Effects of linoleic acid on in vitro modulation of angiogenesis process

• Grant number: 16/15955-4
• Support Opportunities: Scholarships in Brazil - Master
• Start date: March 01, 2017
• End date: February 28, 2019
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: Hosana Gomes Rodrigues
• Grantee: Jessica Rondoni Silva
• Host Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil
• Associated research grant: 13/06810-4 - Mechanisms of action of omega-3 and omega-6 in the tissue repair process: neuro-immune focus, AP.JP

Abstract

Angiogenesis is defined as the formation of new blood vessels from existing vessels, and is involved in physiological and pathological processes. Angiogenesis is a highly complex and dynamic process regulated in each stage by various pro- and anti-angiogenic molecules, such as vascular endothelial growth factor (VEGF). The VEGF-receptor binding triggers a signaling cascade that culminates in the transcription of genes involved in processes such as proliferation, differentiation, actin reorganization and control of vascular permeability, essential processes for angiogenesis to occur. Another important modulator of angiogenesis is a factor induced by hypoxia (HIF). HIF is a transcription factor activated by hypoxia, when translocated to the nucleus induces the expression of genes as VEGF, angiopoietin-2 glucose transporter, which in addition to participate in angiogenesis, also assist the adaptation of the cells to low concentration oxygen. It has been observed that the fatty acids of the É-3 and É-6 families can modulate the angiogenic process, they affect migration, proliferation and tube formation, events essential for new vessel formation. In previous studies we observed that the linoleic acid (LA, 18: 2 É-6) increased VEGF levels and the number of new blood vessels in the skin. Thus, the aim of this study is to evaluate the in vitro effects of LA on angiogenesis, and the possible involvement of VEGF and HIF pathways on it. To do so, we will isolated primary endothelial culture of mouse lung to evaluate the effects of LA on the proliferation, migration, spreading and tube formation in the presence and absence of activators/inhibitors of pathways of VEGF and HIF evaluating phosphorylation of key proteins such as Akt, p38, Ras and PKC. We will also consider the production of VEGF, MMP-9, TIMP-1 and angiostatin on cell culture supernatants. To evaluate the participation of the HIF pathway, we will conduct the experiments in hypoxic conditions (concentration of 1% oxygen), and we will use a pharmacological activator of the pathway, IOX2, which stabilizes HIF, thereby preventing its degradation via the proteasome. Also will perform experiments with zebrafish model, to confirm and deepen the mechanisms of action by which LA can modulate angiogenesis. (AU)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

SILVA, Jessica Rondoni. Linoleic fatty acid and wound healing: focus on angiogenesis. 2019. Master's Dissertation - Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Aplicadas Limeira, SP.