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

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 o35 years with body mass index 430 kg m À2 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 ¼ 0.39, Po0.001 and r ¼ À0.40, Po0.001, respectively), peak systolic strain rate (r ¼ 0.38, Po0.001 and r ¼ À0.27, Po0.03, respectively) and peak early diastolic strain rate (r ¼ 0.40, Po0.001 and r ¼ À0.24, Po0.05, 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.

Evaluation of plasmatic MMP-8, MMP-9, TIMP-1 and MPO levels in obese and lean women

“…The findings reported here confirmed previous findings that showed higher circulating levels of MMP-9 in obese women as compared to lean women [5,10,11]. To our knowledge, we are the first to report a decreased plasma MMP-8 concentration in obese women.…”

“…Excessive production and release of MMP-9 are observed in adipose tissue; this contributes to tissue remodeling and expansion [20] and may contribute to higher plasma MMP-9 levels in obesity [5,10,11]. Clinically, it is important to note that the increased MMP-9 concentrations reported here may increase the risk of cardiovascular diseases in obese women [5,6]; this observation suggests the potential use of this biomarker as a nontraditional cardiovascular risk factor [21].…”

“…MMP-9 seems to play an important role in this process in obese individuals, as evident by its elevated plasma concentrations in these subjects [5,10,11]. In addition, clinical studies have shown that alteration in the expression or activity of MMPs and/or TIMPs is an important mechanism underlying the pathophysiology of some cardiovascular diseases [5][6][7][8] and contributes to ventricular dysfunction [6] and atherosclerotic lesions [9].…”

Expression of matrix metalloproteinases in patients with bipolar disorder

“…26 Downregulation of MMP-2 activity has been demonstrated in premenopausal obese women, and is associated with attenuated ECM degradation and abnormalities of left ventricular function. 27 Although MMP-2 and MMP-9 are similar enzymes, our results corroborate a study that showed distinct promoter Figure 1 Effect of body mass index (BMI) on matrix metalloproteinase 2 expression in patients with bipolar disorder (during mania and euthymia) and controls Figure 2 Effect of body mass index (BMI) on matrix metalloproteinase 9 expression in patients with bipolar disorder (during mania and euthymia) and controls elements and different spatial and temporal expression patterns of these proteases during ischemia/reperfusion injury. 11 It is possible that the type of upstream stimuli operative in BD will ultimately determine the transcriptional activity of selected MMP types.…”

Effects of eplerenone on the activation of matrix metalloproteinase-2 stimulated by high glucose and interleukin-1β in human cardiac fibroblasts

“…MMPs degrade ECM structural proteins (Jun et al, 2011), and TIMPs are the major endogenous regulators of MMP activities in tissues (Kandalam et al, 2011). MMPs and their tissue inhibitors represent a regulatory system that plays a crucial role in ECM metabolism (Kosmala et al, 2008). A previous study found that HG altered the level of MMPs and cytokines in fibroblasts (Westermann et al, 2007).…”