg·year/dL, and prevalence of CCA plaque occurred from cumulative LDL-C exposure of 6000 mg·year/dL. CLINICAL TRIAL REGISTRY INFORMATION: http://www.umin.ac.jp (UMIN000012950, UMIN000012951, and UMIN000012952, UMIN000003409).
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LDL-Colesterol , Vasodilatação , Humanos , Masculino , Feminino , LDL-Colesterol/sangue , Pessoa de Meia-Idade , Vasodilatação/efeitos dos fármacos , Estudos Transversais , Idoso , Nitroglicerina/administração & dosagem , Placa Aterosclerótica/sangue , Aterosclerose/sangue , Aterosclerose/epidemiologia , Adulto , Artéria Carótida Primitiva/efeitos dos fármacos , Artéria Carótida Primitiva/diagnóstico por imagem , Artéria Carótida Primitiva/patologiaRESUMO
The percentage of mean arterial pressure (%MAP) is the height of the mean arterial waveform divided by the peak amplitude of the waveform of pulse volume recording. The purpose of this study was to determine whether the cutoff value of 45% for %MAP at the ankle, which is recommended for the diagnosis of lower extremity artery disease, in combination with ankle-brachial index (ABI) is useful for detecting patients with clinical coronary artery disease (CAD) and investigate the optimal cutoff value of %MAP to diagnose patients with CAD.ãWe measured ABI and %MAP in 2213 subjectsã(mean age: 61.2 ± 15.5 years). Multivariate analysis revealed that %MAP ≥ 45% was significantly associated with a higher risk of CAD after adjusting for traditional cardiovascular risk factors (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.43-3.21; p < 0.001). However, the association was no longer significant after adjusting for ABI (OR, 1.39; 95% CI, 0.83-2.33; p = 0.21), whereas ABI was significantly associated with CAD (OR, 0.98; 95% CI, 0.97-0.99; p = 0.005). The optimal cutoff value of %MAP derived from a receiver operating characteristic curve to diagnose CAD was 40.3%. Multivariate analysis revealed that %MAP ≥ 40.3% was significantly associated with a higher risk of CAD (OR, 1.63; 95% CI, 1.19-2.24; p = 0.002) independent of ABI (OR, 0.98; 95% CI, 0.97-0.99; p = 0.002). The cutoff value of 40.3%, but not 45%, for %MAP may be useful for detecting patients with advanced atherosclerosis and for cardiovascular risk assessment independent of ABI. REGISTRATION INFORMATION: http://www.umin.ac.jp (University Hospital Medical Information Network Clinical Trials Registry) (UMIN000039512).
Assuntos
Aterosclerose , Doença da Artéria Coronariana , Humanos , Pessoa de Meia-Idade , Idoso , Doença da Artéria Coronariana/diagnóstico , Pressão Arterial , Aterosclerose/diagnóstico , Índice Tornozelo-Braço , Tornozelo/irrigação sanguínea , Fatores de RiscoRESUMO
Cardiovascular mortality has been shown to vary seasonally. However, it has not been determined whether vascular function is affected by the season. The purpose of this study was to investigate the associations of vascular function with season and outdoor temperature. Between April 2007 and March 2022, measurements of flow-mediated vasodilation (FMD) of the brachial artery as an index of endothelial function and nitroglycerine-induced vasodilation (NID) as an index of endothelium-independent vasodilation were performed in 2190 subjects. There was no significant seasonal difference in FMD (spring, 3.9 ± 3.1%; summer, 3.5 ± 3.0%; fall, 3.7 ± 3.0%; winter, 3.6 ± 3.2%; P = 0.14). There was no significant correlation between FMD and daily mean outdoor temperature (r = -0.02, P = 0.25). Multivariate analyses revealed that neither season (ß = -0.020, P = 0.31) nor outdoor temperature (ß = 0.005, P = 0.81) was significantly associated with FMD after adjustment for other confounding factors. There were significant seasonal differences in NID (spring, 12.8 ± 6.3%; summer, 12.0 ± 6.1%; fall, 11.7 ± 6.1%; winter, 12.3 ± 5.9%; P = 0.02). However, multivariate analysis revealed that there was no significant association between season and NID after adjustment for other confounding factors (ß = -0.012, P = 0.56). There was no significant correlation between NID and daily outdoor mean temperature (r = -0.03, P = 0.17). Multivariate analysis revealed that outdoor temperature was not significantly associated with NID (ß = -0.006, P = 0.78). There was no significant association of FMD or NID with season or outdoor temperature, suggesting that it is not necessary to take into account the effects of season and outdoor temperature on vascular function when interpreting the results of FMD and NID measurements. Public trials registry number: UMIN000039512.
Assuntos
Endotélio Vascular , Vasodilatação , Humanos , Estações do Ano , Nitroglicerina/farmacologia , Artéria BraquialRESUMO
Measurement of flow-mediated vasodilation (FMD) in the brachial artery by using ultrasound is a well-established technique for evaluating endothelial function. To make the measurement quicker and simpler than the measurements of conventional ultrasound FMD (uFMD), we have developed a new noninvasive method, plethysmographic FMD (pFMD), to assess vascular response to reactive hyperemia in the brachial artery. The aim of this study was to determine the accuracy of measurement of pFMD in comparison to that of measurement of conventional uFMD. This study was a multi-center, cross-sectional study. We compared pFMD by a new device using cuff pressure and volume with conventional uFMD using ultrasound in 50 men (mean age, 41 ± 9 years). pFMD significantly correlated with conventional uFMD (ß = 0.59, P < 0.001). In Bland-Altman plot analysis of pFMD and conventional uFMD, the mean difference of pFMD and conventional uFMD was 0.78%, and limits of agreement (mean difference ±2 standard deviations of the difference) ranged from -4.53% to 6.11%. We demonstrated validity of the new method for measurement of pFMD, which can automate the evaluation of endothelial function in a short time. Measurement of pFMD is simpler than measurement of conventional uFMD and may have reduced artificial bias compared to that of conventional uFMD measurement (URL for Clinical Trial: https://ethics.hiroshima-u.ac.jp/site/wp-content/uploads/2022/12/eki_giji20221213.pdf . Registration Number for Clinical Trial: E2022-0131).
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Upstroke time (UT) and percentage of mean arterial pressure (%MAP) at the ankle have been shown to serve as atherosclerotic markers. The purpose of this study was to directly compare the diagnostic accuracy of UT with that of %MAP for clinical coronary artery disease (CAD) in subjects with a normal ankle-brachial index (ABI) in both legs. We measured UT and %MAP in 1953 subjects with a normal ABI. The optimal cutoff values of UT and %MAP derived from a receiver operating characteristic (ROC) curve to diagnose CAD were 148 ms and 40.4%, respectively. Multivariable analyses revealed that both UT ≥ 148 ms (odds ratio [OR], 2.72; p < 0.001) and %MAP ≥ 40.4% (OR, 1.28; p = 0.003) were significantly associated with CAD. When the subjects were divided into four groups according to the cutoff values of UT and %MAP, there was no significant difference in the risk of CAD between subjects with UT ≥ 148 ms and %MAP < 40.4% and those with UT ≥ 148 ms and %MAP ≥ 40.4% (OR, 1.45; p = 0.09). ROC curve analyses revealed that the area under the curve value of UT was significantly higher than that of %MAP (0.69 vs. 0.53, p < 0.001). The addition of UT to traditional risk factors significantly improved the diagnostic accuracy for CAD (0.82 to 0.84, p = 0.004), whereas the addition of %MAP to traditional risk factors did not improve the diagnostic accuracy for CAD (0.82 to 0.82, p = 0.84). UT is more useful than %MAP for identifying individuals with CAD among those with a normal ABI.
Assuntos
Índice Tornozelo-Braço , Pressão Arterial , Aterosclerose , Doença da Artéria Coronariana , Humanos , Masculino , Feminino , Doença da Artéria Coronariana/fisiopatologia , Doença da Artéria Coronariana/diagnóstico , Pessoa de Meia-Idade , Idoso , Aterosclerose/fisiopatologia , Aterosclerose/diagnóstico , Pressão Arterial/fisiologia , Curva ROC , Adulto , Pressão Sanguínea/fisiologiaRESUMO
BACKGROUND: A Body Shape Index (ABSI) has been reported to have associations with cardiovascular risk factors. However, there is no information on the association between ABSI and incidence of cardiovascular events. METHODS: We investigated the associations between ABSI and first major cardiovascular events (death from cardiovascular disease, nonfatal acute coronary syndrome, and nonfatal stroke) in 1857 subjects from the database of Flow-Mediated Dilation Japan registry and from Hiroshima University Vascular Function registry. RESULTS: The areas under the curves of ABSI to predict the first major cardiovascular events were superior to BMI (men: P=0.032, women: P=0.015) and waist circumference in women (men: P=0.078, women: P=0.002). The subjects were divided into two groups based on the cutoff value of ABSI for predicting first major cardiovascular events: a low ABSI group (<0.0822 in men and <0.0814 in women) and a high ABSI group (≥0.0822 in men and ≥0.0814 in women). During a median follow-up period of 41.6 months, 56 subjects died (23 from cardiovascular causes), 16 had nonfatal acute coronary syndrome, and 14 had nonfatal stroke. The Kaplan-Meier curves for first major cardiovascular events were significantly different between the two groups (men, P<0.001; women, P<0.001). Multivariate analysis revealed that high ABSI remained an independent predictor of first major cardiovascular events (men: hazard ratio, 2.33; 95% CI, 1.07 to 5.06; P=0.033; women: hazard ratio, 8.33; 95% CI, 1.06 to 65.49; P=0.044). CONCLUSIONS: High ABSI is independently associated with incidence of cardiovascular events. ABSI calculation should be performed for evaluation of risk of cardiovascular events.
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The effects of Covid-19 vaccines on vascular function are still controversial. We evaluated the effects of BNT162b2 vaccine (BioNTech and Pfizer) on endothelial function assessed by flow-mediated vasodilation (FMD) and vascular smooth muscle function assessed by nitroglycerine-induced vasodilation (NID). This study was a prospective observational study. A total of 23 medical staff at Hiroshima University Hospital were enrolled in this study. FMD and NID were measured before vaccination and two weeks and six months after the 2nd dose of vaccination. FMD was significantly smaller two weeks after the 2nd dose of vaccination than before vaccination (6.5±2.4% and 8.2±2.6%, p = 0.03). FMD was significantly larger at six months than at two weeks after the 2nd dose of vaccination (8.2±3.0% and 6.5±2.4%, p = 0.03). There was no significant difference between FMD before vaccination and that at six months after the 2nd dose of vaccination (8.2±2.6% to 8.2±3.0%, p = 0.96). NID values were similar before vaccination and at two weeks, and six months after vaccination (p = 0.89). The BNT162b2 Covid-19 vaccine temporally impaired endothelial function but not vascular smooth muscle function, and the impaired endothelial function returned to the baseline level within six months after vaccination.
Assuntos
Vacina BNT162 , COVID-19 , Vasodilatação , Humanos , Vacina BNT162/administração & dosagem , Masculino , Feminino , Vasodilatação/efeitos dos fármacos , Adulto , COVID-19/prevenção & controle , Pessoa de Meia-Idade , Vacinas contra COVID-19/administração & dosagem , Estudos Prospectivos , SARS-CoV-2/imunologia , Endotélio Vascular/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , VacinaçãoRESUMO
AIM: There is little information on the relationships of serum small dense low-density lipoprotein cholesterol (sdLDL-C) levels and serum triglyceride (TG) levels with cardiovascular events in patients with coronary artery disease (CAD) and type 2 diabetes mellitus (DM) who are receiving statins. The aim of this study was to evaluate the relationships of serum TG levels and sdLDL-C levels as residual risks for cardiovascular events in patients with CAD and type 2 DM who were being treated with statins. METHODS: The subjects were divided into four groups based on TG levels and sdLDL-C levels: sdLDL-C of ï¼40.0 mg/dL and TG of ï¼150 mg/dL, sdLDL-C of ≥ 40.0 mg/dL and TG of ï¼150 mg/dL, sdLDL-C of ï¼40.0 mg/dL and TG of ≥ 150 mg/dL, and sdLDL-C of ≥ 40.0 mg/dL and TG of ≥ 150 mg/dL. During a median follow-up period of 1419 days, cardiovascular events occurred in 34 patients. RESULTS: The incidences of cardiovascular events were significantly higher in patients with sdLDL-C of ≥ 40.0 mg/dL and TG of ï¼150 mg/dL and in patients with sdLDL-C of ≥ 40.0 mg/dL and TG of ≥ 150 mg/dL, but not in patients with sdLDL-C of ï¼40.0 mg/dL and TG of ≥ 150 mg/dL, than in patients with sdLDL-C of ï¼40.0 mg/dL and TG of ï¼150 mg/dL. CONCLUSIONS: Under the condition of treatment with statins, patients with CAD and type 2 DM who had sdLDL-C levels of ≥ 40.0 mg/dL had a high risk for cardiovascular events even though serum TG levels were controlled at ï¼150 mg/dL.
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Doença da Artéria Coronariana , Diabetes Mellitus Tipo 2 , Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , Doença da Artéria Coronariana/tratamento farmacológico , LDL-Colesterol , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Fatores de Risco , TriglicerídeosRESUMO
The purpose of this study was to evaluate the effects of administration of overnight 1 mg dexamethasone on vascular function in patients with nonfunctioning adrenal adenomas (NFA). Flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation (NID) were measured to assess vascular function in 22 patients with NFA who had hypertension and/or diabetes mellitus (DM) and 272 patients without adrenal incidentalomas who had hypertension and/or DM (control patients with hypertension and/or DM). FMD and NID were measured in the morning before and after administration of 1 mg of dexamethasone at 2300 h in 18 patients with NFA. There were no significant differences in FMD and NID between control patients with hypertension and/or DM and patients with NFA who had hypertension and/or DM (3.4 ± 2.8% vs. 2.9 ± 1.9% and 11.5 ± 5.7% vs. 11.4 ± 4.3%, P = 0.46, and P = 0.99, respectively). There were no significant differences in vascular function between control patients with hypertension and/or DM and patients with NFA who had hypertension and/or DM even after adjustment for cardiovascular risk factors. Overnight 1 mg dexamethasone increased FMD from 2.4 ± 1.9% to 5.3 ± 3.2% (P < 0.01) and increased NID from 12.1 ± 4.2% to 14.0 ± 2.8% (P < 0.01) in patients with NFA. The overnight 1 mg dexamethasone suppression test does not impair FMD and NID in patients with NFA. Decreases in circulating levels of cortisol may improve vascular function.Clinical Trial Registration: This study was approved by principal authorities and ethical issues in Japan (URL for Clinical Trial: http://www.umin.ac.jp/ctr/index.htm Registration Number for Clinical Trial: UMIN000039512).
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Neoplasias das Glândulas Suprarrenais , Adenoma Adrenocortical , Dexametasona , Humanos , Neoplasias das Glândulas Suprarrenais/complicações , Neoplasias das Glândulas Suprarrenais/tratamento farmacológico , Adenoma Adrenocortical/complicações , Adenoma Adrenocortical/tratamento farmacológico , Dexametasona/farmacologia , Hipertensão/complicações , Hipertensão/tratamento farmacológico , VasodilataçãoRESUMO
Heart failure (HF) is associated with endothelial dysfunction. Vascular function per se plays an important role in cardiac function, whether it is a cause or consequence. However, there is no information on vascular function in patients with wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM). The purpose of this study was to evaluate vascular function in patients with ATTRwt-CM. We measured flow-mediated vasodilation (FMD) as an index of endothelial function and nitroglycerine-induced vasodilation (NID) as an index of vascular smooth muscle function and brachial artery intima-media thickness (bIMT) and brachial-ankle pulse wave velocity (baPWV) as indices of arterial stiffness in 22 patients with ATTRwt-CM and in 22 one-by-one matched control patients using vascular function confounding factors. FMD was significantly greater in patients with ATTRwt-CM than in the controls (5.4 ± 3.4% versus 3.5 ± 2.4%, p = 0.038) and the N-terminal pro-brain natriuretic peptide (NT-proBNP) level was significantly greater in patients with ATTRwt-CM than in the controls (2202 ± 1478 versus 470 ± 677 pg/mL, p < 0.001). There were no significant differences in NID, bIMT or baPWV between the two groups. There was a significant relationship between NT-proBNP and FMD in patients with ATTRwt-CM (r = 0.485, p = 0.022). NT-proBNP showed no significant relationships with NID, bIMT or baPWV. Conclusions: Endothelial function was preserved in patients with ATTRwt-CM. Patients with ATTRwt-CM may have compensatory effects with respect to endothelial function through elevation of BNP.
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The relationship of KCNJ5 mutation with vascular function and vascular structure in aldosterone-producing adenoma (APA) patients before and after adrenalectomy remains unclear. The purpose of this study was to evaluate the influence of KCNJ5 mutation on vascular function and vascular structure in APA and the effects of adrenalectomy on vascular function and vascular structure in APA patients with and those without KCNJ5 mutation. Flow-mediated vasodilation (FMD), nitroglycerine-induced vasodilation (NID), brachial artery intima-media thickness (IMT), and brachial-ankle pulse wave velocity (baPWV) were measured to assess vascular function and vascular structure in 46 APA patients with KCNJ5 mutation and 23 APA patients without KCNJ5 mutation and in 69 matched pairs of patients with essential hypertension (EHT). FMD, NID, brachial IMT and baPVW were evacuated before adrenalectomy and at 12 weeks after adrenalectomy in APA patients with KCNJ5 mutation and APA patients without KCNJ5 mutation. FMD and NID were significantly lower in APA patients than in patients with EHT. There was no significant difference in FMD or NID between patients with and those without KCNJ5 mutation. In APA patients with KCNJ5 mutation, FMD and NID after adrenalectomy were significantly higher than those before adrenalectomy. In APA patients without KCNJ5 mutation, only NID after adrenalectomy was significantly higher than that before adrenalectomy. Endothelial function in APA patients with KCNJ5 mutation was improved by adrenalectomy in the early postoperative period. KCNJ5 mutation is a predictor for early resolution of endothelial function by adrenalectomy. This study was approved by principal authorities and ethical issues in Japan (URL for Clinical Trial: http://www.umin.ac.jp/ctr/index.htm Registration Number for Clinical Trial: UMIN000003409).
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Adenoma , Hiperaldosteronismo , Humanos , Aldosterona , Índice Tornozelo-Braço , Adrenalectomia , Hiperaldosteronismo/genética , Hiperaldosteronismo/cirurgia , Análise de Onda de Pulso , Hipertensão Essencial , Mutação , Canais de Potássio Corretores do Fluxo de Internalização Acoplados a Proteínas G/genéticaRESUMO
Background: The purpose of this study was to evaluate the effects of exposure to radiation caused by an atomic bomb in atomic bomb survivors on vascular function and vascular structure and to evaluate the relationships of radiation dose from the atomic bomb with vascular function and vascular structure in atomic bomb survivors. Methods: Flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation (NID) as indices of vascular function, brachial-ankle pulse wave velocity (baPWV) as an index of vascular function and vascular structure, and brachial artery intima-media thickness (IMT) as an index of vascular structure were measured in 131 atomic bomb survivors and 1,153 control subjects who were not exposed to the atomic bomb. Ten of the 131 atomic bomb survivors with estimated radiation dose in a cohort study of Atomic Bomb Survivors in Hiroshima were enrolled in the study to evaluate the relationships of radiation dose from the atomic bomb with vascular function and vascular structure. Results: There was no significant difference in FMD, NID, baPWV, or brachial artery IMT between control subjects and atomic bomb survivors. After adjustment of confounding factors, there was still no significant difference in FMD, NID, baPWV, or brachial artery IMT between control subjects and atomic bomb survivors. Radiation dose from the atomic bomb was negatively correlated with FMD (ρ = -0.73, P = 0.02), whereas radiation dose was not correlated with NID, baPWV or brachial artery IMT. Conclusion: There were no significant differences in vascular function and vascular structure between control subjects and atomic bomb survivors. Radiation dose from the atomic bomb might be negatively correlated with endothelial function.
RESUMO
In medical and occupational settings, ionizing irradiation of the circulatory system occurs at various dose rates. We previously found sparing and enhancing dose protraction effects for aortic changes in wild-type mice at 6 months after starting irradiation with 5 Gy of photons. Here, we further analyzed changes at 12 months after stating irradiation. Irrespective of irradiation regimens, irradiation little affected left ventricular function, heart weight, and kidney weight. Irradiation caused structural disorganizations and intima-media thickening in the aorta, along with concurrent elevations of markers for proinflammation, macrophage, profibrosis, and fibrosis, and reductions in markers for vascular functionality and cell adhesion in the aortic endothelium. These changes were qualitatively similar but quantitatively less at 12 months than at 6 months. The magnitude of such changes at 12 months was not smaller in 25 fractions (Frs) but was smaller in 100 Frs and chronic exposure than acute exposure. The magnitude at 6 and 12 months was greater in 25 Frs, smaller in 100 Frs, and much smaller in chronic exposure than acute exposure. These findings suggest that dose protraction changes aortic damage, in a fashion that depends on post-irradiation time and is not a simple function of dose rate.
RESUMO
BACKGROUNDS: Poor oral care is associated with cardiovascular disease. The aim of this study was to determine the impact of tooth brushing behavior on the incidences of future cardiovascular events in a general population including patients with cardiovascular disease. METHODS: This was a prospective observational study which included 692 participants (437 men and 255 women, mean age, 63 ± 16 years). The participants were divided into three groups according to the frequency and duration of tooth brushing: low frequency and short duration group (Assuntos
Infarto do Miocárdio
, Escovação Dentária
, Idoso
, Feminino
, Humanos
, Incidência
, Masculino
, Pessoa de Meia-Idade
, Estudos Prospectivos
, Fatores de Tempo
RESUMO
Hypoxia preconditioning enhances the paracrine abilities of mesenchymal stem cells (MSCs) for vascular regeneration and tissue healing. Implantation of hypoxia-induced mesenchymal stem cells (hi-MSCs) may further improve limb perfusion in a murine model of hindlimb ischemia. This study is aimed at determining whether implantation of hi-MSCs is an effective modality for improving outcomes of treatment of ischemic artery diseases. We evaluated the effects of human bone marrow-derived MSC implantation on limb blood flow in an ischemic hindlimb model. hi-MSCs were prepared by cell culture under 1% oxygen for 24 hours prior to implantation. A total of 1 × 105 MSCs and hi-MSCs and phosphate-buffered saline (PBS) were intramuscularly implanted into ischemic muscles at 36 hours after surgery. Restoration of blood flow and muscle perfusion was evaluated by laser Doppler perfusion imaging. Blood perfusion recovery, enhanced vessel densities, and improvement of function of the ischemia limb were significantly greater in the hi-MSC group than in the MSC or PBS group. Immunochemistry revealed that hi-MSCs had higher expression levels of hypoxia-inducible factor-1 alpha and vascular endothelial growth factor A than those in MSCs. In addition, an endothelial cell-inducing medium showed high expression levels of vascular endothelial growth factor, platelet endothelial cell adhesion molecule-1, and von Willebrand factor in hi-MSCs compared to those in MSCs. These findings suggest that pretreatment of MSCs with a hypoxia condition and implantation of hi-MSCs advances neovascularization capability with enhanced therapeutic angiogenic effects in a murine hindlimb ischemia model.
RESUMO
AIM: An experimental study showed that potassium inhibits the formation of reactive oxygen species by vascular cells. The purpose of this study was to investigate the association between serum potassium levels and vascular function. METHODS: We measured flow-mediated vasodilation (FMD) as an index of endothelial function in 3045 subjects (1964 men; mean age, 62.3±13.8 years) and nitroglycerine-induced vasodilation (NID) as an index of vascular smooth muscle function in 1578 subjects (1001 men; mean age, 61.8±16.3 years). RESULTS: In the 3045 subjects, there was a significant positive correlation between FMD and serum potassium levels (r=0.09, Pï¼0.001). Multivariate analysis revealed that serum potassium levels were significantly associated with FMD (ß=0.109, Pï¼0.001). When subjects were divided into two groups based on treatment with drugs that could alter serum potassium levels, the association between serum potassium levels and FMD was significant both in subjects with (ß=0.096, Pï¼0.001) and subjects without (ß=0.123, Pï¼0.001) treatment with drugs that could alter serum potassium levels. In the 1578 subjects, there was a significant positive correlation between NID and serum potassium levels (r=0.11, Pï¼0.001). Multivariate analysis revealed that serum potassium levels were significantly associated with NID (ß=0.098, Pï¼0.001). The association between serum potassium levels and NID was significant both in subjects with (ß=0.121, P=0.001) and subjects without (ß=0.083, P=0.03) treatment with drugs that could alter serum potassium levels. CONCLUSIONS: Serum potassium levels of 4.5-ï¼5.0 mmol/L are associated with better vascular function regardless of the presence or absence of treatment with drugs that could alter serum potassium levels.