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1.
Am J Hypertens ; 36(2): 90-101, 2023 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-36053278

RESUMO

BACKGROUND: Inconsistencies between the office and out-of-office blood pressure (BP) values (described as white-coat hypertension or masked hypertension) may be attributable in part to differences in the BP monitoring devices used. METHODS: We studied consistency in the classification of BP control (well-controlled BP vs. uncontrolled BP) among office, home, and ambulatory BPs by using a validated "all-in-one" BP monitoring device. In the nationwide, general practitioner-based multicenter HI-JAMP study, 2,322 hypertensive patients treated with antihypertensive drugs underwent office BP measurements and 24-hour ambulatory BP monitoring (ABPM), consecutively followed by 5-day home BP monitoring (HBPM), for a total of seven BP measurement days. RESULTS: Using the thresholds of the JSH2019 and ESC2018 guidelines, the patients with consistent classification of well-controlled status in the office (<140 mmHg) and home systolic BP (SBP) (<135 mmHg) (n = 970) also tended to have well-controlled 24-hour SBP (<130 mmHg) (n = 808, 83.3%). The patients with the consistent classification of uncontrolled status in office and home SBP (n = 579) also tended to have uncontrolled 24-hour SBP (n = 444, 80.9%). Among the patients with inconsistent classifications of office and home BP control (n = 803), 46.1% had inconsistent ABPM-vs.-HBPM out-of-office BP control status. When the 2017 ACC/AHA thresholds were applied as an alternative, the results were essentially the same. CONCLUSIONS: The combined assessment of the office and home BP is useful in clinical practice. Especially for patients whose office BP classification and home BP classification conflict, the complementary clinical use of both HBPM and ABPM might be recommended.


Assuntos
Hipertensão , Hipertensão do Jaleco Branco , Humanos , Pressão Sanguínea , Monitorização Ambulatorial da Pressão Arterial/métodos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Determinação da Pressão Arterial/métodos , Hipertensão do Jaleco Branco/diagnóstico
2.
J Med Ultrason (2001) ; 48(2): 137-144, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33837866

RESUMO

PURPOSE: We previously reported that acoustic radiation force impulse (ARFI) with concomitant administration of perfluorobutane as an ultrasound contrast agent (UCA)-induced arrhythmias at a mechanical index (MI) of 1.8 or 4.0 in a rabbit model. The present study identified the location of arrhythmias with a MI < 1.8 using a new system that can transmit ARFI with B-mode imaging. METHODS: Under general anesthesia, six male Japanese white rabbits were placed in a supine position. Using this system, we targeted ARFI to the exact site of the heart. ARFI exposure with MI 0.9-1.2 was performed to the right or left ventricle of the heart 2 min after UCA injection. RESULTS: ARFI with a MI lower than previously reported to rabbit heart evoked extrasystolic waves with single UCA infusion. Arrhythmias were not observed using ARFI without UCA. Extrasystolic waves were observed significantly more frequently in the right ventricle group than in the left ventricle group, with arrhythmias showing reversed shapes. No fatal arrhythmias were observed. CONCLUSION: ARFI applied to simulate clinical conditions in rabbit heart evoked extrasystolic waves with single UCA infusion. The right ventricle group was significantly more sensitive to ARFI exposure, resulting in arrhythmias, than the left ventricle group. The shapes of PVCs that occurred in the right ventricle group and the left ventricle group were reversed. Ultrasound practitioners who use ARFI should be aware of this adverse reaction, even if the MI is below the previously determined value of 1.9.


Assuntos
Arritmias Cardíacas/induzido quimicamente , Arritmias Cardíacas/diagnóstico por imagem , Meios de Contraste/efeitos adversos , Técnicas de Imagem por Elasticidade/métodos , Fluorocarbonos/efeitos adversos , Aumento da Imagem/métodos , Animais , Arritmias Cardíacas/fisiopatologia , Meios de Contraste/administração & dosagem , Modelos Animais de Doenças , Fluorocarbonos/administração & dosagem , Coração/diagnóstico por imagem , Coração/fisiopatologia , Masculino , Coelhos
3.
Pulse (Basel) ; 6(1-2): 98-102, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30283751

RESUMO

BACKGROUND: New devices have recently been developed using various features of the waveform derived from a brachial cuff for noninvasive estimation of central systolic blood pressure (SBP). Central SBP estimated from brachial oscillometry has never been compared with that estimated from radial tonometry in a Japanese population. SUBJECTS AND METHODS: We recruited 155 Japanese volunteers (mean age 58 ± 16 years, range 18-99 years; 66.5$ women) and estimated their central SBP using brachial oscillometry (Mobil-O-Graph) or radial tonometry (SphygmoCor). RESULTS: The mean (standard deviation) peripheral SBP and central SBP measured with brachial oscillometry was 128 ± 18 mm Hg and 118 ± 16 mm Hg, respectively, while the central SBP estimated using radial tonometry was 119 ± 18 mm Hg. The mean (standard deviation) difference in estimated central SBP between brachial oscillometry and radial tonometry was 0.36 ± 5.9 mm Hg, and the central SBPs estimated using these devices were strongly correlated (r = 0.946, intraclass correlation coefficient = 0.940, p < 0.001). CONCLUSION: Central SBP estimated using brachial oscillometry was similar to that estimated from radial tonometry in a Japanese population.

4.
J Med Ultrason (2001) ; 43(1): 3-7, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26703160

RESUMO

PURPOSE: Acoustic radiation force impulse (ARFI) is a modality for elasticity imaging of various organs using shear waves. In some situations, the heart is a candidate for elasticity evaluation with ARFI. Additionally, an ultrasound contrast agent (UCA) provides information on the blood flow conditions of the cardiac muscle. This study aimed to evaluate ARFI's effect on the heart concomitantly with UCA administration (i.e., perfluorobutane). METHODS: Ultrasound with ARFI was applied to the hearts of male Japanese white rabbits (n = 3) using a single-element focused transducer with or without UCA administration. They were exposed to ultrasound for 0.3 ms with a mechanical index (MI) of 1.8. UCA was administered in two ways: a single (bolus) injection or drip infusion. Electrocardiograms were recorded to identify arrhythmias during ultrasound exposure. RESULTS: Extrasystolic waves were observed following ultrasound exposure with drip infusion of UCA. Life-threatening arrhythmia was not observed. The frequency of the extra waves ranged from 4.2 to 59.6 %. With bolus infusion, extra waves were not observed. CONCLUSIONS: Arrhythmogenicity was observed during ultrasound (MI 1.8) with ARFI and concomitant administration of UCA in rabbits. Although the bolus administration of UCA was similar to its clinical use, which may not cause extra cardiac excitation, cardiac ultrasound examinations with ARFI should be carefully performed, particularly with concomitant use of UCA.


Assuntos
Arritmias Cardíacas/etiologia , Meios de Contraste/administração & dosagem , Ecocardiografia/efeitos adversos , Ecocardiografia/métodos , Técnicas de Imagem por Elasticidade/efeitos adversos , Técnicas de Imagem por Elasticidade/métodos , Animais , Arritmias Cardíacas/fisiopatologia , Ecocardiografia/instrumentação , Técnicas de Imagem por Elasticidade/instrumentação , Eletrocardiografia , Coração/fisiopatologia , Masculino , Coelhos , Fluxo Sanguíneo Regional
6.
J Med Ultrason (2001) ; 42(1): 47-50, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26578489

RESUMO

PURPOSE: Acoustic radiation force (ARF) impulse can be used to estimate the elasticity of cardiac muscle. The purpose of this study was to evaluate the effect of ARF on the heart with concomitant administration of the ultrasound contrast agent (UCA) perfluorobutane for recently developed elasticity imaging such as shear wave imaging. METHODS: Ultrasound with ARF was applied to the heart of Japanese white rabbit with or without UCA administration. During the exposure, electrocardiographs were recorded. RESULTS: Following the exposure of ultrasound with a duration of 10 ms and a mechanical index (MI) of 4.0 to the heart, extra waves (QRS complex) were observed only after UCA administration. Although life-threatening arrhythmia was not observed, a greater increase in the frequency of the extra waves was observed following a drip infusion compared with a single (bolus) UCA infusion. In addition, 16.3 % of extra waves were followed by arterial pressure pulse. CONCLUSIONS: Cardiac ultrasound with higher MI and longer duration should be carefully considered, particularly with the concomitant use of UCA and higher MI.


Assuntos
Técnicas de Imagem por Elasticidade , Coração/efeitos da radiação , Animais , Arritmias Cardíacas/diagnóstico por imagem , Arritmias Cardíacas/etiologia , Meios de Contraste , Técnicas de Imagem por Elasticidade/efeitos adversos , Técnicas de Imagem por Elasticidade/métodos , Fluorocarbonos , Masculino , Coelhos
8.
J Clin Hypertens (Greenwich) ; 15(9): 630-6, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24034655

RESUMO

The relationships between home blood pressure (BP), masked hypertension defined by home BP, and integrated flow-mediated vasodilation (FMD) response remain unclear. The authors enrolled 257 patients (mean age, 63.5 years; 51% men) who had at least one cardiovascular risk factor. FMD of the brachial artery was measured with a semiautomatic edge-detection algorithm. The integrated FMD response was calculated as the area under the dilation curve during 120 seconds after deflation (FMD-AUC120) and the FMD magnitude as the percentage change in peak diameter (ΔFMD). Masked hypertension was defined by office BP <140/90 mm Hg and home BP ≥135 mm Hg and/or 85 mm Hg. Home systolic BP was inversely correlated with FMD-AUC120 and ΔFMD (FMD-AUC120: r=-.23, P<.001; ΔFMD: r=-.13, P=.041), and office systolic BP was inversely associated with FMD-AUC120 (r=-.16, P=.011), but not with ΔFMD. After adjusting for covariates, home systolic BP (ß=-.27, P=.003), but not office BP, was inversely associated with FMD-AUC120, whereas ΔFMD was not associated with office or home systolic BP. FMD-AUC120 was significantly lower in patients with masked hypertension compared with those with normotension (7.7±6.7 vs 11.5±8.8 mm × s, P=.048). Home systolic BP and masked hypertension defined by home BP were associated with a decrease in FMD-AUC120.


Assuntos
Monitorização Ambulatorial da Pressão Arterial , Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/epidemiologia , Hipertensão Mascarada/fisiopatologia , Vasodilatação/fisiologia , Idoso , Algoritmos , Artéria Braquial/fisiologia , Doenças Cardiovasculares/fisiopatologia , Feminino , Humanos , Masculino , Hipertensão Mascarada/diagnóstico , Pessoa de Meia-Idade , Visita a Consultório Médico , Fluxo Sanguíneo Regional/fisiologia , Fatores de Risco , Sístole/fisiologia
9.
Rinsho Byori ; 60(9): 887-94, 2012 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-23157119

RESUMO

The present topic of vascular function concerns how we detect the earliest arteriosclerotic changes. If we could diagnose the early phase of atherosclerosis, we would be able to intervene to prevent cardiovascular events caused by atherosclerosis. Recently, it became possible to examine vascular function non-invasively by pulse wave velocity (PWV), the augmentation index (AI) and flow-mediated dilatation (FMD) of the brachial artery induced by reactive hyperemia. Carotid ultrasonography is used to observe the morphological change and arterial stiffness of the carotid artery. This review focuses on the relation between arterial function tests and diseases, the method for measuring vascular function, and new technology for arterial stiffness.


Assuntos
Aterosclerose/diagnóstico , Aterosclerose/fisiopatologia , Velocidade do Fluxo Sanguíneo/fisiologia , Artérias Carótidas/fisiopatologia , Rigidez Vascular/fisiologia , Pressão Sanguínea/fisiologia , Diagnóstico Precoce , Humanos
10.
J Am Soc Hypertens ; 6(2): 109-16, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22321961

RESUMO

The relationship between having a cardiovascular risk factor and endothelial dysfunction observed on a time-course analysis of brachial artery flow-mediated vasodilation (FMD) remains unclear. We enrolled 257 patients who had at least one cardiovascular risk factor. We measured FMD magnitude of the percentage change in peak diameter (ΔFMD), maximum FMD rate calculated as the maximum slope of dilation (FMD-MDR), and integrated FMD response calculated as the area under the dilation curve during the 60- and 120-second dilation periods (FMD-AUC60 and FMD-AUC120) using a semiautomatic edge-detection algorithm. FMD-AUC60 and FMD-AUC120 were negatively correlated with the Framingham risk score (FMD-AUC60: r = -0.15, P = .023; FMD-AUC120: r = -0.17, P = .007), whereas this association was not found in the case of either the ΔFMD or the FMR-MDR. The Framingham risk score was significantly higher in patients in the lowest tertile for FMD-AUC120 (FMD-AUC120 <5.0 mm × second) than in those in the highest tertile for FMD-AUC120 (FMD-AUC120 ≥11.0 mm × second) (12.9 ± 8.7 vs. 8.6 ± 7.8%, P = .002). The lowest tertile for FMD-AUC120 was independently associated with the Framingham risk score (ß = 0.10, P = .011), after adjustments were made for age, gender, and smoking and drinking status. FMD-AUC120 was associated with cardiovascular risk.


Assuntos
Aterosclerose/epidemiologia , Aterosclerose/fisiopatologia , Endotélio Vascular/fisiologia , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Vasodilatação/fisiologia , Idoso , Pressão Sanguínea/fisiologia , Artéria Braquial/fisiologia , Complicações do Diabetes/epidemiologia , Complicações do Diabetes/fisiopatologia , Feminino , Humanos , Hipercolesterolemia/epidemiologia , Hipercolesterolemia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Tempo de Reação/fisiologia , Fluxo Sanguíneo Regional/fisiologia , Fatores de Risco
11.
Nephrol Dial Transplant ; 20(7): 1385-91, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15871986

RESUMO

BACKGROUND: The characteristics of adenovirus-mediated gene transfer into the kidney are not well examined. We studied the effects of contact time and temperature on adenovirus-mediated transgene expression in rat kidneys, using catheter-based in vivo gene transfer and a rat renal transplant model ex vivo. METHODS: An adenovirus vector containing the luciferase (Ad-Luc) or beta-galactosidase (Ad-LacZ) gene was introduced in vivo into the kidney via a renal artery catheter. Various contact times and temperatures were evaluated. Ex vivo, the renal graft was injected with Ad-Luc through the renal artery, chilled for 60 min and then transplanted. Luciferase expression was evaluated periodically by a non-invasive bioimaging system or histology. Cells expressing the LacZ gene were identified by immunoelectron microscopy. RESULTS: In in vivo gene transfer, successful transgene expression was achieved; however, its efficiency was independent of contact time or temperature. In ex vivo gene transfer, transgene expression in the renal graft peaked early and gradually decreased. Strong gene expression was observed in the recipients' livers. LacZ expression was detected in fibroblasts, parietal epithelial cells of Bowman's capsule, mesangial cells, podocytes and tubular cells. CONCLUSIONS: This study generated new information about in vivo and ex vivo gene transfer into the kidney, which would be useful for renal gene therapy.


Assuntos
Adenoviridae , Técnicas de Transferência de Genes , Vetores Genéticos , Rim/fisiologia , Óperon Lac/fisiologia , Luciferases de Vaga-Lume/metabolismo , Animais , Expressão Gênica/fisiologia , Masculino , Ratos , Ratos Endogâmicos Lew , Temperatura , Fatores de Tempo , Transgenes/fisiologia
13.
Drug News Perspect ; 16(7): 446-52, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-14668940

RESUMO

It is now widely accepted that two forms of cell death, apoptosis and necrosis, occur in cardiomyocytes, and increasing evidence indicates that apoptosis plays an important role in the pathophysiology of cardiovascular diseases. Currently, two major pathways in the induction of apoptosis are known to occur in cardiomyocytes, the mitochondrial pathway and the death receptor pathway. Bcl-2 family proteins are key regulators of apoptosis in the mitochondrial pathway. Among them, Bcl-x(L), which is structurally similar to Bcl-2 and functions as an antiapoptotic molecule, is involved in diseases such as ischemic heart diseases and heart failure. In this review, we focus on the role of Bcl-x(L) in apoptosis in cardiomyocytes and discuss the potential use of Bcl-x(L) as a cardioprotective therapy for cardiac diseases.


Assuntos
Apoptose/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Humanos , Miócitos Cardíacos/metabolismo , Proteína bcl-X
14.
Hypertension ; 41(5): 1156-63, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12668584

RESUMO

Apoptosis of cardiac myocytes is thought to be a feature of many pathological disorders, including congestive heart failure (CHF) and ischemic heart disease (IHD). Because recent investigations indicate that endothelin-1 (ET-1) plays an important role in CHF and IHD, we investigated the effect of ET-1 on cardiomyocyte apoptosis. The presence of apoptosis in rat cardiomyocytes (H9c2 and neonatal) was evaluated by morphological criteria, electrophoresis of DNA fragments, 4',6'-diamidine-2'-phenylindole staining, and TUNEL analysis. ET-1, but not angiotensin II, prevented apoptosis induced by serum deprivation via ETA receptors in a dose-dependent manner (1 to 100 nmol/L). ET-1 also prevented cytochrome c release from mitochondria to the cytosol. The use of specific pharmacological inhibitors demonstrated that the antiapoptotic effect of ET-1 was mediated through a tyrosine kinase pathway (genistein and AG490) but not through protein kinase C (PKC; calphostin C), mitogen-activated protein kinases (PD98059 and SB203580), or PKA (KT5270) pathways. Adenovirus-mediated gene transfer of kinase-inactive (KI) c-Src reversed the antiapoptotic effect of ET-1. We further investigated whether Bcl-xL, an antiapoptotic molecule, would be upregulated by using a luciferase-based reporter system. ET-1 upregulated Bcl-xL, and this upregulation was inhibited by genistein or AG490 but not by calphostin C. The experiments with KI mutants for various tyrosine kinases revealed that c-Src and Pyk2 (but not JAK1, Jak2, Syk, and Tec) are involved in ET-1-induced upregulation of Bcl-xL expression. These findings suggest that ET-1 prevents apoptosis in cardiac myocytes through the ETA receptor and the subsequent c-Src/Bcl-xL-dependent pathway.


Assuntos
Apoptose/efeitos dos fármacos , Endotelina-1/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Western Blotting , Proteína Tirosina Quinase CSK , Linhagem Celular , Células Cultivadas , Meios de Cultura Livres de Soro/farmacologia , Grupo dos Citocromos c/metabolismo , Proteínas de Ligação a DNA/metabolismo , Antagonistas dos Receptores de Endotelina , Ativação Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Genisteína/farmacologia , Marcação In Situ das Extremidades Cortadas , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Oligopeptídeos/farmacologia , Peptídeos Cíclicos/farmacologia , Fosforilação/efeitos dos fármacos , Piperidinas/farmacologia , Proteínas Tirosina Quinases/antagonistas & inibidores , Proteínas Tirosina Quinases/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Sprague-Dawley , Receptor de Endotelina A , Receptor de Endotelina B , Fator de Transcrição STAT3 , Transativadores/metabolismo , Tirfostinas/farmacologia , Proteína bcl-X , Quinases da Família src
15.
J Cardiovasc Pharmacol ; 40(6): 907-15, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12451324

RESUMO

Hydroxymethylglutaryl CoA (HMG-CoA) reductase inhibitors (statins) have been shown to reduce atherosclerotic cardiovascular mortality and morbidity. Recent evidence indicates that statins may also exert direct effects on vascular wall cells (including endothelial cells and smooth muscle cells) independently of their hypocholesterolemic properties. However, little is known about whether statins have direct effects on myocardium. The effect of lipophilic and hydrophilic statins (fluvastatin and pravastatin) on apoptosis and protein synthesis in rat neonatal cardiac myocytes was investigated. The presence of apoptosis was evaluated by morphologic criteria, electrophoresis of DNA fragments, 4",6"-diamidine-2"-phenylindole (DAPI) staining, and TUNEL assay. Protein synthesis was measured by H-leucine incorporation into the cells. Fluvastatin, but not pravastatin, induced apoptosis in cardiac myocytes in a time- and dose-dependent manner. The pro-apoptotic effect of fluvastatin was reversed in the presence of mevalonate or geranylgeranyl-pyrophosphate (GGPP), but not in the presence of squalene. The addition of protein prenylation inhibitor perillic acid and Rho-kinase inhibitor Y27632 significantly increased apoptosis. Fluvastatin decreased RhoA protein in the membrane fraction, whereas there were no significant changes of the RhoA protein in the cytosol fraction. Interleukin-1beta-stimulated H-leucine incorporation was completely inhibited by fluvastatin, but not by pravastatin. The findings suggest that fluvastatin induces apoptosis in cardiac myocytes via protein prenylation and the subsequent inhibition of Rho, and may play a role in the pathogenesis of cardiac hypertrophy and remodeling.


Assuntos
Apoptose/efeitos dos fármacos , Cardiomegalia/etiologia , Ácidos Graxos Monoinsaturados/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Indóis/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Células Cultivadas , Fluvastatina , Marcação In Situ das Extremidades Cortadas , Proteínas Monoméricas de Ligação ao GTP/biossíntese , Pravastatina/farmacologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
16.
Atherosclerosis ; 162(2): 307-13, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11996950

RESUMO

beta-very low-density lipoprotein (beta-VLDL), a collective term for VLDL and chylomicron remnants, has recently shown to potently promote the development of atherosclerosis. However, the effects of beta-VLDL on the accumulation of nitric oxide (NO) and the expression of inducible NO synthase (iNOS) in vascular smooth muscle cells (VSMC) have not been determined. In this study, we measured the accumulation of nitrite, stable metabolite of NO and examined the expression of iNOS protein and mRNA using Western blotting and RT-PCR, respectively, in VSMC. NF-kappaB activation in VSMC was examined by gel retardation assay. Incubation of cell cultures with interleukin-1beta (IL-1beta) for 24 h caused a significant increase in nitrite accumulation. Although beta-VLDL alone did not increase nitrite accumulation in unstimulated VSMC, beta-VLDL significantly enhanced nitrite accumulation in IL-1beta-stimulated VSMC in a time- and dose-dependent manner. beta-VLDL-induced nitrite accumulation in IL-1beta-stimulated VSMC was accompanied by an increase in iNOS protein and mRNA expression. In addition, IL-1beta induced NF-kappaB activation in VSMC, an effect that was increased by the addition of beta-VLDL. Use of specific tyrosine kinase inhibitor herbimycin A, genistein, or PP2 (Src family kinase inhibitor) indicated that tyrosine kinases are required for IL-1beta-stimulated and beta-VLDL-enhanced nitrite accumulation, while specific inhibition of ERK1/2 or p38-MAP kinase had no effects. Our results suggest that beta-VLDL enhances iNOS expression and nitrite accumulation in IL-1beta-stimulated VSMC through tyrosine kinase(s)-dependent mechanisms.


Assuntos
Interleucina-1/farmacologia , Lipoproteínas VLDL/farmacologia , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/enzimologia , Óxido Nítrico Sintase/metabolismo , Animais , Células Cultivadas , Inibidores Enzimáticos/farmacologia , Lipoproteínas/farmacologia , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Músculo Liso Vascular/citologia , NF-kappa B/fisiologia , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase Tipo II , Nitritos/metabolismo , Proteínas Tirosina Quinases/antagonistas & inibidores , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley
17.
Atherosclerosis ; 161(2): 387-94, 2002 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11888522

RESUMO

Lysophosphatidylcholine (lysoPC) is a component of oxidized low density lipoprotein (LDL) and is involved in the pathogenesis of atherosclerosis and inflammation. Previous studies demonstrated that lysoPC can induce various protein kinases including tyrosine kinases, protein kinase C (PKC), and mitogen-activated protein kinases (MAPK) in vascular endothelial cells. However, the role of lysoPC-activated kinases remains undefined. In this study, we examined the effect of lysoPC on apoptosis and investigated the role of lysoPC-activated protein kinases in human umbilical vein endothelial cells (HUVEC). The presence of apoptosis was evaluated by morphological criteria, MTT assay, and electrophoresis of DNA fragments showing the characteristic apoptotic ladder, TUNEL analysis, and quantified as the proportion of hypodiploid cells by flow cytometry. The lysoPC induced apoptosis in a time- and dose-dependent manner. It stimulated the phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2) and p38-MAPK in HUVEC. The use of specific pharmacologic inhibitors indicated that the p38-MAPK-signaling pathway (SB203580) is required for lysoPC-induced apoptotic signals. Furthermore, lysoPC-induced apoptosis was inhibited by DEVD-FMK (a caspas-3/CPP32 inhibitor), suggesting involvement of an important segment in the apoptosis. These results demonstrate that lysoPC induces apoptosis in human endothelial cells through a p38-MAPK-dependent pathway.


Assuntos
Apoptose/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Lisofosfatidilcolinas/farmacologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Transdução de Sinais/efeitos dos fármacos , Análise de Variância , Apoptose/fisiologia , Arteriosclerose/fisiopatologia , Células Cultivadas , Endotélio Vascular/fisiologia , Citometria de Fluxo , Humanos , Marcação In Situ das Extremidades Cortadas , Microscopia Eletrônica , Proteínas Quinases Ativadas por Mitógeno/fisiologia , Probabilidade , Sensibilidade e Especificidade , Veias Umbilicais/citologia , Proteínas Quinases p38 Ativadas por Mitógeno
18.
J Cardiovasc Pharmacol ; 39(2): 310-7, 2002 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11791017

RESUMO

Hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) have been shown to attenuate proliferation of vascular smooth muscle cells (VSMCs) by mechanisms independent of lipid reduction. In the current study, we investigated the effect of lipophilic and hydrophilic statins (fluvastatin and pravastatin) on apoptosis in unstimulated or cytokine-stimulated VSMCs. The presence of apoptosis in rat VSMCs was evaluated by electrophoresis of DNA fragments and 4'6'-diamidine-2'-phenylindole staining and quantified by flow cytometry. Fluvastatin but not pravastatin enhanced apoptosis in interleukin-1beta-stimulated VSMCs. The proapoptotic effect of fluvastatin was fully reversed by mevalonate and geranylgeranyl-pyrophosphate, and partially by farnesyl-pyrophosphate, but not by squalene. Inhibition of the extracellular signal-regulated protein kinase (ERK1/2) pathway significantly increased fluvastatin-enhanced apoptosis, whereas inhibition of the p38-mitogen-activated protein kinase (MAPK) pathway significantly prevented this increase. However, fluvastatin showed no effect on the activity of ERK1/2 and p38-MAPK. Furthermore, fluvastatin-induced apoptosis was inhibited by YVAD-FMK (a caspase-1/interleukin-1beta-converting enzyme-like protease inhibitor) and DEVD-FMK (a caspase-3/CPP32 inhibitor), indicating involvement of an important segment in the apoptosis signaling pathway. These findings suggest that fluvastatin enhances apoptosis in cytokine-stimulated VSMCs and that protein prenylation, MAPK (ERK1/2 and p38-MAPK), and caspases are critically involved in the pathways of fluvastatin-enhanced apoptosis.


Assuntos
Apoptose/efeitos dos fármacos , Ácidos Graxos Monoinsaturados/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Indóis/farmacologia , Interleucina-1/farmacologia , Músculo Liso Vascular/efeitos dos fármacos , Animais , Aorta Torácica/citologia , Apoptose/fisiologia , Western Blotting , Inibidores de Caspase , Caspases/metabolismo , Células Cultivadas , Fragmentação do DNA/efeitos dos fármacos , Ácidos Graxos Monoinsaturados/química , Citometria de Fluxo , Fluvastatina , Inibidores de Hidroximetilglutaril-CoA Redutases/química , Indóis/química , Masculino , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Músculo Liso Vascular/citologia , Pravastatina/química , Pravastatina/farmacologia , Prenilação de Proteína/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
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