High-fat diet increases O-GlcNAc levels in cerebral arteries: a link to vascular dysfunction associated with hyperlipidaemia/obesity?

Autor(es)

Lima, Victor V. ^[1] ; Giachini, Fernanda R. ^[1] ; Matsumoto, Takayuki ^[2] ; Li, Weiguo ^[3] ; Bressan, Alecsander F. M. ^[1] ; Chawla, Dhruv ^[3] ; Webb, R. Clinton ^[3] ; Ergul, Adviye ^[3] ; Tostes, Rita C. ^[4]

Afiliação do(s) autor(es)

^[1] Univ Fed Mato Grosso, Inst Biol & Hlth Sci, Barra Do Garcas, MT - Brazil

^[2] Hoshi Univ, Inst Med Chem, Dept Physiol & Morphol, Shinagawa Ku, Ebara 2-4-41, Tokyo 142 - Japan

^[3] Augusta Univ, Dept Physiol, Augusta, GA - USA

^[4] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, BR-14049 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Clinical Science; v. 130, n. 11, p. 871-880, JUN 1 2016.
• Citações Web of Science: 13

Resumo

Obesity and high fat intake induce alterations in vascular function and structure. Aberrant O-GlcNAcylation (O-GlcNAc) of vascular proteins has been implicated in vascular dysfunction associated with cardiovascular and metabolic diseases. In the present study, we tested the hypothesis that high-fat diet (HFD)-mediated increases in O-GlcNAc-modified proteins contribute to cerebrovascular dysfunction. O-GlcNAc-protein content was increased in arteries from male Wistar rats treated with a HFD (45% fat) for 12 weeks compared with arteries from rats on control diet (CD). HFD augmented body weight {[}(g) 550 +/- 10 compared with 502 +/- 10 CD], increased plasma triacylglycerols {[}(mg/dl) 160 +/- 20 compared with 95 +/- 15 CD] and increased contractile responses of basilar arteries to serotonin {[}5-hydroxytryptamine (5-HT)] {[}(pD(2)) 7.0 +/- 0.1 compared with 6.7 +/- 0.09 CD] and the thromboxane analogue 9,11-dideoxy-9(alpha),11(alpha)-methanoepoxy prostaglandin F-2 alpha (U-46619) {[}(pD(2)) 7.2 +/- 0.1 compared with 6.8 +/- 0.09 CD]. Of importance, increased levels of O-GlcNAc {[}induced by 24 h-incubation of vessels with a potent inhibitor of O-GlcNAcase (OGA), O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino-N-phenylcarbamate (PugNAc)] increased basilar artery contractions in response to U-46619 {[}(pD2) 7.4 +/- 0.07 compared with 6.8 +/- 0.08 CD] and 5-HT {[}(pD2) 7.5 +/- 0.06 compared with 7.1 +/- 0.1 CD]. Vessels from rats on the HFD for 12 weeks and vessels treated with PugNAc displayed increased phosphorylation of p38 (Thr180/182) and extracellular signal-regulated kinase 1/2 (Erk1/2) (Ser180/221). Increased 5HT-induced contractions in arteries from rats on the HFD or in arteries incubated with PugNAc were abrogated by mitogen-activated protein kinase (MAPK) inhibitors. Our data show that HFD augments cerebrovascular O-GlcNAc and this modification contributes to increased contractile responses and to the activation of the MAPK pathway in the rat basilar artery. (AU)

• Processo FAPESP: 08/58142-7 - Papel da o-glicosilacao-nac na (dis)funcao vascular de ratos hipertensos
• Beneficiário: Rita de Cassia Aleixo Tostes Passaglia
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/08216-2 - CPDI - Centro de Pesquisa em Doenças Inflamatórias
• Beneficiário: Fernando de Queiroz Cunha
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs