Reduced Endothelial Leptin Signaling Increases Vascular Adrenergic Reactivity in a Mouse Model of Congenital Generalized Lipodystrophy.
Reduced Endothelial Leptin Signaling Increases Vascular Adrenergic Reactivity in a Mouse Model of Congenital Generalized Lipodystrophy.
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DOI：
10.3390/ijms221910596
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发表时间：
2021-09-30
影响因子：
5.6
通讯作者：
Belin de Chantemèle EJ
中科院分区：
文献类型：
--
作者：
Bruder-Nascimento T;Kress TC;Pearson M;Chen W;Kennard S;Belin de Chantemèle EJ
脂肪因子瘦素以其在代谢功能控制中的作用而闻名，也是心血管功能的主要调节剂。虽然瘦素已被批准用于治疗先天性全身性脂肪营养不良 (CGL) 患者的代谢紊乱，但慢性瘦素缺乏和治疗对血管收缩力的影响仍不清楚。在此，我们研究了瘦素缺乏和治疗（0.3 mg/天/7 天）对雄性 Berardinelli-Seip 2 基因缺陷小鼠（gBscl2-/-，CGL 模型）及其野生型对照（gBscl2+/+）以及内皮瘦素受体选择性缺陷小鼠（LepREC-/-）的主动脉收缩力的影响。脂肪营养不良通过不依赖NO的机制选择性地增加血管肾上腺素能收缩力并诱导肥大性血管重塑。瘦素治疗和Nox1抑制减弱了gBscl2-/-小鼠的肾上腺素能过度收缩性，然而，瘦素未能挽救血管中膜厚度。内皮瘦素受体的选择性缺陷不会改变基线肾上腺素能收缩力，但消除了瘦素介导的肾上腺素能收缩力降低，支持内皮依赖性机制的贡献。这些数据揭示了内皮瘦素受体在控制血管收缩性和稳态中的新的直接作用，并表明瘦素是治疗 CGL 血管疾病的安全疗法。
The adipokine leptin, which is best-known for its role in the control of metabolic function, is also a master regulator of cardiovascular function. While leptin has been approved for the treatment of metabolic disorders in patients with congenital generalized lipodystrophy (CGL), the effects of chronic leptin deficiency and the treatment on vascular contractility remain unknown. Herein, we investigated the effects of leptin deficiency and treatment (0.3 mg/day/7 days) on aortic contractility in male Berardinelli-Seip 2 gene deficient mice (gBscl2-/-, model of CGL) and their wild-type control (gBscl2+/+), as well as in mice with selective deficiency in endothelial leptin receptor (LepREC-/-). Lipodystrophy selectively increased vascular adrenergic contractility via NO-independent mechanisms and induced hypertrophic vascular remodeling. Leptin treatment and Nox1 inhibition blunted adrenergic hypercontractility in gBscl2-/- mice, however, leptin failed to rescue vascular media thickness. Selective deficiency in endothelial leptin receptor did not alter baseline adrenergic contractility but abolished leptin-mediated reduction in adrenergic contractility, supporting the contribution of endothelium-dependent mechanisms. These data reveal a new direct role for endothelial leptin receptors in the control of vascular contractility and homeostasis, and present leptin as a safe therapy for the treatment of vascular disease in CGL.
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影响因子：
4.6
作者：
Fernández-Riejos P;Najib S;Santos-Alvarez J;Martín-Romero C;Pérez-Pérez A;González-Yanes C;Sánchez-Margalet V
通讯作者：
Sánchez-Margalet V
DOI：
10.1161/atvbaha.112.300962
发表时间：
2013-04-01
影响因子：
8.7
作者：
Auclair, Martine;Vigouroux, Corinne;Caron-Debarle, Martine
通讯作者：
Caron-Debarle, Martine
影响因子：
6
作者：
Bruder-Nascimento, Thiago;Callera, Glaucia E.;Touyz, Rhian M.
通讯作者：
Touyz, Rhian M.
影响因子：
5.4
作者：
Bruder-Nascimento T;Kress TC;Kennard S;Belin de Chantemèle EJ
通讯作者：
Belin de Chantemèle EJ
DOI：
10.1161/atvbaha.112.251140
发表时间：
2012-07-01
影响因子：
8.7
作者：
Benkhoff, Sebastian;Loot, Annemarieke E.;Schroeder, Katrin
通讯作者：
Schroeder, Katrin