Circulating and adipose tissue matrix metalloproteinases in cardiometabolic risk environments: pathophysiological aspects

BERG, GABRIELA; SCHREIER, LAURA ESTER; MIKSZTOWICZ, VERONICA

Hormone Molecular Biology and Clinical Investigation

De Gruyter

Año: 2014

1868-1883

Abstract: Matrix metalloproteinases (MMPs) play animportant role during physiological tissue remodelingin embryonic development and angiogenesis, as well asin pathophysiological conditions such as obesity anddevelopment and vulnerability of atherosclerotic plaque.Moreover, MMP circulating levels have emerged as potentialbiomarkers of cardiovascular disease. MMP expressionand activity are regulated by different factors such as insulinresistance and obesity. Expanded fat tissue has beendemonstrated to be an active organ, where MMPs also exerta role in adipogenesis, angiogenesis, and proliferationof extracellular matrix (ECM). However, the lack of associationbetween adipose tissue and plasma levels of someMMPs, specifically MMP-2 and MMP-9, suggests that thistissue is not a major contributor to circulating gelatinases.MMPs are also co-expressed or co-repressed in response toinflammatory adipocytokines, like adiponectin and leptin.Adiponectin may also play a protective role in plaque rupturethrough selectively increasing the tissue inhibitor ofmetalloproteinase (TIMP) expression. Leptin induces theexpression of MMP-2 activators as well as the expression ofMMP-2, MMP-9, and TIMP-1 in different human cells. Furthermore,sex hormones also participate in MMP regulation.In postmenopausal women, hormone replacementtherapy produces an increase in MMP activity, leading toa breakdown in ECM homeostasis and accelerated progressionof vascular pathologies. Besides, in men, an inverserelationship between testosterone levels and MMP-2 activityhas been described. It is still necessary to go forward inthe study of MMPs in different metabolic situations to corroboratetheir role as vulnerable plaque biomarkers.