Modulation of MMP-2 and MMP-9 levels in hypertensive disorders of pregnancy by genetic polymorphisms

• Grant number: 10/06579-2
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2010
• End date: June 30, 2012
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Jose Eduardo Tanus dos Santos
• Grantee: Jose Eduardo Tanus dos Santos
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Hypertensive disorders of pregnancy are major complications of pregnacy and include preeclampsia and gestational hypertension. Preeclampsia includes gestational hypertension with proteinuria and is the major cause of mortality and morbidity in pregnancy. Its pathophysiology involves significant reductions in blood flow to the fetus and this isquemia induces the release of mediators that cause endothelial dysfunction and increases in arterial pressure. Matrix metalloproteinases (MMPs) are involved in tissue remodeling and play a role in the control of vascular tonus. It is possible that altered regulation of MMPs play a role in the pathophysiology of preeclampsia or gestational hypertension. In fact, we have shown increased MMP-9 levels in gestational hypertension, but not increased MMP-2 levels. However, it is possible that genetic polymorphisms of MMP-9 or MMP-2 may affect the circulating levels of these enzymes and thus affect the susceptibility or the severity of gestational hypertension or preeclampsia. Here, we aimed at examining the effects of these genetic polymorphisms on MMP levels in healthy pregnant women and in women with gesational hypertension and with preeclampsia. The circulating MMPs and TIMPs (tissue inhibitors of metalloproteinases) will be measured in the three group of women (n=200 per group) and will be associated with genotypes and haplotypes. (AU)