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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.<\/jats:p>","DOI":"10.1093\/function\/zqae024","type":"journal-article","created":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T09:27:42Z","timestamp":1718616462000},"source":"Crossref","is-referenced-by-count":6,"title":["Sex-Specific Effects of Cholesteryl Ester Transfer Protein (CETP) on the Perivascular Adipose Tissue"],"prefix":"10.1152","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1034-3042","authenticated-orcid":false,"given":"C M","family":"Lazaro","sequence":"first","affiliation":[{"name":"Departamento de Biologia Estrutural e Funcional, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP) , CEP 13083-862, Campinas, SP , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I N","family":"Freitas","sequence":"additional","affiliation":[{"name":"Departamento de Biologia Estrutural e Funcional, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP) , CEP 13083-862, Campinas, SP , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V S","family":"Nunes","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de L\u00edpides (LIM10), Hospital das Cl\u00ednicas (HCFMUSP) da Faculdade de Medicina da Universidade de S\u00e3o Paulo , CEP 01246-903, S\u00e3o Paulo, SP , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D M","family":"Guizoni","sequence":"additional","affiliation":[{"name":"Obesity and Comorbidities Research Center, Universidade Estadual de Campinas (UNICAMP) , CEP 13083-864, Campinas, SP , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J A","family":"Victorio","sequence":"additional","affiliation":[{"name":"Laboratory of Female Vascular Biology, Departamento de Ci\u00eancias Fisiol\u00f3gicas, Centro de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Santa Catarina (UFSC) , CEP 88037-000, Santa Catarina, SC , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H C F","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Departamento de Biologia Estrutural e Funcional, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP) , CEP 13083-862, Campinas, SP , Brazil"},{"name":"Obesity and Comorbidities Research Center, Universidade Estadual de Campinas (UNICAMP) , CEP 13083-864, Campinas, SP , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A P","family":"Davel","sequence":"additional","affiliation":[{"name":"Departamento de Biologia Estrutural e Funcional, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP) , CEP 13083-862, Campinas, SP , Brazil"},{"name":"Obesity and Comorbidities Research Center, Universidade Estadual de Campinas (UNICAMP) , CEP 13083-864, Campinas, SP , 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