Understanding the effects of high density lipoprotein on human macrophages

• Grant number: 19/25702-4
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: October 01, 2020
• End date: February 28, 2025
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Graziella Eliza Ronsein
• Grantee: Douglas Ricardo de Souza Junior
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 16/00696-3 - Proteomic as a tool to understand HDL function and composition, AP.JP

Abstract

Cardiovascular diseases are the leading cause of death worldwide, and atherosclerosis is its major underlying cause. Atherosclerosis is characterized by a chronic inflammatory process that begins with accumulation of Low-Density Lipoprotein (LDL) in subendothelial space. After that, LDL is oxidized and phagocytized by macrophages, turning them into foam cells that accumulate free, esterified and oxidized cholesterol. On the other hand, High-Density Lipoprotein (HDL) is considered an atheroprotective particle, thus promoting cholesterol efflux from cells, including macrophage foam cells. Our preliminary experiments showed that cholesterol accumulation in human macrophages lead to alterations in their secreted protein pattern, altering biological processes related to the immune system, oxidative stress, actin cytoskeleton regulation, and vesicle-mediated transport. However, the role of HDL in this process is still controversial. In this matter, the present project aims to understand the molecular mechanisms triggered by HDL on human macrophages in a cholesterol homeostasis context. To reach this goal, alterations in human macrophages obtained from peripheral blood circulation, as well as HDL effects on them will be evaluated using proteomics, statistic and bioinformatics tools. The obtained results will be further corroborated with biochemical assays. HDL effects on macrophage polarization and expression of proteins from signaling pathways such as NF-ºB, inflammassome and IFN will also be investigated. (AU)

Scientific publications

(4)

(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)

SOUZA JUNIOR, DOUGLAS RICARDO; SILVA, AMANDA RIBEIRO MARTINS; RONSEIN, GRAZIELLA ELIZA. Strategies for consistent and automated quantification of HDL proteome using data-independent acquisition. Journal of Lipid Research, v. 64, n. 7, p. 14-pg., 2023-07-03. (17/07725-1, 16/00696-3, 13/07937-8, 19/25702-4)

DE FATIMA MELLO SANTANA, MONIQUE; SAWADA, MARIA ISABELA BLOISE ALVES CALDAS; SOUZA JUNIOR, DOUGLAS RICARDO; GIACAGLIA, MARCIA BENACCHIO; REIS, MOZANIA; XAVIER, JACIRA; CORREA-GIANNELLA, MARIA LUCIA; SORIANO, FRANCISCO GARCIA; GEBRIM, LUIZ HENRIQUE; RONSEIN, GRAZIELLA ELIZA; et al. Proteomic Profiling of HDL in Newly Diagnosed Breast Cancer Based on Tumor Molecular Classification and Clinical Stage of Disease. CELLS, v. 13, n. 16, p. 19-pg., 2024-08-01. (19/18431-4, 19/25702-4, 21/02401-9, 16/15603-0, 23/00995-4)

SOUZA JUNIOR, DOUGLAS RICARDO; MARTINS SILVA, AMANDA RIBEIRO; ROSA-FERNANDES, LIVIA; REIS, LORENNA ROCHA; ALEXANDRIA, GABRIELLY; BHOSALE, SANTOSH D.; GHILARDI, FABIO DE ROSE; DALCOQUIO, TALIA FALCAO; BERTOLIN, ADRIADNE JUSTI; NICOLAU, JOSE CARLOS; et al. HDL proteome remodeling associates with COVID-19 severity. JOURNAL OF CLINICAL LIPIDOLOGY, v. 15, n. 6, p. 796-804, NOV-DEC 2021. (15/26722-8, 16/00696-3, 20/04923-0, 19/25702-4, 17/07725-1, 18/15549-1, 18/18257-1, 13/07937-8)

REIS, LORENNA ROCHA; JUNIOR, DOUGLAS RICARDO SOUZA; TOMASIN, REBEKA; BRUNI-CARDOSO, ALEXANDRE; DI MASCIO, PAOLO; RONSEIN, GRAZIELLA ELIZA. Citrullination of actin-ligand and nuclear structural proteins, cytoskeleton reorganization and protein redistribution across cellular fractions are early events in ionomycin-induced NETosis. REDOX BIOLOGY, v. 64, p. 14-pg., 2023-06-23. (13/07937-8, 16/00696-3, 17/17270-1, 19/25702-4)