Influence of advanced albumin glycation on lipid cell accumulation

• Grant number: 05/00242-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2005
• End date: September 30, 2006
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Marisa Passarelli
• Grantee: Paula Bravos Philipson
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Intensive glycemic control is fundamental for the prevention of acute and long term complications of diabetes mellitus, including the atherosclerotic disease. In diabetes mellitus, glycation of lipids and proteins leads to alterations in plasma lipids and lipoprotein profile and may contribute to atherogenesis. We have recently shown that albumin and cellular modification by advanced glycated end products (AGE) reduce the HDL-mediated cholesterol efflux from cells. This event damages the reverse cholesterol transport system by which cholesterol is removed from peripheral cells, transported to the liver and secreted into the bile. Intracellular cholesterol content, especially in macrophages, is determined by the modified LDL uptake by scavenger receptors and its removal by HDL. Cholesterol efflux is regulated by the intracellular cholesterol content, HDL receptors in the cell surface and HDL size and composition. In this study we aim at investigating the role of advanced glycated albumin on the intracellular cholesterol accumulation, namely determined by the modified -LDL uptake by cells, oleic acid incorporation into lipids and cholesterol driving form Golgi apparatus to the cell surface, as well as the role of AGE inhibitors (aminoguanidine and metformin) on these process. These drugs may be helpful to prevent disturbances in the reverse cholesterol transport system in diabetes mellitus.