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1.
Int J Mol Sci ; 22(16)2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34445501

RESUMO

Lipid dysregulation in diabetes mellitus escalates endothelial dysfunction, the initial event in the development and progression of diabetic atherosclerosis. In addition, lipid-laden macrophage accumulation in the arterial wall plays a significant role in the pathology of diabetes-associated atherosclerosis. Therefore, inhibition of endothelial dysfunction and enhancement of macrophage cholesterol efflux is the important antiatherogenic mechanism. Rosmarinic acid (RA) possesses beneficial properties, including its anti-inflammatory, antioxidant, antidiabetic and cardioprotective effects. We previously reported that RA effectively inhibits diabetic endothelial dysfunction by inhibiting inflammasome activation in endothelial cells. However, its effect on cholesterol efflux remains unknown. Therefore, in this study, we aimed to assess the effect of RA on cholesterol efflux and its underlying mechanisms in macrophages. RA effectively reduced oxLDL-induced cholesterol contents under high glucose (HG) conditions in macrophages. RA enhanced ATP-binding cassette transporter A1 (ABCA1) and G1 (ABCG1) expression, promoting macrophage cholesterol efflux. Mechanistically, RA differentially regulated ABCA1 expression through JAK2/STAT3, JNK and PKC-p38 and ABCG1 expression through JAK2/STAT3, JNK and PKC-ERK1/2/p38 in macrophages. Moreover, RA primarily stabilized ABCA1 rather than ABCG1 protein levels by impairing protein degradation. These findings suggest RA as a candidate therapeutic to prevent atherosclerotic cardiovascular disease complications related to diabetes by regulating cholesterol efflux in macrophages.


Assuntos
Transportador 1 de Cassete de Ligação de ATP/metabolismo , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Colesterol/metabolismo , Cinamatos/farmacologia , Depsídeos/farmacologia , Glucose/efeitos adversos , Lipoproteínas LDL/efeitos adversos , Macrófagos/citologia , Transportador 1 de Cassete de Ligação de ATP/química , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Modelos Biológicos , Proteólise/efeitos dos fármacos , Transdução de Sinais , Células THP-1
2.
Biochem Pharmacol ; 182: 114246, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33011160

RESUMO

Elevated glucose levels in diabetes mellitus is associated with increased oxidized low density lipoprotein (oxLDL). High glucose (HG) and oxLDL are key inducers of oxidative stress and inflammatory processes responsible for diabetic vascular disorders. Rosmarinic acid is a polyphenol with antioxidant, anti-inflammatory and insulin-sensitizing effects. However, whether rosmarinic acid protects against diabetic atherosclerosis remains unknown. In this study, we aimed to investigate the protective effect of rosmarinic acid against diabetic atherosclerosis and the related signaling pathway. oxLDL-mediated oxidative stress upregulated thioredoxin-interacting protein (TXNIP) and subsequently induced binding of TXNIP to NLRP3 to mediate NLRP3 inflammasome assembly and activation under HG conditions in ECs. Reactive oxygen species (ROS) scavengers, p38 and FOXO1 inhibitors and TXNIP siRNA inhibited TXNIP protein upregulation and NLRP3 inflammasome assembly and activation. Rosmarinic acid abrogated TXNIP protein upregulation and the interaction between TXNIP and NLRP3 to attenuate NLRP3 inflammasome assembly and activation and eventually IL-1ß secretion in ECs through downregulating ROS production, p38 phosphorylation and FOXO1 protein induction in ECs. These findings show that rosmarinic acid inhibits endothelial dysfunction which is shown in diabetic atherosclerosis through downregulating the p38-FOXO1-TXNIP pathway and inhibiting inflammasome activation.


Assuntos
Proteínas de Transporte/metabolismo , Cinamatos/farmacologia , Depsídeos/farmacologia , Proteína Forkhead Box O1/metabolismo , Glucose/toxicidade , Inflamassomos/metabolismo , Lipoproteínas LDL/toxicidade , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Antioxidantes/farmacologia , Proteínas de Transporte/antagonistas & inibidores , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/fisiologia , Proteína Forkhead Box O1/antagonistas & inibidores , Humanos , Inflamassomos/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores
3.
BMC Health Serv Res ; 20(1): 697, 2020 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-32727609

RESUMO

BACKGROUND: Adolescents are still getting pregnant and contracting Human Immunodeficiency Virus (HIV) and Sexually Transmitted Infections (STIs) in Rwanda as elsewhere. Quality and comprehensive SRH services and information for adolescents is valuable for adolescents' wellbeing. This study aimed at understanding SRH services providers' viewpoints on accessibility, availability, and quality of SRH services provided to adolescents in selected cities of Rwanda. METHOD: The study was a descriptive cross-sectional survey conducted between May 2018 and May 2019 in six selected cities of Rwanda using a mixed-methods approach. A checklist was used to collect data from 159 conveniently selected SRH services providers. The survey tool was validated. SPSS version 20 was used to describe quantitative data and ATLAS TI version 5.2 was used to code and analyze the qualitative data thematically. RESULTS: Qualitatively, health care providers reported that the availability of adolescent SRHS are satisfactory with access to accurate SRH information, contraceptive methods, prevention and management of STIs and HIV services, and counselling. However, the accessibility of some services remains limited. According to respondents, some products such as female condoms are less in demand and often expire before they can be distributed. One nurse clarified that they render services at a low price if an adolescent has insurance medical coverture. Religious leaders and family members may hinder adolescents from health-seeking behavior by promoting abstinence and discouraging use of protective means. Quantitatively, we found that 94.3% of health facilities provide information to adolescents on SRH services that were available and 51.6% affirmed delivering services at a low cost. Only 57.2% of respondents mentioned that adolescents are involved in designing the feedback mechanisms at their facilities. CONCLUSION: SRH services in Rwanda are available for the general population and are not specifically designed for adolescents. These SRH services seem to be fairly accessible to adolescents with insufficient quality as adolescents themselves do not get to be fully involved in service provision among other aspects of quality SRH as stated by the World Health Organization (WHO). Therefore, there is a need to improve the present quality of these services to meet adolescents' needs in an urban setting.


Assuntos
Serviços de Saúde do Adolescente/estatística & dados numéricos , Serviços de Saúde do Adolescente/normas , Pessoal de Saúde/estatística & dados numéricos , Serviços de Saúde Reprodutiva/estatística & dados numéricos , Adolescente , Estudos Transversais , Feminino , Infecções por HIV/prevenção & controle , Instalações de Saúde/estatística & dados numéricos , Humanos , Masculino , Gravidez , Serviços de Saúde Reprodutiva/organização & administração , Ruanda , Doenças Sexualmente Transmissíveis/prevenção & controle , Inquéritos e Questionários
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