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Sex-Specific Effects of Cholesteryl Ester Transfer Protein (CETP) on the Perivascular Adipose Tissue.
Lazaro, C M; Freitas, I N; Nunes, V S; Guizoni, D M; Victorio, J A; Oliveira, H C F; Davel, A P.
Afiliação
  • Lazaro CM; Departamento de Biologia Estrutural e Funcional, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), CEP 13083-862, Campinas, SP, Brazil.
  • Freitas IN; Departamento de Biologia Estrutural e Funcional, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), CEP 13083-862, Campinas, SP, Brazil.
  • Nunes VS; Laboratório de Lípides (LIM10), Hospital das Clínicas (HCFMUSP) da Faculdade de Medicina da Universidade de São Paulo, CEP 01246-903, São Paulo, SP, Brazil.
  • Guizoni DM; Obesity and Comorbidities Research Center, Universidade Estadual de Campinas (UNICAMP), CEP 13083-864, Campinas, SP, Brazil.
  • Victorio JA; Laboratory of Female Vascular Biology, Departamento de Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina (UFSC), CEP 88037-000, Santa Catarina, SC, Brazil.
  • Oliveira HCF; Departamento de Biologia Estrutural e Funcional, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), CEP 13083-862, Campinas, SP, Brazil.
  • Davel AP; Obesity and Comorbidities Research Center, Universidade Estadual de Campinas (UNICAMP), CEP 13083-864, Campinas, SP, Brazil.
Function (Oxf) ; 5(4)2024 Jul 11.
Article em En | MEDLINE | ID: mdl-38984977
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Camundongos Transgênicos / Tecido Adiposo / Estresse Oxidativo / Proteínas de Transferência de Ésteres de Colesterol Limite: Animals / Female / Humans / Male Idioma: En Revista: Function (Oxf) Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Brasil País de publicação: Reino Unido
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Camundongos Transgênicos / Tecido Adiposo / Estresse Oxidativo / Proteínas de Transferência de Ésteres de Colesterol Limite: Animals / Female / Humans / Male Idioma: En Revista: Function (Oxf) Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Brasil País de publicação: Reino Unido