Role of matrix metalloproteinases (MMPs) and inflammation in arterial stiffness in patients with resistant hypertension

• Grant number: 12/23292-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2013
• End date: July 31, 2014
• Field of knowledge: Biological Sciences - Pharmacology - Cardiorenal Pharmacology
• Principal Investigator: Heitor Moreno Junior
• Grantee: Isabella Fagian Pansani
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Resistant hypertension (RHTN) is defined as the blood pressure (BP) that remains above the target despite the concurrent use of three antihypertensive agents of different classes with a rational combination of maximum doses, at least one being a diuretic. Also, are considered resistant subjects those patients that are able to control BP when using four or more classes of antihypertensive drugs. The two subgroups of patients with resistant hypertension, the controlled (C-RHTN) and uncontrolled (UC-RHTN), differ in several aspects. It is known that vascular stiffness (VS), an important marker of cardiovascular risk, is more pronounced in those patients resistant to antihypertensive therapy and who cannot get control of BP. There are several determinants of VS, for instance, the actions of matrix metalloproteinases (MMPs), especially MMPs -2 and -9, and their tissue inhibitors (TIMPs), respectively TIMPs -2 and -1. Also, inflammation is involved in the pathophysiologic mechanism of hypertension (HBP), but there is doubt whether this has responsibility in the genesis of RHTN. This project aims to evaluate the role of MMPs -2 and -9, as well as TIMPs -1 and -2 in the genesis of the VS in patients with resistant hypertension. It will be further verified the influence of inflammatory cytokines interleukin IL-1 and -6 and tumor necrosis factor (TNF-±) in this process. This study will be included 80 patients with resistant hypertension with proven adherence to pharmacological and nonpharmacological treatment from the Ambulatory of Resistant Hypertension from the HC-FCM/UNICAMP and from the HMCP / PUC-Campinas. They will be subdivided into two groups: UC-RHTN (n = 40) and C-RHTN (n = 40), as described above. Hemodynamic parameters related to the RV will be determined by measuring the pulse wave velocity (PWV) carotid-femoral. Plasma levels of MMPs -2 and -9 and TIMPs -2 and -1, and the inflammatory cytokines IL-1, -6, and TNF-± will be determined by immunoassay. The results of this study will provide a better understanding of the role of MMPs and their inhibitors in arterial stiffness in resistant hypertensive patients.(AU)