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Association between metalloproteinase-9 polimorphisms and inflammation on ventricular hypertrophy and vascular stiffness in resistant hypertension

Grant number: 12/23410-7
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): May 01, 2013
Effective date (End): June 30, 2016
Field of knowledge:Biological Sciences - Pharmacology - Cardiorenal Pharmacology
Principal Investigator:Heitor Moreno Junior
Grantee:Natália Ruggeri Barbaro
Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated scholarship(s):14/17300-0 - The role of salt in activation of immune system in hypertension, BE.EP.DR


Hypertension (HTN) is a multifactorial clinical condition characterized by high levels of blood pressure (BP) and represents a risk factor for fatal and non-fatal cardiovascular events. Several factors are involved in lack of blood pressure control such as treatment non-adherence, inappropriate treatment and finally, resistant hypertension (RHTN). Increasing the blood pressure leads to target-organ damage, mainly heart and vasculature. The two more frequent target-organ damage in hypertension are left ventricular hypertrophy (LVH) and arterial stiffness. It is well established that matrix metalloproteinases, especially the subgroup of gelatinases, among them, MMP-9, is involved in remodeling associated with LVH and arterial stiffness, demonstrated in experimental hypertensive animal models and humans, however it is unknown in RHTN. Some MMP-9 gene polymorphisms as -1562C>T and R279Q are related with increased MMP-9 levels and cardiovascular events. Also, a study showed R279Q polymorphism affects arterial stiffness in health subjects. Moreover, some studies suggest that inflammation could be associated with hypertension development and target-organ damage. MMP-9 is an endopeptidase closely related with immune system, neutrophil migration and tissue injury. MMP-9 high levels were found in inflammatory conditions. This project aims to evaluate the relationship between LVH, arterial stiffness with plasmatic MMP-9 and its inhibitor TIMP-1 levels. Indeed, we will study the association of MMP-9 genotypes(-1562C>T and R279Q) and haplotypes with different degrees of hypertension and resistant hypertension. Secondly, it will be measure inflammatory markers (TNF-± e IL-1²) and evaluate their correlation with target-organ damage in these patients

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Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
BARBARO, Natália Ruggeri. Assessment of matrix metalloproteinase 9 genetic polymorphisms, circulating levels and its inhibitor TIMP-1 in resistant hypertension. 2016. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas Campinas, SP.

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