内科学
内分泌学
脂肪组织
小RNA
主动脉
收缩(语法)
胸主动脉
内皮功能障碍
医学
化学
生物
生物化学
基因
作者
Camila S. Balbino-Silva,Gisele Kruger Couto,Caroline Antunes Lino,Tábatha de Oliveira-Silva,Guilherme Lunardon,Zhan-Peng Huang,William Festuccia,Maria Luiza Barreto-Chaves,Dazhi Wang,Luciana Venturini Rossoni,Gabriela Placoná Diniz
出处
期刊:Life Sciences
[Elsevier]
日期:2023-03-01
卷期号:316: 121416-121416
被引量:2
标识
DOI:10.1016/j.lfs.2023.121416
摘要
Blood vessels are surrounded by perivascular adipose tissue (PVAT), which plays an important role in vascular tonus regulation due to its anticontractile effect; however, this effect is impaired in obesity. We previously demonstrated that miRNA-22 is involved in obesity-related metabolic disorders. However, the impact of miRNA-22 on vascular reactivity and PVAT function is unknown. To investigate the role of miRNA-22 on vascular reactivity and its impact on obesity-induced PVAT dysfunction. Wild-type and miRNA-22 knockout (KO) mice were fed a control or a high-fat (HF) diet. To characterize the vascular response, concentration-responses curves to noradrenaline were performed in PVAT- or PVAT+ thoracic aortic rings in absence and presence of L-NAME. Expression of adipogenic and thermogenic markers and NOS isoforms were evaluated by western blotting or qPCR. HF diet and miRNA-22 deletion reduced noradrenaline-induced contraction in PVAT- aortic rings. Additionally, miRNA-22 deletion increased noradrenaline-induced contraction in PVAT+ aortic rings without affecting its sensitivity; however, this effect was not observed in miRNA-22 KO mice fed a HF diet. Interestingly, miRNA-22 deletion reduced the contraction of aortic rings to noradrenaline via a NOS-dependent mechanism. Moreover, HF diet abolished the NOS-mediated anticontractile effect of PVAT, which was attenuated by miRNA-22 deletion. Mechanistically, we found that PVAT from miRNA-22 KO mice fed a HF diet presented increased protein expression of nNOS. These results suggest that miRNA-22 is important for aorta reactivity under physiological circumstances and its deletion attenuates the loss of the NOS-mediated anticontractile effect of PVAT in obesity.
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