The role of MMP-9 in the pathogenesis of osteoporosis in animal models of atherosclerosis

• Grant number: 15/16194-4
• Support Opportunities: Regular Research Grants
• Start date: December 01, 2015
• End date: July 31, 2018
• Field of knowledge: Health Sciences - Medicine - Surgery
• Principal Investigator: João Paulo Mardegan Issa
• Grantee: João Paulo Mardegan Issa
• Host Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Osteoporosis is the second cause of death in the world loosing for cardiovascular disease that is the first cause of death. This number will further increase with the growth of the older population in the next decades. Several studies shown that patients with a low bone mineral density presents higher risks for developing cardiovascular diseases, including, severe coronary atherosclerosis and vascular calcification, regardless age and sex. Despite recent studies, the pathological, physiological and molecular mechanisms that correlate the atherosclerosis and osteoporosis are still unknown.The matrix metalloproteinase-9 (MMP-9) has been described in the literature as overexpressed in atherosclerosis models and their activity correlated with increased bone resorption in the osteoporosis, and hence it may be a key molecule in charge for coupled these two pathologies. For this purpose we will investigate the expression levels of MMP-9 in the femur and tibia bones from Apolipoprotein E knockout mice and their respective controls (C57BL/6), as well as evaluate the effects of drugs that act on MMP-9 activity, in the treatment of atherosclerosis and of osteoporosis, and observe the pathogenic reversal.The MMP-9 levels will be evaluate by quantitative real time (qPCR), western blotting, zymography gel and fluorimetric assays, in addition, the bone microarchitecture will be investigate by densitometry, micro-CT assay, histological and immunohistochemical assays. The discovery of a molecule responsible for associate these two pathologies as well their biochemical and molecular characterization may be target for future therapies. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

AZEVEDO, ALINE; PRADO, ALEJANDRO F.; FELDMAN, SARA; DE FIGUEIREDO, FELLIPE A. T.; DOS SANTOS, MARIA CECILIA G.; ISSA, JOAO PAULO M.. MMPs are Involved in Osteoporosis and are Correlated with Cardiovascular Diseases. CURRENT PHARMACEUTICAL DESIGN, v. 24, n. 16, p. 1801-1810, 2018. (15/16194-4)

SHIMANO, R. C.; YANAGIHARA, G. R.; MACEDO, A. P.; YAMANAKA, J. S.; SHIMANO, A. C.; TAVARES, J. M. R. S.; ISSA, J. P. M.. Effects of high-impact exercise on the physical properties of bones of ovariectomized rats fed to a high-protein diet. SCANDINAVIAN JOURNAL OF MEDICINE & SCIENCE IN SPORTS, v. 28, n. 5, p. 1523-1531, MAY 2018. (15/16194-4, 14/10733-8, 14/25879-8, 15/26142-1)