miR-4432 Targets FGFBP1 in Human Endothelial Cells

SIMPLE SUMMARY: The inner layer of blood vessels is formed by endothelial cells. When these cells do not work properly, several issues ensue in the human body. One of these issues is elevated blood pressure, also known as hypertension, which is an established risk factor for ischemic heart disease, stroke, chronic kidney disease, and dementia. However, the exact mechanisms linking dysfunctional endothelium and hypertension are not fully defined. In this work, we discovered that a small nucleic acid (miR-4432) is able to target and inhibit a specific gene (fibroblast growth factor binding protein 1, FGFBP1) in human brain microvascular endothelial cells, and we demonstrate for the first time that this miR-4432 significantly reduces endothelial oxidative stress, a well-established feature of hypertension. Taken together, our findings provide unprecedented mechanistic insights and open the field to new studies aimed at ameliorating endothelial dysfunction by harnessing miR-4432-based strategies. ABSTRACT: 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.