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Thrombospondin-1 possible new effector in macrophages inflammatory response to LDL

Grant number: 14/25079-1
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): February 01, 2015
Effective date (End): May 31, 2016
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal researcher:Maristela de Oliveira Hernandez
Grantee:Vanessa Barbosa Moura
Home Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Understanding the progression of atherosclerosis is an urgent challenge, since cardiovascular diseases are the leading cause of death worldwide. Macrophages represent the majority of atherosclerotic lesions in leukocytes and the secretion of various mediators, including proteases proinflammatory cytokines and matrix degradation seems to be related to the degradation of the fibrous cap, and plaque rupture. Several studies have sought to identify systemic proinflammatory factors released locally and influencing the evolution of the plate to an unstable phenotype. And in this context, the family of thrombospondin (TSP) have attracted great interest. The TSP matricelulares belong to the family of proteins, which are extracellular matrix proteins, which do not have a structural role, but when incorporated to the matrix can modulate a variety of biological processes including cell interaction: cell and cell: matrix. Although studies indicate the presence of TSP-1 in the lesions and also higher concentrations are found in the serum of patients with atherosclerosis, the role of this protein in the pathology of the disease is not well defined. With the development of this project, we intend to test whether the TSP-1 modulates the function of foam cells, macrophages cytoplasm rich in lipids, particularly oxidized LDL found in atherosclerotic lesions. Let us investigate whether the absence of TSP-1 by using siRNA in vitro modulating the secretion of cytokines, matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in response to lipoprotein occurs. We also intend to clarify whether these cells then exhibit reduced ability to induce angiogenesis. We will also investigate by confocal microscopy is colocalization of TSP-1 with lesion areas containing different populations of macrophages occurs. With the results we want to understand how high levels of TSP-1 observed in patients' blood may contribute to the inflammatory process and disease progression.