RESUMO
Curcumin is a phenolic compound that exhibits beneficial properties for cardiometabolic health. We previously showed that curcumin reduced the infiltration of immune cells into the vascular wall and prevented atherosclerosis development in mice. This study aimed to investigate the effect of curcumin on monocyte adhesion and transendothelial migration (TEM) and to decipher the underlying mechanisms of these actions. Human umbilical vein endothelial cells (HUVECs) were exposed to curcumin (0.5-1µM) for 3h prior to their activation by Tumor Necrosis Factor alpha (TNF-α). Endothelial permeability, monocyte adhesion and transendothelial migration assays were conducted under static condition and shear stress that mimics blood flow. We further investigated the impact of curcumin on signaling pathways and on the expression of genes using macroarrays. Pre-exposure of endothelial cells to curcumin reduced monocyte adhesion and their transendothelial migration in both static and shear stress conditions. Curcumin also prevented changes in both endothelial permeability and the area of HUVECs when induced by TNF-α. We showed that curcumin modulated the expression of 15 genes involved in the control of cytoskeleton and endothelial junction dynamic. Finally, we showed that curcumin inhibited NF-κB signaling likely through an antagonist interplay with several kinases as suggested by molecular docking analysis. Our findings demonstrate the ability of curcumin to reduce monocyte TEM through a multimodal regulation of the endothelial cell dynamics with a potential benefit on the vascular endothelial function barrier.
Assuntos
Movimento Celular/efeitos dos fármacos , Curcumina/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Fenômenos Biomecânicos , Adesão Celular/efeitos dos fármacos , Técnicas de Cocultura , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , Cultura em Câmaras de Difusão , Perfilação da Expressão Gênica , Células Endoteliais da Veia Umbilical Humana/citologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , MAP Quinase Quinase Quinases/antagonistas & inibidores , MAP Quinase Quinase Quinases/química , MAP Quinase Quinase Quinases/genética , Análise em Microsséries , Simulação de Acoplamento Molecular , NF-kappa B/antagonistas & inibidores , NF-kappa B/química , NF-kappa B/genética , Permeabilidade/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/química , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/química , Proteínas Proto-Oncogênicas c-akt/genética , Piruvato Desidrogenase Quinase de Transferência de Acetil , Reologia , Transdução de Sinais , Células THP-1 , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/farmacologiaAssuntos
Angioplastia Coronária com Balão/instrumentação , Cateterismo Cardíaco/instrumentação , Ponte de Artéria Coronária/efeitos adversos , Reestenose Coronária/terapia , Remoção de Dispositivo/instrumentação , Stents Farmacológicos , Infarto do Miocárdio sem Supradesnível do Segmento ST/terapia , Falha de Prótese , Veia Safena/transplante , Idoso de 80 Anos ou mais , Angioplastia Coronária com Balão/efeitos adversos , Angiografia Coronária , Reestenose Coronária/diagnóstico por imagem , Reestenose Coronária/etiologia , Humanos , Masculino , Infarto do Miocárdio sem Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio sem Supradesnível do Segmento ST/etiologia , Desenho de Prótese , Veia Safena/diagnóstico por imagem , Resultado do TratamentoRESUMO
UNLABELLED: Vasospastic angina is a frequent and well-recognized pathology with a high risk of life-threatening ventricular arrhythmias and sudden cardiac death. The diagnosis of vasospastic angina requires the combination of clinical and electrocardiographic variables and the results of provocation tests, such as ergonovine administration. Smoking cessation is the first step in the management of vasospastic angina. Optimal medical treatment using calcium-channel blockers and/or nitrate derivatives can provide protection, but life-threatening ventricular arrhythmias may occur despite optimal medical treatment and several years after the start of treatment. In this review, we evaluate the role of implantable defibrillators as a complement to optimal medical management in patients with life-threatening ventricular arrhythmias due to vasospastic angina; this role is not well characterized in the literature or guidelines. We discuss the role of implantable defibrillators in secondary prevention in light of three recent cases managed in our departments and a review of the literature. An implantable defibrillator was implanted in two of the three cases of vasospastic angina with ventricular arrhythmias that we managed. We considered secondary prevention by implantable defibrillator to be justified even in the absence of any obvious risk factor. Ventricular arrhythmias recurred during implantable defibrillator follow-up in the two patients implanted. CONCLUSION: In patients with life-threatening ventricular arrhythmias due to vasospastic angina, an implantable defibrillator should be considered because of the risk of recurrence despite optimal medical management.