Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 12 de 12
Filtrar
2.
Circulation ; 112(14): 2114-20, 2005 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-16186425

RESUMEN

BACKGROUND: The neurotrophin (NT) family, including nerve growth factor NT-3 and brain-derived neurotrophic factor (BDNF), has a critical role in the survival, growth, maintenance, and death of central and peripheral neurons. NTs and their receptors are expressed in atherosclerotic lesions; however, their significance in cardiovascular disease remains unclear. METHODS AND RESULTS: To clarify the role of NTs in the pathogenesis of coronary artery disease, NT plasma levels in the aorta, coronary sinus, and peripheral veins of patients with unstable angina (n=38), stable effort angina (n=45), and non-coronary artery disease (n=24) were examined. In addition, regional expression of BDNF in coronary arteries was examined in autopsy cases and patients with angina pectoris by directional coronary atherectomy. The difference in BDNF levels, but not NT-3, between the coronary sinus and aorta was significantly greater in the unstable angina group compared with the stable effort angina and non-coronary artery disease groups. Immunohistochemical investigations demonstrated BDNF expression in the atheromatous intima and adventitia in atherosclerotic coronary arteries. BDNF expression was enhanced in macrophages and smooth muscle cells in atherosclerotic coronary arteries. Stimulation with recombinant BDNF significantly enhanced NAD(P)H oxidase activity and the generation of reactive oxygen species in cultured human coronary artery smooth muscle cells. CONCLUSIONS: BDNF has an important role in atherogenesis and plaque instability via the activation of NAD(P)H oxidase.


Asunto(s)
Angina de Pecho/diagnóstico por imagen , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Enfermedad Coronaria/fisiopatología , Estenosis Coronaria/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Angina de Pecho/mortalidad , Autopsia , Biomarcadores/metabolismo , Angiografía Coronaria , Enfermedad Coronaria/diagnóstico por imagen , Enfermedad Coronaria/mortalidad , FMN Reductasa/metabolismo , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Factores de Riesgo , Fumar , Análisis de Supervivencia
3.
Life Sci ; 80(1): 59-66, 2006 Dec 03.
Artículo en Inglés | MEDLINE | ID: mdl-17045300

RESUMEN

Toll-like receptors (TLRs) play important roles in the pathogenesis of atherosclerosis. On the other hand, serum high sensitivity C-reactive protein (hsCRP) is known as an independent coronary risk factor, but cardiovascular events do occur even in low hsCRP levels. We investigated whether the TLR4 expression levels on human peripheral blood monocytes were associated with serum hsCRP levels or the occurrence of coronary artery diseases (CAD). One hundred CAD patients and 100 non-CAD subjects were enrolled. There were 72 non-CAD subjects and 53 CAD patients with low serum hsCRP levels. Among the low-hsCRP subjects, the TLR4 expression levels were higher in CAD patients than in non-CAD subjects (P < 0.05, after being adjusted for other risk factors). Moreover, TLR4 expression levels in stable angina pectoris (SAP) patients were elevated compared with those in non-CAD subjects (P < 0.05), and those in acute coronary syndrome patients were higher than SAP patients even in low-hsCRP subjects (P < 0.01). In conclusion, the TLR4 expression levels on peripheral blood monocytes in CAD patients were higher than those in non-CAD subjects and correlated with disease activity, even in low-hsCRP subjects. The combined measurement of serum hsCRP and the TLR4 expression on peripheral blood monocytes, especially among low-hsCRP subjects, may become a new coronary risk marker.


Asunto(s)
Proteína C-Reactiva/análisis , Enfermedad Coronaria/sangre , Monocitos/metabolismo , Receptor Toll-Like 4/sangre , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , ARN Mensajero/análisis , Receptor Toll-Like 4/genética
4.
Int J Cardiol ; 112(1): 52-8, 2006 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-16376442

RESUMEN

BACKGROUND: Inflammation, operated by blood, vascular and immune cells interaction, is implicated in plaque disruption and CD40 ligand (CD40L) was identified on activated T cells and platelets. We sought to investigate the roles of local inflammation in acute myocardial infarction (AMI). METHODS: Coronary sinus (CS) and arterial (A) levels of interleukin (IL)-6 and soluble CD40L (sCD40L) and matrix metalloproteinase (MMP)-9 activity in serial blood samples obtained until 48 h after percutaneous coronary intervention (PCI) were determined. In tissue specimens obtained by aspirating thrombectomy and directional coronary atherectomy, CD40L was immunohistochemically stained. RESULTS: Trans-cardiac gradient (CS-A) of IL-6, indicating cardiac release into the coronary circulation, significantly increased at 24 h after PCI in patients with AMI (group MI, n=17) in contrast with angina pectoris (n=10). Soluble CD40L levels in CS showed earlier peak, yielding trans-cardiac gradient, at 9 h in both groups. The maximum (max) release of IL-6 in MI, but not sCD40L, positively correlated with end-diastolic volume index (R=0.84) and negatively with ejection fraction (R=-0.66) by contrast ventriculography at 6-month follow up. Immunohistological study revealed the expression of CD40L in intra-coronary occlusive and mural thrombi. Aspirating thrombectomy significantly reduced the increase in both sCD40L levels and MMP-9 activity, but not max IL-6 release in MI. CONCLUSIONS: In contrast with myocardial injury represented by IL-6 release, acute rise in sCD40L levels with the MMP-9 activation in the coronary circulation may possibly reflect local inflammation with platelet activation and be a novel marker of plaque damage by PCI.


Asunto(s)
Ligando de CD40/metabolismo , Circulación Coronaria , Interleucina-6/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Infarto del Miocardio/sangre , Infarto del Miocardio/fisiopatología , Anciano , Angina de Pecho/sangre , Angina de Pecho/fisiopatología , Angioplastia Coronaria con Balón , Aterectomía Coronaria , Biomarcadores/sangre , Proteína C-Reactiva/metabolismo , Trombosis Coronaria/sangre , Trombosis Coronaria/fisiopatología , Forma MB de la Creatina-Quinasa/metabolismo , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Infarto del Miocardio/terapia , Miocarditis/sangre , Miocarditis/fisiopatología , Volumen Sistólico , Trombectomía , Resultado del Tratamiento
5.
Arterioscler Thromb Vasc Biol ; 22(12): 2049-53, 2002 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-12482833

RESUMEN

OBJECTIVE: Lysophosphatidylcholine (LPC), a major phospholipid component of oxidized low density lipoprotein, has been demonstrated to induce multiple functional alterations of vasculature that are potentially involved in atherosclerosis. Recently, an orphan G-protein-coupled receptor, G2A, has been identified as a high-affinity receptor for LPC. Although it has been demonstrated that G2A is expressed predominantly in lymphoid tissues and lymphocytes, there are no reports to determine whether G2A is expressed in atherosclerotic lesions and cardiovascular cells. METHODS AND RESULTS: Immunohistochemistry with an anti-G2A antibody revealed that G2A was expressed predominantly by macrophages within atherosclerotic lesions at the aortic root of apolipoprotein E-deficient mice and the thoracic aortas of Watanabe heritable hyperlipidemic rabbits. In atherosclerotic plaques of human coronary arterial specimens, G2A was expressed by macrophages within the lipid-rich plaques, whereas no immunoreactivity of G2A was observed in fibrous plaques where macrophages did not exist. Reverse transcription-polymerase chain reaction analysis demonstrated that G2A mRNA was highly expressed in human and murine monocytes/macrophages. The expression of G2A protein was detected in human and murine monocytes/macrophages by immunoblotting. CONCLUSIONS: These findings demonstrate that monocytes/macrophages abundantly express G2A and suggest that G2A may play a role in the formation and progression of atherosclerotic lesions.


Asunto(s)
Proteínas de Ciclo Celular/biosíntesis , Proteínas de Ciclo Celular/metabolismo , Enfermedad de la Arteria Coronaria/metabolismo , Lisofosfatidilcolinas/metabolismo , Macrófagos/metabolismo , Receptores de Superficie Celular/biosíntesis , Receptores de Superficie Celular/metabolismo , Receptores Acoplados a Proteínas G , Animales , Aorta Torácica/química , Aorta Torácica/metabolismo , Apolipoproteínas E/deficiencia , Sistema Cardiovascular/metabolismo , Sistema Cardiovascular/patología , Proteínas de Ciclo Celular/inmunología , Células Cultivadas , Enfermedad de la Arteria Coronaria/patología , Vasos Coronarios/química , Vasos Coronarios/metabolismo , Vasos Coronarios/patología , Endotelio Vascular/química , Endotelio Vascular/citología , Endotelio Vascular/patología , Humanos , Células Jurkat/química , Células Jurkat/metabolismo , Macrófagos/química , Macrófagos/patología , Macrófagos Peritoneales/química , Macrófagos Peritoneales/metabolismo , Macrófagos Peritoneales/patología , Ratones , Ratones Noqueados , Monocitos/química , Monocitos/metabolismo , Músculo Liso Vascular/química , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patología , Conejos , Receptores de Superficie Celular/inmunología , Células Tumorales Cultivadas , Venas Umbilicales/química , Venas Umbilicales/metabolismo , Venas Umbilicales/patología
6.
Arterioscler Thromb Vasc Biol ; 23(8): 1398-404, 2003 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-12805076

RESUMEN

OBJECTIVE: C-reactive protein (CRP), a predictor of cardiovascular events, localizes in atherosclerotic arteries and exerts proinflammatory effects on vascular cells. Reactive oxygen species (ROS) have been implicated in atherogenesis and plaque instability. METHODS AND RESULTS: Expressional pattern of CRP in directional coronary atherectomy specimens from 39 patients was examined. Characteristics of histological plaque instability and higher levels of serum CRP and fibrinogen were associated with the CRP immunoreactivity. In situ hybridization revealed the presence of CRP mRNA in coronary vasculature. Furthermore, the expression of CRP mRNA and protein was detected in cultured human coronary artery smooth muscle cells (CASMCs) by reverse transcriptase-polymerase chain reaction and Western blotting. In addition, CRP was frequently colocalized with p22phox, an essential component of NADH/NADPH oxidase, which is an important source of ROS in vasculature. Moreover, the incubation of cultured CASMCs with CRP resulted in the enhanced p22phox protein expression and in the generation of intracellular ROS. CONCLUSIONS: The expression of CRP in coronary arteries was associated with histological and clinical features of vulnerable plaque, and it had a prooxidative effect on cultured CASMCs, suggesting that it might play a crucial role in plaque instability and in the pathogenesis of acute coronary syndrome via its prooxidative effect.


Asunto(s)
Proteína C-Reactiva/metabolismo , Enfermedad de la Arteria Coronaria/metabolismo , Proteínas de Transporte de Membrana , NADPH Deshidrogenasa/metabolismo , Estrés Oxidativo , Fosfoproteínas/metabolismo , Arteritis/fisiopatología , Células Cultivadas , Enfermedad de la Arteria Coronaria/patología , Fibrinógeno/metabolismo , Humanos , Peróxido de Hidrógeno/metabolismo , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patología , NAD/metabolismo , NADPH Oxidasas/metabolismo , Especies Reactivas de Oxígeno/análisis , Regulación hacia Arriba
7.
Cardiovasc Res ; 59(4): 988-96, 2003 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-14553839

RESUMEN

OBJECTIVE: The pathogenesis of thoracic aortic aneurysms (TAA) is still unclear. A recent investigation indicated that angiotensin II, a potent activator of NADH/NADPH oxidase, plays an important role in aneurysmal formation. We investigated the potential role of p22phox-based NADH/NADPH oxidase in the pathogenesis of TAA. METHODS: Human thoracic aneurysmal (n=40) and non-aneurysmal (control, n=39) aortic sections were examined, and the localization of p22phox, an essential component of the oxidase, and its expressional differences were investigated by immunohistochemistry and Western blot. In situ reactive oxygen species (ROS) generation was examined by the dihydroethidium method, and the impact of medical treatment on p22phox expression was investigated by multiple regression analysis. RESULTS: In situ production of ROS and the expression of p22phox increased markedly in TAA throughout the wall, and Western blot confirmed the enhanced expression of p22phox. The expression was more intense in the regions where monocytes/macrophages accumulated. In these inflammatory regions, numerous chymase-positive mast cells and angiotensin converting enzyme-positive macrophages were present. Their localization closely overlapped the in situ activity of matrix metalloproteinase and the expression of p22phox. Multiple regression analysis revealed that medical treatment with statin and angiotensin II type 1 receptor blocker (ARB) suppressed p22phox expression in TAA. CONCLUSION: Our findings indicate the role of p22phox-based NADH/NADPH oxidase and the local renin-angiotensin system in the pathogenesis of TAA. Statin and ARB might have inhibitory effects on the formation of aneurysms via the suppression of NADH/NADPH oxidase.


Asunto(s)
Aorta Torácica/metabolismo , Aneurisma de la Aorta Torácica/metabolismo , Estrés Oxidativo , Anciano , Bloqueadores del Receptor Tipo 1 de Angiotensina II , Antihipertensivos/uso terapéutico , Aneurisma de la Aorta Torácica/tratamiento farmacológico , Aneurisma de la Aorta Torácica/inmunología , Western Blotting/métodos , Estudios de Casos y Controles , Quimasas , Femenino , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Inmunohistoquímica/métodos , Inflamación , Macrófagos/enzimología , Masculino , Mastocitos/enzimología , Metaloproteinasas de la Matriz/metabolismo , Proteínas de Transporte de Membrana/análisis , NADPH Deshidrogenasa/análisis , NADPH Oxidasas , Peptidil-Dipeptidasa A/análisis , Fosfoproteínas/análisis , Análisis de Regresión , Serina Endopeptidasas/análisis
9.
Thromb Res ; 113(6): 379-85, 2004.
Artículo en Inglés | MEDLINE | ID: mdl-15226092

RESUMEN

INTRODUCTION: Platelets play a crucial role in arterial thrombosis, which is the main cause of acute coronary syndrome. Some mycobacteriums, such as Chlamydia pneumoniae, were associated with progression of atherosclerosis and they are interacted with Toll-like receptors (TLRs), which have been defined as pathogen-associated molecular pattern recognition molecules in innate immunity. In the present study, we examined whether human platelets express TLRs. MATERIALS AND METHODS: Human platelets were obtained from healthy volunteers and the mRNA and protein level of TLRs on platelets and Meg-01 cells, megakaryoblastic cell line, were investigated. RESULTS: Reverse transcription-polymerase chain reaction (RT-PCR) demonstrated that TLR1 and TLR6 mRNA were expressed in platelets and Meg-01 cells. Furthermore, interferon-gamma up-regulated their mRNA levels in dose and time dependent manners after stimuli. Both TLR1 and TLR6 proteins in platelets were detected by Western blotting, and their expression of platelets was more than that of Meg-01 cells. Flow cytometry analysis revealed the expression of TLR1 and TLR6 on the cell surface of Meg-01 cells. Furthermore, immunohistochemical analysis using human coronary thrombi obtained from patients with acute coronary syndrome confirmed the expression of TLR1 and TLR6 on platelets. CONCLUSION: In summary, we demonstrated that human platelets and Meg-01 cells expressed a family of TLRs for the first time, and our findings indicated that platelets might recognize antigens directly via TLRs. Our findings suggest a possibility that platelets have the ability to recognize the antigens via TLRs and that there are mechanistic relations between infectious inflammation and atherosclerotic vascular diseases.


Asunto(s)
Plaquetas/metabolismo , Trombosis Coronaria/metabolismo , Trombosis Coronaria/patología , Leucemia Megacarioblástica Aguda/metabolismo , Glicoproteínas de Membrana/metabolismo , Monocitos/metabolismo , Receptores de Superficie Celular/metabolismo , Biomarcadores/metabolismo , Línea Celular Tumoral , Células Cultivadas , Humanos , Receptor Toll-Like 1 , Receptor Toll-Like 6 , Receptores Toll-Like
10.
J Cardiol ; 47(6): 313-21, 2006 Jun.
Artículo en Japonés | MEDLINE | ID: mdl-16800375

RESUMEN

A 61-year-old man with hypertrophic obstructive cardiomyopathy was treated twice with percutaneous transluminal septal myocardial ablation (PTSMA). The first procedure improved the left ventricular outflow tract pressure gradient (LVOTG) from 148 to 48 mmHg and the New York Heart Association (NYHA) class from III to II in a week. However, the LVOTG increased to 197 mmHg and the NYHA class worsened to III within 3 months. In spite of medical treatment with beta-blocker, syncope attack occurred suddenly. Repeated PTSMA was performed. Just after the second procedure, the LVOTG did not decrease. However, the LVOTG decreased to 81 mmHg and the NYHA class improved to II with 3 months. The different response of pressure gradient in the acute and chronic phase with repeated PTSMA was interesting.


Asunto(s)
Cardiomiopatía Hipertrófica/cirugía , Ablación por Catéter , Tabiques Cardíacos/cirugía , Función Ventricular Izquierda , Cardiomiopatía Hipertrófica/diagnóstico por imagen , Cardiomiopatía Hipertrófica/fisiopatología , Ecocardiografía , Humanos , Masculino , Persona de Mediana Edad , Presión
11.
J Cardiol ; 46(3): 89-96, 2005 Sep.
Artículo en Japonés | MEDLINE | ID: mdl-16218426

RESUMEN

OBJECTIVES: The metabolic syndrome defined by the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) is a predictor of cardiovascular events. However, the significance of metabolic syndrome for cardiovascular events has been not clarified in Japan. The impact of metabolic syndrome and diabetes mellitus on cardiovascular events was investigated, especially in the high risk group after percutaneous coronary intervention. METHODS: We studied 456 patients (mean age 63 +/- 10 years, range 36-88 years) without ischemia on stress thallium-201 single photon emission computed tomography after percutaneous coronary intervention. The diagnosis of metabolic syndrome was made according to the modified NCEP ATP III criteria. Cardiovascular events were examined for mean 3.7 +/- 1.8 years (range 2.0-8.7 years). There were 196 patients without diabetes mellitus or metabolic syndrome (Group D - M -), 89 patients without diabetes mellitus but with metabolic syndrome (Group D - M +), 61 patients with diabetes mellitus but without metabolic syndrome (Group D + M -), and 110 patients with both diabetes mellitus and metabolic syndrome (Group D + M +). RESULTS: The event-free survival curve in Group D - M + was significantly lower than that in Group D - M - (p < 0.05), but not different from that in Group D + M -. The survival curve was markedly lower in Group D + M + than that in Group D - M + (p < 0.005). The Cox proportional hazard model revealed that diabetes mellitus and metabolic syndrome were independent significant risk factors for events. CONCLUSIONS: The diagnosis of metabolic syndrome was helpful for identification of patients with high cardiovascular event rate even in patients after percutaneous coronary intervention. The combination of metabolic syndrome and diabetes mellitus markedly increases the risk for cardiovascular events.


Asunto(s)
Angioplastia Coronaria con Balón , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Complicaciones de la Diabetes/complicaciones , Síndrome Metabólico/complicaciones , Radioisótopos de Talio , Tomografía Computarizada de Emisión de Fotón Único , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad de la Arteria Coronaria/terapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Riesgo
12.
J Vasc Res ; 41(4): 345-51, 2004.
Artículo en Inglés | MEDLINE | ID: mdl-15340249

RESUMEN

Since oxidative stress plays an important role in dysregulation of the microcirculation as well as the pathogenesis of atherosclerosis, therapeutic intervention with antioxidants has been speculated to prevent cardiovascular diseases. Ascorbic acid (AA) has been reported to improve endothelial function; however, its intracellular metabolic pathway has not been fully determined. Sodium-dependent vitamin C transporter (SVCT) types 1 and 2 were recently cloned. In the present study, we investigated whether SVCT-2 is functionally expressed in vascular endothelial cells and, if so, what factors modulate its activity. The uptake of AA into human umbilical vein endothelial cells (HUVECs) was examined by incubation with radiolabeled AA (14C-AA). AA was transported into HUVECs in a dose- and time-dependent manner. Replacement of sodium chloride with choline chloride in the medium suppressed the uptake of AA. RT-PCR revealed that HUVECs expressed SVCT-2 mRNA, but not SVCT-1. Transfection of HUVECs with the antisense oligonucleotide of SVCT-2 significantly suppressed the uptake of AA. Furthermore, tumor necrosis factor-alpha and interleukin-1beta inhibited the transport activity of AA. Thus, SVCT-2 is functionally expressed in human endothelial cells, and its activity is negatively regulated by inflammatory cytokines. Our findings might provide a new insight into understanding the treatment of cardiovascular diseases with AA.


Asunto(s)
Células Endoteliales/metabolismo , Transportadores de Anión Orgánico Sodio-Dependiente/metabolismo , Simportadores/metabolismo , Ácido Ascórbico/antagonistas & inhibidores , Ácido Ascórbico/farmacocinética , Transporte Biológico , Células Cultivadas , Humanos , Interleucina-1/farmacología , Oligonucleótidos Antisentido/farmacología , Transportadores de Anión Orgánico Sodio-Dependiente/genética , Floretina/farmacología , ARN Mensajero/metabolismo , Transportadores de Sodio Acoplados a la Vitamina C , Simportadores/genética , Acetato de Tetradecanoilforbol/farmacología , Transfección , Factor de Necrosis Tumoral alfa/farmacología
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA