Full text
| |
| Author(s): |
Natália Ruggeri Barbaro
Total Authors: 1
|
| Document type: | Doctoral Thesis |
| Press: | Campinas, SP. |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas |
| Defense date: | 2016-06-23 |
| Examining board members: |
Heitor Moreno Junior;
Gabriel Forato Anhê;
Íscia Teresinha Lopes Cendes;
Riccardo Lacchini;
Michele Mazzaron de Castro;
Fabíola Zakia Mónica
|
| Advisor: | Heitor Moreno Junior; Vanessa Fontana |
| Abstract | |
Resistant hypertension (RHTN) is defined as BP that remains above goals despite of the concurrent use of 3 antihypertensive agents of different classes at optimal dose amounts. Also, patients whose BP are controlled but require 4 or more medications are considered resistant. Left ventricular hypertrophy (LVH) and arterial stiffness are important predictors of mortality and morbidity and it is related to major cardiovascular events. Matrix metalloproteinases (MMPs) are a family of zinc dependent enzymes. MMP-9 participates in cardiovascular remodeling that contributes to LVH and arterial stiffness. These relationships are well described in animal models of hypertension, however in RHTN remains unclear. Genetics polymorphisms in MMP-9 gene including -1562C>T (rs3918242) and R279Q (rs17576) were associated with MMP-9 levels and cardiovascular events. The relationship between R279Q and arterial stiffness was also described in healthy volunteers. Finally, non-synonymous SNP Q668R (rs17577) was related to coronary disease in hypertensive patients treated with Amodipine. To date, no MMP-9 polymorphisms were evaluated in RHTN. Therefore, this study aimed: (1) To evaluate the levels of MMP-9, TIMP-1 and MMP-9/TIMP-1 ratio in RHTN subjects (n=124) and non-RHTN (HTN) (n=136) (2) To evaluate the relationship between MMP-9 and TIMP-1 with arterial stiffness and LVH in both groups (3) To evaluate the frequencies of MMP-9 polymorphisms (rs3918242, rs17576 e rs17577) in HTN vs. RHTN (4) To evaluate the relationship of genetic polymorphisms with MMP-9 levels, LVH and arterial stiffness. Plasma levels of MMP-9 and TIMP-1 were measured by ELISA. RHTN subjects presented decreased levels of MMP-9 and MMP-9/TIMP-1 ratio and higher TIMP-1 compared to HTN. We evaluated the association of these biomarkers with arterial stiffness, measured by pulse wave velocity (PWV), and with LVH, defined by left ventricular mass index (LVMI) (by echocardiogram). MMP-9 and MMP-9/TIMP-1 ratio were positively correlated with LV diastolic diameter (LVDD) in RHTN group. On the other hand, these biomarkers were inversely related to LVDD in HTN group. TIMP-1 was negatively related to LVMI in RHTN subjects, while positive association was found in HTN group. No relationship was found between LVMI and MMP-9, neither between PWV and MMP-9 nor TIMP-1 in both groups. We assessed genotypic frequency of -1562C>T using PCR followed by electrophoresis. R279Q and Q668R polymorphisms were determined using Real Time PCR with Taqman probes. Haplotype frequencies were estimated by PHASE software. There were no significant differences in the genotypes, alleles or haplotypes distributions between the RHTN patients and HTN. Moreover, no differences were found in MMP-9 levels, PWV or LVMI according to MMP-9 genotypes. Our data suggest that MMP/TIMP balance varies according to the severity of hypertension and are associated with resistant hypertension and left ventricular hypertrophy. In addition, genetic polymorphisms in MMP-9 are not associated to RHTN phenotype and do not affect MMP-9 levels in the studied hypertensive patients (AU) | |
| FAPESP's process: | 12/23410-7 - Association between metalloproteinase-9 polimorphisms and inflammation on ventricular hypertrophy and vascular stiffness in resistant hypertension |
| Grantee: | Natália Ruggeri Barbaro |
| Support Opportunities: | Scholarships in Brazil - Doctorate |