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1.
J Clin Med ; 12(18)2023 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-37762944

RESUMO

INTRODUCTION: Risk scores are essential in primary prevention to detect high-risk patients. The most common scores exclude hypertriglyceridemia and abdominal obesity in their risk assessment. We examined the triglyceride/HDL-cholesterol (TG/HDL-c) ratio as a cardiovascular (CV) risk marker in a middle-class urban Mexican population sample. AIM: Our aim was to test the concept of a scoring system reflecting Mexican population characteristics. METHODS: A total of 2602 healthy adults from the Lindavista primary prevention program were considered, evaluating gender, age, blood pressure, smoking, body mass index, waist circumference, lipid profile, and fasting glucose. According to the abnormality, a score from -3 to +3 was assigned. RESULTS: The summation of eleven variables yielded the Lindavista score (LS), which was calibrated versus the TG/HDL ratio and ACC ASCVD Risk Estimator Plus score to determine its correlation with risk categories. The TG/HDL-c ratio had a linear correlation with LS and high-risk ACC ASCVD categories. CONCLUSIONS: Compared with LS and TG/HDL-c, the ACC ASCVD system underestimates the high-risk category. The high prevalence of obesity and lipid triad in the Mexican population requires a scale that considers those traits. The TG/HDL-c ratio is a practical, easy, and economical instrument to categorize risk in Mexicans.

2.
Arq. bras. cardiol ; 107(2): 154-162, Aug. 2016. tab, graf
Artigo em Inglês | LILACS | ID: lil-794564

RESUMO

Abstract Background: Remote ischemic preconditioning (RIPC) represents an attractive therapy for myocardial protection, particularly when ischemic events can be anticipated. Although several hypothetic mechanisms have been proposed, no definite molecular pathways have been elucidated. Objective: We evaluated the effect of brachial circulation cuff occlusion on myocardial ischemic tolerance, necrosis, and nitric oxide (NO) in patients with ischemic heart disease undergoing elective percutaneous coronary interventions (PCI). Methods: 46 patients were randomly allocated into two groups: control and RIPC before PCI procedures. Electrocardiographic analysis, serum concentrations of troponin I (cTn-I) were measured at baseline and 24 hours after PCI. A blood sample from the atherosclerotic plaque was drawn to determine nitrate and nitrites. Results: RIPC increased the availability of NO in the stented coronary artery. Control patients presented a small but significant increase in cTn-I, whilst it remained unchanged in preconditioned group. The preconditioning maneuver not only preserved but also enhanced the sum of R waves. Conclusions: RIPC induced an intracoronary increase of NO levels associated with a decrease in myocardial damage (measured as no increase in cTn-I) with electrocardiographic increases in the sum of R waves, suggesting an improved myocardium after elective PCI.


Resumo Fundamento: Pré-condicionamento isquêmico remoto (PCIR) é uma terapia para proteção miocárdica, em particular quando é possível prever eventos isquêmicos. Embora vários mecanismos hipotéticos tenham sido propostos, nenhuma via molecular definitiva foi elucidada. Objetivo: Avaliar o efeito da oclusão da circulação braquial com manguito sobre a tolerância à isquemia miocárdica, a necrose miocárdica e a biodisponibilidade de óxido nítrico (NO) em pacientes com cardiopatia isquêmica submetidos a intervenção coronariana percutânea (ICP) eletiva. Métodos: 46 pacientes foram alocados aleatoriamente em dois grupos: controle e PCIR antes da ICP. Análise eletrocardiográfica e medidas da concentração sérica de troponina I (cTn-I) foram realizadas na condição basal e 24 horas após ICP. Coletou-se amostra de sangue da placa aterosclerótica para determinar os níveis de nitratos e nitritos. Resultados: O PCIR aumentou a disponibilidade de NO na artéria coronária que recebeu o stent. O grupo controle apresentou um aumento pequeno, mas significativo, da cTn-I, que permaneceu inalterada no grupo pré-condicionado. O pré-condicionamento não só preservou, como melhorou o somatório de ondas R no eletrocardiograma. Conclusões: O PCIR induziu aumento intracoronariano dos níveis de NO associado com redução do dano miocárdico (medido como aumento da cTn-I) e com aumento do somatório de ondas R, sugerindo melhora miocárdica após ICP eletiva.


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Precondicionamento Isquêmico Miocárdico/métodos , Intervenção Coronária Percutânea , Óxido Nítrico/metabolismo , Troponina I/sangue , Creatinina/sangue , Eletrocardiografia/métodos , Óxido Nítrico Sintase Tipo III/metabolismo , Taxa de Filtração Glomerular , Infarto do Miocárdio/metabolismo , Óxido Nítrico/sangue
3.
Rev. mex. cardiol ; 27(1): 16-25, ene.-mar. 2016. ilus, tab
Artigo em Inglês | LILACS-Express | LILACS | ID: lil-782710

RESUMO

Background: Metabolic syndrome foretells several cardiovascular complications, including heart failure (HF). Left ventricular (LV) dysfunction accompanies the MS. Although metformin improves LV function in diabetics with HF, there is no evidence of its effect on LV dysfunction in MS patients. We studied the effect of metformin on LV dysfunction in MS patients using tissue Doppler myocardial imaging and two-dimensional speckle tracking. Aims: To evaluate the effects of metformin on metabolic syndrome (MS) induced left ventricular dysfunction. Material and methods: Patients with MS were randomly allocated into two groups (n = 20 each) receiving, an antagonist of angiotensin 2 receptors and; statins, fibrates or both. One group received 850 mg of metformin daily. LV mass, relative wall thickness (RWT), ejection fraction, E/A and E/E' relationship, systolic tissue Doppler velocity (Sm), mean peak systolic strain (SS), and peak early diastolic strain rate (SR-LVe) echocardiographic measurements, at baseline and six months were obtained. Results: All patients had LH concentric hypertrophy or remodeling. Metformin reduced LV mass and RWT. There were LV systolic and diastolic alterations in both groups that metformin improved significantly. SR-LVe increased nearly 2-fold with metformin. Diastolic function improvement was not related to regression of hypertrophy. Conclusions: Patients with MS experienced subtle alterations of systolic and diastolic functions, which improved significantly with a small dosage of metformin over a treatment period of six months.


Antecedentes: El síndrome metabólico (SM) predice varias complicaciones cardiovasculares, como la insuficiencia cardiaca (IC). La disfunción ventricular izquierda (DVI) acompaña al síndrome metabólico. Aunque la metformina mejora la función del ventrículo izquierdo en pacientes diabéticos con insuficiencia cardiaca, no hay evidencia de su efecto sobre la disfunción ventricular izquierda en pacientes con síndrome metabólico. Se estudió el efecto de la metformina sobre la disfunción ventricular izquierda en pacientes con síndrome metabólico utilizando imágenes Doppler de tejido miocárdico y rastreo de manchas bidimensional. Objetivos: Evaluar los efectos de la metformina sobre la disfunción ventricular izquierda inducida por el SM. Material y métodos: Los pacientes con SM fueron asignados al azar en dos grupos (n = 20 cada uno) que recibieron, un antagonista de la angiotensina 2 y receptores; estatinas, fibratos o ambos. Un grupo recibió 850 mg de metformina diaria. La masa del VI, el espesor relativo de la pared (ERP), fracción de eyección, E/A y relación E/E', la velocidad Doppler tisular sistólica (Sm), el promedio de pico de tensión sistólica (SS), y la velocidad de deformación diastólica precoz pico (VDDPP) se obtuvieron por mediciones ecocardiográficas al inicio del estudio y a los seis meses. Resultados: Todos los pacientes presentaban hipertrofia concéntrica o remodelado. La metformina reduce la masa del VI y el ERP. Había alteraciones del ventrículo izquierdo sistólica y diastólica, alteraciones en ambos grupos que la metformina mejoró significativamente. VDDPP aumentó casi al doble con metformina. La mejoría de la función diastólica no se relacionó con regresión de la hipertrofia. Conclusiones: Los pacientes con SM experimentaron alteraciones sutiles de las funciones sistólica y diastólica, lo que mejoró significativamente con una pequeña dosis de metformina en un periodo de tratamiento de seis meses.

4.
Rev. mex. cardiol ; 26(2): 70-77, Apr.-Jun. 2015. tab
Artigo em Inglês | LILACS-Express | LILACS | ID: lil-757963

RESUMO

Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease, with progressive joint destruction, leading to disability. In half of patients, mortality is associated to coronary events, caused by classical risk factors (RF) and/or the inflammatory process. Objectives: To explore the relevance of systemic inflammatory milieu in RA without the burden of traditional RF. Methods: Women with RA and free of traditional RF (n = 30) were compared against healthy women (n = 31). Body mass index, blood pressure, glycemia, serum creatinine, total cholesterol (TC), high density lipoprotein (HDL-c), low-density lipoprotein cholesterol (LDL-c), triglycerides (TG) and oxidized LDL (oxLDL), erythrocyte sedimentation rate, high-sensitivity C reactive protein (hsCRP), lipid quotients for assessing risk (TC/HDLc, LDLc/HDLc, oxLDL/non HDL cholesterol, TG/HDLc), and ultrasonographic carotid intima media thickness (IMT) were estimated or measured. Results: hsCRP and oxLDL were significantly higher in RA patients. IMT values were among normality, but thickness was slightly increased in left carotid, suggesting early atherosclerotic changes. In RA patients inflammation is associated to a higher concentration of oxLDL. No atherosclerosis was proven but a slight greater thickness in left carotid foretells the development of the disease. Conclusions: In RA patients without vascular RF, a special follow up must be implemented to halt atherosclerosis development.


Antecedentes: La artritis reumatoide (AR) es una enfermedad inflamatoria crónica, con destrucción progresiva de las articulaciones, que lleva a la discapacidad. En la mitad de lospacientes, la mortalidad se asocia con eventos coronarios, causados por factores de riesgo (FR) clásicos y/o el proceso inflamatorio. Objetivo: Explorar la relevancia del medio inflamatorio sistémico en la AR sin la carga de FR tradicionales. Métodos: Las mujeres con AR, sin los FR tradicionales (n = 30) fueron comparados contra mujeres sanas (n = 31). El índice de masa corporal, presión arterial, glucemia, creatinina sérica, colesterol total (CT), lipoproteínas de alta densidad (HDL-c), colesterol de lipoproteínas de baja densidad (LDL-c), triglicéridos (TG) y LDL oxidada (LDLox), velocidad de sedimentación de los eritrocitos, proteína C reactiva de alta sensibilidad (PCR-us), cocientes de lípidos para la evaluación de riesgos (TC/HDLc, LDLc/HDLc, colesterol LDLox/noHDL, TG/HDLc), y el espesor ultrasonográfico de la capa íntima-media carotídea (IMT), fueron estimados o medidos. Resultados: hsCRP y LDLox fueron significativamente mayores en los pacientes con AR. Los valores de IMT estaban dentro de la normalidad, pero el espesor se incrementó ligeramente en la carótida izquierda, lo que sugiere cambios ateroscleróticos tempranos. En los pacientes con AR la inflamación está asociada con una mayor concentración de oxLDL. No se comprobó aterosclerosis pero un espesor ligeramente mayor en la carótida izquierda, los hace propensos a desarrollar la enfermedad. Conclusiones: En los pacientes con AR sin FR vascular, un seguimiento especial debe ser implementado para frenar el desarrollo de la aterosclerosis.

5.
Rev. mex. cardiol ; 26(2): 87-94, Apr.-Jun. 2015. ilus, tab
Artigo em Inglês | LILACS-Express | LILACS | ID: lil-757965

RESUMO

Background: Calcium channel blockers (CCBs) have proved to reduce both blood pressure levels and cardiovascular outcomes, including the development of atherosclerosis. The INSIGHT study showed a less pronounced progression of carotid intima-media thickness (IMT) in patients treated with nifedipine (NIF) vs. those treated with diuretics, but because IMT was normal in both groups, it was difficult to assess the anti-atherosclerotic effect of NIF. We compared the effect of NIF or hydrochlorothiazide (HCTZ) on atherosclerosis regression in hypertensive patients with abnormally thick IMT. Patients and methods: 37 hypertensive patients were randomly assigned to be treated with slow release-NIF (30 mg) and 46 to HCTZ (25 mg), all of them with IMT > 0.6 mm. IMT, lipid profile, and serum uric acid, potassium, and glucose were analyzed at baseline and 12 months later. Results: Blood pressure was equally well controlled with both treatments. No biochemical abnormality was observed in neither groups. IMT was reduced 35% in the NIF group in comparison to 9.3% in HCTZ group. Discussion: BBCs restore endothelial function, exert antioxidant activity and limit smooth muscle cells growth and proliferation, thus inhibiting fundamental atherogenic phenomena. Our results show a clear regression of IMT, marker of subclinical atherosclerosis with NIF. Conclusion: Both treatments were equally effective reducing blood pressure. HCTZ did not cause metabolic disarrays, but only NIF induced IMT regression. Basal IMT is a main determinant of regression.


Antecedentes: Los bloqueadores de los canales de calcio (BCC) han demostrado reducir tanto los niveles de presión arterial como los eventos cardiovasculares, incluyendo el desarrollo de la aterosclerosis. El estudio INSIGHT mostró una progresión menos pronunciada del grosor de la capa íntima-media de la carotídea (GIMC) en pacientes tratados con nifedipina (NIF) vs. los tratados con diuréticos, pero debido a que el GIMC fue normal en ambos grupos, resultó difícil evaluar el efecto anti-aterosclerótico de la NIF. El presente estudio comparó el efecto de la NIF o hidroclorotiazida (HCTZ) en la regresión de aterosclerosis en pacientes hipertensos con GIMC anormalmente gruesa. Pacientes y métodos: 37 pacientes hipertensos fueron asignados al azar para ser tratados con NIF de liberación lenta (30 mg) y 46 a HCTZ (25 mg), todos ellos con GIMC > 0.6 mm. GIMC, perfil lipídico, y ácido úrico en suero, potasio y glucosa se analizaron al principio y 12 meses más tarde. Discusión: Los BCC restauran la función endotelial, ejercen actividad antioxidante y limitan el crecimiento y la proliferación de las células del músculo liso, inhibiendo así fenómenos aterogénicos fundamentales. Nuestros resultados muestran una clara regresión del GIMC, marcador de aterosclerosis subclínica, con NIF. Conclusión: Ambos tratamientos fueron igualmente efectivos para reducir la presión arterial. HCTZ no causó desorden metabólico, pero sólo la NIF induce la regresión del GIMC. El GIMC basal es un determinante principal de la regresión.

6.
Arch. cardiol. Méx ; 83(4): 249-256, oct.-dic. 2013. ilus, tab
Artigo em Inglês | LILACS | ID: lil-703025

RESUMO

Introduction and objective: The aim of this communication is to describe the cardiovascular risk factors affecting a Mexican urban middle-class population. Methods: A convenience sample of 2602 middle class urban subjects composed the cohort of the Lindavista Study, a prospective study aimed to determine if conventional cardiovascular risks factors have the same prognosis impact as in other populations. For the baseline data, several measurements were done: obesity indexes, smoking, blood pressure, fasting serum glucose, total cholesterol, HDL-c, LDL-c and triglycerides. This paper presents the basal values of this population, which represents a sample of the Mexican growing urban middle-class. Results: The mean age in the sample was 50 years; 59% were females. Around 50% of the entire group were overweighed, while around 24% were obese. 32% smoked; 32% were hypertensive with a 20% rate of controlled pressure. 6% had diabetes, and 14% had impaired fasting glucose; 66% had total cholesterol ≥ 200mg/dL; 62% showed HDL-c levels <40mg/dL; 52% triglycerides > 150 mg/dL, and 34% levels of LDL-c ≥ 160 mg/dL. Half of the population studied had the metabolic syndrome. Conclusion: These data show a population with a high-risk profile, secondary to the agglomeration of several cardiovascular risk factors.


Introducción y objetivo: el objetivo de este comunicado es describir los factores de riesgo cardiovascular en la población urbana mexicana de clase media. Métodos: La cohorte del estudio Lindavista se compone de una muestra por conveniencia de 2,602 sujetos de clase media. El estudio es prospectivo y tiene como finalidad determinar si los factores de riesgo cardiovascular tienen el mismo factor pronóstico que en otras poblaciones. Para los datos basales, se hicieron varias determinaciones: índices de obesidad, consumo de tabaco, presión arterial, glucosa, colesterol total, c-HDL, c-LDL y triglicéridos en ayuno. Resultados: La media de edad fue de 50 años; el 59% fueron mujeres. Aproximadamente el 50% de la muestra presentó sobrepeso, mientras que el 24% eran obesos. El 32% fumaban, el 32% eran hipertensos con una tasa de control del 20%. El 6% tenían diabetes y el 14% resistencia a la insulina. El 66% tuvieron colesterol total ≥ 200 mg/dl; el 62% mostraron bajos niveles de c-HDL, el 52% triglicéridos > 150 mg/dl, y el 34% niveles de c-LDL ≥ 160 mg/dl. La mitad de la muestra tenía síndrome metabólico. Conclusión: Los datos revelan una población de alto riesgo cardiovascular debido a la aglomeración de diversos factores de riesgo.


Assuntos
Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Cardiovasculares/epidemiologia , México , Estudos Prospectivos , Fatores de Risco , Classe Social , Saúde da População Urbana , População Urbana
7.
Arch Cardiol Mex ; 83(4): 249-56, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24215681

RESUMO

INTRODUCTION AND OBJECTIVE: The aim of this communication is to describe the cardiovascular risk factors affecting a Mexican urban middle-class population. METHODS: A convenience sample of 2602 middle class urban subjects composed the cohort of the Lindavista Study, a prospective study aimed to determine if conventional cardiovascular risks factors have the same prognosis impact as in other populations. For the baseline data, several measurements were done: obesity indexes, smoking, blood pressure, fasting serum glucose, total cholesterol, HDL-c, LDL-c and triglycerides. This paper presents the basal values of this population, which represents a sample of the Mexican growing urban middle-class. RESULTS: The mean age in the sample was 50 years; 59% were females. Around 50% of the entire group were overweighed, while around 24% were obese. 32% smoked; 32% were hypertensive with a 20% rate of controlled pressure. 6% had diabetes, and 14% had impaired fasting glucose; 66% had total cholesterol ≥ 200 mg/dL; 62% showed HDL-c levels<40 mg/dL; 52% triglycerides>150 mg/dL, and 34% levels of LDL-c ≥ 160 mg/dL. Half of the population studied had the metabolic syndrome. CONCLUSION: These data show a population with a high-risk profile, secondary to the agglomeration of several cardiovascular risk factors.


Assuntos
Doenças Cardiovasculares/epidemiologia , Adulto , Idoso , Feminino , Humanos , Masculino , México , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Classe Social , Saúde da População Urbana , População Urbana
8.
Nutr Hosp ; 28(1): 194-201, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23808450

RESUMO

BACKGROUND: Obesity and the metabolic syndrome affect a considerable segment of the population worldwide, including health professionals. In fact, several studies have reported that physicians tend to have more cardiovascular risk factors than their patients. The present cross-sectional study assessed whether the Health Sciences students had a healthier lifestyle, thus could have a more preventive attitude towards chronic diseases than the general population. MATERIALS AND METHODS: Students of the medical-biological areas were surveyed by answering a questionnaire about familiar cardiovascular risk factors, personal smoking, alcohol drinking, dietary and exercise habits. Blood pressure was also measured, along with weight, height, and abdominal circumference. RESULTS: 23.4% of the participants were overweight and 10% obese. Parental obesity was the most frequent risk factor, followed by social drinking and smoking. We found high consumption of animal derived foods, breakfast- like cereals, pastries, white bread and sweetened beverages; while low intake of fruit and vegetables were reported. More than half the sample reported to practice very little or no exercise at all. DISCUSSION AND CONCLUSIONS: We found similar or even higher rates of risk factors than the average population, that may eventually lead to the development of chronic cardiometabolic diseases. Thus we can infer that biomedical education is inefficient in inducing healthy lifestyles among biomedical students, which could have impact in their future practice as they will most probable become obese health-professionals, thus fail to effectively treat their own patients.


Introducción: La obesidad y el síndrome metabólico afectan a un segmento considerable de la población mundial, incluyendo a los profesionales de la salud. De hecho, diversos estudios han reportado que los médicos tienden a presentar más factores de riesgo cardiovascular que sus propios pacientes. El presente estudio transversal evaluó si los estudiantes del área de la salud tenían un estilo de vida más saludable y, por tanto, una mejor actitud en cuanto a la prevención de las enfermedades crónico-degenerativas, que el resto de la población. Materiales y métodos: Se encuestaron estudiantes del área medico-biológica a través de un cuestionario sobre antecedentes heredo-familiares de riesgo cardiovascular, consumo actual de tabaco y alcohol, así como hábitos alimentarios y de ejercicio físico. Se midió la presión arterial, el peos, la talla y la circunferencia abdominal. Resultados: 23.4% de los participantes presentaban sobrepeso y 10% obesidad. La obesidad paterna fue el factor de riesgo más frecuente, seguido de consumo social de alcohol y tabaquismo. Se encontró un alto consume de alimentos de origen animal, cereales industrializados y refrescos; por otra parte, se reportó un bajo consumo de verduras y frutas. Más de la mitad de la muestra refirió ser sedentario. Discusión y conclusiones: Se encontraron datos muy similares a aquéllos reportados sobre la población general, que eventualmente conducirán al desarrollo de enfermedades cardiometabólicas. Por tanto, es posible inferir que la educación biomédica no es eficiente en la inducción de un estilo de vida saludable entre los estudiantes de ciencias de la salud. Tal fenómeno podría impactar su práctica futura ya que probablemente se convertirán en profesionistas obesos, con la consecuente falla en la prevención primaria y secundaria de sus propios pacientes.


Assuntos
Pressão Sanguínea/fisiologia , Exercício Físico/fisiologia , Comportamento Alimentar/fisiologia , Hábitos , Adolescente , Fatores Etários , Antropometria , Índice de Massa Corporal , Coleta de Dados , Feminino , Humanos , Masculino , México , Obesidade/epidemiologia , Sobrepeso/epidemiologia , Estudantes , Circunferência da Cintura , Adulto Jovem
9.
Steroids ; 73(5): 528-38, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18314151

RESUMO

Several in vitro studies show that in animals and isolated cells, 17 beta-estradiol induces cardiovascular protective effects and it has also been observed that it reduces coronary heart disease risk. However, the use of estrogens to improve or protect cardiovascular function in humans has been controversial, this might be explained by the wide variety of effects, because estrogen receptors (ER) are expressed ubiquitously. Therefore, a cell-specific targeting therapeutic approach might be necessary. 17 beta-Estradiol was coupled to a large modified dextran through an aminocaproic spacer. For this study we used intact and gonadectomized male Wistar rats, 15 days after surgical procedure. Intravascular administration of 17 beta-estradiol-macromolecular conjugate, prior to coronary reperfusion diminishes the area of damage induced by coronary ischemia reperfusion (I/R) injury on an in vivo model. This effect was observed at 17 beta-estradiol sub-physiological concentrations [0.01 nmol/L], it is mediated by luminal endothelial ER alpha activation. 17 beta-Estradiol-macromolecular conjugate decreases phosphorylation level of PKC alpha and Akt, as part of the process to induce myocardial protection against coronary I/R. We proved that the hormone-macromolecular conjugate labeled with [3H]estradiol remained confined in the intravascular space the conjugate was not internalized into organs like heart, lung or liver. It is noteworthy that the 17 beta-estradiol-macromolecular conjugate has a slow renal elimination, which might increase its pharmacological advantage. We concluded that the stimulus of endothelial estrogen receptors is enough to decrease the myocardial damage induced by coronary reperfusion.


Assuntos
Dextranos/uso terapêutico , Estradiol/análogos & derivados , Estradiol/uso terapêutico , Estrogênios/uso terapêutico , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Animais , Estradiol/metabolismo , Masculino , Traumatismo por Reperfusão Miocárdica/metabolismo , Miocárdio/metabolismo , Proteína Oncogênica v-akt/metabolismo , Fosforilação , Proteína Quinase C-alfa/metabolismo , Ratos , Ratos Wistar
10.
Am J Physiol Cell Physiol ; 293(6): C1953-61, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17942630

RESUMO

Caveolae are identifiable plasma membrane invaginations. The main structural proteins of caveolae are the caveolins. There are three caveolins expressed in mammals, designated Cav-1, Cav-2, and Cav-3. It has been postulated that Cav-1 acts as a scaffold protein for signaling proteins; these include ion channels, enzymes, and other ligand receptors like membrane-associated estrogen receptor (ER)alpha or ERbeta. Caveolae-associated membrane proteins are involved in regulating some of the rapid estrogenic effects of 17beta-estradiol. One important system related to the activity of ERalpha and caveolae is the renin-angiotensin system. Angiotensin II (ANG II) has numerous actions in vascular smooth muscle, including modulation of vasomotor tone, cell growth, apoptosis, phosphatidylinositol 3-kinase (PI3K)/Akt activation, and others. Many proteins associated with caveolae are in close relation with the scaffolding domain of Cav-1 (82-101 amino acid residues). It has been proposed that this peptide may acts as a kinase inhibitor. Therefore, to explore the ability of Cav-1 scaffolding peptide (CSP-1) to regulate ANG II function and analyze the relationship between ERalpha and ANG II type 1 and 2 (AT(1) and AT(2)) receptors, we decided to study the effects of CSP-1 on ANG II-induced intracellular Ca(2+) kinetics and the effect of 17beta-estradiol on this modulation using human smooth muscle cells in culture, intracellular Ca(2+) concentration measurements, immuno- and double-immunocytochemistry confocal analysis of receptor expression, immunoblot analysis, and immunocoprecipitation assays to demonstrate coexpression. We hypothesized that CSP-1 inhibits ANG II-mediated increases in intracellular Ca(2+) concentrations by interfering with intracellular signaling including the PI3K/Akt pathway. We also hypothesize that AT(2) receptors associate with Cav-1. Our results show that there is a close association of AT(1), AT(2), and ERalpha with Cav-1 in human arterial smooth muscle cells in culture. CSP-1 inhibits ANG II-induced intracellular signaling.


Assuntos
Angiotensina II/fisiologia , Cálcio/metabolismo , Caveolina 1/fisiologia , Estradiol/fisiologia , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Caveolina 1/metabolismo , Células Cultivadas , Receptor alfa de Estrogênio/metabolismo , Humanos , Immunoblotting , Imuno-Histoquímica , Imunoprecipitação , Masculino , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor Tipo 1 de Angiotensina/metabolismo , Receptor Tipo 2 de Angiotensina/metabolismo , Transdução de Sinais/fisiologia
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