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1.
Medicine (Baltimore) ; 99(1): e18612, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31895813

RESUMO

BACKGROUND: Uterus transplantation is a complex, multi-step experimental procedure used for the treatment of uterus absence or uterus anomaly that prevents embryo implantation or pregnancy completion. METHOD: To date, only 51 uterus transplants worldwide had been performed. When simplified, it is vascularized composite allograft transplantation. While it is still an experimental procedure with encouraging results for the future, there are still many issues that have to be clarified. The most serious complications of uterus transplantation are graft rejection or grafts vascular failure. RESULTS: So far, no reference to the atherosclerotic arterial infiltration of the uterus arteries was suggested and studied as one of the main causes of graft's failure. CONCLUSION: In this review we summarized current knowledge and possible role of uterus arterial damage, including atherosclerotic changes on the graft's survival.


Assuntos
Aterosclerose/etiologia , Artéria Uterina , Útero/transplante , Alotransplante de Tecidos Compostos Vascularizados/efeitos adversos , Feminino , Humanos , Óxido Nítrico/metabolismo , Túnica Íntima/metabolismo , Útero/irrigação sanguínea , Remodelação Vascular
2.
J Ethnopharmacol ; 247: 112232, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31606534

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: 2,3,5,4'-Tetrahydroxy-stilbene-2-O-ß-D-glucoside (TSG) is the main active component of Polygoni Multiflori Radix, a root of the homonymous plant widely used in traditional Chinese medicine. TSG has protective effects on the liver, reduces cholesterol and possesses anti-oxidant, anti-tumor, and anti-atherosclerotic properties. However, the pharmacological effects and mechanisms of action of Polygonum multiflorum on atherosclerosis (AS) have not been studied yet. PURPOSE: The aim of this research was to study the effects of Polygoni Multiflori Radix Praeparata (PMRP) and its major active chemical constituent TSG on AS in ApoE-deficient (ApoE-/-) mice fed with high fat diets to provide a scientific basis in the use of PMRP and TSG against cardiovascular diseases. METHODS: High fat diet induced AS in ApoE-/- mice were treated with PMRP, TSG (low and high doses), and simvastatin (SIM) for 8 weeks. At the end of the treatment, mouse serum lipid levels, triglycerides (TG), and total cholesterol (TC) were measured by an oxidase method (other indicators were determined by ELISA), while the content in oxidized low density lipoprotein (ox-LDL) and the expression of inflammatory factors such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), vascular cell adhesion molecule-1 (VCAM-1), and monocyte chemotactic protein-1 (MCP-1) in the serum and aortic samples were measured by ELISA. Atherosclerotic plaque morphology was evaluated by oil red O in thoracic aorta. In addition, 16S rDNA-V4 hypervariable region genome sequence of all microbes in the fecal sample from each group was analyzed to evaluate potential structure changes in the gut microbiota after treatment with PMRP and TSG. RESULTS: TSG markedly inhibited AS plaque formation in ApoE-/- mice. Furthermore, PMRP and TSG improved lipid accumulation by reducing TG and ox-LDL levels. TSG inhibited inflammation by the down-regulation of IL-6, TNF-α, VCAM-1 and MCP-1 expression in serum, and PMRP inhibited inflammation by reducing VCAM-1, ICAM-1 and CCRA expression in aortic tissue. In addition, TSG reduced or prevented AS by the regulation of the composition of the overall gut microbiota, such as Firmicutes, Bacteroidetes, Tenericutes, Proteobacteria phyla, Akkermensia genera and Helicobacter pylori. CONCLUSION: PMRP and TSG improved lipid accumulation and inflammation, and regulated the intestinal microbial imbalance in ApoE-/- mice. TSG exerted a preventive effect in the development and progression of AS.


Assuntos
Aterosclerose/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Glucosídeos/farmacologia , Inflamação/tratamento farmacológico , Polygonum/química , Estilbenos/farmacologia , Administração Oral , Animais , Aorta/patologia , Aterosclerose/sangue , Aterosclerose/etiologia , Aterosclerose/patologia , Quimiocina CCL2/imunologia , Quimiocina CCL2/metabolismo , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/uso terapêutico , Microbioma Gastrointestinal/imunologia , Glucosídeos/uso terapêutico , Humanos , Inflamação/sangue , Inflamação/etiologia , Molécula 1 de Adesão Intercelular/imunologia , Molécula 1 de Adesão Intercelular/metabolismo , Lipoproteínas LDL/sangue , Masculino , Camundongos , Camundongos Knockout para ApoE , Estilbenos/uso terapêutico , Triglicerídeos/sangue , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Molécula 1 de Adesão de Célula Vascular/imunologia , Molécula 1 de Adesão de Célula Vascular/metabolismo
3.
Medicina (B Aires) ; 79(5): 373-383, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-31671387

RESUMO

Subclinical atherosclerosis is a powerful predictor of cardiovascular events, although it is unknown which of the risk scores is more useful to predict its presence in a Latin American population. The objective was to compare the performance of the risk scores: Framingham, Regicor and Atherosclerotic Cardiovascular Disease Risk Estimator to predict the presence of subclinical atherosclerosis in asymptomatic persons without known cardiovascular disease; as well as determining its prevalence and distribution in the different vascular beds. From 2014 to 2017, patients from 35 to 75 years, asymptomatic and without known cardiovascular disease who underwent a carotid and femoral Doppler echo and calcium score were evaluated. Subclinical atherosclerosis was defined as the presence of plaques in the carotid and/or femoral arteries or the presence of calcium in the coronary arteries (Agatston score > 0). A total of 212 patients were included. The mean age was 53 ± 7 years, of which 60% (128) were male. The prevalence of subclinical atherosclerosis was 62% (131 cases). Of these 131 subjects with a plaque in any of the territories, the Atherosclerotic Cardiovascular Disease Risk Estimator was the one that identified the highest number of cases with high cardiovascular risk (39%), Framingham detected 20%, and Regicor 0% (p < 0.01). The net reclassification was 41%, 50% and 60% respectively (< 0.01). The prevalence of subclinical atherosclerosis in asymptomatic persons without a history of cardiovascular disease was 62%. The Atherosclerotic Cardiovascular Disease Risk Estimator was the most effective predictor of subclinical atherosclerosis in this population.


Assuntos
Aterosclerose/epidemiologia , Aterosclerose/etiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Medição de Risco/métodos , Adulto , Idoso , Argentina/epidemiologia , Doenças Assintomáticas , Feminino , Humanos , Hiperlipidemias/complicações , Hiperlipidemias/epidemiologia , Hipertensão/complicações , Hipertensão/epidemiologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prevalência , Valores de Referência , Estudos Retrospectivos , Fatores de Risco
4.
Int Heart J ; 60(6): 1421-1429, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31735774

RESUMO

Dipeptidyl peptidase-4 (DPP-4) inhibitors are novel antidiabetic agents with possible vascular protection effects. Endothelial dysfunction is an initiation step in atherogenesis. The purpose of this study was to investigate whether vildagliptin (Vilda) attenuates the development of endothelial dysfunction and atherosclerotic lesions in nondiabetic apolipoprotein E-deficient (ApoE-/-) mice. Eight-week-old nondiabetic ApoE-/- mice fed a Western-type diet received Vilda (50 mg/kg/day) for 20 weeks or 8 weeks. After 20 weeks of treatment, Vilda administration reduced atherogenesis in the aortic arch as determined by en face Sudan IV staining compared with the vehicle group (P < 0.05). Vilda also reduced lipid accumulation (P < 0.05) and vascular cell adhesion molecule-1 (VCAM-1) expression (P < 0.05) and tended to decrease macrophage infiltration (P = 0.05) into atherosclerotic plaques compared with vehicle. After 8 weeks of treatment, endothelium-dependent vascular reactivity was examined. Vilda administration significantly attenuated the impairment of endothelial function in nondiabetic ApoE-/- mice compared with the vehicle group (P < 0.05). Vilda treatment did not alter metabolic parameters, including blood glucose level, in both study protocols. To investigate the mechanism, aortic segments obtained from wild-type mice were incubated with exendin-4 (Ex-4), a glucagon-like peptide-1 (GLP-1) analog, in the presence or absence of lipopolysaccharide (LPS). Ex-4 attenuated the impairment of endothelium-dependent vasodilation induced by LPS (P < 0.01). Furthermore, Ex-4 promoted phosphorylation of eNOS at Ser1177 which was decreased by LPS in human umbilical endothelial cells (P < 0.05). Vilda inhibited the development of endothelial dysfunction and prevented atherogenesis in nondiabetic ApoE-/- mice. Our results suggested that GLP-1-dependent amelioration of endothelial dysfunction is associated with the atheroprotective effects of Vilda.


Assuntos
Aterosclerose/prevenção & controle , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Células Endoteliais/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Vildagliptina/uso terapêutico , Animais , Apolipoproteínas E , Aterosclerose/etiologia , Aterosclerose/patologia , Técnicas de Cultura de Células , Modelos Animais de Doenças , Células Endoteliais/fisiologia , Endotélio Vascular/patologia , Camundongos , Camundongos Endogâmicos C57BL , Molécula 1 de Adesão de Célula Vascular/sangue
5.
Nutr Metab Cardiovasc Dis ; 29(12): 1345-1352, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31653520

RESUMO

BACKGROUND AND AIMS: To evaluate the biomarkers related to cardiovascular risk in pre-pubertal preterm children with a birth weight of less than 1,500 g and relate them to current nutritional status, insulin resistance, and inflammation. METHODS & RESULTS: This is a cross-sectional, controlled study with pre-pubertal preterm children aged 5-9 years with a birth weight of less than 1500 g (Preterm group, n = 44) compared to full term children of adequate weight for gestational age (Control group, n = 30). Clinical evaluation: anthropometry and pubertal staging. Laboratory tests: total cholesterol and fractions, triglycerides, paraoxonase 1, apolipoproteins A-I and B, myeloperoxidase (MPO), high sensitivity C-reactive protein (hs-CRP), glycemia and insulin (to calculate HOMA-IR). In the preterm group, 19 (43.2%) were male, with mean birth weight and gestational age of 1157 ± 242 g and 30.0 ± 2.3 weeks, respectively. The preterm group showed lower concentrations of HDL-c (60.1 ± 10.1 vs. 69.0 ± 10.0 mg/dL; p < 0.001); higher concentrations of hs-CRP [0.55 mg/dL (0.30; 39.4) vs. 0.30 mg/dL (0.30; 10.80); p = 0.043], of MPO [21.1 ng/mL (5.7; 120.0) vs. 8.1 ng/mL (2.6; 29.6); p < 0.001] and of MPO/HDL-c ratio [0.39 (0.09; 2.07) ng/mg vs. 0.11 (0.05; 0.58)]. The MPO/HDL-c ratio was the variable that showed the best discriminatory power between the groups (AUC = 0.878; 95% CI; 0.795-0.961). MPO concentrations in the preterm group were correlated with those of hs-CRP (r = 0.390; p = 0.009), insulin (r = 0.448; p = 0.002) and HOMA-IR (r = 0.462; p = 0.002). CONCLUSION: Prepubertal preterm children show high MPO concentrations and MPO/HDL-c ratio that are associated with inflammation and oxidative stress, which, in turn, may be associated with atherosclerosis.


Assuntos
Aterosclerose/sangue , Recém-Nascido Prematuro , Recém-Nascido de muito Baixo Peso , Peroxidase/sangue , Fatores Etários , Aterosclerose/diagnóstico , Aterosclerose/etiologia , Aterosclerose/fisiopatologia , Biomarcadores/sangue , Peso ao Nascer , Glicemia/análise , Proteína C-Reativa/análise , Estudos de Casos e Controles , Criança , Desenvolvimento Infantil , Fenômenos Fisiológicos da Nutrição Infantil , HDL-Colesterol/sangue , Estudos Transversais , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Inflamação/sangue , Inflamação/etiologia , Mediadores da Inflamação/sangue , Insulina/sangue , Resistência à Insulina , Masculino , Estado Nutricional , Estresse Oxidativo , Medição de Risco , Fatores de Risco , Regulação para Cima
6.
Prague Med Rep ; 120(2-3): 39-51, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31586503

RESUMO

Lipoprotein(a) - Lp(a) - is an independent risk factor for cardiovascular disease (CVD). Indeed, individuals with plasma concentrations of Lp(a) > 200 mg/l carry an increased risk of developing CVD. Circulating levels of Lp(a) are remarkably resistant to common lipid lowering therapies, currently available treatment for reduction of Lp(a) is plasma apheresis, which is costly and labour intensive. The Lp(a) molecule is composed of two parts: LDL/apoB-100 core and glycoprotein, apolipoprotein(a) - Apo(a), both of them can interact with components of the coagulation cascade, inflammatory pathways and blood vessel cells (smooth muscle cells and endothelial cells). Therefore, it is very important to determine the molecular pathways by which Lp(a) affect the vascular system in order to design therapeutics for targeting the Lp(a) cellular effects. This paper summarises the cellular effects and molecular mechanisms by which Lp(a) participate in atherogenesis, thrombogenesis, inflammation and development of cardiovascular diseases.


Assuntos
Aterosclerose , Lipoproteína(a) , Trombose , Aterosclerose/etiologia , Células Endoteliais , Humanos , Fatores de Risco , Trombose/etiologia
7.
Life Sci ; 237: 116896, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31605707

RESUMO

AIMS: Population-based studies have shown that exercise has anti-atherosclerotic effects, but the mechanisms underlying this cardiac protection are poorly understood. The aim of this study was to investigate if the anti-atherosclerotic effects of exercise are associated with changes in neuropeptide Y (NPY) expression in apolipoprotein E-deficient (ApoE-/-) mice. MAIN METHODS: Thirty-one male ApoE-/- mice were randomly divided into regular exercise (5 days/week), occasional exercise (1-2 days/week), and sedentary groups. After 8 weeks, atherosclerotic burden and plaque stability were measured by histological and morphological analysis. Quantitative real-time PCR and immunohistochemistry were used to measure the expression of NPY and its receptors in the aorta. KEY FINDINGS: Eight weeks of occasional exercise was equally effective as regular exercise at preventing atherosclerotic plaque formation and enhancing atherosclerotic plaque stability. This was shown by increased plaque collagen and smooth muscle cell content and decreased plaque lipid and macrophage content. The expression of NPY and its receptors in the vasculature was decreased in the regular exercise and occasional exercise groups, and this expression was significantly correlated with the progress of atherosclerosis. Moreover, exercise may reduce the activity of macrophages by down-regulating the expression of NPY Y1 receptors, thereby reducing the release of inflammatory cytokines. SIGNIFICANCE: These results suggest that exercise training can attenuate plaque burden and enhance atherosclerotic plaque stability. The anti-atherosclerotic effect of exercise appears to be, at least in part, dependent on down-regulation of the expression of NPY and its receptors (especially Y1 receptors) in the aorta.


Assuntos
Apolipoproteínas E/fisiologia , Aterosclerose/prevenção & controle , Regulação da Expressão Gênica , Inflamação/prevenção & controle , Neuropeptídeo Y/metabolismo , Condicionamento Físico Animal , Animais , Aorta/metabolismo , Aorta/patologia , Aterosclerose/etiologia , Aterosclerose/metabolismo , Aterosclerose/patologia , Citocinas/metabolismo , Modelos Animais de Doenças , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Neuropeptídeo Y/genética
8.
Medicine (Baltimore) ; 98(42): e17620, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31626142

RESUMO

Anthropometric measurements are simple and useful methods for predicting metabolic syndrome (MetS) because obesity is a predominant feature of MetS. Although carotid intima-medial thickness (IMT) is generally used to evaluate subclinical atherosclerosis, the relationship between the optimal cut-off anthropometric values for predicting MetS and carotid IMT has not been analyzed in a Korean population.Anthropometric measurements including waist circumference (WC), waist hip ratio (WHR), waist height ratio (WHtR), body mass index (BMI), and carotid IMT were assessed in 2560 Korean subjects without previous history of cardiovascular disease, cerebrovascular disease, neurological abnormalities, or malignancy who participated in baseline health examinations in a self-referral setting in the Seoul area between April 2010 and November 2012. MetS was defined using the National Cholesterol Education Program-Adult Treatment Panel III criteria.In both men and women, the levels of all anthropometric indices were significantly higher in subjects with MetS than in those without MetS. According to the receiver operating characteristic curve, the values of 80.8 cm for WC, 0.87 for WHR, 0.52 for WHtR, and 24.6 kg/m for BMI were the optimal cut-offs for predicting MetS in women. The values of 89.3 cm for WC, 0.90 for WHR, 0.52 for WHtR, and 25.1 kg/m for BMI were the optimal cut-offs for predicting MetS in men. After adjusting for confounding factors, the WC optimal cut-off values for predicting MetS were independently associated with carotid IMT in both women and men (women: ß = 0.016, P = .008; men: ß = 0.033, P = .009). The optimal BMI cut-off value was independently associated with carotid IMT in men only (ß = 0.027, P = .032).Among anthropometric indices including WC, WHR, WHtR, and BMI, the WC optimal cut-off values for MetS were independently associated with an increased carotid IMT in both women and men in a Korean population.


Assuntos
Antropometria/métodos , Aterosclerose/epidemiologia , Espessura Intima-Media Carotídea , Síndrome Metabólica/epidemiologia , Medição de Risco/métodos , Aterosclerose/diagnóstico , Aterosclerose/etiologia , Estudos Transversais , Feminino , Seguimentos , Humanos , Incidência , Masculino , Síndrome Metabólica/complicações , Síndrome Metabólica/diagnóstico , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , República da Coreia/epidemiologia , Estudos Retrospectivos
9.
Life Sci ; 237: 116943, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31604109

RESUMO

AIMS: The purpose of this study was to investigate the therapeutic effect of artemisinin (ART) on atherosclerosis and explore the molecular mechanisms involved by RNA sequencing (RNA-Seq). MAIN METHODS: Eight-week-old male ApoE-/- mice were treated with ART for eight weeks. Atherosclerotic lesion sizes were determined by Oil Red O staining, and RNA-Seq was used to detect the profile of differentially expressed genes following the administration of ART. The expressions of contractile phenotypic markers were detected by western blot and qRT-PCR, and the ability of the MOVAS cells to migrate and proliferate were assessed using the wound healing and CCK8 assays. KEY FINDINGS: Artemisinin treatment significantly reduced plaque area in the ApoE-/- mice and increased the expression of contractile phenotypic markers. RNA-Seq of aorta tissue revealed a distinct change in gene expression patterns after the mice were treated with ART. Our bioinformatics analysis demonstrated that the most prominently enriched pathway was a set of genes involved in vascular smooth muscle contractile function. Using an in vitro cell model, we demonstrated that ART could effectively reverse PDGF-activated MOVAS migration and proliferation, and elevate the level of proteins involved in the contractile phenotype. SIGNIFICANCE: We provide in vivo and in vitro evidence supporting a role for ART in the suppression of atherosclerosis, partly through the inhibition of vascular smooth muscle cell phenotype switching to a de-differentiated phenotype. These data further advances our understanding for a potential role for ART and suggests that ART is an excellent candidate for the treatment of atherosclerosis.


Assuntos
Antimaláricos/farmacologia , Apolipoproteínas E/fisiologia , Artemisininas/farmacologia , Aterosclerose/prevenção & controle , Proliferação de Células , Modelos Animais de Doenças , Músculo Liso Vascular/citologia , Animais , Aterosclerose/etiologia , Aterosclerose/patologia , Células Cultivadas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Fenótipo , Transdução de Sinais
10.
Biomed Pharmacother ; 119: 109410, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31518877

RESUMO

AIMS: The present study aimed to investigate the effect of metformin on diabetes-accelerated atherosclerosis and whether Nod-like receptor protein 3 (NLRP3) inflammasome is a target for metformin. MATERIALS AND METHODS: ApoE-/- male mice were divided randomly into control, streptozocin-induced diabetes mellitus and metformin groups. Metabolic parameters, atherosclerotic lesion, activation of NLRP3 inflammasomes and related signaling pathways were detected. THP-1-differentiated macrophages were used in in vitro experiments. RESULTS: Compared with control mice, increased plasma lipids and proinflammatory interleukin-1ß, aggravated macrophage infiltration into the atherosclerotic lesion, and accelerated development of atherosclerosis were observed in diabetic mice, which were associated with the activation of NLRP3 inflammasomes and dysregulation of thioredoxin-1 and thioredoxin-interacting protein. Treatment with metformin alleviated diabetes-induced metabolic disorders and atherosclerosis, as well as NLRP3 inflammasomes activation and dysregulation of thioredoxin-1/thioredoxin-interacting protein. In vitro experiments showed that high glucose induced the accumulation of reactive oxygen species and activated NLRP3 inflammasomes, which was significantly suppressed by treatment with metformin or antioxidant N-acetyl-L-cysteine. Moreover, Compound C, an inhibitor of adenosine 5'-monophosphate-activated protein kinase (AMPK), blocked the anti-inflammatory effect of metformin, indicating that metformin inhibited high glucose-induced NLRP3 inflammasomes activation through AMPK activation. Moreover, high glucose decreased thioredoxin-1 expression and increased thioredoxin-interacting protein expression, which was also reversed by metformin. CONCLUSIONS: Metformin inhibited NLRP3 inflammasomes activation and suppressed diabetes-accelerated atherosclerosis in apoE-/- mice, which at least partially through activation of AMPK and regulation of thioredoxin-1/thioredoxin-interacting protein.


Assuntos
Apolipoproteínas E/deficiência , Aterosclerose/tratamento farmacológico , Aterosclerose/etiologia , Diabetes Mellitus/tratamento farmacológico , Inflamassomos/metabolismo , Metformina/uso terapêutico , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Adenilato Quinase/metabolismo , Animais , Aorta/patologia , Apolipoproteínas E/metabolismo , Aterosclerose/sangue , Aterosclerose/patologia , Glicemia/metabolismo , Proteínas de Transporte/metabolismo , Ativação Enzimática/efeitos dos fármacos , Hiperglicemia/sangue , Hiperglicemia/complicações , Hiperglicemia/patologia , Hiperlipidemias/sangue , Hiperlipidemias/complicações , Hiperlipidemias/metabolismo , Hiperlipidemias/patologia , Lipídeos/sangue , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Metformina/farmacologia , Camundongos Endogâmicos C57BL , Espécies Reativas de Oxigênio/metabolismo , Tiorredoxinas/metabolismo
12.
Artigo em Inglês | MEDLINE | ID: mdl-31538906

RESUMO

This review is directed at increasing awareness of two diverse rare upper gastrointestinal problems that occur at opposite ends of the age spectrum and are difficult to diagnose and treat. The Superior Mesenteric Artery Syndrome (SMAS) likely involves a young patient, especially female, and is especially associated with rapid weight loss, resulting in relative strangulation of the duodenum by a narrowing of the angle between the Superior Mesenteric Artery (SMA) and the aorta. On the other hand, atherosclerosis of the SMA is associated most likely with postprandial upper intestinal ischemia and abdominal pain occurs in the elderly at high risk for cardiovascular (CV) disease. Medical management of the SMAS in the young involves good alimentation and weight gain to overall increase the intestinal fat pad. Medical management of SMA atherosclerotic ischemia in the elderly is directed at marked lipid lowering with atherosclerotic plaque stabilization or even regression. If needed, surgery for SMAS can be attempted laparoscopically with duodenojejunoscopy which is the most popular procedure but there are also more conservative possibilities that avoid division of the duodenum. In addition, sometimes direct vision is needed to successfully operate on SMAS. If surgery is needed for SMA atherosclerotic ischemia, it is usually attempted endoscopically with angioplasty and stent placement. Most important, in the case of these two rare clinical entities, is that the clinician have a suspicion of their presence when indicated so that the young or old patient can be spared unnecessary suffering and return to good health in a timely fashion.


Assuntos
Aterosclerose/etiologia , Aterosclerose/terapia , Síndrome da Artéria Mesentérica Superior/complicações , Síndrome da Artéria Mesentérica Superior/terapia , Fatores Etários , Aterosclerose/diagnóstico , Aterosclerose/cirurgia , Gerenciamento Clínico , Humanos , Artéria Mesentérica Superior/patologia , Artéria Mesentérica Superior/cirurgia , Síndrome da Artéria Mesentérica Superior/diagnóstico , Síndrome da Artéria Mesentérica Superior/cirurgia
13.
Horm Metab Res ; 51(10): 649-654, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31487747

RESUMO

The purpose of the study was to compare serum visfatin levels between patients with acromegaly and healthy controls and to evaluate the relationships between visfatin levels and epicardial fat thickness (EFT), carotid intima media thickness (cIMT), and ankle brachial index (ABI). We conducted a cross-sectional case-control study of 54 patients with acromegaly (37 females and 17 males) and 34 healthy controls (22 females and 12 males). Serum visfatin was measured by ELISA. Acromegalic and control participants and those with active or controlled acromegaly were compared with respect to their serum visfatin, clinical and metabolic parameters, EFT, cIMT, and ABI. Linear correlation was used to identify associations between these parameters and visfatin in all participants. Serum visfatin and glycated hemoglobin (HbA1c) were higher in the acromegaly group than in the control group (p<0.001 and p=0.007, respectively). There was no difference in visfatin between the active and controlled acromegaly groups, but HbA1c was higher in the active than the controlled acromegaly group (p<0.04). EFT, cIMT, and ABI were similar between the acromegaly and control groups and between the active and controlled acromegaly groups. Serum visfatin positively correlated with HbA1c, growth hormone (GH), and insulin-like growth factor-1 (IGF-1)/upper limit of normal ratio (r=0.245, p=0.024; r=0.259, p=0.017; and r=0.282, p=0.009, respectively). This study has revealed that a high visfatin level is associated with glycemic dysregulation and higher levels of GH and IGF-1 in acromegalic patients.


Assuntos
Acromegalia/sangue , Aterosclerose/diagnóstico , Biomarcadores/sangue , Citocinas/sangue , Hemoglobina A Glicada/análise , Hormônio do Crescimento Humano/sangue , Fator de Crescimento Insulin-Like I/análise , Nicotinamida Fosforribosiltransferase/sangue , Acromegalia/complicações , Adulto , Aterosclerose/sangue , Aterosclerose/etiologia , Glicemia/análise , Espessura Intima-Media Carotídea , Estudos de Casos e Controles , Estudos Transversais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
14.
Cardiol Young ; 29(10): 1225-1229, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31486354

RESUMO

Salusins have emerged as a new biomarker that reflects an increased inflammatory state, which is associated with cardiovascular risk. We investigated the predictive value and usefulness of salusins as an inflammatory biomarker in obese children. This prospective cohort study included 75 obese children and 101 healthy children (as a control group). Salusin-α, Salusin-ß, and various cardiovascular parameters were assessed in both groups. Correlation analyses of Salusin-α and Salusin-ß with body mass index standard deviation scores and inflammatory and cardiovascular markers were performed. The mean patient age was 11.9±2.4 years for the obese group and 12.5±2.1 years for the control group. The obese children had a significantly higher heart rate, systolic blood pressure, diastolic blood pressure, epicardial adipose tissue thickness, and left ventricular mass than did the children in the control group. There was no significant correlation between Salusin-α and Salusin-ß and body mass index; however, there was a negative correlation between Salusin- α and diastolic blood pressure (r = 0.277, p = 0.004). Overall, there was no significant difference in the Salusin-α and Salusin-ß levels between obese and healthy children. However, a negative correlation was found between Salusin-α and diastolic blood pressure. Although this result suggests that Salusin-α might be an early marker of cardiovascular involvement in obese children, further studies are needed to demonstrate the predictive value of salusins.


Assuntos
Aterosclerose/sangue , Pressão Sanguínea/fisiologia , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Obesidade Pediátrica/sangue , Adolescente , Aterosclerose/etiologia , Aterosclerose/fisiopatologia , Biomarcadores/sangue , Índice de Massa Corporal , Criança , Diástole , Ecocardiografia , Feminino , Seguimentos , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Obesidade Pediátrica/complicações , Obesidade Pediátrica/fisiopatologia , Prognóstico , Estudos Prospectivos
15.
EBioMedicine ; 47: 598-606, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31416722

RESUMO

Iron is fundamental for life-essential processes. However, it can also cause oxidative damage, which is thought to trigger numerous pathologies, including cardiovascular diseases. The role of iron in the pathogenesis of atherosclerosis is still not completely understood. Macrophages are both key players in the handling of iron throughout the body and in the onset, progression and destabilization of atherosclerotic plaques. Iron itself might impact atherosclerosis through its effects on macrophages. However, while targeting iron metabolism within macrophages may have some beneficial effects on preventing atherosclerotic plaque progression there may also be negative consequences. Thus, the prevailing view of iron being capable of accelerating the progression of coronary disease through lipid peroxidation may not fully take into account the multi-faceted role of iron in pathogenesis of atherosclerosis. In this review, we will summarize the current understanding of iron metabolism in the context of the complex interplay between iron, inflammation, and atherosclerosis.


Assuntos
Aterosclerose/etiologia , Aterosclerose/metabolismo , Inflamação/etiologia , Inflamação/metabolismo , Ferro/metabolismo , Animais , Aterosclerose/patologia , Aterosclerose/terapia , Transporte Biológico , Gerenciamento Clínico , Suscetibilidade a Doenças , Predisposição Genética para Doença , Hepcidinas/metabolismo , Humanos , Inflamação/patologia , Inflamação/terapia
16.
Food Funct ; 10(8): 5124-5139, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31364648

RESUMO

Hyperlipidemia is a major cause of atherosclerosis. Reverse cholesterol transport (RCT) is believed to attenuate hyperlipidemia and the progression of atherosclerosis. Although fucoidans are reported to have hypolipidemic effects, the underlying mechanisms are unclear. Furthermore, few reports have revealed the anti-atherosclerotic effects and the underlying mechanisms of fucoidans. This study was designed to investigate the anti-atherosclerotic effect and mechanisms of the fucoidan from seaweed A. nodosum. Our results demonstrated that the fucoidan administration ameliorated atherosclerotic lesion and lipid profiles in a dose-dependent manner in the apolipoprotein E-deficient (apoE-/-) mice fed a high-fat diet. In the apoE-/- mice liver, the fucoidan treatment significantly increased the expression of scavenger receptor B type 1 (SR-B1), peroxisome proliferator-activated receptor (PPAR) α and ß, liver X receptor (LXR) α, ATP-binding cassette transporter (ABC) A1 and ABCG8; and markedly decreased the expression of PPARγ and sterol regulatory element-binding protein (SREBP) 1c, but not low-density lipoprotein receptor, proprotein convertase subtilisin/kexin type 9, cholesterol 7 alpha-hydroxylase A1, LXRß and ABCG1. In the small intestine of the apoE-/- mice, the fucoidan treatment significantly reduced the expression of Niemann-Pick C1-like 1 (NPC1L1) and dramatically improved ABCG8 levels. These results demonstrated for the first time that the fucoidan from A. nodosum attenuated atherosclerosis by regulating RCT-related genes and proteins expression in apoE-/- mice. In summary, this fucoidan from A. nodosum may be explored as a potential compound for prevention or treatment of hyperlipidemia-induced atherosclerosis.


Assuntos
Apolipoproteínas E/genética , Ascophyllum/química , Aterosclerose/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Polissacarídeos/administração & dosagem , Alga Marinha/química , Animais , Apolipoproteínas E/deficiência , Aterosclerose/etiologia , Aterosclerose/genética , Aterosclerose/metabolismo , Humanos , Hiperlipidemias/complicações , Receptores X do Fígado/genética , Receptores X do Fígado/metabolismo , Masculino , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores de LDL/genética , Receptores de LDL/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo
17.
Int J Mol Med ; 44(4): 1425-1435, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31364743

RESUMO

Mesenchymal stem cells (MSCs) show immunosuppressive activities and alleviate atherosclerosis (AS) formation in apolipoprotein E­knockout (apoE­KO) mice. Human amnion mesenchymal stem cells (hAMSCs), a particular population of mesenchymal stem cells, have been shown to have immunomodulatory abilities. The present study investigated the effects of hAMSCs treatment on early atherosclerotic plaque formation and the progression of established lesion in apoE­KO mice. In total, 36 mice were fed with a high­fat diet. Mice were subjected to hAMSCs­injection treatment simultaneously with high­fat diet (early treatment) or after 8 weeks of high­fat diet (delayed treatment). In each treatment, mice were divided into three groups: i) hAMSCs group with hAMSCs treatment; ii) PBS group injected with PBS; and iii) control group without injection. Histological results showed that the plaque area in the aortic arch of mice was significantly reduced after hAMSCs treatment in the early and delayed treatment groups. In addition, immunohistochemical analysis suggested that the accumulation of macrophages was significantly decreased after hAMSCs treatment. Similarly, the release of the pro­inflammatory cytokine tumor necrosis factor­α was also decreased, whereas the release of the anti­inflammatory cytokine interleukin­10 was increased. In addition, hAMSCs treatment suppressed the phosphorylation of p65 and inhibitor of κB­α, suggesting that NF­κB pathway was involved in the hAMSCs­mediated suppression of immune response. In conclusion, hAMSCs treatment was effective in reducing immune response, which is the one of the major causes of AS, eventually leading to a significant reduction in size of atherosclerotic lesions.


Assuntos
Âmnio/citologia , Aterosclerose/metabolismo , Comunicação Celular , Imunomodulação , Macrófagos/imunologia , Macrófagos/metabolismo , Células-Tronco Mesenquimais/metabolismo , Animais , Aterosclerose/etiologia , Aterosclerose/patologia , Aterosclerose/terapia , Biomarcadores , Diferenciação Celular , Células Cultivadas , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Expressão Gênica , Humanos , Imunofenotipagem , Lipídeos/sangue , Masculino , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Camundongos , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patologia , Fator de Transcrição RelA/metabolismo
18.
Rev Port Cardiol ; 38(8): 531-542, 2019 08.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31447268

RESUMO

INTRODUCTION AND AIMS: Atherogenic dyslipidemia is an important contributor to residual cardiovascular (CV) risk, but it is underdiagnosed and undertreated. This study aimed to assess the opinion of Portuguese experts to generate a consensus concerning the diagnosis and treatment of atherogenic dyslipidemia, as well as to contribute toward standardization of clinical practice in this disorder. METHODS: The study consisted in the application of a questionnaire to an expert panel, following a modified Delphi methodology. RESULTS: The majority (88.4%) of the proposed items were found to be consensual. The expert panel recognized the importance of the atherogenic dyslipidemia phenotype, the role played by low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol as risk markers and therapeutic targets, the choice of statins as first-line lipid-lowering drugs, and the value of associating statins with fenofibrate as a means to reduce residual CV risk. However, the role played by triglycerides in CV risk and the therapeutic value of fibrates lacked consensus. Taking into consideration the state of the art and the opinions expressed in this study, the scientific committee developed a treatment algorithm aimed to improve the perception and treatment of atherogenic dyslipidemia. CONCLUSIONS: The experts involved in this study were shown to be familiar with the concept and the importance of atherogenic dyslipidemia. The few situations in which a consensus could not be found were mainly related to the interpretation and/or relevance of the available evidence.


Assuntos
Aterosclerose/tratamento farmacológico , LDL-Colesterol/sangue , Consenso , Gerenciamento Clínico , Dislipidemias/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipolipemiantes/uso terapêutico , Aterosclerose/sangue , Aterosclerose/etiologia , Biomarcadores/sangue , Dislipidemias/sangue , Dislipidemias/complicações , Humanos , Portugal , Fatores de Risco
19.
Int J Mol Sci ; 20(15)2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31366035

RESUMO

Cervical cancer is associated with a causative role of human papillomavirus (HPV), which is a highly prevalent infection. Recently, women with a genital HPV infection were found to have increased incidence of cardiovascular diseases (CVD), including severe cardiovascular events such as myocardial infarction and stroke. The pathomechanisms of this relation are not yet fully understood, and may significantly affect the health of a large part of the population. Accelerated atherosclerosis is assumed to play a key role in the pathophysiology of this relationship. To identify high-risk groups of the population, it is necessary to stratify the CVD risk. Current algorithms, as widely used for the estimation of CVD risk, seem to be limited by the individual misclassification of high-risk subjects. However, personalised prediction of cardiovascular events is missing. Regarding HPV-related CVD, identification of novel sensitive biomarkers reflecting early atherosclerotic changes could be of major importance for such personalised cardiovascular risk prediction. Therefore, this review focuses on the pathomechanisms leading to HPV-related cardiovascular diseases with respect to atherosclerosis, and the description of potential novel biomarkers to detect the earliest atherosclerotic changes important for the prevention of CVD in HPV infection and cervical cancer.


Assuntos
Aterosclerose/sangue , Biomarcadores/sangue , Infecções por Papillomavirus/sangue , Medicina de Precisão/métodos , Neoplasias do Colo do Útero/sangue , Aterosclerose/epidemiologia , Aterosclerose/etiologia , Aterosclerose/prevenção & controle , Feminino , Humanos , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Neoplasias do Colo do Útero/complicações , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/virologia
20.
J Vasc Res ; 56(4): 181-190, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31266015

RESUMO

BACKGROUND: Coagulant factor Xa inhibitors (XaIs) are prescribed for patients with atrial fibrillation for years. METHODS: Human umbilical venous endothelial cells (HUVECs) were cultured with or without (w/wo) a XaI (rivaroxaban) under high glucose (HG: 22 mM). Endothelial senescence was investigated by assessing senescence-associated-ß-galactosidase (SA-ß-gal), p53, and telomere length. Endothelial function and atherosclerosis were examined by nitric oxide-related-products (NOx: NO2- and NO3-), O2-, endothelial NO synthase (eNOS), NADPH oxidase (p22phox), and ICAM1. PAR1 (protease-activated receptor 1) and PAR2, which were reported to regulate eNOS phosphorylation, were inhibited by small interfering RNAs (siRNAs). Thirty-two male dyslipidemic type 2 diabetic rats (ZFDM LepRfa/fa) were fed a high-cholesterol diet w/wo XaI (50 µg/day/kg) for 1-4 weeks. RESULTS: SA-ß-gal, p53, p21, and p16INK4a were increased by HG and restored by XaI (50 nM) in HUVECs. XaI restored telomerase activity and preserved telomere length. XaI suppressed O2-, p22phox, and ICAM1 and restored NOx and eNOS. XaI decreased PAR1 following elevation by HG, which was confirmed by PAR1 siRNA and PAR2 siRNA. In in vivo experiments, plasma glucose, total cholesterol, and triglycerides were increased for 4 weeks but were not changed by XaI. XaI decreased SA-ß-gal and telomerase and preserved telomere length in the aortic endothelium. XaI activated eNOS, inhibited p22phox, increased plasma NOx, and decreased O2-. CONCLUSION: Rivaroxaban prevents replicative senescence in HUVECs and aortic endothelial cells in dyslipidemic diabetic mice. It restores endothelial function and prevents the progression of atherosclerosis.


Assuntos
Doenças da Aorta/prevenção & controle , Aterosclerose/prevenção & controle , Proliferação de Células/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Dislipidemias/tratamento farmacológico , Inibidores do Fator Xa/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Rivaroxabana/farmacologia , Animais , Doenças da Aorta/sangue , Doenças da Aorta/etiologia , Doenças da Aorta/patologia , Aterosclerose/sangue , Aterosclerose/etiologia , Aterosclerose/patologia , Glicemia/metabolismo , Proteínas de Ciclo Celular/metabolismo , Células Cultivadas , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Dieta Hiperlipídica , Modelos Animais de Doenças , Dislipidemias/sangue , Dislipidemias/complicações , Feminino , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Lipídeos/sangue , Óxido Nítrico/metabolismo , Ratos Zucker , Espécies Reativas de Oxigênio/metabolismo , Receptores Ativados por Proteinase/metabolismo , Transdução de Sinais , Telomerase/metabolismo
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