miR-4432 Targets FGFBP1 in Human Endothelial Cells

Roberta Avvisato; Pasquale Mone; Stanislovas S Jankauskas; Fahimeh Varzideh; Urna Kansakar; Jessica Gambardella; Antonio De Luca; Alessandro Matarese; Gaetano Santulli

doi:10.3390/biology12030459

miR-4432 Targets FGFBP1 in Human Endothelial Cells

Biology (Basel). 2023 Mar 16;12(3):459. doi: 10.3390/biology12030459.

Authors

Roberta Avvisato^{1

2

3}, Pasquale Mone^{1

2}, Stanislovas S Jankauskas^{1

2}, Fahimeh Varzideh^{1

2}, Urna Kansakar^{1

2}, Jessica Gambardella^{1

2

3}, Antonio De Luca⁴, Alessandro Matarese⁵, Gaetano Santulli^{1

2

3

6

7

8}

Affiliations

¹ Division of Cardiology, Department of Medicine, Albert Einstein College of Medicine, New York, NY 10461, USA.
² Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine, New York, NY 10461, USA.
³ Department of Advanced Biomedical Sciences, "Federico II" University, 80131 Naples, Italy.
⁴ Department of Mental and Physical Health and Preventive Medicine, University of Campania "Luigi Vanvitelli", 81100 Caserta, Italy.
⁵ "Antonio Cardarelli" Hospital, 80100 Naples, Italy.
⁶ Department of Molecular Pharmacology, Albert Einstein College of Medicine, New York, NY 10461, USA.
⁷ Fleischer Institute for Diabetes and Metabolism (FIDAM), New York, NY 10461, USA.
⁸ Einstein-Mount Sinai Diabetes Research Center (ES-DRC), Albert Einstein College of Medicine, New York, NY 10461, USA.

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.

Keywords: HUVEC; blood pressure; blood–brain barrier; cerebrovascular disease; endothelial dysfunction; hBMECs; hypertension; miR-4432-3p; miRNA; microRNA.

Grants and funding

The Santulli’s Research Laboratory is supported in part by the National Institutes of Health (NIH); specifically, by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK; R01 DK123259, R01 DK033823), the National Heart, Lung, and Blood Institute (NHLBI; T32 HL144456, R01 HL164772, R01 HL159062, R01 HL146691), the National Center for Advancing Translational Sciences (NCATS; UL1 TR002556-06), to G.S.; by the Diabetes Action Research and Education Foundation (to G.S.); and by the Monique Weill Caulier and Irma T. Hirschl Trusts (to G.S.). S.S.J. is supported in part by a postdoctoral fellowship of the American Heart Association (POST836407 AHA). F.V. is supported in part by a postdoctoral fellowship of the American Heart Association (POST995561 AHA). U.K. is supported in part by a postdoctoral fellowship of the American Heart Association (POST1026190 AHA). J.G. is supported in part by a postdoctoral fellowship of the American Heart Association (POST35211151 AHA).