RESUMEN
This study aimed to identify the combined factors of physical activity and diet associated with non-sarcopenic non-obese status in 1586 diabetic patients aged ≥65 years from the Korean National Health and Nutrition Examination Survey (2016 to 2019). Participants were categorized into non-sarcopenic non-obesity (NSNO), sarcopenia non-obesity (SNO), non-sarcopenic obesity (NSO), and sarcopenic obesity (SO) groups. NSNO had lower insulin, HOMA-IR, and triglycerides compared to NSO and SO. NSNO had lower perceived stress, higher nutrition education and dietary supplement intake. As assessed by the Korean Healthy Eating Index, NSNO scored higher total than SNO and SO, in breakfast and energy balance compared to SO, and in the adequacy of vegetables and meat/fish/egg/bean compared to SNO. NSNO had significantly higher energy and protein intake and physical activity, with BMI/waist circumference lower than NSO, SO, and comparable to SNO. Physical activity was positively associated with NSNO. Low Total KHEI score and protein intake level reduced the odds ratio (OR) of NSNO, particularly when physical activity was insufficient, with OR = 0.38 for KHEI Q1 and OR = 0.32 for protein T1. In conclusion, physical activity, diet quality, and protein intake are associated with NSNO prevalence in Korean elderly with diabetes, and energy balance through active intake and expenditure may be effective.
Asunto(s)
Diabetes Mellitus , Sarcopenia , Anciano , Animales , Humanos , Sarcopenia/epidemiología , Encuestas Nutricionales , Dieta , Obesidad/epidemiología , Diabetes Mellitus/epidemiología , Ejercicio Físico , República de Corea/epidemiologíaRESUMEN
This study aimed to compare the dietary factors related to sarcopenia and obesity status in 5458 elderly individuals (2391 men and 3076 women) aged ≥65 years from the Korean National Health and Nutrition Examination Survey (2016-2019). Participants were categorized into normal, sarcopenia, obesity, and sarcopenic obesity groups. Sarcopenic obesity showed a higher prevalence of diabetes and lower HDL cholesterol levels compared to obesity. Sarcopenic obesity exhibited a lower total KHEI score and lower adequacy, including meat/fish/eggs/beans, than normal or obesity. In women, sarcopenic obesity scored lower than obesity on the total KHEI, adequacy for most foods, and balance of energy intake, and lower than sarcopenia on the adequacy of breakfast and milk/milk products. Sarcopenic obesity showed no significant difference in energy intake compared to sarcopenia, and less physical activity compared to sarcopenia and obesity, with a BMI/waist circumference comparable to that of obesity. Low total KHEI scores and scores for meat/fish/eggs/beans were most closely associated with sarcopenia in men and with sarcopenic obesity in women. In conclusion, low dietary quality and inadequate protein-rich foods are possibly associated with the prevalence of sarcopenic obesity in elderly Koreans, especially in women. Adequate energy intake and dietary diversity may be effective in managing sarcopenic obesity.
Asunto(s)
Dieta , Encuestas Nutricionales , Obesidad , Sarcopenia , Humanos , Masculino , Femenino , Anciano , Sarcopenia/epidemiología , Sarcopenia/etiología , República de Corea/epidemiología , Estudios Transversales , Obesidad/epidemiología , Dieta/estadística & datos numéricos , Factores Sexuales , Prevalencia , Ingestión de Energía , Anciano de 80 o más AñosRESUMEN
We investigated the effects of 6-gingerol on adiposity and obesity-induced inflammation by focusing on the regulation of adipogenesis and adipokines in white adipose tissue (WAT) of diet-induced obese mice. C57BL/6 mice were fed a high-fat diet (HFD) containing 0.05% 6-gingerol for 8 weeks. 6-Gingerol supplementation significantly reduced body weight, WAT mass, serum triglyceride, leptin and insulin levels, and HOMA-IR in HFD-fed mice. Additionally, the size of adipocytes in epididymal fat pads was reduced in HFD-fed mice by 6-gingerol supplementation. 6-Gingerol reduced the mRNA and protein levels of adipogenesis-related transcription factors, such as SREBP-1, PPARγ, and C/EBPα in WAT. Furthermore, 6-gingerol suppressed the expression of lipogenesis-related genes, such as fatty acid synthase and CD36 in WAT. Adiponectin expression was significantly increased, whereas inflammatory adipokines (leptin, resistin, TNF-α, MCP-1, and PAI-1) and the macrophage marker F4/80 were significantly reduced in the WAT of HFD-fed mice by 6-gingerol supplementation. In conclusion, 6-gingerol effectively contributed to the alleviation of adiposity and inflammation in WAT, which is associated with the regulation of adipokines in diet-induced obese mice.
Asunto(s)
Dieta Alta en Grasa , Leptina , Animales , Ratones , Dieta Alta en Grasa/efectos adversos , Adiposidad , Adipoquinas/metabolismo , Ratones Obesos , Ratones Endogámicos C57BL , Obesidad/etiología , Obesidad/complicaciones , Tejido Adiposo/metabolismo , Inflamación/metabolismoRESUMEN
This study aims to determine the relationship between chewing ability and the nutritional status of the elderly in Korea. This study utilized the data from the Korea National Health and Nutrition Examination Survey (KNHANES) conducted from 2013-2018 for persons who were ≥65 years of age. Of the 7835 subjects, 43.2% had chewing difficulty. Compared to the normal group, the chewing difficulty group had more stress, lower exercise frequency, less snack intake, a lower frequency of eating out, and a higher proportion of food insecurity. The chewing difficulty group had significantly lower food intake compared to the normal group, including various food groups such as cereals and grain, potatoes, fruits, meat, and milks and dairy products. The intake of fresh fruits was 24.5% lower and the intake of plant food (fresh fruits and nonstarchy vegetables) was 17.8% lower in the chewing difficulty group compared to the normal group. In addition, the intake of most nutrients (carbohydrates, fat, calcium, phosphorus, sodium, potassium, vitamin A, riboflavin, niacin, and vitamin C) was significantly lower in the chewing difficulty group than in the normal group. The chewing difficulty was significantly associated with undernutrition (OR = 1.63). In conclusion, chewing ability is closely related to food and nutrient intake among the elderly, which can decrease the quantity and quality of diet and is also related to undernutrition. Therefore, it is necessary to develop customized nutrition programs and aging-friendly food products that consider the chewing ability of the elderly.
Asunto(s)
Desnutrición , Estado Nutricional , Anciano , Humanos , Masticación , Encuestas Nutricionales , Frutas , Grano Comestible , República de Corea/epidemiologíaRESUMEN
This study examined the relationship between general population characteristics and diet-related factors pertaining to eating alone for older adults (65 years and older) in Korea. This study used the Korea National Health and Nutrition Examination Survey (KNHANES), 2016-2020, and the target population was 7037 Koreans aged 65 years or older who participated in the nutritional survey and health interview. Eating alone variables were classified as follows. Eating together all day means "eating together", eating only one meal a day means "1/day", eating two meals a day alone means "2/day", and "3/day" means eating three meals a day alone. The main results are as follows. The rate of moderate or severe food insecurity was 3.41% in the "eating together" group to 7.86% in the "3/day" group, which was 4.45% higher in the "3/day" group. Fruit + vegetable intake among food intake lowered by about 35 g from 301.2 g in the "eating together" group to 266.2 g in the "3 day" group. In addition, as a result of analyzing the prevalence of depression using the PHQ-9 score, the "3/day" group had a 1.775 to 2.464 times higher risk of depression than the "eating together" group. Finally, EQ-5D variables and quality of life scores were significantly lowered from the "eating together" group to the "3/day" group. Overall, higher frequency of eating alone was associated with food safety, essential food intake, and quality of life. Based on these results, it is thought that a dietary life support program such as the eating together program is necessary to improve the quality of life of the older people who eat alone.
Asunto(s)
Conducta Alimentaria , Calidad de Vida , Anciano , Humanos , Encuestas Nutricionales , República de Corea/epidemiología , Pueblos del Este de Asia , Estado de Salud , DietaRESUMEN
We developed a theoretical model for the relationship between the input and amplified laser beams of energy stability and spatial uniformity in the amplification process. 10 Hz, 8 ns, 1064 nm Nd:YAG Q-switched resonator with Nd:YAG main amplifier was employed for the experiment. The theoretical model simulation and Frantz-Nodvik simulation were performed by utilizing the obtained beam image, acquired energy from the experiment, and stored fluence from the gain medium. The result indicated that the fluctuation of the spatial distribution in a single beam influences the stability of temporally distributed energy during the amplification process of the laser beam, thereby improving energy stability.
RESUMEN
In this study, we simultaneously measured the group refractive index dispersion and thickness of fused silica using a scanning white light interferometer on a spectral range from 800 to 1050 nm. A delay error correction was performed using a He-Ne laser. The accuracy of the measured group refractive index dispersion of fused silica, when compared to the temperature-dependent Sellmeier equation, is within 4 × 10-5.
RESUMEN
This study aimed to observe the relationship between iodine nutrition status (dietary iodine intake and estimated iodine intake based on urinary iodine concentration (UIC)) and thyroid disease-related hormones. This study involved 6090 subjects >19 years old with valid UIC, assessed between 2013 and 2015 by the Korean National Health and Nutrition Examination Survey, using a stratified, multistage, clustered probability-sampling design. The estimated iodine intake in participants was measured using UIC and urine creatinine. To examine the effect of iodine intake on thyroid disease, the iodine intake was divided into Korean Dietary Reference Intakes groups, and logistic regression analysis was performed via the surveylogistic procedure to obtain odds ratios (ORs) and 95% confidence intervals (CIs). The estimated iodine intake showed a significant positive correlation with dietary iodine intake (r = 0.021, p < 0.001), UIC (r = 0.918, p < 0.001), and thyroid-stimulating hormone (TSH) (r = 0.043, p < 0.001), but a significant negative correlation with free thyroxine (FT4) (r = -0.037, p < 0.001). Additionally, as the estimated iodine intake increased, age, TSH, and UIC increased, but FT4 decreased (p for trend < 0.0001). The risk of thyroid disease was higher in the "≥tolerable upper intake level (UL ≥ 2400 µg/day)" group than in the "Asunto(s)
Encuestas Epidemiológicas
, Yodo/administración & dosificación
, Estado Nutricional
, Enfermedades de la Tiroides/epidemiología
, Enfermedades de la Tiroides/metabolismo
, Adulto
, Femenino
, Humanos
, Masculino
, República de Corea/epidemiología
, Hormonas Tiroideas
, Adulto Joven
RESUMEN
Dietary inorganic sulfur is the minor component in our diet, but some studies suggested that inorganic sulfur is maybe effective to treat cancer related illness. Therefore, this study aims to examine the effects of inorganic sulfur on cell proliferation and gene expression in MDA-MB-231 human breast cancer cells. MDA-MB-231 cells were cultured the absence or presence of various concentrations (12.5, 25, or 50 µmol/L) of inorganic sulfur. Inorganic sulfur significantly decreased proliferation after 72 h of incubation (P < 0.05). The protein expression of ErbB2 and its active form, pErbB2, were significantly reduced at inorganic sulfur concentrations of 50 µmol/L and greater than 25 µmol/L, respectively (P < 0.05). The mRNA expression of ErbB2 was significantly reduced at an inorganic sulfur concentration of 50 µmol/L (P < 0.05). The protein expression of ErbB3 and its active form, pErbB3, and the mRNA expression of ErbB3 were significantly reduced at inorganic sulfur concentrations greater than 25 µmol/L (P < 0.05). The protein and mRNA expression of Akt were significantly reduced at an inorganic sulfur concentration of 50 µmol/L (P < 0.05), but pAkt was not affected by inorganic sulfur treatment. The protein and mRNA expression of Bax were significantly increased with the addition of inorganic sulfur concentration of 50 µmol/L (P < 0.05). In conclusion, cell proliferation was suppressed by inorganic sulfur treatment through the ErbB-Akt pathway in MDA-MB-231 cells.
RESUMEN
AIMS: The present study investigated the detailed mechanism by which fractalkine (Fkn), a CX3C chemokine, induces angiogenesis and its functional implication in alleviating ischaemia in vivo. METHODS AND RESULTS: Fkn induced new vessel formation on the excised rat aorta and chick chorioallantoic membrane (CAM) through CX3CR1 activation. Immunoblotting analysis, promoter assay and electrophoretic mobility shift assay showed that Fkn upregulated hypoxia-inducible factor-1 alpha (HIF-1alpha) by cultured human aortic endothelial cells (ECs), which in turn induced mRNA and protein levels of vascular endothelial growth factor (VEGF)-A through a p42/44 mitogen-activated protein kinase pathway. In vivo Fkn-induced angiogenesis on CAM was completely blocked by functional inhibition of VEGF receptor 2 kinase insert domain-containing receptor (KDR) and Rho GTPase. C57/BL6 mice with CX3CR1(-/-) bone marrow-derived cells developed angiogenesis in the implanted Fkn-mixed Matrigel plug, suggesting CX3CR1 activation in vascular ECs is sufficient for Fkn-induced angiogenesis in vivo. The condition of rat hindlimb ischaemia, which rapidly stimulated mRNA expression of both Fkn and VEGF-A, was significantly alleviated by the injection of whole-length Fkn protein. CONCLUSION: Fkn-induced activation of CX3CR1 by ECs leads to in vivo angiogenesis through two sequential steps: the induction of HIF-1alpha and VEGF-A gene expression by CX3CR1 activation and the subsequent VEGF-A/KDR-induced angiogenesis. The potent induction of angiogenesis by Fkn can be used as a therapeutic strategy for alleviating peripheral ischaemia.
Asunto(s)
Proteínas Angiogénicas/metabolismo , Quimiocina CX3CL1/metabolismo , Células Endoteliales/metabolismo , Isquemia/metabolismo , Músculo Esquelético/irrigación sanguínea , Neovascularización Fisiológica , Receptores CXCR/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Proteínas Angiogénicas/farmacología , Animales , Receptor 1 de Quimiocinas CX3C , Línea Celular , Células Cultivadas , Quimiocina CX3CL1/genética , Quimiocina CX3CL1/farmacología , Embrión de Pollo , Modelos Animales de Enfermedad , Células Endoteliales/efectos de los fármacos , Células Endoteliales/enzimología , Miembro Posterior , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Isquemia/fisiopatología , Isquemia/terapia , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Neovascularización Fisiológica/efectos de los fármacos , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Receptores CXCR/genética , Receptores de Quimiocina/metabolismo , Proteínas Recombinantes/metabolismo , Flujo Sanguíneo Regional , Factores de Tiempo , Factor A de Crecimiento Endotelial Vascular/genética , Proteínas de Unión al GTP rho/metabolismoRESUMEN
The characteristics of rheumatoid arthritis (RA) pathology include the infiltration of inflammatory leukocytes, the proliferation of synovial cells, and the presence of extensive angiogenesis, referred to as rheumatoid pannus. Fas ligand is critical to the homeostatic regulation of the immune response, but its role in the angiogenic process of RA remains to be defined. In this study, we investigated whether soluble Fas ligand (sFasL) induces synoviocyte apoptosis and regulates angiogenesis of endothelial cells in RA. The levels of sFasL were elevated in the synovial fluids of RA patients when compared to those of osteoarthritis (OA) patients, and they correlated inversely with vascular endothelial growth factor165 (VEGF165) concentrations. sFasL, ranging from 10 to 100 ng/ml, induced the apoptosis of RA fibroblast-like synoviocytes (FLS) in vitro, and thereby decreased VEGF165 production. In addition, sFasL inhibited VEGF165-induced migration and chemotaxis of endothelial cells to basal levels in a manner independent of the Fas-mediated cell death. sFasL dose-dependently suppressed the VEGF165-stimulated increase in pAkt expression in endothelial cells, which might be associated with its anti-migratory effect on endothelial cells. Moreover, sFasL strongly inhibited neovascularization in the Matrigel plug in vivo. Our data suggest that sFasL shows anti-angiogenic activity within RA joints not only by inducing apoptosis of VEGF165-producing cells but also by blocking VEGF165-induced migration of endothelial cells, independent of Fas-mediated apoptosis.
Asunto(s)
Artritis Reumatoide/metabolismo , Proteína Ligando Fas/metabolismo , Neovascularización Patológica/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Apoptosis/fisiología , Artritis Reumatoide/patología , Western Blotting , Movimiento Celular/fisiología , Células Cultivadas , Células Endoteliales/metabolismo , Células Endoteliales/patología , Ensayo de Inmunoadsorción Enzimática , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Líquido Sinovial/química , Líquido Sinovial/metabolismoRESUMEN
Rheumatoid arthritis (RA) synoviocytes are resistant to apoptosis and exhibit a transformed phenotype, which might be caused by chronic exposure to genotoxic stimuli including reactive oxygen species and growth factors. In this study, we investigated the role of vascular endothelial growth factor165 (VEGF165), a potent angiogenic factor, and its receptor in the apoptosis of synoviocytes. We demonstrated here that neuropilin-1, rather than fms-like tyrosine kinase-1 and kinase insert domain-containing receptor, is the major VEGF165 receptor in the fibroblast-like synoviocytes. Neuropilin-1 was highly expressed in the lining layer, infiltrating leukocytes, and endothelial cells of rheumatoid synovium. The production of VEGF165, a ligand for neuropilin, was significantly higher in the RA synoviocytes than in the osteoarthritis synoviocytes. The ligation of recombinant VEGF165 to its receptor prevented the apoptosis of synoviocytes induced by serum starvation or sodium nitroprusside (SNP). VEGF165 rapidly triggered phospho-Akt and phospho-ERK activity and then induced Bcl-2 expression in the rheumatoid synoviocytes. The Akt or ERK inhibitor cancelled the protective effect of VEGF165 on SNP-induced synoviocyte apoptosis. Moreover, VEGF165 blocks SNP-induced Bcl-2 down-regulation as well as SNP-induced Bax translocation from the cytosol to the mitochondria. The down-regulation of the neuropilin-1 transcripts by short interfering RNA caused spontaneous synoviocyte apoptosis, which was associated with both the decrease in Bcl-2 expression and the increase in Bax translocation to mitochondria. Collectively, our data suggest that the interaction of VEGF165 with neuropilin-1 is crucial to the survival of rheumatoid synoviocytes and provide important implications for the abnormal growth of synoviocytes and therapeutic intervention in RA.
Asunto(s)
Apoptosis/efectos de los fármacos , Artritis Reumatoide/patología , Regulación de la Expresión Génica/efectos de los fármacos , Neuropilina-1/fisiología , Proteínas Proto-Oncogénicas c-bcl-2/genética , Membrana Sinovial/patología , Factor A de Crecimiento Endotelial Vascular/farmacología , Proteína X Asociada a bcl-2/metabolismo , Humanos , Neuropilina-1/metabolismo , Nitroprusiato/farmacología , Osteoartritis/patología , Unión Proteica , Transporte de Proteínas/efectos de los fármacos , ARN Interferente Pequeño/farmacología , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
The CC chemokine, monocyte chemoattractant protein-1 (MCP-1), plays a crucial role in the initiation of atherosclerosis and has direct effects that promote angiogenesis. To develop a specific inhibitor for MCP-1-induced angiogenesis, we performed in vitro selection employing phage display random peptide libraries. Most of the selected peptides were found to be homologous to the second extracellular loops of CCR2 and CCR3. We synthesized the peptide encoding the homologous sequences of the receptors and tested its effect on the MCP-1 induced angiogenesis. Surface plasmon resonance measurements demonstrated specific binding of the peptide to MCP-1 but not to the other homologous protein, MCP-3. Flow cytometry revealed that the peptide inhibited the MCP-1 binding to THP-1 monocytes. Moreover, CAM and rat aortic ring assays showed that the peptide inhibited MCP-1 induced angiogenesis. Our observations indicate that the MCP-1-binding peptide exerts its anti-angiogenic effect by interfering with the interaction between MCP-1 and its receptor.
Asunto(s)
Inhibidores de la Angiogénesis/farmacología , Quimiocina CCL2/antagonistas & inhibidores , Neovascularización Fisiológica/efectos de los fármacos , Oligopéptidos/farmacología , Inhibidores de la Angiogénesis/síntesis química , Animales , Aorta/efectos de los fármacos , Bioensayo , Quimiocina CCL2/fisiología , Humanos , Oligopéptidos/síntesis química , Biblioteca de Péptidos , Ratas , Receptores CCR2 , Receptores de Quimiocina/efectos de los fármacos , Receptores de Quimiocina/fisiología , Resonancia por Plasmón de SuperficieRESUMEN
BACKGROUND: The migration of circulating monocytes to the arterial wall during atherogenesis is largely modulated by activation of the CC chemokine receptor 2 (CCR2), a dominant monocyte chemotaxis receptor. The present study investigated whether 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibition affects CCR2 gene expression and CCR2-dependent monocyte recruitment. METHODS AND RESULTS: Competitive reverse transcription-polymerase chain reaction analysis and flow cytometry showed that simvastatin, an HMG-CoA reductase inhibitor, dose-dependently reduced monocyte CCR2 mRNA and protein expression. Treatment of 21 normocholesterolemic men with simvastatin (20 mg/d for 2 weeks) decreased CCR2 protein and mRNA expression in circulating monocytes. Promoter and electrophoretic mobility shift assays showed that simvastatin activated a peroxisome proliferator response element in THP-1 monocytes. Moreover, simvastatin-induced CCR2 downregulation was completely reversed by the synthetic peroxisome proliferator-activated receptor-gamma antagonist GW9662. Simvastatin-treated monocytes showed little chemotaxis movement in response to monocyte chemoattractant protein-1 (MCP-1), a specific CCR2 ligand. Treatment of C57/BL6 mice with simvastatin (0.2 microg/g body weight IP, daily for 1 week) inhibited transmigration of CD80+ monocytes to the MCP-1-injected intraperitoneal space. Moreover, few circulating inflammatory cells from simvastatin-treated Sprague-Dawley rats (0.2 microg/g body weight IP, daily for 2 weeks) were recruited to the aortic wall of hypercholesterolemic littermates. CONCLUSIONS: The inhibition of CCR2/MCP-1-dependent monocyte recruitment by simvastatin may prevent excessive accumulation of monocytes in the arterial wall during atherogenesis.
Asunto(s)
Quimiocina CCL2/metabolismo , Quimiotaxis de Leucocito/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Monocitos/efectos de los fármacos , Receptores de Quimiocina/biosíntesis , Simvastatina/farmacología , Anilidas/farmacología , Animales , Aorta/metabolismo , Aorta/patología , Células Cultivadas/efectos de los fármacos , Células Cultivadas/metabolismo , Depresión Química , Dieta Aterogénica , Evaluación Preclínica de Medicamentos , Femenino , Humanos , Hipercolesterolemia/metabolismo , Hipercolesterolemia/patología , Masculino , Ácido Mevalónico/análisis , Ratones , Ratones Endogámicos C57BL , Monocitos/química , PPAR gamma/antagonistas & inhibidores , PPAR gamma/fisiología , Fosfatos de Poliisoprenilo/análisis , ARN Mensajero/biosíntesis , Ratas , Ratas Sprague-Dawley , Receptores CCR2 , Receptores de Quimiocina/genética , Rosiglitazona , Sesquiterpenos , Tiazolidinedionas/farmacologíaRESUMEN
Matrix metalloproteinase-9 (MMP-9) has been implicated in the pathogenesis of cancer, autoimmune disease, and various pathologic conditions characterized by excessive fibrosis. In this study, we investigated the expression of MMP-9 and its clinical significance in systemic sclerosis (SSc). The patients (n = 42) with SSc had higher concentrations of MMP-9 and of tissue inhibitor of metalloproteinase-1 (TIMP-1) and a higher ratio of MMP-9 to TIMP-1 in sera than healthy controls (n = 32). Serum MMP-9 concentrations were significantly higher in the diffuse type (n = 23) than the limited type of SSc (n = 19). Serum concentrations of MMP-9 correlated well with the degree of skin involvement, as determined by the Rodnan score and with serum concentrations of transforming growth factor beta. Moreover, dermal fibroblasts from patients with SSc produced more MMP-9 than those from healthy controls when they were stimulated with IL-1beta, tumor necrosis factor alpha, or transforming growth factor beta. Such an increase in MMP-9 production was partially blocked by treatment with cyclosporin A. In summary, the serum MMP-9 concentrations were elevated in SSc patients and correlated well with skin scores. The increased MMP-9 concentrations may be attributable to overproduction by dermal fibroblasts in SSc. These findings suggest that the enhanced production of MMP-9 may contribute to fibrogenic remodeling during the progression of skin sclerosis in SSc.
Asunto(s)
Metaloproteinasa 9 de la Matriz/sangre , Esclerodermia Sistémica/sangre , Adulto , Anciano , Biomarcadores , Células Cultivadas/efectos de los fármacos , Células Cultivadas/enzimología , Ensayo de Inmunoadsorción Enzimática , Femenino , Fibroblastos/efectos de los fármacos , Fibroblastos/enzimología , Humanos , Interleucina-1/farmacología , Masculino , Metaloproteinasa 2 de la Matriz/sangre , Persona de Mediana Edad , Esclerodermia Sistémica/enzimología , Esclerodermia Sistémica/patología , Índice de Severidad de la Enfermedad , Piel/patología , Inhibidor Tisular de Metaloproteinasa-1/sangre , Factor de Crecimiento Transformador beta/sangre , Factor de Crecimiento Transformador beta/farmacología , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
Monocyte chemoattractant protein-1 (MCP-1) has been recognized as an angiogenic chemokine. In the present study, we investigated the detailed mechanism by which MCP-1 induces angiogenesis. We found that MCP-1 up-regulated hypoxia-inducible factor 1 alpha (HIF-1 alpha) gene expression in human aortic endothelial cells (HAECs), which induced vascular endothelial growth factor-A(165) (VEGF-A(165)) expression in the aortic wall and HAECs through activation of p42/44 mitogen-activated protein kinase (MAPK). In vivo angiogenesis assay using chick chorioallantoic membrane (CAM) showed that MCP-1-induced angiogenesis was as potent as that induced by VEGF-A(165) and completely inhibited by a VEGF inhibitor, Flt(2-11). The inhibition of RhoA small G protein did not affect MCP-1-induced VEGF-A(165) production and secretion but completely blocked both MCP-1- and VEGF-A-induced new vessel formation, as determined by CAM assay. These results suggest that MCP-1-induced angiogenesis is composed largely of 2 sequential steps: the induction of VEGF-A gene expression by MCP-1 and the subsequent VEGF-A-induced angiogenesis.
Asunto(s)
Inductores de la Angiogénesis/administración & dosificación , Quimiocina CCL2/administración & dosificación , Neovascularización Fisiológica/fisiología , Factor A de Crecimiento Endotelial Vascular/fisiología , Animales , Aorta Abdominal/fisiología , Aorta Torácica/fisiología , Células Cultivadas , Quimiocina CCL2/metabolismo , Endotelio Vascular/citología , Endotelio Vascular/metabolismo , Endotelio Vascular/fisiología , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia , Masculino , ARN Mensajero/biosíntesis , Ratas , Ratas Sprague-Dawley , Factores de Transcripción/biosíntesis , Factores de Transcripción/genética , Factor A de Crecimiento Endotelial Vascular/biosíntesis , Factor A de Crecimiento Endotelial Vascular/genéticaRESUMEN
Oxidized low-density lipoprotein (OxLDL) is an inflammatory modulator in the atherosclerotic plaque. We examined the effect of lysophosphatidylcholine (lysoPC), a main phospholipid component of OxLDL, on inflammatory responses in human CD4 T cells. We found that lysoPC dose- and time-dependently increased expression of CXCR4, the chemokine receptor on CD4 T cells. This increase was inhibited by caffeic acid phenethyl ester or SN50, nuclear factor-kappaB inhibitors, and also by suppression of G2A expression, the specific receptor for lysoPC, using antisense oligonucleotide. lysoPC enhanced CD4 T cell chemotaxis in response to stromal cell-derived factor-1 (SDF-1), the exclusive ligand for CXCR4. lysoPC also enhanced SDF-1-stimulated production of inflammatory cytokines interleukin-2 and interferon-gamma by CD4 T cells activated by anti-CD3 immunoglobulin G. In conclusion, this study demonstrates that lysoPC directly modulates inflammatory responses in human CD4 T cells. The data suggest that the presence of lysoPC and SDF-1 in atherosclerotic lesions may trigger inflammatory responses mediated by CD4 T cells, which may play an important role in progression of atherosclerosis.
Asunto(s)
Linfocitos T CD4-Positivos/metabolismo , Lisofosfatidilcolinas/farmacología , Receptores CXCR4/efectos de los fármacos , Arteriosclerosis/inmunología , Linfocitos T CD4-Positivos/efectos de los fármacos , Proteínas de Ciclo Celular/metabolismo , Quimiocina CXCL12 , Quimiocinas/metabolismo , Quimiocinas CXC/farmacología , Quimiotaxis de Leucocito/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Citometría de Flujo , Humanos , FN-kappa B/metabolismo , Reacción en Cadena de la Polimerasa , Receptores CXCR4/biosíntesis , Receptores Acoplados a Proteínas G/metabolismo , Factores de Tiempo , Regulación hacia ArribaRESUMEN
BACKGROUND: Inflammation plays a crucial role in atherosclerosis. An elevated serum C-reactive protein (CRP) level is a strong marker for future atherosclerotic cardiovascular diseases. In addition, recent data suggest that CRP may directly promote atherogenesis. In this study, we investigated whether CRP can directly activate human circulating monocytes. METHODS AND RESULTS: Incubation of THP-1 monocytes with CRP (10 microg/mL) increased CC chemokine receptor 2 (CCR2) expression at both the protein and transcript levels, which in turn enhanced chemotaxis mediated by monocyte chemoattractant protein-1 (MCP-1) up to 2-fold. The CRP-induced upregulation of CCR2 expression involved binding of CRP to the FcgammaR, most notably FcgammaRI, and phospholipase D1 activation. Serum high-sensitivity CRP levels in 52 normocholesterolemic human subjects were positively correlated with CCR2 surface expression on circulating monocytes (r=0.62, P<0.001) and MCP-1-mediated monocyte chemotaxis (r=0.53, P<0.001). CONCLUSIONS: Elevated blood CRP levels may promote accumulation of monocytes in the atherogenic arterial wall by increasing chemotactic activities of monocytes in response to MCP-1.
Asunto(s)
Arteriosclerosis/fisiopatología , Proteína C-Reactiva/farmacología , Quimiocina CCL2/fisiología , Quimiotaxis/efectos de los fármacos , Monocitos/efectos de los fármacos , Receptores de Quimiocina/biosíntesis , Arteriosclerosis/sangre , Células Cultivadas/efectos de los fármacos , Quimiotaxis/fisiología , Colesterol/sangre , Activación Enzimática , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Monocitos/fisiología , Músculo Liso Vascular/citología , Miocitos del Músculo Liso/citología , Miocitos del Músculo Liso/efectos de los fármacos , Fosfolipasa D/metabolismo , Receptores CCR2 , Receptores de Quimiocina/genética , Receptores de IgG/efectos de los fármacos , Receptores de IgG/fisiología , Proteínas Recombinantes/farmacología , Transcripción Genética/efectos de los fármacos , Regulación hacia Arriba/efectos de los fármacosRESUMEN
OBJECTIVE: Uncoupling protein 2 (UCP2) belongs to the mitochondrial anion carrier family and regulates production of reactive oxygen species in macrophages. Previous studies have shown that selective genetic disruption of UCP2 in bone marrow cells results in excess accumulation of monocytes/macrophages in the vascular wall of hypercholesterolemic low-density lipoprotein receptor-deficient (LDLR-/-) mice. Here we investigated whether UCP2 regulates expression of genes involved in monocyte recruitment. METHODS AND RESULTS: UCP2 overexpression in THP1 monocytes, which induced a 10-fold increase in mitochondrial UCP2 protein levels, reduced steady-state level of intracellular reactive oxygen species (ROS) and H2O2-induced ROS production. THP1 monocytes with UCP2 overexpression showed lower intracellular calcium levels and less H2O2-triggered intracellular calcium mobilization, and less protein and mRNA levels of beta2 integrins, most notably CD11b. UCP2 overexpression reduced beta2 integrin-mediated firm adhesion of monocytes to either tumor necrosis factor-alpha (TNF-alpha)-stimulated human aortic endothelial cell (HAEC) monolayers or to plates coated with intercellular adhesion molecule-1, not vascular cell adhesion molecule-1. UCP2 overexpression also inhibited cell spreading and actin polymerization in monocytes treated with TNF-alpha and monocyte chemoattractant protein-1 (MCP-1), and reduced MCP-1-induced transmigration of monocytes through HAEC monolayers. CONCLUSIONS: Mitochondrial UCP2 in circulating monocytes may prevent excessive accumulation of monocytes/macrophages in the arterial wall, thereby reducing atherosclerotic plaque formation.