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Genetic polymorphisms of matrix metalloproteinases in resistant hypertension

Grant number: 14/05635-7
Support type:Scholarships abroad - Research
Effective date (Start): September 01, 2015
Effective date (End): August 31, 2016
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Heitor Moreno Junior
Grantee:Heitor Moreno Junior
Host: Felipe Fregni
Home Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Local de pesquisa : Harvard University, Boston, United States  
Associated research grant:13/07607-8 - OCRC - Obesity and Comorbidities Research Center, AP.CEPID

Abstract

Genetic polymorphisms of matrix metalloproteinases in resistant hypertension CEPID Prof. Dr. Heitor Moreno Junior Faculdade de Ciências Médicas-UNICAMP Prof. Dr. Felipe Fregni Harvard Medical School. Abstract. Resistant hypertension (RH) is characterized by high blood pressure in spite of concurrent use of three antihypertensive agents of different classes, combined at optimal doses and including a diuretic. Indeed, RH includes patients with controlled blood pressure using four or more agents. Resistant hypertensive patients have an unfavorable prognostic and the morbidity and mortality occur in consequence of the high prevalence of target-organ damage in these patients, including left ventricular hypertrophy and arterial stiffness. Metalloproteinases (MMPs) are a family of enzymes that degrade extracellular matrix proteins and are involved in cardiovascular remodeling related to target-organ damage in cardiovascular diseases, including hypertension (HT). Several studies in experimental models and in humans showed increased levels of MMPs-2 and -9 in HT. Furthermore, increased levels of MMP-9 were described as predictors of cardiovascular mortality. MMP-9 has an important role in inflammatory pathways. However, there is no study in resistant hypertension showing the role of MMPs in target-organ damage in this group of patients. The aim of this study is to evaluate the association of the levels and activity of MMP-2 and -9 and their inhibitors, TIMP-1 and TIMP-2, and how the polymorphisms in these two enzymes (MMP-2 -1575G>A; MMP-2 -1306C>T; MMP-2 -735C>T; MMP-9 -1562C>T; MMP-9 R279Q e MMP-9 R668Q) affect the left ventricular hypertrophy, arterial stiffness of the RH and HT diseases, as the presence of obstructive sleep apnea and lack of blood pressure control. (AU)