Effect of uric acid on atherosclerosis development

• Grant number: 22/05623-5
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Effective date (Start): September 05, 2022
• Effective date (End): September 04, 2023
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Flavia Carla Meotti
• Grantee: Beatriz Pereira da Silva
• Supervisor: Christoph J. Binder
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Research place: Medical University of Vienna, Austria
• Associated to the scholarship: 19/26473-9 - The role of urate hydroperoxide in macrophage polarization, BP.DD

Abstract

Atherosclerosis is a chronic, lipid-induced disease of the arterial wall and is the leading cause of heart attacks and strokes, causing the majority of deaths and morbidity worldwide. The accumulation of oxidized low-density lipoproteins (OxLDL) and the infiltration of immune cells into the tissues trigger an inflammatory cellular response that leads to lesions and the formation of atherosclerotic plaques in the vascular wall. Several causes of cardiovascular disease have been identified, with uric acid being an emerging risk factor for atherosclerosis development. Indeed, hyperuricemia is known to be linked to the development of many inflammatory diseases. Importantly, we have previously found that induction of hyperuricemia in mice increases the secretion of pro-inflammatory cytokines, and the presence of uric acid in a pro-oxidant milieu can increase the oxidation of LDL. Moreover, the protective role of IgM in chronic inflammation has been described by the ability of IgM to recognize endogenous structures generated by lipid peroxidation, such as OxLDL. Therefore, we hypothesize that hyperuricemia is associated with altered IgM antibodies that target oxidized lipids, thereby leading to increased development of atherosclerosis. We intend to evaluate this hyperuricemic effect in the laboratory of Prof. Binder (Medical University of Vienna, Austria), a specialist in the field of immunology in arteriosclerosis. Together, this project will provide important novel insights into the mechanisms by which increased uric acid levels contribute to chronic inflammatory processes during cardiovascular disease. (AU)