Matrix metalloproteinases 2 and 9 and their tissue inhibitors 1 and 2 in premenopausal obese women: relationship to cardiac function

Int J Obes (Lond). 2008 May;32(5):763-71. doi: 10.1038/sj.ijo.0803794. Epub 2008 Jan 15.

Abstract

Background: Myocardial fibrosis is one of the mechanisms underlying left ventricular (LV) dysfunction in obese patients and may result from dysregulation of extracellular matrix (ECM) turnover. Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) represent a regulatory system playing a crucial role in ECM metabolism.

Objectives: We sought to assess plasma levels of MMP-2, MMP-9, TIMP-1 and TIMP-2 in obese young women and to evaluate the association between MMP/TIMP system components and LV function in this population.

Design: Prospective, cross-sectional study.

Setting: University hospital.

Patients: Seventy-one women aged < 35 years with body mass index > 30 kg m(-2) and 30 healthy slim female controls.

Main outcome measures: Plasma MMP-2, MMP-9, TIMP-1 and TIMP-2 measurements and echocardiographic studies, including LV strain/strain rate evaluation.

Results: We demonstrated increased levels of MMP-9 and TIMP-1 and decreased MMP-2 in the obese population. LV dysfunction shown in patients with obesity was characterized by significantly lower values of strain/strain rate parameters. Plasma MMP-2 correlated positively and TIMP-1 negatively with systolic strain (r = 0.39, P < 0.001 and r = -0.40, P < 0.001, respectively), peak systolic strain rate (r = 0.38, P < 0.001 and r = -0.27, P < 0.03, respectively) and peak early diastolic strain rate (r = 0.40, P < 0.001 and r = -0.24, P < 0.05, respectively). Plasma MMP-2, fasting insulin and body mass index proved the only independent determinants of strain/strain rate parameters of LV systolic and diastolic performance in obese subjects.

Conclusions: In premenopausal obese women (1) plasma MMP/TIMP profile is altered, (2) abnormalities of LV function are related to the changes in the MMP/TIMP system that might promote attenuated ECM degradation, mainly to the downregulation of MMP-2.

MeSH terms

  • Adult
  • Body Mass Index
  • Cardiomyopathies / enzymology
  • Cardiomyopathies / epidemiology
  • Down-Regulation
  • Female
  • Humans
  • Matrix Metalloproteinase 2 / blood*
  • Matrix Metalloproteinase 9 / blood*
  • Obesity / blood*
  • Obesity / physiopathology
  • Premenopause / blood
  • Tissue Inhibitor of Metalloproteinase-1 / blood*
  • Tissue Inhibitor of Metalloproteinase-2 / blood*
  • Ventricular Dysfunction, Left / enzymology
  • Ventricular Dysfunction, Left / etiology*

Substances

  • Tissue Inhibitor of Metalloproteinase-1
  • Tissue Inhibitor of Metalloproteinase-2
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9