Hypercholesterolemic diet causes atherosclerosis in abdominal aortic aneurysm: study of the mechanisms in an experimental model

• Grant number: 12/00601-1
• Support Opportunities: Regular Research Grants
• Start date: June 01, 2012
• End date: February 28, 2014
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Simone Gusmão Ramos
• Grantee: Simone Gusmão Ramos
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Abdominal aortic aneurysm (AAA) is a chronic disease associated to atherosclerosis. The mechanisms of formation and progression of AAAs are not completely understood, because just 10% of patients with severe atherosclerosis develop aneurysms. Atherosclerosis increases smooth muscle cells (SMC) apoptosis in the middle layer of aorta, and it is considered a crucial event in aneurysms formation. This programmed death is associated with proteolytic enzymes related to the lysosomal cysteine proteases family known as cathepsins. Apoptosis may be initiated by extrinsic factors, by cell receptors activation, or intrinsic factors in response to cellular damage and oxidative stress. However, there are no studies comparing cathepsins action on these two pathways in atherosclerosis and AAA development.A pilot study showed that the administration of a hypercholesterolemic diet develops fat plaques in the aneurysmal wall. These two findings provided this project, whose objective is investigate the cathepsins action on the mechanisms of development and/or maintenance of smooth muscle cell (SMC) apoptosis with or without atherosclerotic plaques. The collaboration established with Prof. Dr. Guo-Ping Shi at the Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA, will help the development of this project. (AU)