Gelatinases and their tissue inhibitors in a group of subjects with obstructive sleep apnea syndrome

Abstract

Abstract. Obstructive sleep apnea syndrome (OSAS) is associated with an elevated risk of cardiovascular events and stroke. Matrix metalloproteinases (MMPs) are endopeptidases involved in extracellular matrix degradation and then in the development and progression of cardiovascular diseases. Our aim was to evaluate plasma levels of gelatinases (MMP-2 and MMP-9) and their tissue inhibitors (TIMP-1 and TIMP-2) in a group of subjects with OSAS. We enrolled 48 subjects (36 men and 12 women; mean age 49.7 ± 14.68 yrs) with OSAS diagnosed with a 1-night cardiorespiratory study and then we subdivided these subjects into two subgroups according to the apnea/hypopnea index (AHI): Low (L = 21 subjects with AHI <30) and High (H = 27 subjects with AHI >30). We measured plasma concentration of the gelatinases and their inhibitors using ELISA kits. We observed a significant increase in plasma concentration of MMP-9, MMP-2, TIMP-1 and TIMP-2 in the entire group of OSAS subjects and in the two subgroups, with higher levels in the H in comparison with the L subgroup. In the whole group of OSAS subjects we also noted a significant decrease in MMP-9/TIMP-1 ratio in comparison with normal controls. Only MMP-9 was significantly correlated with the severity of the disease, expressed as AHI, with the oxygen desaturation index and also with the mean oxygen saturation. MMPs pattern is altered in OSAS and significantly influenced by the severity of the disease; it probably contributes to the vascular remodeling that leads to the atherosclerotic disease and cardiovascular complications.

Relaxin in Obstructive Sleep Apnea: Relationship with Blood Pressure and Inflammatory Mediators

“…However, MMP-9 and TIMP-1 did not significantly differ between patients with and without severe OSA. Actually, although most authors reported increased MMP-9 in OSA [6,7,8,9], other authors did not [30,31]. Our data show a trend to increased MMP-9 in the severe OSA patients, which did not reach statistical significance.…”

“…Few data are available on MMP-2 in OSA. One study reported no relationship between OSA severity and MMP-2 [8], while another study described increased MMP-2 levels in OSA [9]. Further studies would be useful to better understand the behavior of this molecule in OSA.…”

“…This detrimental effect is partly due to the stimulation of the synthesis of angiogenetic and inflammatory factors through an increased activation of transcription factors such as hypoxia-inducible factor-1 (HIF-1) and nuclear factor-κB (NF-κB) [1]. In fact, increased levels of circulating molecules, such as vascular endothelial growth factor (VEGF) [2,3,4,5] and metalloproteinases (MMPs) [6,7,8,9], have been reported in OSA. One of the most common OSA comorbidities is systemic hypertension [10].…”

Subclinical impairment of dynamic left ventricular systolic and diastolic function in patients with obstructive sleep apnea and preserved left ventricular ejection fraction

“…There is evidence of a consistent relationship between OB and OSA [9]. OB has been suggested as a marker of upper airway obstructive episodes and hypoxemia causing local oropharyngeal inflammation [10], and has been associated with cardiovascular complications [11,12].…”

Lipid peroxidation and nitric oxide metabolites in a group of subjects with obstructive sleep apnea syndrome

“…The role carried out by oxidative stress, endothelial dysfunction and sympathetic activation in the pathogenesis of the cardiovascular risk may be worsened by the simultaneous deregulation of the gelatinases (MMP-2 and MMP-9) and their tissue inhibitors (TIMPs), as found by us [14] in OSAS subjects. Considering the cardiovascular risk that follows the OSAS, it is useful to underscore that the gelatinases activity produces elevated levels of angiostatin through the proteolytic cleavage of plasminogen.…”