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1.
J Oral Rehabil ; 51(7): 1123-1134, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38491740

RESUMO

OBJECTIVE: Previous studies focused on the benefits of adequate prosthodontic treatment, while few studies have investigated the prosthodontic-related risks to health. As a modifiable oral health indicator, the association of ill-fitting prosthesis (IFP) with hypertension has not been fully explored. METHODS: This cross-sectional study involved 158,659 adults in Beijing (2009-2017) receiving intra-oral examinations and blood pressure measurements. Logistic regression models were applied to assess the association of IFP with the prevalence of hypertension, systolic blood pressure (SBP) ≧ 140 mmHg and diastolic blood pressure (DBP) ≧ 90 mmHg, as well as subgroup analyses by different fixed IFP subgroups (according to involved teeth number) and removable IFP subgroup. We further investigated effect modifications among stratified populations. RESULTS: 158,659 individuals were included for analysis, 346 (26.86%) in IFP group and 27,380 (17.40%) in non-IFP group (p < 0.001) were hypertensive. After adjustment of sex, age, obesity, dyslipidaemia, diabetes, hsCRP, family history of CVD, self-reported smoking, self-reported drinking and WC, ORs of hypertension, SBP ≧ 140 mmHg and DBP ≧ 90 mmHg were 1.330 (95% CI: 1.162-1.522), 1.277 (95% CI: 1.098-1.486) and 1.376 (95% CI: 1.186-1.596), respectively (p < 0.05). Furthermore, after full adjustment, the number of involved teeth showed a significant incremental trend with hypertension risk in the population with and without IFP (p for trend <0.001). The IFP-blood pressure associations were more pronounced in females, 18-60 years, non-obese and diabetic participants. CONCLUSION: As a modifiable oral indicator, IFP was significantly associated with a higher risk of hypertension.


Assuntos
Hipertensão , Humanos , Hipertensão/epidemiologia , Feminino , Estudos Transversais , Masculino , Pessoa de Meia-Idade , Adulto , Fatores de Risco , Prevalência , Idoso , Ajuste de Prótese , Pressão Sanguínea/fisiologia , Pequim/epidemiologia , Prótese Dentária/efeitos adversos
2.
Adv Mater ; 36(21): e2313926, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38376851

RESUMO

Electrocatalytic ethylene (C2H4) evolution from CO2 reduction is an intriguing route to mitigate both the energy and environmental crises; however, to acquire industrially relevant high productivity and selectivity at low energy cost remains to be challenging. Membrane assembly electrode has shown great prospect and tailoring its architecture for maximizing C2H4 yield at minimum voltage with long-term stability becomes critical. Here a freestanding Cu membrane cathode is designed and constructed by electrochemically depositing mesoporous Cu film on Cu foam to simultaneously manage CO2, electron, water, and product transport, which shows an extraordinary C2H4 Faradaic efficiency of 85.6% with a full cell power conversion efficiency of 33% at a current density of 368 mA cm-2, heading the techno-economic viability for electrocatalytic C2H4 production.

3.
Oral Oncol ; 140: 106369, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36989963

RESUMO

BACKGROUND: Immunotherapy, especially anti-PD-1 and anti-PD-L1 antibodies, have observably improved the overall survival of patients with advanced solid tumors following the unavoidable immune-related adverse events (irAEs). Camrelizumab is a novel anti-PD-1 agent with the reported most common irAEs of reactive cutaneous capillary endothelial proliferation (RCCEP). Despite it is widely occurred in the skin, oral RCCEP is rarely reported. CASE SUMMARY: A 59-year-old man complained about a painless nodule on left mandibular gingiva for two weeks. He started to inject Camrelizumab because of the recurrence of esophageal squamous cell carcinoma two month ago. An 8 mm lesion was observed on his mucosa. Several disseminated bright purple red papules were then found on his skins. The oral lesion and one lesion on his face was removed by surgery. After the final diagnosis of reactive cutaneous capillary endothelial proliferation was confirmed by histological examination. Other operable lesions on his face were removed by ligation. All the removed lesions had a good prognosis without recurrence within the follow-up visit. CONCLUSION: With the widespread use of Camrelizumab in other solid tumors, the occurrence of oral RCCEP will increase. Surgery and ligation are both effective treatment for RCCEP with a good prognosis.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Doenças da Gengiva , Masculino , Humanos , Pessoa de Meia-Idade , Proliferação de Células
4.
Front Med (Lausanne) ; 9: 1002325, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36530914

RESUMO

Background: Gallbladder and biliary diseases are common gastrointestinal conditions associated with huge socioeconomic costs and are considered risk factors for cardiovascular diseases and digestive system cancers. The prevalence and incidence of gallbladder and biliary diseases have not received enough attention from 1990 to 2019. Several non-communicable diseases were associated with the incidence of gallbladder and biliary diseases. It is necessary to clarify the change in the incidence and disability burden of gallbladder and biliary diseases worldwide. Methods: Data on high body mass index (BMI)-related disease burden and incidence, years of life lost prematurely, and years lived with disability (YLDs) due to gallbladder and biliary diseases were obtained from the Global Burden of Disease 2019. The estimated annual percentage change was calculated to qualify the gallbladder and biliary disease burden change. Results: The global age-standardized incidence rate has increased from 585.35 per 100,000 (95% UI: 506.05-679.86) in 1990 to 634.32 per 100,000 (95% UI: 540.21-742.93) in 2019. And the increase in incidence was positively correlated with rising high BMI-related summary exposure value. The high BMI-related YLDs of gallbladder and biliary diseases have increased worldwide over time. Globally, the 25-49 age group suffered a rapid rise in incidence and high BMI attributable to the YLDs rate of gallbladder and biliary diseases. Conclusion: The global incidence and high BMI-related YLDs of gallbladder and biliary diseases remain prominent to increase over the past 30 years. Notably, the incidence and high BMI-related YLDs among people aged 25-49 years have rapidly increased over time. Therefore, high BMI should be emphasized in strategic priorities for controlling gallbladder and biliary diseases.

5.
Environ Sci Pollut Res Int ; 29(44): 66578-66590, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35504990

RESUMO

Toilet revolution is driven by the urgent need for solutions to improve sanitation and access to high-quality organic fertilizer for rural areas, which is tagged "resource recovery from human waste." This study provides a possible solution via semi-solid anaerobic co-digestion (Aco-D) of source-separated fecal slag (SFS) and food waste (FW) (3:1). A comprehensive investigation of Aco-D at different inoculum/substrate ratios (ISR) was conducted. Results revealed that the reactor with ISR of 1:4 reached the highest methane yield (255.05 mL/gVS), which enhanced Methanosaetaceae, Methanomicrobiales, and Syntrophomonas. Additionally, the reactor with low feedstock (ISR of 1:2) showed higher removal efficiency of antibiotics (74.75%). The ecological risk of digestate decreased to an insignificant hazard quotient level, and the contents of nutrients and heavy metals were in line with the standard requirement for fertilizer. This study could serve as an alternative technology to support further research in SFS management and digestate utilization as fertilizer.


Assuntos
Metais Pesados , Eliminação de Resíduos , Anaerobiose , Antibacterianos , Biocombustíveis , Reatores Biológicos , Digestão , Fertilizantes , Alimentos , Humanos , Metano , Medição de Risco , Esgotos/química
6.
Ann Med ; 54(1): 553-564, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35139697

RESUMO

RATIONALE: Aortic aneurysm (AA) is a serious condition that largely increases the risk of aortic dissection and sudden death. Exploring the global burden of disease and changes in risk factors for AA is essential for public health policy development. OBJECTIVE: To project the death burden from AA and its attributable risk factors in the following decade based on the epidemiological data over the past 30 years. METHODS AND RESULTS: We analysed the death burden of AA and trends of four risk factors from 1990-2019 using the updated 2019 Global Burden of Disease study database by Joinpoint regression analysis. Furthermore, we project the AA-related death burden for the next decade using the Bayesian age-period-cohort model. This study discovered that the global burden of death attributable to AA began to increase after decreasing for two decades. This upward trend will continue in the subsequent decade (average annual percent change: 0.318%, 95% CI: 0.288 to 0.348). Meanwhile, the disease burdens in all economic regions except high-middle socio-demographic index (SDI) regions will continuously increase in the next decade, with the fastest acceleration in the low-middle SDI region (average annual percent change: 1.183%, 95% CI: 1.166 to 1.200). Notably, high systolic blood pressure will surpass the contribution of smoking to become the most important risk factor for mortality due to AA. CONCLUSION: This study discovered a rebounding trend in the aortic aneurysm-related death burden globally. High systolic blood pressure will be the top risk factor attributed to death from AA. Therefore, it should be considered as the first-degree risk factor in the guidance of AA management and criteria for population-based screening programs.Key messagesThe death burden of aortic aneurysms is beginning to rebound globally, and the trend will continue for the next decade.High systolic blood pressure will replace smoking as the most important risk factor associated with aortic aneurysm death.


Assuntos
Aneurisma Aórtico , Carga Global da Doença , Aneurisma Aórtico/epidemiologia , Teorema de Bayes , Pressão Sanguínea , Saúde Global , Humanos , Anos de Vida Ajustados por Qualidade de Vida , Fatores de Risco
7.
Toxicol Appl Pharmacol ; 435: 115829, 2022 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-34919946

RESUMO

Type I co-activator-associated arginine methyltransferase 1 (CARM1) and type II protein arginine methyltransferase 5 (PRMT5) are highly expressed in multiple cancers including liver cancer and their overexpression contributes to poor prognosis, thus making them promising therapeutic targets. Here, we evaluated anti-tumor activity of ribavirin in hepatocellular carcinoma (HCC). We found that ribavirin significantly inhibited the proliferation of HCC cells in a time- and dose-dependent manner. Furthermore, ribavirin suppressed the growth of subcutaneous and orthotopic xenograft of HCC in mice, decreased vascular endothelial growth factor (VEGF) and peritoneal permeability to reduce ascites production, and prolonged the survival of mice in HCC ascites tumor models. Mechanistically, ribavirin potently down-regulated global protein expression of CARM1 and PRMT5, and concurrently decreased accumulation of H3R17me2a and H3R8me2s/H4R3me2s. However, ribavirin did not affect the activity and mRNA levels of both CARM1 and PRMT5 in vivo and in vitro HCC cells. In addition, our ChIP results shown that ribavirin inhibited CARM1 which in turn decreased the H3R17me2a, binds to the eukaryotic translation initiation factor 4E (eIF4E) and VEGF promoter region, and reduced the relative mRNA expression level of eIF4E and VEGF in HCC cells. Our findings suggested a potential therapeutic strategy for patients with HCC through inhibition of the abnormal activation/expression of both CARM1 and PRMT5.


Assuntos
Antimetabólitos Antineoplásicos/farmacologia , Ascite/tratamento farmacológico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Proteína-Arginina N-Metiltransferases/antagonistas & inibidores , Ribavirina/farmacologia , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Epigênese Genética/efeitos dos fármacos , Fator de Iniciação 4E em Eucariotos/biossíntese , Fator de Iniciação 4E em Eucariotos/genética , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Camundongos , Proteína-Arginina N-Metiltransferases/genética , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/genética , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Food Chem ; 363: 130277, 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34303061

RESUMO

Chestnut skin is rich in polyphenols that have been linked to health for their antioxidant activity. However, chestnut outer-skin extract (COE), chestnut inner-skin extract (CIE), and their digested products have different compositions of polyphenols, and therefore their antioxidant activities might differ as well. Here, we study the effect of in vitro digestion on their total phenol content, antioxidant capacity, and individual phenolic profile to clarify the relationship between biotransformation and antioxidant activity. Compared to undigested samples, total phenol content and antioxidant activity of digested chestnut outer-skin extract (DCOE) and digested chestnut inner-skin extract (DCIE) had significantly higher values. The changes of phenolic composition and antioxidant activity after digestion were mainly due to the anthocyanin biosynthesis involving glycosylation, acylation, methoxylation and their reverse processes. All these data suggest that as chestnut processing by-products, COE and CIE are raw material sources of antioxidant-rich active substances and need more sufficient utilization.


Assuntos
Antioxidantes , Polifenóis , Biotransformação , Digestão , Metabolômica
9.
J Health Psychol ; 26(7): 1096-1108, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-32009442

RESUMO

This study was a randomised controlled study on the effects of the individual computer magnanimous therapy and group computer magnanimous therapy on emotional, psychosomatic and immune function among advanced lung cancer patients. Patients were examined at baseline and 2 weeks later using the Psychosomatic Status Scale for Cancer Patients, Hospital Anxiety Depression Scale and IgA, IgG, IgM and natural killer cell functions. The results showed that individual computer magnanimous therapy and group computer magnanimous therapy were beneficial for advanced lung cancer patients in improving depression, anxiety, psychosomatic status and immune functions. The improvements of immune functions may be related to the improvements of the participants' emotional and psychosocial status.


Assuntos
Neoplasias Pulmonares , Ansiedade , Depressão , Humanos , Imunidade , Transtornos Psicofisiológicos , Psicoterapia
10.
Cytokine ; 136: 155269, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32919254

RESUMO

Lactobacillus species are typical members of gut microflora that immunomodulatory effects and can regulate a variety of immune cells, such as dendritic cells (DCs). Notably, DCs possess the unique ability to initiate primary immune responses. Notably, DCs possess the unique ability to initiate primary immune responses. In this study, we investigated the effects of Lactobacillus johnsonii (L. johnsonii) on the maturation and activation of chicken bone marrow-derived dendritic cells (chBM-DCs). The chBM-DCs generated from chicken bone marrow monocytes were stimulated using lethally irradiated L. johnsonii. L. johnsonii-stimulated chBM-DCs upregulated the expression of major histocompatibility complex class II (MHC-II), CD40, and CD86, decreased phagocytosis, and increased the ability to induce the proliferation of allogeneic T cells, which displayed a mature phenotype and function. Upon maturation with L. johnsonii, the expression of Th1-type cytokines [interleukin (IL)-12, interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α)], a Th2-type cytokine (IL-10), pro-inflammatory cytokines (IL-1ß and IL-6), and chemokines (CXCLi1 and CXCLi2) greatly increased; however, a high expression of IL-10 was only observed at mid-late time points for chBM-DCs stimulated with high doses of L. johnsonii. Moreover, L. johnsonii upregulated the mRNA levels of TLR2 and TLR5. These results reveal that L. johnsonii plays a potentially important role in modulating the immunological functions of chBM-DCs, suggesting that it influences and mediates immune responses in vitro.


Assuntos
Proteínas Aviárias/imunologia , Células da Medula Óssea/imunologia , Quimiocinas/imunologia , Galinhas/imunologia , Células Dendríticas/imunologia , Regulação da Expressão Gênica/imunologia , Lactobacillus johnsonii/imunologia , Animais , Receptor 2 Toll-Like/imunologia , Receptor 5 Toll-Like/imunologia
11.
J Food Biochem ; 44(5): e13186, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32163603

RESUMO

Black soldier fly larvae protein (BLP) was hydrolyzed using alcalase, neutrase, trypsin, and papain. The BLP hydrolysates (BLPHs) were fractionated by ultrafiltration into three peptide fractions of molecular weight (<3 kDa, 3-10 kDa and >10 kDa). Their antioxidant activities in vitro and the amino acid composition were determined. Results showed that the alcalase was more efficient in hydrolyzing the BLP into oligopeptides. BLPHs-I presented the best scavenging activity to superoxide radicals, hydroxyl radicals, DPPH, and ABTS radicals. The best scavenging activities were found in BLPHs-I containing high levels of aromatic and hydrophobic amino acids. Seventeen novel sequences with typical features of well-known antioxidant proteins were identified by LC-MS/MS. Results demonstrated that BLPHs-I possesses a great capacity as antioxidant peptides applied in functional foods. PRACTICAL APPLICATIONS: Black soldier fly larvae protein (BLP) can also be hydrolyzed to produce antioxidant peptides and their sequences were identified. It can be used in pharmaceutical products and functional foods.


Assuntos
Antioxidantes , Dípteros , Animais , Cromatografia Líquida , Larva , Peptídeos , Espectrometria de Massas em Tandem
12.
Front Immunol ; 10: 1853, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31447851

RESUMO

Dendritic cells (DCs), as antigen-presenting cells, can initiate adaptive immune responses efficiently. Although the DC-targeting strategy has attracted more attention, relevant studies on chicken are rare. Here, specific chicken bone marrow DC-binding peptides were selected using a phage display peptide library and confirmed through ELISA, flow cytometry, fluorescence microscopy, and laser confocal microscopy. The peptide candidate SPHLHTSSPWER, named SP, was fused to the infectious bursal disease virus (IBDV) structural protein and protective antigen VP2. In vitro, the expression of DC markers (CD80, CD83, CD86, DEC205, and MHCII) and some cytokines (IFN-γ, IL-12, TNF-α, IL-1ß, IL-6, and CXCLi1) by VP2-SP-stimulated DCs was significantly higher than that by DCs treated with the VP2-control peptide at 4 h (p < 0.001). In addition, an oral vaccine targeting DCs was generated using chicken-borne Lactobacillus saerimneri M11 (L. sae M11) to deliver VP2 fused with SP. Anti-IBDV mucosal and humoral immune responses were induced efficiently via oral administration, resulting in higher protective efficacy in the VP2-SP group than the VP2 group. Therefore, chicken DC targeting of IBDV protective antigen VP2 delivered by L. sae provides effective immune protection in chicken. Our study may promote research on the DC-targeting strategy to enhance the effectiveness of chicken vaccines.


Assuntos
Células Dendríticas/imunologia , Vírus da Doença Infecciosa da Bursa/imunologia , Biblioteca de Peptídeos , Vacinas Virais/imunologia , Animais , Bacteriófagos/metabolismo , Embrião de Galinha , Galinhas , Vacinas Sintéticas/imunologia , Proteínas Estruturais Virais/imunologia
13.
Viruses ; 9(11)2017 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-29068402

RESUMO

Porcine epidemic diarrhea virus (PEDV), an enteric coronavirus, is the causative agent of porcine epidemic diarrhea (PED) that damages intestinal epithelial cells and results in severe diarrhea and dehydration in neonatal suckling pigs with up to 100% mortality. The oral vaccine route is reported as a promising approach for inducing protective immunity against PEDV invasion. Furthermore, dendritic cells (DCs), professional antigen-presenting cells, link humoral and cellular immune responses for homeostasis of the intestinal immune environment. In this study, in order to explore an efficient oral vaccine against PEDV infection, a mucosal DC-targeting oral vaccine was developed using Lactobacillus casei to deliver the DC-targeting peptide (DCpep) fused with the PEDV core neutralizing epitope (COE) antigen. This probiotic vaccine could efficiently elicit secretory immunoglobulin A (SIgA)-based mucosal and immunoglobulin G (IgG)-based humoral immune responses via oral vaccination in vivo. Significant differences (p < 0.05) in the immune response levels were observed between probiotics expressing the COE-DCpep fusion protein and COE antigen alone, suggesting better immune efficiency of the probiotics vaccine expressing the DC-targeting peptide fused with PEDV COE antigen. This mucosal DC-targeting oral vaccine delivery effectively enhances vaccine antigen delivery efficiency, providing a useful strategy to induce efficient immune responses against PEDV infection.


Assuntos
Antígenos Virais/imunologia , Células Dendríticas/imunologia , Vírus da Diarreia Epidêmica Suína/imunologia , Probióticos/administração & dosagem , Vacinas Virais/administração & dosagem , Administração Oral , Animais , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Antígenos Virais/administração & dosagem , Antígenos Virais/genética , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/veterinária , Infecções por Coronavirus/virologia , Citocinas/sangue , Epitopos/imunologia , Feminino , Imunogenicidade da Vacina , Imunoglobulina A Secretora/sangue , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Ativação Linfocitária , Camundongos Endogâmicos BALB C , Peptídeos/administração & dosagem , Peptídeos/genética , Peptídeos/imunologia , Suínos , Doenças dos Suínos/imunologia , Doenças dos Suínos/prevenção & controle , Doenças dos Suínos/virologia , Vacinação , Vacinas Virais/genética , Vacinas Virais/imunologia
14.
J Dairy Sci ; 98(7): 4869-81, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25958276

RESUMO

The objectives of this study were to systematically determine effects of conditioning temperature (70, 80, and 90°C), time (50 and 75 s), and interaction (temperature × time) during the pelleting process on co-products from bio-oil processing (canola meal) in terms of processing-induced changes on (1) protein molecular structure, (2) pellet durability index, (3) detailed chemical profile, (4) metabolic features and fractions of protein and carbohydrate, (5) total digestible nutrients and energy values, and (6) rumen degradable and undegradable content. Pellet durability was increased with increasing conditioning time. Chemical and carbohydrate profiles of co-products were not altered by pelleting process under different conditioning temperatures and times. With regard to protein fraction profiles, pellets conditioned for 50 s had higher soluble crude protein (SCP) and lower neutral detergent insoluble crude protein (NDICP) contents than those conditioned for 75 s (21.7 vs. 20.1% SCP, 16.0 vs. 16.5% NDICP, respectively). Total digestible nutrients and energy values were not altered by processing. Samples conditioned for 50 s had a higher content of rapidly degradable protein fraction (PA2) than those conditioned for 75 s (21.7 vs. 21.1% crude protein). In addition, the slowly degradable true protein fraction (PB2) was affected by the interaction of conditioning temperature and time. However, carbohydrate fractions did not differ with different conditioning temperatures and time. Different temperatures and time of conditioning during pelleting process greatly affect protein profiles without altering carbohydrate profiles. Molecular structure analyses also showed that pelleting altered inherent protein molecular structures of the co-products from bio-oil processing. Future study is needed to detect how molecular structure changes affect nutrient availability in dairy cattle.


Assuntos
Bovinos/metabolismo , Carboidratos da Dieta/metabolismo , Proteínas Alimentares/metabolismo , Digestão , Metabolismo Energético , Manipulação de Alimentos/métodos , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Proteínas Alimentares/química , Feminino , Temperatura Alta , Estrutura Molecular , Rúmen/metabolismo , Fatores de Tempo
15.
J Mol Cell Cardiol ; 34(10): 1399-1409, 2002 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-12393000

RESUMO

The activation of vascular smooth muscle cells (SMCs) in neointimal hyperplasia involves signaling through receptor tyrosine kinases as well as G protein-coupled receptors. Overexpression of G protein-coupled receptor kinase-2 (GRK2) in SMCs can attenuate mitogenic signaling and proliferation in response to not only several G protein-coupled receptor agonists, but also platelet-derived growth factor (PDGF). To test whether overexpression of GRK2 could inhibit other SMC responses implicated in neointimal hyperplasia, we assessed SMC chemotaxis and mitogenic signaling evoked by PDGF and G(q)-coupled receptor agonists. To test the effects of GRK2 overexpression on neointimal hyperplasia in vivo, we employed a rabbit autologous vein graft model system. GRK2 overexpression reduced PDGF-promoted SMC chemotaxis by 85% (P<0.01), but had no effect on chemotaxis promoted by epidermal growth factor (EGF). Congruently, GRK2 overexpression reduced by approximately 50% (P<0.05) the [(3)H]thymidine incorporation induced by combinations of PDGF and Gq-coupled receptor agonists, but had no effect on that induced by PDGF plus EGF. PDGF-, but not EGF-promoted phosphoinositide 3-kinase activity in SMCs was also inhibited by GRK2 overexpression. In rabbit vein grafts, we achieved GRK2 overexpression in medial SMCs, reduced cell proliferation during the first week after graft implantation, and reduced steady state neointimal thickness by 29% (P<0.01), without affecting medial thickness or potentiating SMC apoptosis. Because of its ability to dampen chemotactic and mitogenic signaling through PDGF and Gq-coupled receptors, GRK2 overexpression in SMCs may be a useful therapeutic approach for neointimal hyperplasia.


Assuntos
Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Proteínas Heterotriméricas de Ligação ao GTP/metabolismo , Hiperplasia/enzimologia , Hiperplasia/patologia , Miócitos de Músculo Liso/enzimologia , Túnica Íntima/enzimologia , Túnica Íntima/patologia , Animais , Aorta , Divisão Celular/efeitos dos fármacos , Células Cultivadas , Quimiotaxia/efeitos dos fármacos , Proteínas Quinases Dependentes de AMP Cíclico/genética , Fator de Crescimento Epidérmico/farmacologia , Veias Jugulares/citologia , Veias Jugulares/metabolismo , Veias Jugulares/transplante , Veias Jugulares/ultraestrutura , Microscopia Eletrônica , Mitógenos/farmacologia , Miócitos de Músculo Liso/patologia , Fator de Crescimento Derivado de Plaquetas/farmacologia , Coelhos , Quinases de Receptores Adrenérgicos beta
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