Gelatinases and Their Tissue Inhibitors in a Group of Subjects with Metabolic Syndrome

Abstract

An altered pattern of MMPs and their inhibitors is demonstrated in MS; the presence of diabetes mellitus strongly influences the concentration of MMP and TIMP, contributing probably to the increased cardiovascular risk of MS subjects.

Evaluation of plasma MMP-8, MMP-9 and TIMP-1 identifies candidate cardiometabolic risk marker in metabolic syndrome: results from double-blinded nested case–control study

“…Reports of MMPs in MetS are scarce and discrepant [15][16][17][18][19][20][21]; more importantly they should be interpreted with caution due to different criteria [30,35] and heterogeneous clustering of MetS in each study. Nevertheless, higher MMP-8 [15,17], higher TIMP-1 [17,18,20], and lower MMP-9/TIMP-1 [18,19] in MetS individuals and comparable MMP-9 levels between MetS cases/controls [21] are supported by previous reports. Pro-MMP-9 requires a proteolytic process to become active and this activation is tightly regulated at the transcription level, at precursor zymogens activation, through interaction with specific ECM components, and by inhibition of endogenous inhibitors.…”

“…Regulation of MMPs is, however, complex, where transcriptional regulators and tissue inhibitors of MMP (TIMPs) modulate MMP levels and activity, respectively. Published articles concerning MMPs profiles in MetS are scarce and controversial [15][16][17][18][19][20][21]. Due to the pro-inflammatory nature of MetS [3] and the fact circulating MMPs levels reflect their activity within atherosclerotic plaques [22], we evaluated plasma concentrations of MMP-8, MMP-9 and TIMP-1 in a group of MetS cases and healthy controls.…”

The extracellular matrix and insulin resistance

“…MMP dysregulation has been implicated in the pathophysiology of obesity and diabetes. Plasma MMP2 and MMP9 concentrations are increased in obese [79] and diabetic [80, 81] individuals. Additionally, gene expression of adipose MMP9 correlates positively with altered HOMA-IR index in morbidly obese individuals [82].…”

“…Circulating TIMP-1 and TIMP-2 are increased in patients with metabolic syndrome and diabetes [81]. Overexpression of TIMP1 in pancreatic β-cells protects mice from streptozotocin-induced β-cell death and diabetes [84].…”

Study of the Correlations among Some Parameters of the Oxidative Status, Gelatinases, and Their Inhibitors in a Group of Subjects with Metabolic Syndrome

“…In the last years, we have been interested in the evaluation of the redox balance [6–10] and of the MMPs profile [11, 12] in MS. MMPs are related to atherosclerotic disease and to cardiovascular morbidity and mortality [13–18]; these are endopeptidases responsible for the degradation of several extracellular matrix proteins, such as collagen, laminin, gelatin, and fibronectin [19] which are produced into the vascular wall and are denominated in relation to their target (collagenase, gelatinase, stromelysin, or matrilysin). Gelatinases A and B (MMP-2 and -9) are involved in the vascular remodelling that precedes the atherosclerosis development and also in its worse outcomes [20, 21].…”