Cardiovascular effects of increased Matrix metalloproteinase 2 (MMP-2) in healthy and atherosclerotic mice in vivo

• Grant number: 11/20712-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: February 01, 2012
• End date: November 30, 2015
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Raquel Fernanda Gerlach
• Grantee: Alejandro Ferraz Do Prado
• Host Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Currently atherosclerosis is the main cause of infarct in the world. The MMP-2 seems one of the proteases that plays a major role in this disease because it has been related to rupture of atherosclerotic plaques. Several studies demonstrated that inhibitors that act on MMP-2 activity are beneficial for cardiovascular diseases. However, to date, few studies have demonstrated the direct actions of this protease in cardiovascular system. It is unclear, for example, whether this protease leaves the vascular compartment and diffuses into the vascular wall ant into certain target organs that are typically affected in cardiovascular diseases. In this proposal we plan to use a fluorescent MMP-2 (MMP-2 fused with green fluorescent protein), in order to map directly the destiny of this circulating molecule, as well as their involvement in processes of target organ damage in atherosclerosis. Therefore, we will use infusion pumps to release fluorescent MMP-2 for 4 weeks into atherosclerotic mice (LDLr-/-). Thereafter this time, we will study the morphological and functional changes of arteries, as well as the destiny of the fluorescent MMP-2 in vivo, mainly by observing the heart, kidney and thoracic aorta. This project was previously approved as individual Research Grant by FAPESP, Process 2011/10336-0.