Molecular mechanisms of angiogenesis and vascular heterogeneity

• Grant number: 19/25828-8
• Support Opportunities: Research Projects - Thematic Grants
• Start date: June 01, 2022
• End date: May 31, 2027
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Ricardo Jose Giordano
• Grantee: Ricardo Jose Giordano
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Pesquisadores principais: João Carlos Setubal
• Associated researchers: Antonia Tavares Do Amaral ; Bettina Malnic ; Daniele de Paula Faria ; Diana Noronha Nunes ; Emmanuel Dias-Neto ; Fabiano Pinheiro da Silva ; Fabio Ceneviva Lacerda Almeida ; Fabio Luiz Navarro Marques ; Graziella Eliza Ronsein ; João Carlos Setubal ; Roberto Kopke Salinas ; Sayuri Miyamoto
• Associated scholarship(s): 24/23577-6 - Molecular mechanisms of pathological angiogenesis, BP.TT; 23/16980-6 - Studying pathological angiogenesis: drug discovery using artificial inteligence., BP.TT; 22/15432-2 - Rational drug design: development of angiogenesis inhibitors targeting VEGF and TIE1 receptor pathways, BP.PD; + associated scholarships 23/03734-7 - Development of two new inhibotors of angiogenesis (VEGF and TIE1 pathways), BP.TT; 23/02258-7 - Structural studies of peptides involved in the molecular mechanisms of pathological angiogenesis using Nuclear Magnetic Resonance (NMR), BP.TT; 22/11277-2 - Validation of new miRNA in the angiogenic retina, BP.IC - associated scholarships

Abstract

Blood vessels play a central role in the most diverse physiological and pathological processes. Over the past few years, our group has been studying two important aspects of vascular biology: the process of formation of new blood vessels by angiogenesis and the molecular heterogeneity of vascular networks in different organs and tissues of the body. Understanding the molecular mechanisms of blood vessel formation from existing vessels (angiogenesis) is an important step towards the development of new therapies for the various diseases that have angiogenesis as a common element for the onset and progression of the disease. In this project, we will continue the studies initiated to: (a) develop two new angiogenesis inhibitors (VEGF and TIE1 pathways) and (b) study the gene regulation network of neovascularization in retinopathy. On the other hand, identifying specific molecular markers of endothelial cells from different vascular beds of an organism can contribute to understand the participation of blood vessels in the physiology of these tissues, as well as to the development of new therapeutic alternatives for the most diverse diseases, including therapies for precision (targeted to specific organ and tissues). Our group has focused its efforts to understand the heterogeneity of the cerebral vasculature and, in this project, we will expand these studies to validate a peptide motif binding brain cell junctions as a potential diagnostic/therapeutic tool, as well as expand the initial studies to identify new vascular markers associated with brain health and disease. We hope to contribute to a better understanding of the vascular contribution to the functioning of this fascinating organ, as well as the development of new diagnostic and therapeutic tools for neurodegenerative diseases. (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)

INAGUE, ALEX; ALECRIM, LILIAN COSTA; MONTEIRO, JHONATAS SIRINO; YOSHINAGA, MARCOS YUKIO; SETUBAL, JOAO CARLOS; MIYAMOTO, SAYURI; GIORDANO, RICARDO JOSE. Oxygen-induced pathological angiogenesis promotes intense lipid synthesis and remodeling in the retina. ISCIENCE, v. 26, n. 6, p. 22-pg., 2023-06-16. (19/25828-8, 13/07937-8, 17/13804-1)