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Nesfatin-1 suppresses peripheral arterial remodeling without elevating blood pressure in mice.
Mori, Yusaku; Shimizu, Hiroyuki; Kushima, Hideki; Saito, Tomomi; Hiromura, Munenori; Terasaki, Michishige; Koshibu, Masakazu; Ohtaki, Hirokazu; Hirano, Tsutomu.
Afiliação
  • Mori Y; Division of Diabetes, Metabolism, and Endocrinology, Department of Internal Medicine, Showa University School of Medicine, Shinagawa, Tokyo, Japan.
  • Shimizu H; Division of Diabetes, Metabolism, and Endocrinology, Department of Internal Medicine, Showa University School of Medicine, Shinagawa, Tokyo, Japan.
  • Kushima H; Maebashi Hirosegawa Clinic, Maebashi, Gunma, Japan.
  • Saito T; Division of Diabetes, Metabolism, and Endocrinology, Department of Internal Medicine, Showa University School of Medicine, Shinagawa, Tokyo, Japan.
  • Hiromura M; Division of Diabetes, Metabolism, and Endocrinology, Department of Internal Medicine, Showa University School of Medicine, Shinagawa, Tokyo, Japan.
  • Terasaki M; Division of Diabetes, Metabolism, and Endocrinology, Department of Internal Medicine, Showa University School of Medicine, Shinagawa, Tokyo, Japan.
  • Koshibu M; Division of Diabetes, Metabolism, and Endocrinology, Department of Internal Medicine, Showa University School of Medicine, Shinagawa, Tokyo, Japan.
  • Ohtaki H; Division of Diabetes, Metabolism, and Endocrinology, Department of Internal Medicine, Showa University School of Medicine, Shinagawa, Tokyo, Japan.
  • Hirano T; Department of Anatomy, Showa University School of Medicine, Shinagawa, Tokyo, Japan.
Endocr Connect ; 8(5): 536-546, 2019 May 01.
Article em En | MEDLINE | ID: mdl-30939447
ABSTRACT
Nesfatin-1 is a novel anorexic peptide hormone that also exerts cardiovascular protective effects in rodent models. However, nesfatin-1 treatment at high doses also exerts vasopressor effects, which potentially limits its therapeutic application. Here, we evaluated the vasoprotective and vasopressor effects of nesfatin-1 at different doses in mouse models. Wild-type mice and those with the transgene nucleobindin-2, a precursor of nesfatin-1, were employed. Wild-type mice were randomly assigned to treatment with vehicle or nesfatin-1 at 0.2, 2.0 or 10 µg/kg/day (Nes-0.2, Nes-2, Nes-10, respectively). Subsequently, mice underwent femoral artery wire injury to induce arterial remodeling. After 4 weeks, injured arteries were collected for morphometric analysis. Compared with vehicle, nesfatin-1 treatments at 2.0 and 10 µg/kg/day decreased body weights and elevated plasma nesfatin-1 levels with no changes in systolic blood pressure. Furthermore, these treatments reduced neointimal hyperplasia without inducing undesirable remodeling in injured arteries. However, nesfatin-1 treatment at 0.2 µg/kg/day was insufficient to elevate plasma nesfatin-1 levels and showed no vascular effects. In nucleobindin-2-transgenic mice, blood pressure was slightly higher but neointimal area was lower than those observed in littermate controls. In cultured human vascular endothelial cells, nesfatin-1 concentration-dependently increased nitric oxide production. Additionally, nesfatin-1 increased AMP-activated protein kinase phosphorylation, which was abolished by inhibiting liver kinase B1. We thus demonstrated that nesfatin-1 treatment at appropriate doses suppressed arterial remodeling without affecting blood pressure. Our findings indicate that nesfatin-1 can be a therapeutic target for improved treatment of peripheral artery disease.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Revista: Endocr Connect Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Japão

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Revista: Endocr Connect Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Japão