Effects of iNOS and Metalloproteinases 2 and 9 in the development and progression of abdominal aortic aneurysms in a new experimental model

• Grant number: 07/00342-8
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2007
• End date: August 31, 2010
• 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 aneurysms (AAA) primarily affect elderly males with a prevalence of 5%. The natural history of aneurysms is to expand and eventually rupture, being responsible for 1,5% of the total mortality in males over 55 years of age. Despite the high frequency, much little it is known about their mechanisms of development and progression. This scarce knowledge must be, in part, to the lack of models animals comparable to this illness. We developed in our laboratory, one new model of AAA associating extrinsic stenosis and adventitial injury wall in aortas of rats. These two phenomena together contribute to development and progression of AAA during 30 days of experiment. There was adventitial inflammatory infiltrate followed for intense elastolytic activity and replacement of the arterial wall for abundant mesenchymal proliferation, predominantly smooth muscular cells (SMCs) embedded in extracellular matrix. The arterial dilatation is restricted to the remodeled area. Without the rheologic alterations promoted in this model, the aneurisms are not developed.Nitric oxide (NO) production by nitric oxide synthase (NOS) plays a major role in inflammation and aneurysm pathogenesis. NO production by the inducible form of nitric oxide synthase (iNOS) occurs primarily by inflammatory cells resulting in high NO levels and toxic products that degrade elastin and disrupt the extracellular matrix. Matrix metalloproteinases (MMPs) are known to degrade extracellular matrix and be up-regulated in aneurismal disease. The relation between NO and MMPs is conflicting in the literature and their relationship to aneurismal disease is currently unknown. The aim of this study is to evaluate the participation of metalloproteinases 2 and 9 (MMPs 2 and 9) and iNOS (oxide nitric sintase induced) in the development e progression of AAA in this model. (AU)