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1.
Phytochemistry ; 214: 113789, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37482264

RESUMO

In botanical extracts, highly abundant constituents can mask or dilute the effects of other, and often, more relevant biologically active compounds. To facilitate the rational chemical and biological assessment of these natural products with wide usage in human health, we introduced the DESIGNER approach of Depleting and Enriching Selective Ingredients to Generate Normalized Extract Resources. The present study applied this concept to clinical Red Clover Extract (RCE) and combined phytochemical and biological methodology to help rationalize the utility of RCE supplements for symptom management in postmenopausal women. Previous work has demonstrated that RCE reduces estrogen detoxification pathways in breast cancer cells (MCF-7) and, thus, may serve to negatively affect estrogen metabolism-induced chemical carcinogenesis. Clinical RCE contains ca. 30% of biochanin A and formononetin, which potentially mask activities of less abundant compounds. These two isoflavonoids are aryl hydrocarbon receptor (AhR) agonists that activate P450 1A1, responsible for estrogen detoxification, and P450 1B1, producing genotoxic estrogen metabolites in female breast cells. Clinical RCE also contains the potent phytoestrogen, genistein, that downregulates P450 1A1, thereby reducing estrogen detoxification. To identify less abundant bioactive constituents, countercurrent separation (CCS) of a clinical RCE yielded selective lipophilic to hydrophilic metabolites in six enriched DESIGNER fractions (DFs 01-06). Unlike solid-phase chromatography, CCS prevented any potential loss of minor constituents or residual complexity (RC) and enabled the polarity-based enrichment of certain constituents. Systematic analysis of estrogen detoxification pathways (ERα-degradation, AhR activation, CYP1A1/CYP1B1 induction and activity) of the DFs uncovered masked bioactivity of minor/less abundant constituents including irilone. These data will allow the optimization of RCE with respect to estrogen detoxification properties. The DFs revealed distinct biological activities between less abundant bioactives. The present results can inspire future carefully designed extracts with phytochemical profiles that are optimized to increase in estrogen detoxification pathways and, thereby, promote resilience in women with high-risk for breast cancer. The DESIGNER approach helps to establish links between complex chemical makeup, botanical safety and possible efficacy parameters, yields candidate DFs for (pre)clinical studies, and reveals the contribution of minor phytoconstituents to the overall safety and bioactivity of botanicals, such as resilience promoting activities relevant to women's health.


Assuntos
Neoplasias da Mama , Isoflavonas , Trifolium , Feminino , Humanos , Trifolium/química , Trifolium/metabolismo , Isoflavonas/farmacologia , Isoflavonas/metabolismo , Estrogênios , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Neoplasias da Mama/tratamento farmacológico
2.
J Korean Med Sci ; 38(18): e136, 2023 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-37158772

RESUMO

BACKGROUND: This study aimed to evaluate the prevalence of dysmenorrhea and to investigate the effect of weight changes or unhealthy weight control behaviors on dysmenorrhea in young Korean women. METHODS: We used large-scale data of women, aged 14 to 44 years, who participated in the Korean Study of Women's Health-Related Issues. Dysmenorrhea was measured using a visual analog scale and was categorized as none, mild, moderate, and severe according to the severity. Weight changes and unhealthy weight control behaviors (any of the behaviors, fasting/meal skipping, drugs, the use of unapproved dietary supplements, and one-food diets) over the past year were self-reported. We used multinomial logistic regression to investigate the association between weight changes or unhealthy weight control behaviors and dysmenorrhea. RESULTS: Of the 5,829 young women participating in the study, 5,245 (90.0%) participants experienced dysmenorrhea [2,184 (37.5%) had moderate and 1,358 (23.3%) had severe]. After adjusting for confounders, the odds ratios for moderate and severe dysmenorrhea in participants with weight changes ≥ 3 kg (vs. < 3 kg) were 1.19 (95% confidence interval: 1.05-1.35) and 1.25 (95% confidence interval: 1.08-1.45), respectively. The odds ratios in participants with any unhealthy weight control behaviors were 1.22 (95% confidence interval: 1.04-1.42) and 1.41 (95% confidence interval: 1.19-1.67) for those with moderate and severe dysmenorrhea, respectively. CONCLUSION: Weight changes (≥ 3 kg) or unhealthy weight control behaviors are common among young women, which may adversely affect dysmenorrhea. Therefore, attention needs to be paid to excessive weight changes and unhealthy weight control behaviors to improve dysmenorrhea in young women.


Assuntos
Dismenorreia , Comportamentos Relacionados com a Saúde , Feminino , Humanos , Povo Asiático , Suplementos Nutricionais , Dismenorreia/epidemiologia , Refeições , Adolescente , Adulto Jovem , Adulto
3.
J Inflamm Res ; 14: 6251-6264, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34866924

RESUMO

This review covers the preclinical and clinical literature supporting the role of melatonin in the management of brain injury-induced oxidative stress, neuroinflammation, and neurodegeneration, and reviews the past and current therapeutic strategies. Traumatic brain injury (TBI) is a neurodegenerative condition, unpredictably and potentially progressing into chronic neurodegeneration, with permanent cognitive, neurologic, and motor dysfunction, having no standard therapies. Due to its complex and multi-faceted nature, the TBI has highly heterogeneous pathophysiology, characterized by the highest mortality and disability worldwide. Mounting evidence suggests that the TBI induces oxidative and nitrosative stress, which is involved in the progression of chronic and acute neurodegenerative diseases. Defenses against such conditions are mostly dependent on the usage of antioxidant compounds, the majority of whom are ingested as nutraceuticals or as dietary supplements. A large amount of literature is available regarding the efficacy of antioxidant compounds to counteract the TBI-associated damage in animal and cellular models of the TBI and several clinical studies. Collectively, the studies have suggested that TBI induces oxidative stress, by suppressing the endogenous antioxidant system, such as nuclear factor erythroid 2-related factor-2 (Nrf-2) increasing the lipid peroxidation and elevation of oxidative damage. Moreover, elevated oxidative stress may induce neuroinflammation by activating the microglial cells, releasing and activating the inflammatory cytokines and inflammatory mediators, and energy dyshomeostasis. Thus, melatonin has shown regulatory effects against the TBI-induced autophagic dysfunction, regulation of mitogen-activated protein kinases, such as ERK, activation of the NLRP-3 inflammasome, and release of the inflammatory cytokines. The collective findings strongly suggest that melatonin may regulate TBI-induced neurodegeneration, although further studies should be conducted to better facilitate future therapeutic windows.

4.
Molecules ; 26(13)2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34203560

RESUMO

A number of plants used in folk medicine in Thailand and Eastern Asia are attracting interest due to the high bioactivities of their extracts. The aim of this study was to screen the edible leaf extracts of 20 plants found in Thailand and investigate the potential neuroprotective effects of the most bioactive sample. The total phenol and flavonoid content and 2,2-diphenyl-1-picrylhydrazyl radical-scavenging activity were determined for all 20 leaf extracts. Based on these assays, Glochidion littorale leaf extract (GLE), which showed a high value in all tested parameters, was used in further experiments to evaluate its effects on neurodegeneration in Caenorhabditis elegans. GLE treatment ameliorated H2O2-induced oxidative stress by attenuating the accumulation of reactive oxygen species and protected the worms against 1-methyl-4-phenylpyridinium-induced neurodegeneration. The neuroprotective effects observed may be associated with the activation of the transcription factor DAF-16. The characterization of this extract by LC-MS identified several phenolic compounds, including myricetin, coumestrin, chlorogenic acid, and hesperidin, which may play a key role in neuroprotection. This study reports the novel neuroprotective activity of GLE, which may be used to develop treatments for neurodegenerative diseases such as Parkinson's syndrome.


Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Fármacos Neuroprotetores , Estresse Oxidativo/efeitos dos fármacos , Phyllanthus/química , Extratos Vegetais , Animais , Peróxido de Hidrogênio/farmacologia , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia
5.
Cells ; 9(3)2020 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-32182943

RESUMO

In this work, we evaluated the effects of alpha linoleic acid (ALA), an omega-3 polyunsaturated fatty acid, on amyloid-beta-induced glial-cell-mediated neuroinflammation, amyloidogenesis, and cognitive dysfunction in mice. After an infusion of Aß1-42 (Aß1-42, 5 µL/5 min/mouse, intracerebroventricular injection (i.c.v), and respective treatments of ALA (60 mg/kg per oral for six weeks), neuroinflammation, apoptotic markers, and synaptic markers were evaluated by Western blot and immunofluorescence analyses. According to our findings, the infusion of Aß1-42 activated Toll-like receptor 4 (TLR4), glial fibrillary acidic protein (GFAP), and ionized calcium adaptor molecule 1 (Iba-1) in the frontal cortices and hippocampi of the Aß1-42-injected mice to a greater extent than the Aß1-42 + ALA-cotreated mice. Similarly, there was an elevated expression of phospho-c-Jun-N-terminal kinase (p-JNK), phospho-nuclear factor-kB p65 (p-NF-kB p65 (Ser536)), and tissue necrosis factor (TNF) in the Aß1-42 infused mouse brains; interestingly, these markers were significantly reduced in the Aß + ALA-cotreated group. The elevated expression of pro-apoptotic markers was observed during apoptotic cell death in the Aß1-42-treated mouse brains, whereas these markers were markedly reduced in the Aß + ALA-cotreated group. Moreover, Aß1-42 infusion significantly increased amyloidogenesis, as assessed by the enhanced expression of the amyloid precursor proteins (APP) beta-amyloid cleaving enzyme-1 (BACE-1) and amyloid-beta (Aß1-42) in the mouse brains, whereas these proteins were markedly reduced in the Aß + ALA-cotreated group. We also checked the effects of ALA against Aß-triggered synaptic dysfunction and memory dysfunction, showing that ALA significantly improved memory and synaptic functions in Aß-treated mouse brains. These results indicated that ALA could be an applicable intervention in neuroinflammation, apoptotic cell loss, amyloidogenesis, and memory dysfunction via the inhibition of TLR4 and its downstream targets in Aß + ALA-cotreated mouse brains.


Assuntos
Disfunção Cognitiva/tratamento farmacológico , Inflamação/tratamento farmacológico , Ácido Linoleico/farmacologia , Microglia/efeitos dos fármacos , Administração Oral , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/farmacologia , Animais , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/metabolismo , Modelos Animais de Doenças , Ácido Linoleico/administração & dosagem , Ácido Linoleico/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Fragmentos de Peptídeos/farmacologia
6.
BMC Pregnancy Childbirth ; 20(1): 121, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32085746

RESUMO

BACKGROUND: Caffeine can easily cross the placenta, and maternal caffeine intake, thus, has an effect on fetal growth. However, it is still unclear whether coffee consumption is an independent risk factor for bleeding in early pregnancy. The objective of this study was to examine the association between pre-pregnancy coffee consumption patterns and the risk of bleeding in early pregnancy. METHODS: A cross-sectional analysis was conducted among 3510 pregnant women from the Korean Pregnancy Outcome Study who underwent baseline examination and for whom the results of the pregnancy were available. Coffee consumption patterns before pregnancy were examined using a questionnaire. The participants were classified according to the frequency of coffee consumption into seldom (< 1 cup/week), light (< 1 cup/day), moderate (1 cup/day), and heavy coffee drinker (≥2 cups/day) groups. Bleeding in early pregnancy was defined as the occurrence of vaginal bleeding in the first 20 weeks of pregnancy. Multiple logistic regression models were applied to examine the association between pre-pregnancy coffee consumption and the risk of bleeding in early pregnancy, after adjusting for age, body mass index (BMI), systolic blood pressure, cigarette smoking and alcohol consumption behavior, previous and current physical activity levels, stress levels, history of depression, antenatal depressive symptoms during the first trimester, type of emesis, parity, and the number of livebirths, stillbirths, miscarriages, and abortions. RESULTS: Women who were light, moderate, and heavy coffee drinkers before pregnancy had adjusted ORs of 1.086, 1.225, and 1.358, respectively, for bleeding in early pregnancy. In a fully adjusted model, heavy coffee drinkers showed a significantly higher risk of bleeding in early pregnancy, even in women aged 35 years and younger (OR 1.680) and in those with a normal body mass index (OR 1.389), who were at relatively low risk for pregnancy-related complications. CONCLUSIONS: Our results showed that heavy coffee drinking was independently associated with a higher risk of bleeding in early pregnancy among pregnant Korean women, suggesting that caffeine intake before conception and during pregnancy should be reduced. Our study highlights the need for nutritional interventions for healthy coffee drinking among pregnant women in Korea.


Assuntos
Cafeína/efeitos adversos , Café/efeitos adversos , Complicações na Gravidez/epidemiologia , Hemorragia Uterina/epidemiologia , Adulto , Índice de Massa Corporal , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Gravidez , Complicações na Gravidez/etiologia , Resultado da Gravidez , Primeiro Trimestre da Gravidez , República da Coreia/epidemiologia , Fatores de Risco , Inquéritos e Questionários , Hemorragia Uterina/etiologia
7.
Planta Med ; 81(12-13): 1133-40, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26132853

RESUMO

Five new lupane triterpene coumaroyl esters (1-5), together with betulin (6) and a known Buxus alkaloid, N-3-benzoyldihydrocyclomicrophylline F (7), were isolated from a CHCl3-soluble partition of a methanol extract of Buxus cochinchinensis Pierre ex Gagnep. (Buxaceae) collected in Vietnam. Isolation work was monitored using human colon cancer cells (HT-29). The structures of the new compounds (1-5) were determined on the basis of spectroscopic data interpretation. In addition to their cytotoxicity against HT-29 cells and nuclear factor-kappa B (p65) inhibitory activity in an enzyme-linked immunosorbent assay, all isolates as well as two semisynthetic compounds derived from betulin and 5, respectively, were also evaluated for their in vitro antiplasmodial activities against the drug-resistant Dd2 strain of Plasmodium falciparum and antifungal effects on the growth of the pathogenic yeast Candida albicans. The new lupane triterpene coumaroyl esters (1-5), along with a betulin derivative and the known Buxus alkaloid, were found to show significant in vitro antimalarial activities, with IC50 values ranging from 0.26 to 2.07 µM.


Assuntos
Alcaloides/química , Antimaláricos/química , Buxus/química , Extratos Vegetais/química , Triterpenos/química , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Antimaláricos/isolamento & purificação , Antimaláricos/farmacologia , Ésteres/química , Ésteres/isolamento & purificação , Ésteres/farmacologia , Células HT29 , Humanos , Concentração Inibidora 50 , Estrutura Molecular , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Triterpenos/isolamento & purificação , Triterpenos/farmacologia , Vietnã
8.
J Nat Med ; 68(1): 242-5, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23516045

RESUMO

Screening with a cell-based luciferase assay was conducted to identify bioactive natural products which inhibit Wnt signaling activity-guided separation of an MeOH extract of Bauhinia malabarica (Caesalpiniaceae) leaves yielded five compounds, which were identified as ß-sitosterol (1), quercetin (2), 6,8-C-dimethyl kaempferol-3-O-rhamnopyranoside (3), hyperin (4), and 6,8-C-dimethyl kaempferol-3-methyl ether (5). The tested compounds 1, 3, and 5 exhibited Wnt signaling inhibitory activity, with IC50 values of 0.77, 0.74, and 16.6 µM, respectively.


Assuntos
Bauhinia , Flavonoides/farmacologia , Extratos Vegetais/farmacologia , Sitosteroides/farmacologia , Via de Sinalização Wnt/efeitos dos fármacos , Bauhinia/química , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Flavonoides/química , Flavonoides/isolamento & purificação , Genes Reporter , Células HCT116 , Células HEK293 , Humanos , Concentração Inibidora 50 , Quempferóis/farmacologia , Luciferases/genética , Luciferases/metabolismo , Metanol/química , Fitoterapia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Folhas de Planta , Plantas Medicinais , Quercetina/análogos & derivados , Quercetina/farmacologia , Sitosteroides/química , Sitosteroides/isolamento & purificação , Solventes/química , Transfecção
9.
Korean Circ J ; 42(2): 86-94, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22396695

RESUMO

BACKGROUND AND OBJECTIVES: The purpose of this study was to estimate the prevalence, awareness and treatment of high low density lipoprotein-cholesterol (LDL-C) level in Korean adults without coronary heart disease. SUBJECTS AND METHODS: National representative cross-sectional surveys, data of 5248 Korean adults (2246 men and 3002 women) aged between 20 and 79 years from the Third Korea National Health and Nutrition Examination Survey (KNHANES III, 2005) was used. High LDL-C level was defined with the risk prediction algorithm published by the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III). RESULTS: The prevalence of the Korean adults with high LDL-C level who need therapeutic lifestyle changes was 19.9%, treatment with lipid-lowing medication was 2.1% and awareness of this condition was 7.9%. Meanwhile, the prevalence of the Korean with very high LDL-C level who should be considered for drug therapy was 13.5%, treatment with lipid-lowing medication was 2.7% and awareness of this condition was 8.1%. Overall, 47.9% (60.3% in male and 39.1% in female) of participants had a single lipid disorder (high LDL-C, high triglycerides: ≥200 mg/dL, low high density lipoprotein-cholesterol: <40 mg/dL), whereas 15.5% (23.5% in male and 9.7% in female) had at least two. Only 1.9% (2.8% in male and 1.2% in female) of all participants had all three lipid abnormalities as defined. CONCLUSION: These findings indicate that continuous efforts are needed to increase awareness and treatment of high LDL-C level in our population to prevent cardiovascular disease.

10.
Planta Med ; 77(13): 1528-30, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21347999

RESUMO

The roots of Cyathula officinalis Kuan are widely used in Chinese medicine for the treatment of inflammatory disorders. Here, the ability of C. officinalis Kuan to downregulate matrix metalloproteinase (MMP)-13 was examined since MMP-13 is an important enzyme for the degradation of the cartilage collagen matrix, especially under arthritic conditions. The ethanol extract of C. officinalis Kuan as well as the N-hexane and chloroform soluble fractions were found to potently inhibit MMP-13 induction in IL-1 ß-treated SW1353 cells, a human chondrosarcoma cell line, at 50-200 µg/mL. Activity-guided separation led to the isolation of six compounds, palmitic acid (1), ß-sitosterol (2), α-spinasterol (3), atractylenolide I (4), 1,3-diacetoxy-tetradeca-6E,12E-dien-8,10-dyn (5), and N-trans-feruloyl-3-methyldopamine (6). Among these, 4 and 5 exhibited MMP-13 downregulating activity in IL-1 ß-treated SW1353 cells. And 4 also showed anti-oedematous activity against λ-carageenan-induced paw edema in mice at 20-200 mg/kg, p. o. The results of this study provide information that can help elucidate the action mechanism of C. officinalis Kuan. In addition, the results presented here suggest that C. officinalis Kuan and its constituents may have the potential for chondroprotection against cartilage degrading disorders.


Assuntos
Amaranthaceae/química , Condrócitos/efeitos dos fármacos , Edema/tratamento farmacológico , Lactonas/farmacologia , Metaloproteinase 13 da Matriz/metabolismo , Extratos Vegetais/farmacologia , Sesquiterpenos/farmacologia , Acetatos/química , Acetatos/farmacologia , Alcinos/química , Alcinos/farmacologia , Animais , Carragenina/farmacologia , Cartilagem/metabolismo , Linhagem Celular Tumoral , Condrócitos/metabolismo , Condrossarcoma/metabolismo , Modelos Animais de Doenças , Dopamina/análogos & derivados , Dopamina/química , Dopamina/farmacologia , Regulação para Baixo/efeitos dos fármacos , Edema/induzido quimicamente , Humanos , Hipolipemiantes/química , Hipolipemiantes/farmacologia , Interleucina-1beta/farmacologia , Lactonas/química , Masculino , Medicina Tradicional Chinesa , Camundongos , Camundongos Endogâmicos ICR , Fitoterapia , Extratos Vegetais/química , Raízes de Plantas/química , Sesquiterpenos/química , Sitosteroides/química , Sitosteroides/farmacologia , Estigmasterol/análogos & derivados , Estigmasterol/química , Estigmasterol/farmacologia
11.
Arch Pharm Res ; 33(8): 1159-63, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20803117

RESUMO

Two new dihydrofuranoisoflavanones, 2',4',5-trihydroxy-[5''-(1,2-dihydroxy-1-methylethyl)-dihydrofurano(2'',3'':7,8)]-(3S)-isoflavanone (1) and 2', 4', 5-trihydroxy-[5''-(1,2-dihydroxy-1-methylethyl)-dihydrofurano(2'',3'':7,8)]-(3R)-isoflavanone (2) as well as one already-known compound, (+)-catechin (3), were isolated from an n-BuOH soluble fraction from the leaves of Lespedeza maximowiczi. Spectroscopic data was used to elucidate the structures of compounds 1 and 2. All of the isolates were evaluated in vitro for their inhibitory activity on the formation of advanced glycation end products (AGEs). Among these, compounds 1, 2, and 3 exhibited inhibitory activity against AGEs formation with IC(50) values of 20.6, 18.4, and 5.6 microM, respectively.


Assuntos
Produtos Finais de Glicação Avançada/antagonistas & inibidores , Isoflavonas/farmacologia , Extratos Vegetais/farmacologia , Concentração Inibidora 50 , Isoflavonas/administração & dosagem , Isoflavonas/isolamento & purificação , Lespedeza/química , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Folhas de Planta , Análise Espectral
12.
Atherosclerosis ; 186(1): 29-37, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16098530

RESUMO

Berberine, an alkaloid isolated from Chinese medicinal herbs, long been known for its anti-microbial activity and used to treat various infectious disorders in traditional Chinese medicine. In the present study, we have tested the hypothesis that berberine could inhibit vascular smooth muscle cell (VSMC) proliferation as it did in endothelial cells or cancer cells. Our results show that berberine significantly inhibits growth factor, mainly angiotensin II (AngII) and heparin binding epidermal growth factor (HB-EGF), induced VSMC proliferation and migration in vitro, and this effect is achieved by delaying or partially suppressing activation of Akt pathway rather than ERK pathway. Furthermore, we have examined its effect in vivo using a rat carotid artery injury model. A 28 days of chronic berberine treatment using an osmotic pump (100 microg kg(-1)d(-1), 2 weeks before and 2 weeks after the injury) improved neointima formation. The Neointima/Media ratio for control group and berberine treated group were 1.14+/-0.11 and 0.85+/-0.06 (p<0.05), respectively, and the reduction was approximately 25%. The result of the present study suggests a possibility of berberine being a potent agent to control restenosis after balloon angioplasty and warrants further study to gain a more complete understanding of its underlying mechanisms at a cellular level.


Assuntos
Berberina/farmacologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Músculo Liso Vascular/patologia , Túnica Íntima/patologia , Angioplastia com Balão/efeitos adversos , Angiotensina II/antagonistas & inibidores , Angiotensina II/metabolismo , Animais , Aorta Torácica/efeitos dos fármacos , Aorta Torácica/lesões , Aorta Torácica/patologia , Western Blotting , Lesões das Artérias Carótidas/patologia , Lesões das Artérias Carótidas/prevenção & controle , Artéria Carótida Primitiva/efeitos dos fármacos , Artéria Carótida Primitiva/metabolismo , Artéria Carótida Primitiva/patologia , Células Cultivadas , Modelos Animais de Doenças , Fator de Crescimento Epidérmico/antagonistas & inibidores , Fator de Crescimento Epidérmico/metabolismo , Fator de Crescimento Semelhante a EGF de Ligação à Heparina , Técnicas In Vitro , Peptídeos e Proteínas de Sinalização Intercelular , Masculino , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Ratos , Ratos Sprague-Dawley , Túnica Íntima/efeitos dos fármacos , Túnica Íntima/lesões
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