RESUMEN
Olive products contain high levels of monounsaturated fatty acids as well as other minor components such as triterpenic alcohols and other pentacyclic triterpenes, which together form the main triterpenes of virgin olive oil. Olive fruits and leaves contain significant amounts of hydrophilic and lipophilic bioactives including flavones, phenolic acids and phenolic alcohols, amongst others. Several studies have shown the benefits of these substances on the cardiovascular system. Regardless, little is known about the specific combination of bioactive compounds in cardiovascular health. Thus, we aimed to test the combination of a triterpenes (TT70) and a polyphenols (HT60) olive oil bioactive extract in H9c2 cells under stress conditions: LPS and H2O2 stimulation. To evaluate the effectiveness of the combination, we measured cell viability, superoxide production and protein expression of caspase 3, eNOS, peNOS, TNF-α and Il-6. Overall, cells stimulated with LPS or H2O2 and co-incubated with the combination of triterpenes and polyphenols had increased cell survival, lower levels of superoxide anion, lower protein expression of eNOS and higher expression of peNOS, increased protein expression of SOD-1 and lower protein expression of TNF-α and Il-6. The specific combination of HT60+TT70 is of great interest for further study as a possible treatment for cardiovascular damage.
Asunto(s)
Olea , Triterpenos , Polifenoles/farmacología , Interleucina-6 , Factor de Necrosis Tumoral alfa , Triterpenos/farmacología , Peróxido de Hidrógeno , Lipopolisacáridos , Aceite de Oliva/farmacología , Aceite de Oliva/análisis , AlcoholesRESUMEN
Insulin resistance plays a key role in the development and progression of obesity, diabetes, and their complications. Moreover, insulin resistance is considered the principal link between metabolic diseases and cardiovascular diseases. Heart disease associated with insulin resistance is one of the most important consequences of both obesity and diabetes, and it is characterized by impaired cardiac energetics, diastolic dysfunction, and finally heart failure. Mitochondrion plays a key role in cell energy homeostasis and is the main source of reactive oxygen species. Obesity and diabetes are associated with alterations in mitochondrial function and dynamics. Mitochondrial dysfunction is characterized by changes in mitochondrial respiratory chain with reduced ATP production and elevated reactive oxygen species production. These mitochondrial alterations together with inflammation contribute to the development and progression of heart disease under insulin resistance conditions. Finally, numerous miRNAs participate in the regulation of energy substrate metabolism, reactive oxygen species production, and apoptotic pathways within the mitochondria. This notion supports the relevance of interactions between miRNAs and mitochondrial dysfunction in the pathophysiology of metabolic heart disease.
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Cardiopatías/metabolismo , Resistencia a la Insulina , Mitocondrias Cardíacas/metabolismo , Animales , Transporte de Electrón , Humanos , MicroARNs/metabolismoRESUMEN
Excess aldosterone promotes pathological remodeling of the heart and imbalance in cardiac ion homeostasis of sodium, potassium and calcium. Novel treatment with proanthocyanidins in aldosterone-treated rats has resulted in downregulation of cardiac SGK1, the main genomic aldosterone-induced intracellular mediator of ion handling. It therefore follows that proanthocyanidins could be modulating cardiac ion homeostasis in aldosterone-treated rats. Male Wistar rats received aldosterone (1 mg kg-1 day-1) +1% NaCl for three weeks. Half of the animals in each group were simultaneously treated with the proanthocyanidins-rich extract (80% w/w) (PRO80, 5 mg kg-1 day-1). PRO80 prevented cardiac hypertrophy and decreased calcium content. Expression of ion channels (ROMK, NHE1, NKA and NCX1) and calcium transient mediators (CAV1.2, pCaMKII and oxCaMKII) were reduced by PRO80 treatment in aldosterone-treated rats. To conclude, our data indicate that PRO80 may offer an alternative treatment to conventional MR-blockade in the prevention of aldosterone-induced cardiac pathology.
Asunto(s)
Insuficiencia Cardíaca/metabolismo , Hipertensión/metabolismo , Proantocianidinas/metabolismo , Aldosterona/metabolismo , Aldosterona/farmacología , Animales , Cardiomegalia/metabolismo , Corazón/fisiopatología , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/fisiopatología , Homeostasis/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Hipertensión/fisiopatología , Canales Iónicos/metabolismo , Masculino , Miocardio/metabolismo , Proantocianidinas/fisiología , Ratas , Ratas WistarRESUMEN
PURPOSE: To investigate the mechanism implicated in the effect of an insoluble fiber (obtained from carob pod) rich in polyphenols (IFCP) in lipid metabolism in the liver. METHODS: Male New Zealand rabbits were fed with the following diets for 8 weeks: control diet (CT group), dyslipidemic diet supplemented with 0.5% cholesterol + 14% coconut oil (DL group) and dyslipidemic diet containing 0.5% cholesterol + 14% coconut oil plus 3% IFCP (DL + IFCP group). RESULTS: Dyslipidemic diet with IFCP was able to reduce development of mixed dyslipidemia, liver relative weight and collagen I protein expression compared to DL rabbits. Analyses of the main enzymes implicated in cholesterol and triglycerides metabolism revealed that IFCP increased hepatic concentration of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase) and cytochrome P450, family 7, subfamily a, polypeptide 1C (CYP7A1) (82.34, 114.42%, respectively) as well as protein expression of LDL receptor (42.48%) in DL rabbits. Importantly, IFCP also increased hepatic lipase (HL) levels (91.43%) and decreased glycerol phosphate acyltransferase (GPAT) and sterol regulatory element-binding protein 1C (SREBP1c) liver expression levels (20.38 and 41.20%, respectively). Finally, sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1α) hepatic expression increased in DL + IFCP group compared with DL (159.81 and 48.00%, respectively). CONCLUSIONS: These findings show that IFCP is able to abrogate the deleterious effects of hepatic dyslipidemia by modulating SIRT1 and PGC-1α pathways.
Asunto(s)
Fibras de la Dieta/farmacología , Dislipidemias/prevención & control , Galactanos/farmacología , Metabolismo de los Lípidos/efectos de los fármacos , Hígado/metabolismo , Mananos/farmacología , Gomas de Plantas/farmacología , Polifenoles/farmacología , Animales , Fibras de la Dieta/administración & dosificación , Fibras de la Dieta/metabolismo , Dislipidemias/sangre , Dislipidemias/metabolismo , Galactanos/administración & dosificación , Galactanos/metabolismo , Hígado/efectos de los fármacos , Masculino , Mananos/administración & dosificación , Mananos/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma , Gomas de Plantas/administración & dosificación , Gomas de Plantas/metabolismo , Polifenoles/administración & dosificación , Polifenoles/metabolismo , Conejos , Sirtuina 1RESUMEN
BACKGROUND: The direct use of phenolic extracts from grape by-products can be useful when formulating functional food to improve consumer health. The use of phenolic extracts instead of pure polyphenols as an ingredient is relevant in this context. The present study investigated the bioavailability and absorption of polyphenols from grape by-product extracts and their health effect on cholesterolemia, by adding the extract (GE) to Wistar rats diet (50 g kg-1 ) in vivo. RESULTS: GE caused the appearance of (+)-catechin, myricetin and quercetic acid in plasma and liver. (+)-Catechin was the most abundant compound (6 µg mL-1 in plasma and 0.7 µg mg-1 protein in liver), whereas no phenolic compounds were detected in plasma or liver in the control group. Similarly, 3,4-hydroxyphenylacetic, a major product of polyphenol digestion, was detected in the plasma, liver and urine of the GE-group only. GE-group had significantly lower cholesterol level and lower total cholesterol/high-density lipoprotein ratio in plasma. Total bile acid content significantly increased in fecal matter after 24 h administration of the GE-enriched diet. CONCLUSION: Grape extract polyphenols are partially bioavailable and showed improvement in lipid metabolism. Thus, the results suggest that GE is promising as a functional ingredient in the prevention of hypercholesterolemia. © 2018 Society of Chemical Industry.
Asunto(s)
Hipercolesterolemia/prevención & control , Hiperlipidemias/tratamiento farmacológico , Extractos Vegetales/farmacocinética , Polifenoles/farmacocinética , Vitis/química , Animales , Disponibilidad Biológica , Colesterol/metabolismo , Humanos , Hipercolesterolemia/metabolismo , Hiperlipidemias/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Polifenoles/administración & dosificación , Polifenoles/química , Polifenoles/aislamiento & purificación , Ratas , Ratas Wistar , Residuos/análisisRESUMEN
Mitochondria are essential for the maintenance of normal physiological function of tissue cells. Mitochondria are subject to dynamic processes in order to establish a control system related to survival or cell death and adaptation to changes in the metabolic environment of cells. Mitochondrial dynamics includes fusion and fission processes, biogenesis, and mitophagy. Modifications of mitochondrial dynamics in organs involved in energy metabolism such as the pancreas, liver, skeletal muscle, and white adipose tissue could be of relevance for the development of insulin resistance, obesity, and type 2 diabetes. Mitochondrial dynamics and the factors involved in its regulation are also critical for neuronal development, survival, and function. Modifications in mitochondrial dynamics in either agouti-related peptide (AgRP) or pro-opiomelanocortin (POMC), circuits which regulates feeding behavior, are related to changes of food intake, energy balance, and obesity development. Activation of the sympathetic nervous system has been considered as a crucial point in the pathogenesis of hypertension among obese individuals and it also plays a key role in cardiac remodeling. Hypertension-related cardiac hypertrophy is associated with changes in metabolic substrate utilization, dysfunction of the electron transport chain, and ATP synthesis. Alterations in both mitochondrial dynamics and ROS production have been associated with endothelial dysfunction, development of hypertension, and cardiac hypertrophy. Finally, it might be postulated that alterations of mitochondrial dynamics in white adipose tissue could contribute to the development and maintenance of hypertension in obesity situations through leptin overproduction. Leptin, together with insulin, will induce activation of sympathetic nervous system with consequences at renal, vascular, and cardiac levels, driving to sodium retention, hypertension, and left ventricular hypertrophy. Moreover, both leptin and insulin will induce mitochondrial alterations into arcuate nucleus leading to signals driving to increased food intake and reduced energy expenditure. This, in turn would perpetuate white adipose tissue excess and its well-known metabolic and cardiovascular consequences.
Asunto(s)
Hipertensión/fisiopatología , Mitocondrias/metabolismo , Enfermedades Mitocondriales/complicaciones , Obesidad/fisiopatología , Animales , Metabolismo Energético , Humanos , Hipertensión/complicaciones , Resistencia a la Insulina , Obesidad/complicaciones , Sistema Nervioso Simpático/metabolismoRESUMEN
There is interest to analyse newer biomarkers to identify healthy individuals at risk to develop cardiovascular disease (CVD) incidents and death. To determine in healthy individuals new circulating protein biomarkers, whose systemic levels may be associated with the risk of future development of CVD incidents and death. The study was performed in 82 individuals from the Malmö Diet and Cancer study cohort, free from CVD of whom 41 developed CVD and 41 did not. Plasma proteins related to inflammation and thrombo-coagulating processes were analysed. α1-antitrypsin isotype 3 plasma levels were significantly higher while apolipoprotein J plasma levels were lower in participants that developed CVD incidents than those that did not develop acute cardiovascular episode. Of 82 participants, 17 died by CVD causes. There were proteins whose expression in plasma was significantly higher in participants suffering CVD death as compared with those that did not die by CVD. These proteins included: fibrinogen ß-chain isotypes 1 and 3, fibrinogen-γ-chain isotype 2, vitamin D-binding protein isotypes 1, 2 and 3, α1-antitrypsin isotypes 3 and 6, haptoglobin isotypes 3,4,5 and 5, haemopexin isotypes 1 and 2, and Rho/Rac guanine nucleotide exchange factor 2. Moreover, apolipoprotein J plasma levels were found lower in participants that died by cardiovascular cause. Association between plasma levels of proteins and CVD death was independent of age, gender, conventional risk factors and plasma C-reactive protein levels. Several protein plasma levels and protein isotypes related to inflammation and thrombo-coagulating phenomena were independently associated with the risk of future CVD death.
Asunto(s)
Biomarcadores/sangre , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/mortalidad , Salud , Anciano , Proteínas Sanguíneas/metabolismo , Estudios de Casos y Controles , Femenino , Fibrinógeno/metabolismo , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Proteína de Unión a Vitamina D/sangreRESUMEN
BACKGROUND: It has been reported that increased expression of UCP-2 in the vasculature may prevent the development of atherosclerosis in patients with increased production of reactive oxygen species, as in the diabetes, obesity or hypertension. Thus, a greater understanding in the modulation of UCP-2 could improve the atherosclerotic process. However, the effect of TNF-α or insulin modulating UCP-2 in the vascular wall is completely unknown. In this context, we propose to study new molecular mechanisms that help to explain whether the moderate hyperinsulinemia or lowering TNF-α levels might have a protective role against vascular damage mediated by UCP-2 expression levels. METHODS: We analyzed the effect of insulin or oleic acid in presence or not of TNF-α on UCP-2 expression in murine endothelial and vascular smooth muscle cells. At this step, we wondered if some mechanisms studied in vitro could be of any relevance in vivo. We used the following experimental models: ApoE-/- mice under Western type diet for 2, 6, 12 or 18 weeks, BATIRKO mice under high-fat diet for 16 weeks and 52-week-old BATIRKO mice with o without anti-TNF-α antibody pre-treatment. RESULTS: Firstly, we found that TNF-α pre-treatment reduced UCP-2 expression induced by insulin in vascular cells. Secondly, we observed a progressive reduction of UCP-2 levels together with an increase of lipid depots and lesion area in aorta from ApoE-/- mice. In vivo, we also observed that moderate hyperinsulinemic obese BATIRKO mice have lower TNF-α and ROS levels and increased UCP-2 expression levels within the aorta, lower lipid accumulation, vascular dysfunction and macrovascular damage. We also observed that the anti-TNF-α antibody pre-treatment impaired the loss of UCP-2 expression within the aorta and relieved vascular damage observed in 52-week-old BATIRKO mice. Finally, we observed that the pretreatment with iNOS inhibitor prevented UCP-2 reduction induced by TNF-α in vascular cells. Moreover, iNOS levels are augmented in aorta from mice with lower UCP-2 levels and higher TNF-α levels. CONCLUSIONS: Our data suggest that moderate hyperinsulinemia in response to insulin resistance or lowering of TNF-α levels within the aorta attenuates vascular damage, this protective effect being mediated by UCP-2 expression levels through iNOS.
Asunto(s)
Insulina/farmacología , Canales Iónicos/antagonistas & inhibidores , Canales Iónicos/biosíntesis , Proteínas Mitocondriales/antagonistas & inhibidores , Proteínas Mitocondriales/biosíntesis , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/metabolismo , Factor de Necrosis Tumoral alfa/farmacología , Animales , Células Cultivadas , Regulación de la Expresión Génica , Masculino , Ratones , Ratones Noqueados , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/patología , Miocitos del Músculo Liso/efectos de los fármacos , Miocitos del Músculo Liso/patología , Proteína Desacopladora 2RESUMEN
BACKGROUND: Several mechanisms have been proposed to explain why some platelets have a reduced response to aspirin (ASA). Among them, it was reported an increased circulating level of vitamin-D-binding protein (DBP). In addition, nitric oxide (NO) released from mononuclear cells was involved in the antiplatelet effects of ASA. The aim was to analyse the relationship between platelet response to ASA and both NO generation and vitamin-D-binding protein content in mononuclear cells. MATERIALS AND METHODS: Mononuclear cells were obtained from patients with stable coronary artery disease that were divided by a platelet functionality test (PFA-100) as ASA-sensitive (n=23) and ASA resistant (n=27). RESULTS: Both the release of NO (determined by nitrite+nitrate concentration) and the expression of endothelial-type NO synthase (eNOS) were higher in mononuclear cells from ASA sensitive as compared with those from ASA-resistant patients. There was a positive correlation between either the release of NO and the expression of eNOS protein in mononuclear cells with the ability of ASA to inhibit platelet activity. DBP content in mononuclear cells was higher in ASA resistant than in ASA sensitive. The level of DBP content in mononuclear cells was negatively associated with the ability of ASA to inhibit platelets. However, in vitro experiments suggested that there was no association between DBP and NO production by mononuclear cells. CONCLUSIONS: Mononuclear cells from patients with platelets with lower responsiveness to ASA showed a reduced ability to produce NO.
Asunto(s)
Aspirina/farmacología , Óxido Nítrico/biosíntesis , Inhibidores de Agregación Plaquetaria/farmacología , Anciano , Plaquetas , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Enfermedad de la Arteria Coronaria/metabolismo , Resistencia a Medicamentos , Femenino , Humanos , Interleucina-6/biosíntesis , Leucocitos Mononucleares/metabolismo , Masculino , Óxido Nítrico Sintasa de Tipo II/metabolismo , Óxido Nítrico Sintasa de Tipo III/metabolismo , Proteína de Unión a Vitamina D/metabolismoRESUMEN
The aim of this study was to evaluate the potential effects of an insoluble dietary fiber from carob pod (IFC) (1 g â kg(-1) â d(-1) in the diet) on alterations associated with atherosclerosis in rabbits with dyslipidemia. Male New Zealand rabbits (n = 30) were fed the following diets for 8 wk: 1) a control diet (SF412; Panlab) as a control group representing normal conditions; 2) a control supplemented with 0.5% cholesterol + 14% coconut oil (DL) (SF302; Panlab) for 8 wk as a dyslipidemic group; and 3) a control containing 0.5% cholesterol + 14% coconut oil plus IFC (1 g â kg(-1) â d(-1)) (DL+IFC) for 8 wk. IFC was administered in a pellet mixed with the DL diet. The DL-fed group developed mixed dyslipidemia and atherosclerotic lesions, which were associated with endothelial dysfunction, inflammation, and fibrosis. Furthermore, sirtuin-1 (SIRT1) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) protein expression in the aorta were reduced to 77% and 63% of the control group, respectively (P < 0.05), in these rabbits. Administration of IFC to DL-fed rabbits reduced the size of the aortic lesion significantly (DL, 15.2% and DL+IFC, 2.6%) and normalized acetylcholine-induced relaxation (maximal response: control, 89.3%; DL, 61.6%; DL+IFC, 87.1%; P < 0.05) and endothelial nitric oxide synthase expression (DL, 52% and DL+IFC, 104% of the control group). IFC administration to DL-fed rabbits also reduced cluster of differentiation 36 (DL, 148% and DL+IFC, 104% of the control group; P < 0.05), plasminogen activator inhibitor-1 (DL, 141% and DL+IFC, 107% of the control group), tumor necrosis factor-α (DL, 166% and DL+IFC, 120% of the control group), vascular cell adhesion molecule-1 (DL, 153% and DL+IFC, 110% of the control group), transforming growth factor-ß (DL, 173% and DL+IFC, 99% of the control group), and collagen I (DL, 157% and DL+IFC, 112% of the control group) in the aorta. These effects were accompanied by an enhancement of SIRT1 and PGC-1α (160% and 121% of the control group, respectively; P < 0.05) vascular expression. In summary, we demonstrated for the first time, to our knowledge, that administration of IFC reduces the development of atherosclerosis in rabbits. This effect seems to be related to an improvement in endothelial function and a reduction of inflammation and fibrosis, most probably as a consequence of the reduction of serum concentrations of cholesterol and triglycerides. Increased expression of aortic SIRT1 and PGC-1α could play an important role in the observed effects of IFC in rabbits with dyslipidemia.
Asunto(s)
Fibras de la Dieta/uso terapéutico , Dislipidemias/tratamiento farmacológico , Fabaceae/química , Galactanos/uso terapéutico , Mananos/uso terapéutico , Gomas de Plantas/uso terapéutico , Placa Aterosclerótica/prevención & control , Sirtuina 1/metabolismo , Factores de Transcripción/sangre , Animales , Aorta/efectos de los fármacos , Aorta/metabolismo , Aterosclerosis/sangre , Aterosclerosis/etiología , Aterosclerosis/patología , Aterosclerosis/prevención & control , Colesterol en la Dieta/farmacología , Aceite de Coco , Dieta Alta en Grasa , Fibras de la Dieta/farmacología , Suplementos Dietéticos , Dislipidemias/sangre , Dislipidemias/etiología , Endotelio Vascular/efectos de los fármacos , Fibrosis , Frutas , Galactanos/farmacología , Inflamación/sangre , Inflamación/etiología , Inflamación/prevención & control , Mediadores de Inflamación/sangre , Masculino , Mananos/farmacología , PPAR gamma/sangre , Gomas de Plantas/farmacología , Aceites de Plantas/farmacología , Placa Aterosclerótica/sangre , Placa Aterosclerótica/etiología , Conejos , Vasodilatación/efectos de los fármacosRESUMEN
(1) Background: Artificial intelligence using machine learning techniques may help us to predict and prevent obesity. The aim was to design an interpretable prediction algorithm for overweight/obesity risk based on a combination of different machine learning techniques. (2) Methods: 38 variables related to sociodemographic, lifestyle, and health aspects from 1179 residents in Madrid were collected and used to train predictive models. Accuracy, precision, and recall metrics were tested and compared between nine classical machine learning techniques and the predictive model based on a combination of those classical machine learning techniques. Statistical validation was performed. The shapely additive explanation technique was used to identify the variables with the greatest impact on weight gain. (3) Results: Cascade classifier model combining gradient boosting, random forest, and logistic regression models showed the best predictive results for overweight/obesity compared to all machine learning techniques tested, reaching an accuracy of 79%, precision of 84%, and recall of 89% for predictions for weight gain. Age, sex, academic level, profession, smoking habits, wine consumption, and Mediterranean diet adherence had the highest impact on predicting obesity. (4) Conclusions: A combination of machine learning techniques showed a significant improvement in accuracy to predict risk of overweight/obesity than machine learning techniques separately.
RESUMEN
BACKGROUND: Heart produces ATP through long-chain fatty acids beta oxidation. PURPOSE: To analyze whether in ventricular myocardium, high-fat diet may modify the expression of proteins associated with energy metabolism before myocardial function was affected. METHODS: Wistar Kyoto rats were divided into two groups: (a) rats fed standard diet (control; n = 6) and (b) rats fed high-fat diet (HFD; n = 6). Proteins from left ventricles were analyzed by two-dimensional electrophoresis, mass spectrometry and Western blotting. RESULTS: Rats fed with HFD showed higher body weight, insulin, glucose, leptin and total cholesterol plasma levels as compared with those fed with standard diet. However, myocardial functional parameters were not different between them. The protein expression of 3-ketoacyl-CoA thiolase, acyl-CoA hydrolase mitochondrial precursor and enoyl-CoA hydratase, three long-chain fatty acid ß-oxidation-related enzymes, and carnitine-O-palmitoyltransferase I was significantly higher in left ventricles from HFD rats. Protein expression of triosephosphate isomerase was higher in left ventricles from HFD rats than in those from control. Two α/ß-enolase isotypes and glyceraldehyde-3-phosphate isomerase were significantly increased in HFD rats as compared with control. Pyruvate and lactate contents were similar in HFD and control groups. Expression of proteins associated with Krebs cycle and mitochondrial oxidative phosphorylation was higher in HFD rats. CONCLUSIONS: Expression of proteins involved in left ventricle metabolic energy was enhanced before myocardial functionality was affected in rats fed with HFD. These findings may probably indicate higher cardiac energy requirement due to weight increase by HFD.
Asunto(s)
Dieta Alta en Grasa , Metabolismo Energético , Redes y Vías Metabólicas/fisiología , Miocardio/metabolismo , Sobrepeso/metabolismo , Acetil-CoA C-Aciltransferasa/genética , Acetil-CoA C-Aciltransferasa/metabolismo , Animales , Western Blotting , Peso Corporal , Carnitina O-Palmitoiltransferasa/genética , Carnitina O-Palmitoiltransferasa/metabolismo , Colesterol/sangre , Enoil-CoA Hidratasa/genética , Enoil-CoA Hidratasa/metabolismo , Ácidos Grasos/metabolismo , Gliceraldehído 3-Fosfato/genética , Gliceraldehído 3-Fosfato/metabolismo , Procesamiento de Imagen Asistido por Computador , Insulina/sangre , Ácido Láctico/análisis , Leptina/sangre , Masculino , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/metabolismo , Fosforilación Oxidativa , Palmitoil-CoA Hidrolasa/genética , Palmitoil-CoA Hidrolasa/metabolismo , Fosfopiruvato Hidratasa/genética , Fosfopiruvato Hidratasa/metabolismo , Ácido Pirúvico/análisis , Ratas , Ratas Endogámicas WKY , Triglicéridos/sangre , Triosa-Fosfato Isomerasa/genética , Triosa-Fosfato Isomerasa/metabolismoRESUMEN
BACKGROUND: Garlic (Allium sativum) has been shown to have important benefits in individuals at high cardiovascular risk. The aim of the present study was to evaluate the effects of the administration of aged garlic extract (AGE) on the risk factors that constitute the cluster of metabolic syndrome (MS). METHODS AND DESIGN: Double-blind, crossover, randomized, placebo-controlled clinical trial to assess the effect of 1.2 g/day of AGE (Kyolic), for 24 weeks of treatment (12 weeks of AGE and 12 weeks of placebo), on subjects with MS. RESULTS: The administration of AGE increased the plasma levels of adiponectin (P = 0.027). No serious side effects associated with the intervention were reported. CONCLUSION: The present results have shown for the first time that the administration of AGE for 12 weeks increased plasma adiponectin levels in patients with MS. This suggests that AGE might be a useful, novel, nonpharmacological therapeutic intervention to increase adiponectin and to prevent cardiovascular (CV) complications in individuals with MS.
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Adiponectina/sangre , Ajo/química , Síndrome Metabólico/sangre , Síndrome Metabólico/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Adulto , Estudios Cruzados , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The effect of adiponectin and leptin on the proliferation of the human microvascular endothelial cell line (HMEC-1) was studied in the absence or presence of fetal bovine serum (FBS). The participation of extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3-kinase/Akt (PI-3K/Akt) pathways in this effect were evaluated. We studied the effect of both adipokines on the motility, mitosis, proliferation and cell death processes of HMEC-1 cells using live-cell imaging techniques. Adiponectin but not leptin further increased the proliferative effect induced by FBS on HMEC-1. This effect seems to be the consequence of an increase in the mitotic index in adiponectin-treated cells when compared to untreated ones. The presence of either the mitogen-activated protein kinase (MAPK) inhibitor (PD98059), or PI-3K inhibitor (LY294002), reduced the effect of adiponectin in a dose-dependent manner. Neither adipokine was able to affect HMEC-1 proliferation in FBS-free conditions. Duration of mitosis, cell motility and the cell death process were similar in all conditions. These data suggest that adiponectin and leptin exert different effects on endothelial cell function. Adiponectin was able to potentiate proliferation of HMEC-1. This effect involves the activation of both PI3-K/Akt and ERK/MAPK pathways. However, it seems to exert minimal effects on HMEC-1 function in the case of leptin.
Asunto(s)
Adiponectina/farmacología , Proliferación Celular/efectos de los fármacos , Leptina/farmacología , Línea Celular , Movimiento Celular/efectos de los fármacos , Cromonas/farmacología , Endotelio Vascular/citología , Quinasas MAP Reguladas por Señal Extracelular/efectos de los fármacos , Flavonoides/farmacología , Humanos , Microcirculación , Quinasas de Proteína Quinasa Activadas por Mitógenos/antagonistas & inhibidores , Morfolinas/farmacología , Inhibidores de las Quinasa Fosfoinosítidos-3RESUMEN
Persistent ß-adrenergic receptor stimulation with isoproterenol is associated with cardiac hypertrophy as well as cardiac synthesis of angiotensin II. Serum- and glucocorticoid-regulated kinase type 1 (SGK-1) is a key mediator in structural, functional and molecular cardiac effects of aldosterone in rats. This study was designed to investigate the cardiac effects of the mineralocorticoid receptor antagonist spironolactone on the response to isoproterenol treatment in rats, as well as the involvement of the main mediator of cellular aldosterone action, SGK-1, in the heart. Male Wistar rats received isoproterenol (3 mg kg(-1) day(-1)) or vehicle for 15 days. Half of the animals in each group were simultaneously treated with spironolactone (200 mg kg(-1) day(-1)). Systolic and diastolic blood pressures were not significantly different among groups. Treatment with spironolactone normalized the increased left ventricular end-diastolic pressure observed in isoproterenol-treated rats. Isoproterenol treatment induced cardiac hypertrophy and increased collagen content, both of which were normalized by spironolactone treatment. The mRNA levels of transforming growth factor ß, connective tissue growth factor, matrix metalloprotease 2, matrix metalloprotease inhibitor 2, tumour necrosis factor α, interleukin 1ß, p22phox and xanthine dehydrogenase were increased (P < 0.05) in isoproterenol-treated rats, and this effect was prevented by spironolactone (P < 0.05). Spironolactone also reduced the elevated SGK-1 expression in isoproterenol-treated rats. The observed reduction of the principal mediator of aldosterone cellular actions, SGK-1, by spironolactone in hearts from isoproterenol-treated rats suggests a role of mineralocorticoids in the cardiac hypertrophy, fibrosis, inflammation, oxidation and diastolic dysfunction induced by isoproterenol treatment in rats.
Asunto(s)
Cardiomegalia/tratamiento farmacológico , Cardiomegalia/patología , Proteínas Inmediatas-Precoces/metabolismo , Antagonistas de Receptores de Mineralocorticoides/farmacología , Proteínas Serina-Treonina Quinasas/metabolismo , Espironolactona/farmacología , Aldosterona/metabolismo , Animales , Presión Sanguínea/efectos de los fármacos , Cardiomegalia/inducido químicamente , Cardiomegalia/metabolismo , Fibrosis/tratamiento farmacológico , Fibrosis/metabolismo , Corazón/efectos de los fármacos , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Isoproterenol , Masculino , Oxidación-Reducción/efectos de los fármacos , Ratas , Ratas Wistar , Receptores de Mineralocorticoides/metabolismoRESUMEN
The concept of "aging" is defined as the set of gradual and progressive changes in an organism that leads to an increased risk of weakness, disease, and death. This process may occur at the cellular and organ level, as well as in the entire organism of any living being. During aging, there is a decrease in biological functions and in the ability to adapt to metabolic stress. General effects of aging include mitochondrial, cellular, and organic dysfunction, immune impairment or inflammaging, oxidative stress, cognitive and cardiovascular alterations, among others. Therefore, one of the main harmful consequences of aging is the development and progression of multiple diseases related to these processes, especially at the cardiovascular and central nervous system levels. Both cardiovascular and neurodegenerative pathologies are highly disabling and, in many cases, lethal. In this context, melatonin, an endogenous compound naturally synthesized not only by the pineal gland but also by many cell types, may have a key role in the modulation of multiple mechanisms associated with aging. Additionally, this indoleamine is also a therapeutic agent, which may be administered exogenously with a high degree of safety. For this reason, melatonin could become an attractive and low-cost alternative for slowing the processes of aging and its associated diseases, including cardiovascular and neurodegenerative disorders.
RESUMEN
Aerobic exercise training (ET) produces beneficial adaptations in skeletal muscles, including angiogenesis. The renin-angiotensin system (RAS) is highly involved in angiogenesis stimuli. However, the molecular mechanisms underlying capillary growth in skeletal muscle induced by aerobic ET are not completely understood. This study aimed to investigate the effects of volume-dependent aerobic ET on skeletal muscle angiogenesis involving the expression of miRNAs-27a and 27b on RAS and oxidant-antioxidant balance. Eight-week-old female Wistar rats were divided into three groups: sedentary control (SC), trained protocol 1 (P1), and trained protocol 2 (P2). P1 consisted of 60 min/day of swimming, 5×/week, for 10 weeks. P2 consisted of the same protocol as P1 until the 8th week, but in the 9th week, rats trained 2×/day, and in the 10th week, trained 3×/day. Angiogenesis and molecular analyses were performed in soleus muscle samples. Furthermore, to establish ET-induced angiogenesis through RAS, animals were treated with an AT1 receptor blocker (losartan). Aerobic ET promoted higher VO2 peak and exercise tolerance values. In contrast, miRNA-27a and -27b levels were reduced in both trained groups, compared with the SC group. This was in parallel with an increase in the ACE1/Ang II/VEGF axis, which led to a higher capillary-to-fiber ratio. Moreover, aerobic ET induced an antioxidant profile increasing skeletal muscle SOD2 and catalase gene expression, which was accompanied by high nitrite levels and reduced nitrotyrosine concentrations in the circulation. Additionally, losartan treatment partially re-established the miRNAs expression and the capillary-to-fiber ratio in the trained groups. In summary, aerobic ET promoted angiogenesis through the miRNA-27a/b-ACE1/Ang II/VEGF axis and improved the redox balance. Losartan treatment demonstrates the participation of RAS in ET-induced vascular growth. miRNAs and RAS components are promising potential targets to modulate angiogenesis for combating vascular diseases, as well as potential biomarkers to monitor training interventions and physical performance.
RESUMEN
Hyperaldosteronim is associated with left ventricular (LV) hypertrophy (LVH) and fibrosis. Cardiotrophin (CT)-1 is a cytokine that induces myocardial remodeling. We investigated whether CT-1 mediates aldosterone (Aldo)-induced myocardial remodeling in two experimental models. Wistar rats were treated with Aldo-salt (1 mg·kg(-1)·day(-1)) with or without spironolactone (200 mg·kg(-1)·day(-1)) for 3 wk. Wild-type (WT) and CT-1-null mice were infused with Aldo (1 mg·kg(-1)·day(-1)) for 3 wk. Hemodynamic parameters were analyzed. LVH, fibrosis, inflammation, and CT-1 expression were evaluated in both experimental models by histopathological analysis, RT-PCR, Western blot analysis, and ELISA. Hypertensive Aldo-treated rats exhibited increased LV end-diastolic pressure and -dP/dt compared with controls. The cardiac index, LV cross-sectional area and wall thickness, cardiomyocyte size, collagen deposition, and inflammation were increased in Aldo-salt-treated rats. Myocardial expression of molecular markers assessing LVH and fibrosis as well as CT-l levels were also augmented by Aldo-salt. Spironolactone treatment reversed all the above effects. CT-1 correlated positively with hemodynamic, histological, and molecular parameters showing myocardial remodeling. In WT and CT-1-null mice, Aldo infusion did not modify blood pressure. Whereas Aldo treatment induced LVH, fibrosis, and inflammation in WT mice, the mineralocorticoid did not provoke cardiac remodeling in CT-1-null mice. In conclusion, in experimental hyperaldosteronism, the increase in CT-1 expression was associated with parameters showing LVH and fibrosis. CT-1-null mice were resistant to Aldo-induced LVH and fibrosis. These data suggest a key role for CT-1 in cardiac remodeling induced by Aldo independent of changes in blood pressure levels.
Asunto(s)
Aldosterona , Citocinas/metabolismo , Hiperaldosteronismo/complicaciones , Hipertensión/metabolismo , Hipertrofia Ventricular Izquierda/metabolismo , Miocardio/metabolismo , Remodelación Ventricular , Animales , Presión Sanguínea , Western Blotting , Colágeno/metabolismo , Citocinas/deficiencia , Citocinas/genética , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Fibrosis , Frecuencia Cardíaca , Hiperaldosteronismo/inducido químicamente , Hiperaldosteronismo/tratamiento farmacológico , Hiperaldosteronismo/metabolismo , Hiperaldosteronismo/patología , Hiperaldosteronismo/fisiopatología , Hipertensión/etiología , Hipertensión/genética , Hipertensión/patología , Hipertensión/fisiopatología , Hipertensión/prevención & control , Hipertrofia Ventricular Izquierda/etiología , Hipertrofia Ventricular Izquierda/genética , Hipertrofia Ventricular Izquierda/patología , Hipertrofia Ventricular Izquierda/fisiopatología , Hipertrofia Ventricular Izquierda/prevención & control , Inflamación/etiología , Inflamación/metabolismo , Inflamación/fisiopatología , Mediadores de Inflamación/sangre , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Antagonistas de Receptores de Mineralocorticoides/farmacología , Miocardio/patología , Ratas , Ratas Wistar , Reacción en Cadena en Tiempo Real de la Polimerasa , Cloruro de Sodio Dietético , Espironolactona/farmacología , Función Ventricular Izquierda , Presión Ventricular , Remodelación Ventricular/efectos de los fármacosRESUMEN
Increased cardiovascular risk after mercury exposure has been described but cardiac effects resulting from controlled chronic treatment are not yet well explored. We analyzed the effects of chronic exposure to low mercury concentrations on hemodynamic and ventricular function of isolated hearts. Wistar rats were treated with HgCl2 (1st dose 4.6 µg/kg, subsequent dose 0.07 µg/kg/day, im, 30 days) or vehicle. Mercury treatment did not affect blood pressure (BP) nor produced cardiac hypertrophy or changes of myocyte morphometry and collagen content. This treatment: 1) in vivo increased left ventricle end diastolic pressure (LVEDP) without changing left ventricular systolic pressure (LVSP) and heart rate; 2) in isolated hearts reduced LV isovolumic systolic pressure and time derivatives, and ß-adrenergic response; 3) increased myosin ATPase activity; 4) reduced Na+-K+ ATPase (NKA) activity; 5) reduced protein expression of SERCA and phosphorylated phospholamban on serine 16 while phospholamban expression increased; as a consequence SERCA/phospholamban ratio reduced; 6) reduced sodium/calcium exchanger (NCX) protein expression and α-1 isoform of NKA, whereas α-2 isoform of NKA did not change. Chronic exposure for 30 days to low concentrations of mercury does not change BP, heart rate or LVSP but produces small but significant increase of LVEDP. However, in isolated hearts mercury treatment promoted contractility dysfunction as a result of the decreased NKA activity, reduction of NCX and SERCA and increased PLB protein expression. These findings offer further evidence that mercury chronic exposure, even at small concentrations, is an environmental risk factor affecting heart function.