Intracellular effect of matrix metalloproteinase (MMP)-2 in hypertension-mediated cardiovascular dysfunction

• Grant number: 14/11412-0
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2014
• End date: October 31, 2016
• Field of knowledge: Biological Sciences - Pharmacology - Cardiorenal Pharmacology
• Principal Investigator: Michele Mazzaron de Castro
• Grantee: Michele Mazzaron de Castro
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Matrix metalloproteinases (MMPs) are well known for their ability in degrading several components of the extracellular matrix, thus mediating the pathophysiological tissue remodeling. MMP-2 notably contributes to hypertension-induced cardiovascular dysfunction and chronic maladaptive remodeling. In this project, we aim to investigate whether MMP-2 mediates hypertension-induced cardiovascular alterations by degrading intracellular proteins responsible for regulating either the cardiac contraction or vascular tone. Both calponin-1 and troponin I will be examined as potential targets to be degraded by MMP-2 in the vascular smooth muscle cells and cardiomyocytes during hypertension, since they mainly regulate the cardiac contractile apparatus and vascular tone. Previous studies showed that calponin-1 and troponin I were cleaved by MMP-2 in the vasculature of endotoxemic rats and in hearts subjected to ischemia and reperfusion injury, respectively. The results from this project will assist in the understanding of how the cardiac and vascular contractile apparatus are regulated during hypertension, in addition to show new mechanisms in regulating vascular smooth muscle cells migration and proliferation. The MMP inhibitors may be useful not only as pharmacological tools in experimental research, but instead, as adjuvant therapy in the treatment of hypertension and its cardiovascular complications. This project may work as a bridge to connect many areas of research, thus encouraging the cooperation and collaboration between laboratories and the departments in the university. (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)

BELO, VANESSA DE ALMEIDA; PARENTE, JULIANA MONTENEGRO; TANUS-SANTOS, JOSE EDUARDO; CASTRO, MICHELE M.. Matrix metalloproteinase (MMP)-2 decreases calponin-1 levels and contributes to arterial remodeling in early hypertension. Biochemical Pharmacology, v. 118, p. 50-58, OCT 15 2016. (14/11412-0)

PARENTE, JULIANA MONTENEGRO; MELLO, MARCELA MARIA BLASCKE DE; SILVA, PEDRO HENRIQUE LEITE DA; OMOTO, ANA CAROLINA MIEKO; PERNOMIAN, LAENA; OLIVEIRA, ISADORA SOUSA DE; MAHMUD, ZABED; FAZAN, JR., RUBENS; ARANTES, ELIANE CANDIANI; SCHULZ, RICHARD; et al. MMP inhibition attenuates hypertensive eccentric cardiac hypertrophy and dysfunction by preserving troponin I and dystrophin. Biochemical Pharmacology, v. 193, NOV 2021. (17/03580-9, 16/09345-9, 14/11412-0)

PEREIRA, SHERLIANE C.; PARENTE, JULIANA M.; BELO, VANESSA A.; MENDES, ATLANTE S.; GONZAGA, NATALIA A.; DO VALE, GABRIEL T.; CERON, CARLA S.; TANUS-SANTOS, JOSE EDUARDO; TIRAPELLI, CARLOS R.; CASTRO, MICHELE M.. Quercetin decreases the activity of matrix metalloproteinase-2 and ameliorates vascular remodeling in renovascular hypertension. ATHEROSCLEROSIS, v. 270, p. 146-153, MAR 2018. (14/11412-0)