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β-Adrenergic Stimulation-Induced PVAT Dysfunction in Male Sex: A Role for 11β-Hydroxysteroid Dehydrogenase-1

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Autor(es):
Victorio, Jamaira Aparecida ; Barssotti, Leticia ; Aprahamian, Tamar ; Costa, Raul Gobato ; Mousovich-Neto, Felippe ; Oliveira, Helena Coutinho Franco ; Mori, Marcelo ; Rossoni, Luciana Venturini ; Davel, Ana Paula
Número total de Autores: 9
Tipo de documento: Artigo Científico
Fonte: Endocrinology; v. 165, n. 6, p. 7-pg., 2024-04-29.
Resumo

Long-term beta-adrenoceptor (beta-AR) stimulation is a pathological mechanism associated with cardiovascular diseases resulting in endothelial and perivascular adipose tissue (PVAT) dysfunction. In this study, we aimed to identify whether beta-adrenergic signaling has a direct effect on PVAT. Thoracic aorta PVAT was obtained from male Wistar rats and cultured ex vivo with the beta-AR agonist isoproterenol (Iso; 1 mu M) or vehicle for 24 hours. Conditioned culture medium (CCM) from Iso-treated PVAT induced a marked increase in aorta contractile response, induced oxidative stress, and reduced nitric oxide production in PVAT compared to vehicle. In addition, Iso-treated PVAT and PVAT-derived differentiated adipocytes exhibited higher corticosterone release and protein expression of 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1), an enzyme responsible for de novo synthesis of corticosterone. Macrophages exposed to Iso also exhibited increased corticosterone release in response to beta-AR stimulation. Incubation of Iso-treated PVAT and PVAT-derived differentiated adipocytes with beta 3-AR antagonist restored aorta contractile function modulated by Iso-CCM and normalized 11 beta-HSD1 protein expression. These results show that beta 3-AR signaling leads to upregulation of 11 beta-HSD1 in PVAT, thus increasing corticosterone release and contributing to impair the anticontractile function of this tissue. (AU)

Processo FAPESP: 14/07947-6 - Possível interação entre estimulação beta-adrenérgica e ativação do receptor de mineralocorticóide em células endoteliais, musculares lisas e do tecido adiposo perivascular
Beneficiário:Ana Paula Couto Davel
Modalidade de apoio: Auxílio à Pesquisa - Regular
Processo FAPESP: 18/16505-8 - Disfunção e inflamação do tecido adiposo perivascular na obesidade: papel do receptor de mineralocorticoides
Beneficiário:Ana Paula Couto Davel
Modalidade de apoio: Auxílio à Pesquisa - Regular