RESUMO
Background: The decline of estrogen levels increases cardiovascular risk in women. Platelets express estrogen receptors and 17β-estradiol- (E2) can produce a protective effect on thrombus formation. The hydroxylation of cholesterol generates several sterols and 27-hydroxycholesterol (27HC) predominates in circulation. Aim: To evaluate the effect of 27HC as an endogenous antagonist of the anti-aggregating properties of E2 in platelets of postmenopausal women. Material and Methods: Platelet function of postmenopausal women was evaluated ex-vivo. Platelets pre-incubated with 27HC in the presence or absence of E2, were stimulated with collagen. Aggregation was evaluated using turbidimetry using a Chrono-log aggregometer. Results: Collagen-stimulated platelet aggregation was significantly inhibited by E2. The inhibitory effect of E2 on collagen-stimulated platelet aggregation was significantly reversed in the presence of 27HC. Conclusions: The suppressive effect of E2 on platelet aggregation is inhibited by 27HC, which could contribute to increase cardiovascular risk in postmenopausal women.
Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Agregação Plaquetária/efeitos dos fármacos , Pós-Menopausa/sangue , Antagonistas de Estrogênios/farmacologia , Estrogênios/farmacologia , Hidroxicolesteróis/farmacologia , Valores de Referência , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Inibidores da Agregação Plaquetária , Doenças Cardiovasculares/etiologia , Fatores de Risco , Colágeno/farmacologia , Estatísticas não Paramétricas , Estradiol/metabolismoRESUMO
Programmed necrosis or necroptosis is an alternative form of cell death that is executed through a caspase-independent pathway. Necroptosis has been implicated in many pathological conditions. Genetic or pharmacological inhibition of necroptotic signaling has been shown to confer neuroprotection after traumatic and ischemic brain injury. Therefore, the necroptotic pathway represents a potential target for neurological diseases that are managed by neurosurgeons. In this review, we summarize recent advances in the understanding of necroptotic signaling pathways and explore the role of necroptotic cell death in craniocerebral trauma, brain tumors, and cerebrovascular diseases.
Assuntos
Humanos , Apoptose/fisiologia , Lesões Encefálicas/terapia , Transtornos Cerebrovasculares/terapia , Necrose/terapia , Receptores de Morte Celular/fisiologia , Lesões Encefálicas/patologia , Lesões Encefálicas/fisiopatologia , Morte Celular , Transtornos Cerebrovasculares/patologia , Transtornos Cerebrovasculares/fisiopatologia , Proteínas Adaptadoras de Sinalização de Receptores de Domínio de Morte/fisiologia , Hidroxicolesteróis/farmacologia , Necrose/fisiopatologia , Fármacos Neuroprotetores/antagonistas & inibidores , Transdução de Sinais/fisiologia , Receptores Toll-Like/fisiologiaRESUMO
Incubation of murine peritoneal macrophages with 7beta-hydroxycholesterol (7beta-OH) for 24 hr led to dose-dependent reduction in cellular glutathione content as well as nitrite levels in the medium. Treatment with an inorganic form of selenium, sodium selenite which is a potent antioxidant, elevated the cellular glutathione levels and decreased nitrite levels. Our results suggest that 7beta-OH may exert its pro-atherogenic effect by inhibiting glutathione synthesis and nitric oxide production by macrophages present in the arterial wall and thus, impair the cellular antioxidant defense system.