Serum concentrations of atherogenic proteins neutrophil gelatinase-associated lipocalin and its complex with matrix metalloproteinase-9 are significantly lower in women with polycystic ovary syndrome: hint of a protective mechanism?

Abstract

Background: Neutrophil gelatinase-associated lipocalin (NGAL) and matrix metalloproteinase-9 (MMP-9) have been considered as important mediators of vascular remodeling and plaque instability. The formation of a complex with NGAL and MMP-9 is crucial for atherotic plaque erosion and thrombus formation. In women with polycystic ovary syndrome (PCOS), the incidence of cardiovascular clinical events is not increased, despite the fact that they display a wide spectrum of risk factors. Since the instability of atherosclerotic plaque is a key factor in the clinical manifestations of cardiovascular disease, molecules challenging the plaque stability should be investigated. Aim: To determine serum levels of NGAL and MMP-9/NGAL complex in women with PCOS. Subjects and methods: PCOS subjects (40) were compared with those (40) matched for age and body mass index (BMI) controls. In each subject, fasting levels of glucose, insulin, gonadotropins, estradiol, androgens, C-reactive protein, NGAL, and MMP-9/NGAL were determined. Results: NGAL and MMP-9/NGAL complex levels were significantly lower in the PCOS group compared with controls (30.4G24.3 vs 70.7G37.9 mg/l, P!0.0001) and (31.5G26.6 vs 115.1G66.9 mg/l, P!0.0001) respectively. When patients and controls were stratified according to BMI, it was shown that NGAL and MMP-9/NGAL levels were significantly lower in lean (P!0.0002 and P!0.0001 respectively) and overweight (P!0.0004 and P!0.002 respectively) PCOS subjects compared with controls. Conclusions: These findings indicate that NGAL and MMP-9/NGAL complex, two molecules that activate atherotic plaque erosion, is in lower concentrations in PCOS subjects. The role of NGAL and MMP-9/NGAL complex needs to be further investigated, since suppression of these atheromatous molecules might have a protective role in women with PCOS.

Matrix metalloproteinases 2 and 9 and MMP9/NGAL complex activity in women with PCOS

“…While increased levels of MMP2 and/or MMP9 have shown in PCOS patients (Lewandowski et al 2006, Liu et al 2007, no significant differences have been observed between PCOS and control in the study by Gomes et al (2011), or a reduced MMP9 level has been reported by Diamanti-Kandarakis et al (2008). Similar conflicting results are also available about serum TIMP1 and TIMP2 levels (Lewandowski et al 2006, Liu et al 2008, Gomes et al 2011.…”

Związek między stężeniami lipokaliny-2 i testosteronu wolnego w zespole policystycznych jajników

“…Moreover, lipocalin-2 was not associated with cardiovascular risk indicators as defined by echocardiographic examination [10]. Diamanti-Kandarakis et al demonstrated that circulating lipocalin-2 levels were significantly lower in women with PCOS and were not associated with obesity, insulin resistance, and estradiol concentrations [3]. Although women with PCOS have numerous risk factors that can cause cardiovascular disease, it was reported that the incidence of cardiovascular events was not elevated in PCOS [29].…”

“…Although women with PCOS have numerous risk factors that can cause cardiovascular disease, it was reported that the incidence of cardiovascular events was not elevated in PCOS [29]. Therefore, the results of Diamanti-Kandarakis highlighted that lipocalin-2 is related to cardiovascular events rather than atherosclerotic heart disease; lipocalin-2 may have a protective role in PCOS [3,10].…”

“…Polycystic ovary syndrome (PCOS) is the one of the most common hormonal disorders in women of reproductive age [1][2][3]. It has been proposed that insulin resistance may have a pivotal role in the development of PCOS; nonetheless, the pathophysiology of this disease has not been wholly elucidated [4].…”

“…Lipocalin-2 binds to bacterial iron-laden siderophores to inhibit bacterial growth [9]. Several studies have been published reporting either increased, decreased, or unchanged lipocalin levels in both PCOS and other insulin resistance-related disorders, but the potential mechanism underlying these inconsistent results has not been wholly elucidated [3,[6][7][8][10][11][12][13][14].…”