RESUMEN
Atherosclerosis (AS) is the main pathological basis of cardiovascular diseases such as coronary heart disease. Black phosphorus quantum dots (BPQDs) are a novel nanomaterial with good optical properties and biocompatibility, which was applied in the treatment of AS in mice, with good results shown in our previous study. In this study, BPQDs were injected into high-fat diet-fed apolipoprotein E knockout mice as a preventive drug for 12 weeks. Simvastatin, a classic preventive drug for AS, was used as a control to verify the preventive effect of BPQDs. The results showed that after preventive treatment with BPQDs, the plaque area in mice was significantly reduced, the vascular elasticity was increased, and serum lipid levels were significantly lower than those in the model group. To explore the mechanism, macrophages were induced to become foam cells using oxidized low-density lipoprotein. We found that BPQDs treatment could increase cell autophagy, thereby regulating intracellular lipid metabolism. Taken together, these data revealed that BPQDs may serve as a functional drug in preventing the development of AS.
Asunto(s)
Aterosclerosis , Dieta Alta en Grasa , Fósforo , Puntos Cuánticos , Animales , Dieta Alta en Grasa/efectos adversos , Aterosclerosis/prevención & control , Ratones , Fósforo/sangre , Ratones Noqueados , Apolipoproteínas E/genética , Masculino , Autofagia/efectos de los fármacos , Ratones Noqueados para ApoE , Metabolismo de los Lípidos/efectos de los fármacos , Modelos Animales de Enfermedad , Placa Aterosclerótica/prevención & control , Lipoproteínas LDL/metabolismo , Lipoproteínas LDL/sangre , Simvastatina/farmacología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Células Espumosas/efectos de los fármacos , Células Espumosas/metabolismoRESUMEN
Natural products have been widely recognized in clinical treatment because of their low toxicity and high activity. It is worth paying attention to modifying the biopolymer into nanostructures to give natural active ingredients additional targeting effects. In this study, based on the multifunctional modification of ß-cyclodextrin (ß-CD), a nanoplatform encapsulating the unstable drug (-)-epicatechin gallate (ECG) was designed to deliver to atherosclerotic plaques. Acetalization cyclodextrin (PH-CD), which responds to low-pH environments, and hyaluronic acid cyclodextrin, which targets the CD44 receptor on macrophage membranes, were synthesized from ß-CD and hyaluronic acid using acetalization and transesterification, respectively. The resulting dual-carrier nanoparticles (Double-NPs) loaded with ECG were prepared using a solvent evaporation method. The Double-NPs effectively scavenged reactive oxygen species, promoted macrophage migration, inhibited macrophage apoptosis, and suppressed abnormal proliferation and migration of vascular smooth muscle cells. Furthermore, the Double-NPs actively accumulated in atherosclerotic plaques in ApoE-/- mice fed with a high-fat diet, leading to a reduced plaque area, inflammatory infiltration, and plaque instability. Our findings demonstrate that the newly developed ECG nanopreparation represents an effective and safe nanotherapy for diseases such as atherosclerosis.
Asunto(s)
Aterosclerosis , Ácido Hialurónico , Nanopartículas , beta-Ciclodextrinas , Ácido Hialurónico/química , Animales , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/prevención & control , Ratones , beta-Ciclodextrinas/química , Nanopartículas/química , Catequina/análogos & derivados , Catequina/química , Catequina/farmacología , Células RAW 264.7 , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Apoptosis/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Portadores de Fármacos/química , Movimiento Celular/efectos de los fármacos , Humanos , Placa Aterosclerótica/tratamiento farmacológico , Placa Aterosclerótica/prevención & control , Proliferación Celular/efectos de los fármacosAsunto(s)
Placa Aterosclerótica , Humanos , Placa Aterosclerótica/prevención & control , Ensayos Clínicos Controlados Aleatorios como Asunto , Enfermedad de la Arteria Coronaria/prevención & control , Enfermedad de la Arteria Coronaria/terapia , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéuticoRESUMEN
This article aims to investigate the effect of Zhuyu Pills on atherosclerosis and decipher the underlying mechanism. The mouse model of atherosclerosis was induced by a high-fat diet, and the total modeling period was 12 weeks. A total of 47 ApoE~(-/-) mice successfully modeled were randomized into 5 groups, including 10 in the model group, 9 in each of low-, medium-, and high-dose(130.54, 261.08 and 522.16 mg·kg~(-1)·d~(-1), respectively) Zhuyu Pills groups, and 10 in the atorvastatin calcium(10.40 mg·kg~(-1)·d~(-1)) group. In addition, 10 C57BL/6J mice were included as the normal group. The mice in the normal group and model group were administrated with an equal volume of sterile distilled water, and those in other groups with corresponding agents by gavage once a day for 12 weeks. At the end of drug intervention, the levels of total cholesterol(TC), triglyceride(TG), high-density lipoprotein cholesterol(HDL-C), and low-density lipoprotein cholesterol(LDL-C) were measured by the biochemical method. Hematoxylin-eosin(HE) staining was employed to observe the plaque distribution in the aortic region. The serum levels of pro-inflammatory cytokines tumor necrosis factor-α(TNF-α) and interleukin(IL)-6 in M1 macrophages and anti-inflammatory cytokines IL-13 and IL-4 in M2 macrophages were determined by enzyme-linked immunosorbent assay(ELISA). The expression levels of inducible nitric oxide synthase(iNOS) and arginase-1(Arg-1) were examined by immunofluorescence. Real-time fluorescence quantitative polymerase chain reaction(real-time PCR) was employed to measure the mRNA levels of peroxisome proliferator-activated receptor γ(PPARγ), nuclear factor-κB(NF-κB), Arg-1, and iNOS in the aorta. Western blot was employed to determine the protein levels of PPARγ and NF-κB in the aorta. The results showed that compared with the normal group, the modeling elevated the TC, TG, and LDL-C levels, lowered the HDL-C level, caused large area thickening of the aortic intima, elevated the TNF-α and IL-6 levels, lowered the IL-4 and IL-13 levels, down-regulated the mRNA and protein levels of PPARγ and Arg-1, and up-regulated the mRNA and protein levels of iNOS and NF-κB in the aorta(P<0.01). Compared with the model group, low-, medium-, and high-dose Zhuyu Pills and atorvastatin calcium lowered the TC, TG, and LDL-C levels, elevated the HDL-C level, reduced the plaque area in a concentration-dependent manner, lowered the TNF-α and IL-6 levels, elevated the IL-4 and IL-13 levels, up-regulated the mRNA and protein levels of PPARγ and Arg-1, and down-regulated the mRNA and protein levels of NF-κB and iNOS in the aorta(P<0.05 or P<0.01). In conclusion, Zhuyu Pills may play an anti-atherosclerosis role by regulating PPARγ/NF-κB signaling pathway, inhibiting the polarization of macrophages toward the M1 phenotype, promoting the polarization of macrophages toward the M2 phenotype, and improving the inflammatory microenvironment of macrophages.
Asunto(s)
Aterosclerosis , Placa Aterosclerótica , Ratones , Animales , FN-kappa B/genética , FN-kappa B/metabolismo , PPAR gamma/genética , Factor de Necrosis Tumoral alfa , Interleucina-6 , Interleucina-13/genética , LDL-Colesterol , Atorvastatina/farmacología , Interleucina-4 , Ratones Endogámicos C57BL , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/genética , Aterosclerosis/prevención & control , Transducción de Señal , Placa Aterosclerótica/tratamiento farmacológico , Placa Aterosclerótica/genética , Placa Aterosclerótica/prevención & control , Citocinas/metabolismo , Macrófagos/metabolismo , Fenotipo , ARN MensajeroRESUMEN
Introducción: La aterosclerosis subclínica es predictora de eventos vasculares futuros y es diagnosticada por imágenes y biomarcadores sin que existan manifestaciones clínicas. Objetivo: Identificar los factores pronósticos asociados con la aterosclerosis subclínica en pacientes dislipidémicos. Método: Se realizó un estudio de cohorte en el Hospital Hermanos Ameijeiras en 1028 pacientes en el periodo de 2016 al 2019. Resultados: La existencia de placa de ateroma fue de 26,9 por ciento. Existieron diferencias significativas relacionadas al tabaquismo (30,0 por ciento vs 23,7 por ciento). En las variables lipídicas, el promedio de los valores de la LDLc fue superior en los pacientes con placa de ateroma y la relación CT/LDL fue mayor en los que no tienen esta alteración. La frecuencia de engrosamiento del complejo íntima-media mayor de 1,0 mm fue de 37,1 por ciento. Existieron diferencias significativas relacionadas al tabaquismo (30,4 por ciento vs 22,4 por ciento) y la presencia de HTA (56,7 por ciento vs 48,8 por ciento ) en las variables lipídicas el promedio de los valores de la HDLc fue superior en los pacientes sin aumento del grosor del complejo íntima-media y la elevación CT/HDL fue mayor en los que presentan dicha alteración. Conclusiones: Los factores que influyen de manera independiente en la probabilidad de formación de las placas de ateroma son la LDLc (elevada), la edad, los triglicéridos y el sexo masculino y los que influyen en la probabilidad para el engrosamiento del complejo íntima-media son la HDLc (baja), el tabaquismo, y la hipertensión arterial(AU)
Introduction: Subclinical atherosclerosis is a predictor of future vascular events and is diagnosed by imaging and biomarkers without any clinical manifestations. Objective: To identify the prognostic factors that are associated with subclinical atherosclerosis in dyslipidemic patients. Method: A cohort study was carried out at the Hermanos Ameijeiras Hospital in 1028 patients in the period from 2016 to 2019. Results: The existence of atheroma plaque was 26.9 percent. There were significant differences related to smoking (30.0 percent vs 23.7 percent). In the lipid variables, the average of the LDLc values is higher in patients with atheroma plaque and the CT/LDL ratio is higher in those without this alteration. Regarding the frequency of thickening of the intima-media complex greater than 1.0 mm, it was 37.1 percent. There were significant differences related to smoking (30.4 percent vs 22.4 percent) and the presence of HTA (56.7 percent vs 48.8 percent in the lipid variables, the average of the HDLc values is higher in the patients without an increase in the thickness of the intima-media complex and the CT/HDL elevation is greater in those with said alteration. Conclusions: The factors that independently influence the probability of atheroma plaque formation are LDLc (elevated), age, triglycerides and male sex, and those that influence the probability of thickening of the intima-media complex. They are HDLc (low), smoking, and high blood pressure(AU)
Asunto(s)
Humanos , Masculino , Femenino , Pronóstico , Aterosclerosis/diagnóstico por imagen , Dislipidemias/complicaciones , Placa Aterosclerótica/prevención & control , Estudios de CohortesRESUMEN
Las enfermedades cardiovasculares siguen siendo la principal causa de morbimortalidad en el mundo occidental. Entre los principales factores de riesgo de estas enfermedades están las hiperlipemias, entre ellas la hipercolesterolemia y la dislipemia aterogénica. Los tratamientos habituales de la hipercolesterolemia incluyen los inhibidores de la HMG-CoA reductasa (estatinas), los inhibidores de la NPC1L1 (ezetimiba), los fitosteroles, la menacolina K, los secuestradores de las sales biliares y los inhibidores de la PCSK9. Los fármacos hipolipemiantes en desarrollo son los inhibidores de la proteína transportadora del colesterol esterificado (CETP), los oligonucleótidos antisentido y los inhibidores de la proteína microsomal de transferencia de triglicéridos. La relación entre hiperlipemia y ateroesclerosis está bien documentada. Un fenómeno clave en la evolución de la ateroesclerosis coronaria es el remodelado positivo, descrito por Glagov hace más de 3 décadas, que consiste en el incremento del diámetro de la arteria a medida que progresa la placa de ateroma y aumenta su volumen, de modo que se atenúa la reducción de la luz vascular que tendría lugar como consecuencia del crecimiento de la placa de ateroma. Así, solo en fases muy finales, cuando el aumento del diámetro del vaso no es capaz de compensar el crecimiento de la placa de ateroma, tendrían lugar la reducción del flujo coronario y las consecuencias clínicas de esta. En este artículo se revisan los mecanismos de acción de los fármacos hipolipemiantes y la implicación de controlar las concentraciones lipídicas en la regresión de la placa ateroesclerótica (AU)
Cardiovascular disease continues to be the most common cause of morbidity and mortality in western countries. Hyperlipidaemia, including hypercholesterolemia and atherogenic dyslipidaemia, is one the main risk factors for atherosclerotic heart disease. Routine therapies for hypercholesterolaemia include HMG-CoA reductase inhibitors (statins), NPC1L1 inhibitors (ezetimibe), phytosterols, menacholyne K, bile salt sequestrants and PCSK9 inhibitors. New drugs under development are CEPT inhibitors, antisense oligonucleotides and inhibitors of microsomal triglyceride transfer protein. The association between hyperlipidaemia and atherosclerosis is well documented. Arterial wall remodelling, described by Glagov more than 3 decades ago, is a key phenomenon in coronary artery atherosclerosis. When atherosclerotic plaque increases, artery diameter also increases to compensate lumen reduction. It is only in the final stage of the process, when the increase in diameter is unable to compensate for plaque growth, that clinical ischaemia develops. In this article, we review the mechanisms of action of drugs used for the treatment of dyslipidaemia, and the role of lipid level control in plaque reversal (AU)
Asunto(s)
Humanos , Investigación Biomédica Traslacional/métodos , Investigación Biomédica Traslacional/tendencias , Hiperlipidemias/prevención & control , Hiperlipidemias/terapia , Placa Aterosclerótica/terapia , Placa Aterosclerótica/epidemiología , Placa Aterosclerótica/prevención & control , Proproteína Convertasa 9/uso terapéutico , Combinación Ezetimiba y Simvastatina/uso terapéutico , Ezetimiba/uso terapéutico , Fitosteroles/uso terapéutico , Sistemas de Liberación de Medicamentos/métodosRESUMEN
Resumen Introducción. Las estrías de grasa en la pared arterial pueden aparecer desde el tercer año Resumende vida y se relacionan con factores de riesgo aterogénico, como la hipertensión arterial sistémica y el contenido de sodio en la dieta. En pocos estudios se reporta el consumo de sodio en la dieta debido a la dificultad para la recolección de los datos. Objetivo. Determinar el consumo promedio de sodio en la dieta de niños de uno a 18 meses de edad, mediante una encuesta sobre la dieta a lo largo de tres días. Materiales y métodos. Se hizo un estudio de corte transversal con 48 niños sin enfermedad renal ni restricciones en la dieta, atendidos en consulta pediátrica entre enero y junio del 2011, el cual incluyó una encuesta sobre la dieta a los padres y la clasificación del estado nutricional por antropometría y medición de la presión arterial. Se analizaron el contenido de sodio y demás nutrientes de la dieta con el Programa Internacional de Consumo de Alimentos (CERES), las medidas antropométricas con el programa Anthro de la Organización Mundial de la Salud y las características sociodemográficas con el programa de Epi-info. Resultados. El 69 % de los niños tenía un consumo alto de sodio, el 6,2 % presentaba presión arterial elevada, y el 20,7 %, sobrepeso y obesidad. Conclusiones. La prevalencia de hipertensión arterial sistémica superó la informada para Colombia (1 a 3 %). Dos de los tres niños con presión arterial elevada tenían una dieta rica en sodio, así como sobrepeso y obesidad con valores superiores a lo informado para Colombia (16 %). Se sugiere medir la presión arterial tempranamente, recomendar la restricción de sal y azúcar en la alimentación de los menores de dos años, desarrollar estudios más grandes para obtener datos poblacionales sobre la ingestión de sodio, y diseñar estrategias de intervención, adecuadas y oportunas, para disminuir los riesgos en la edad adulta.
Abstract Introduction: The fatty streaks in an arterial wall can appear from the third year of age, and they show an association with atherogenic risk factors such as hypertension and sodium in the diet. Given the difficulty of data gathering, few studies report the intake of sodium in the diet. Objective: To determine average sodium intake in the diet of children between one and 18 months of age through a three-day dietary survey. Materials and methods: This was a cross-sectional study with 48 children without renal disease or diet restrictions seen in pediatric practice between January and June, 2011. It included a dietary survey for the parents, nutritional status classification by anthropometry, and blood pressure measurements. Sodium content and other nutrients in the diet program were analyzed with the International Food Consumption Program (CERES), anthropometry with the World Health Organization Anthro program, and Epi-info for socio-demographic characteristics. Results: In total, 69% of children had high sodium consumption, 6.2% had high blood pressure, and 20.7% were overweight and obese. Conclusions: The prevalence of hypertension exceeds that reported for Colombia (1-3%). Two of the three children with high blood pressure had high sodium intake and they were overweight and obese, with values above those reported for Colombian children (16%). We suggest to measure blood pressure early, and to restrict salt and sugar in food for infants and children under two years of age. Also, larger studies should be conducted to collect population data on sodium intake and develop appropriate and timely intervention strategies to reduce risks in adulthood.
Asunto(s)
Femenino , Humanos , Lactante , Masculino , Sodio en la Dieta/efectos adversos , Sobrepeso/epidemiología , Hipertensión/epidemiología , Alimentos Infantiles , Factores Socioeconómicos , Población Urbana , Antropometría , Encuestas sobre Dietas , Prevalencia , Estudios Transversales , Colombia , Edad de Inicio , Sobrepeso/etiología , Placa Aterosclerótica/etiología , Placa Aterosclerótica/prevención & control , Hipertensión/etiología , Obesidad/etiología , Obesidad/epidemiologíaRESUMEN
Estudos têm associado a doença periodontal com a aterosclerose e as doenças cardiovasculares. Este trabalho apresenta resultados de importante estudo que evidencia essa relação. Esta é a primeira evidência que comprova que a melhora no periodonto, definido pelos aspectos clínicos e microbiológicos, está associada a menor progressão de aterosclerose das carótidas. O trabalho, uma coorte de base populacional,ressalta a importância de uma abordagem multidisciplinar para os pacientes, especialmente dos médicos e cirurgiões-dentistas, para a prevenção e controle das doenças cardiovasculares. Futuros estudos poderão mostrar que a saúde bucal pode ser um importante indicador prognóstico da saúde geral do paciente.
Studies have linked periodontal disease to atherosclerosis and cardiovascular diseases. This paper presents the results of a major study that underscores this relationship. This is the first evidence showing that better periodontal conditions, defined through clinical and microbiological aspects, are associated with less progression incarotid atherosclerosis. This population-based cohort study highlights the importance of a multidisciplinary approach to patients, especially for physicians and dentists, in order to prevent and control cardiovascular diseases. Future studies might well show that oral health could be an important prognostic indicator of general patient health.