Evaluation of exosomal microRNA-protein profile in familial hypercholesterolemia patients

• Grant number: 19/22147-0
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Effective date (Start): January 28, 2020
• Effective date (End): January 27, 2021
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Mario Hiroyuki Hirata
• Grantee: Renata Caroline Costa de Freitas
• Supervisor: Elena Aikawa
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Research place: Harvard University, Boston, United States
• Associated to the scholarship: 17/19043-2 - Evaluation of exosomal microRNA profile in Familial Hypercholesterolemia carriers, BP.DR

Abstract

Familial Hypercholesterolemia (FH) is a hereditary disorder characterized by elevated low-density lipoprotein (LDL) cholesterol and premature cardiovascular disease, which has genetic basis not fully understood yet. Exosomes molecular content can be useful for diagnostic purposes. Particularly proteins and miRNAs has been identified in exosomes purified from different biological fluids and can represent potential biomarker of disease (pathophysiology and follow-up), including thus related to cholesterol metabolism like FH, contributing to diagnostic and therapy. The present study aims to search for new molecular targets, based on exosomal proteomic and miRNA profile to diagnose FH and to predict cardiovascular risk. For this, 46 FH patients without lipid lowering therapy at 6 weeks and 46 normolipidemic subjects were selected (FAPESP # 2016/12899-6). Clinical data and blood samples were obtained for laboratory analysis, miRNome and proteome plasma exosomes analyzes. Global miRNA analysis was performed by NGS sequencing in IDPC. Proteomic analysis will be performed by Orbitrap Fusion Lumos mass spectrometer (Thermo Fisher Scientific) in collaboration with Dr. Elena Aikawa, where the BEPE will be realized. The biological interactions between the differentially expressed miRNAs and gene targets that coding the statistically increased proteins in FH will be performed using the iCTNet2 at Dr Elena Aikawa laboratory. The results of exosomes molecular content, particularly miRNA and protein profile, will be essential to improve the knowledge of molecular mechanism related to FH development. Moreover, these results will contribute in the search for new biomarkers to diagnosis, with high sensitivity and reproductivity, as well as for further new molecular therapeutic targets. The project will be also important to improve the knowledge of the PhD student and research team in Brazil about new technologies applied for diagnosis and bigdata analysis tools, as well as will contributed for establishing of new collaborations with an important international research center of cardiology. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SCHLOTTER, FLORIAN; FREITAS, RENATA C. C. DE; ROGERS, MAXIMILLIAN A.; BLASER, MARK C.; WU, PIN-JOU; HIGASHI, HIDEYUKI; HALU, ARDA; IQBAL, FARWAH; ANDRASKI, ALLISON B.; RODIA, CAYLA N.; et al. ApoC-III is a novel inducer of calcification in human aortic valves. Journal of Biological Chemistry, v. 296, JAN-JUN 2021. (19/22147-0)

DE FREITAS, RENATA CAROLINE COSTA; HIRATA, ROSARIO DOMINGUEZ CRESPO; HIRATA, MARIO HIROYUKI; AIKAWA, ELENA. Circulating Extracellular Vesicles As Biomarkers and Drug Delivery Vehicles in Cardiovascular Diseases. BIOMOLECULES, v. 11, n. 3, MAR 2021. (19/22147-0)