Avvisato Roberta, Mone Pasquale, Jankauskas Stanislovas S, Varzideh Fahimeh, Kansakar Urna, Gambardella Jessica, De Luca Antonio, Matarese Alessandro, Santulli Gaetano
Division of Cardiology, Department of Medicine, Albert Einstein College of Medicine, New York, NY 10461, USA.
Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine, New York, NY 10461, USA.
Biology (Basel). 2023 Mar 16;12(3):459. doi: 10.3390/biology12030459.
MicroRNAs (miRs) are small non-coding RNAs that modulate the expression of several target genes. Fibroblast growth factor binding protein 1 (FGFBP1) has been associated with endothelial dysfunction at the level of the blood-brain barrier (BBB). However, the underlying mechanisms are mostly unknown and there are no studies investigating the relationship between miRs and FGFBP1. Thus, the overarching aim of the present study was to identify and validate which miR can specifically target FGFBP1 in human brain microvascular endothelial cells, which represent the best in vitro model of the BBB. We were able to identify and validate miR-4432 as a fundamental modulator of FGFBP1 and we demonstrated that miR-4432 significantly reduces mitochondrial oxidative stress, a well-established pathophysiological hallmark of hypertension.
微小RNA(miR)是一类小的非编码RNA,可调节多个靶基因的表达。成纤维细胞生长因子结合蛋白1(FGFBP1)与血脑屏障(BBB)水平的内皮功能障碍有关。然而,其潜在机制大多未知,且尚无研究探讨miR与FGFBP1之间的关系。因此,本研究的总体目标是鉴定并验证哪种miR能在人脑微血管内皮细胞中特异性靶向FGFBP1,人脑微血管内皮细胞是血脑屏障最佳的体外模型。我们能够鉴定并验证miR-4432是FGFBP1的重要调节因子,并且我们证明miR-4432能显著降低线粒体氧化应激,线粒体氧化应激是高血压公认的病理生理特征。