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1.
Curr Mol Med ; 15(10): 905-31, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26592248

RESUMO

Atherosclerosis and its complications represent the leading death cause worldwide, despite many therapeutic developments. Atherosclerosis is a complex, multistage disease whereby perturbed lipid metabolism leads to cholesterol accumulation into the vascular walls and plaque formation. Generation of apoE-/- and LDLR-/- atherosclerosis mouse models opened the avenue for investigating the mechanisms of action for specific molecules. We focus herein on the involvement of non-lipoprotein receptors in atherogenesis, as revealed by their total or site-specific ablation in the aforementioned murine models. The receptors reviewed span a broad range, from molecules related to lipid metabolism (adiponectin receptors) to molecules whose connection with atherogenesis is less obvious (cannabinoid receptors). We also outline cross-transplantation studies which allowed uncoupling the lipid modulating effects from the inflammatory ones. For certain receptors, since knockouts were unavailable, pharmacological data are presented instead. We emphasize the contribution of the receptors to the pathology, based on functional criteria, such as oxidative stress, immune response, inflammation, angiogenesis. Controversial aspects regarding the pro- or anti- atherogenic activity of some receptors are highlighted. We assume these discrepancies are due to the experimental setup, animal models used, tissue-specific action, various isoforms analyzed, divergent signaling or cross-talk between metabolic and immune pathways. Understanding the influences of cellular receptors in the progression of atherosclerosis allows their modulation towards an antiatherogenic phenotype. The experimental studies in animal models were in some cases successfully extrapolated to humans leading to atheroma reduction, and we expect this to occur even to a greater extent, based on the newest achievements.


Assuntos
Anticolesterolemiantes/uso terapêutico , Aterosclerose/tratamento farmacológico , Terapia de Alvo Molecular/métodos , Placa Aterosclerótica/tratamento farmacológico , Animais , Apolipoproteínas E/deficiência , Apolipoproteínas E/genética , Aterosclerose/genética , Aterosclerose/metabolismo , Aterosclerose/patologia , Modelos Animais de Doenças , Regulação da Expressão Gênica , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Camundongos , Camundongos Knockout , Estresse Oxidativo/efeitos dos fármacos , Placa Aterosclerótica/genética , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patologia , Receptores de Adiponectina/antagonistas & inibidores , Receptores de Adiponectina/genética , Receptores de Adiponectina/metabolismo , Receptores de Canabinoides/genética , Receptores de Canabinoides/metabolismo , Receptores de LDL/deficiência , Receptores de LDL/genética , Receptores para Leptina/agonistas , Receptores para Leptina/genética , Receptores para Leptina/metabolismo , Receptores Nicotínicos/genética , Receptores Nicotínicos/metabolismo , Transdução de Sinais
2.
Bioelectrochemistry ; 87: 124-31, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22341625

RESUMO

Controlled-diameter TiO(2) nanotubes were obtained by electrochemical anodizing of two different substrates (Ti and Ti6Al7Nb) in an aqueous electrolyte. As-formed TiO(2) nanotubes are amorphous and by subjecting to thermal treatments, the structure becomes crystalline. An optimal thermal treatment with a specific anatase/rutile ratio was chosen, determined from X-ray diffraction (XRD). The electrochemical behaviour of annealed and as-formed samples was followed with Tafel plots and Electrochemical impedance spectroscopy (EIS), while surface analysis involved scanning electron microscopy (SEM) and contact angle measurements (CA). Annealed samples have a more hydrophilic character than as-formed as well as a better stability in bioliquids. Such behaviour of annealed samples is connected with a better biocompatibility expressed in terms of cell morphology and gene expression of bone specific markers obtained from Reverse Transcription Polymerase Chain Reaction (RT-PCR).


Assuntos
Materiais Revestidos Biocompatíveis/síntese química , Nanotubos/química , RNA Mensageiro/biossíntese , Titânio/química , Biomarcadores/metabolismo , Linhagem Celular Tumoral , Materiais Revestidos Biocompatíveis/farmacologia , Cristalização , Espectroscopia Dielétrica , Eletrólitos , Expressão Gênica/efeitos dos fármacos , Humanos , Sialoproteína de Ligação à Integrina/genética , Sialoproteína de Ligação à Integrina/metabolismo , Microscopia Eletrônica de Varredura , Nanotubos/ultraestrutura , Osteocalcina/genética , Osteocalcina/metabolismo , Osteonectina/genética , Osteonectina/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Espalhamento a Baixo Ângulo , Propriedades de Superfície , Água , Difração de Raios X
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