ABSTRACT
Cholesteryl ester transfer protein (CETP) increases the atherosclerosis risk by lowering HDL-cholesterol levels. It also exhibits tissue-specific effects independent of HDL. However, sexual dimorphism of CETP effects remains largely unexplored. Here, we hypothesized that CETP impacts the perivascular adipose tissue (PVAT) phenotype and function in a sex-specific manner. PVAT function, gene and protein expression, and morphology were examined in male and female transgenic mice expressing human or simian CETP and their non-transgenic counterparts (NTg). PVAT exerted its anticontractile effect in aortas from NTg males, NTg females, and CETP females, but not in CETP males. CETP male PVAT had reduced NO levels, decreased eNOS and phospho-eNOS levels, oxidative stress, increased NOX1 and 2, and decreased SOD2 and 3 expressions. In contrast, CETP-expressing female PVAT displayed increased NO and phospho-eNOS levels with unchanged NOX expression. NOX inhibition and the antioxidant tempol restored PVAT anticontractile function in CETP males. Ex vivo estrogen treatment also restored PVAT function in CETP males. Moreover, CETP males, but not female PVAT, show increased inflammatory markers. PVAT lipid content increased in CETP males but decreased in CETP females, while PVAT cholesterol content increased in CETP females. CETP male PVAT exhibited elevated leptin and reduced Prdm16 (brown adipocyte marker) expression. These findings highlight CETP sex-specific impact on PVAT. In males, CETP impaired PVAT anticontractile function, accompanied by oxidative stress, inflammation, and whitening. Conversely, in females, CETP expression increased NO levels, induced an anti-inflammatory phenotype, and preserved the anticontractile function. This study reveals sex-specific vascular dysfunction mediated by CETP.
Subject(s)
Adipose Tissue , Cholesterol Ester Transfer Proteins , Mice, Transgenic , Oxidative Stress , Cholesterol Ester Transfer Proteins/metabolism , Cholesterol Ester Transfer Proteins/genetics , Animals , Male , Female , Mice , Adipose Tissue/metabolism , Humans , Sex Characteristics , Nitric Oxide/metabolismABSTRACT
Vários estudos têm demonstrado a preocupação em relação ao HBV devido a sua evolução para formas crônicas e o aparecimento de hepatocarcinoma. Hoje temos um novo arsenal de medicamentos para diminuir a carga viral dos portadores HBV quando em atividade replicativa, sendo a carga viral extremamente importante, num futuro próximo os genótipos também orientarão para o prognóstico