Increase in MMP-2 activity in overweight and obese women is associated with menopausal status

Abstract

Background Metalloproteinases (MMPs) are synthesized in the subendothelium and are involved in the atherosclerosis and cardiovascular disease process because of their major significance in vascular remodeling and plaque rupture. MMPs are also synthesized in adipose tissue during angiogenesis; however, the role of these enzymes in obesity and insulin-resistant states is still controversial. Objective To evaluate MMP-2 activity in the circulation of overweight and obese women and in normal-weight controls, and to associate the levels of these factors with metabolic, adipose tissue and inflammation biomarkers. Methods Plasma MMP-2 activity, adiponectin and C-reactive protein concentration, lipoprotein profile and HOMA were determined in 39 healthy women (13 normal weight and 26 overweight/obese). Results Overweight/obese women were older (p <0.001) than normal-weight women; 20/26 of overweight/obese women were postmenopausal compared with 4/13 of normal-weight women. Overweight/obese women had significantly higher plasma activity of MMP-2 than controls (mean relative area: 0.81 (range 0.4-1.92) vs. 1.33 (range 0.4-3.1); p <0.005); this difference was lost after adjusting for menopausal status. MMP-2 activity positively correlated with waist circumference (p <0.002), HOMA (p <0.003), and high-sensitivity C-reactive protein (p <0.05), apolipoprotein B (p =0.006) and triglyceride/high density lipoprotein (HDL) cholesterol index (p <0.001), and negatively with HDL cholesterol (p <0.001), HDL2 cholesterol (p <0.008), HDL3 cholesterol (p <0.05) and adiponectin (p <0.05). The association with HOMA and adiponectin persisted even after adjusting for menopausal status. Conclusion Our finding of increased plasma activity of MMP-2 in overweight/obese women, associated with menopausal status, is important given that it fits in with an early stage of cardiovascular disease; the association of MMP-2 activity with obesity markers may be a link between adipose tissue and risk for cardiovascular disease.