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?
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.


OBJECTIVE
To determine serum levels of NGAL and MMP-9/NGAL complex in women with PCOS.


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 (30.4+/-24.3 vs 70.7+/-37.9 microg/l, P<0.0001) and (31.5+/-26.6 vs 115.1+/-66.9 microg/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.
Diamanti-Kandarakis
Evanthia
E
Endocrine Section, First Department of Medicine, Medical School, Laiko General Hospital, University of Athens, 11527 Athens, Greece.
Livadas
Sarantis
S
Kandarakis
Stylianos A
SA
Margeli
Alexandra
A
Papassotiriou
Ioannis
I
D000209:Acute-Phase Proteins / Q000378:metabolism / Q000502:physiology; D000328:Adult; D000367:Age Factors; D050197:Atherosclerosis / Q000097:blood; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000097:blood* / Q000209:etiology*; D016022:Case-Control Studies; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D015536:Down-Regulation; D005260:Female; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood* / Q000378:metabolism / Q000502:physiology; D020780:Matrix Metalloproteinase 9 / Q000097:blood* / Q000378:metabolism / Q000502:physiology; D046912:Multiprotein Complexes / Q000097:blood; D009994:Osmolar Concentration; D050177:Overweight / Q000097:blood; D011085:Polycystic Ovary Syndrome / Q000097:blood* / Q000150:complications; D011518:Proto-Oncogene Proteins / Q000097:blood* / Q000378:metabolism / Q000502:physiology; D012307:Risk Factors; D013739:Testosterone / Q000097:blood; D013851:Thinness / Q000097:blood
D000209:Acute-Phase Proteins; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D046912:Multiprotein Complexes; D011518:Proto-Oncogene Proteins; D013739:Testosterone; D019314:Dehydroepiandrosterone Sulfate; D020780:Matrix Metalloproteinase 9