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

Abstract

Background: Obstructive sleep apnea (OSA) is associated with nocturnal intermittent hypoxia, which may be responsible for increased circulating levels of vascular endothelial growth factor (VEGF) and inflammatory mediators, such as metalloproteinases (MMPs), and which contributes to the pathogenesis of systemic hypertension. Why some OSA patients remain normotensive is poorly understood. Relaxin-2, a pregnancy hormone, may sometimes circulate in men and could increase in hypoxic conditions. It exerts a vasodilatory activity and can modulate the release of molecules, such as MMPs and VEGF. Objectives: The objective of this study was to explore if circulating relaxin-2 in male OSA subjects may be related to OSA severity, to circulating levels of MMPs, of their inhibitors (tissue inhibitors of metalloproteinases; TIMPs), and of VEGF, and if it may protect from hypertension. Patients andMethods: Fifty untreated male subjects with suspected OSA were recruited. After nocturnal polysomnography, a morning venous blood sample was withdrawn. Then, 24-hour ambulatory blood pressure (BP) monitoring was performed. Results: The respiratory disturbance index in the sample was 30.4 [interquartile range (IQR) 15.6-55.2]. Relaxin-2 was detectable in 20 subjects. These subjects did not differ in OSA severity or diurnal and nocturnal BP from subjects with undetectable relaxin-2, but they showed lower TIMP-1 (126.8 ± 29.1 vs. 156.9 ± 41.7 pg/ml, respectively; p = 0.007) and a marginally higher MMP-9/TIMP-1 molar ratio [0.58 (IQR 0.23-1.35) vs. 0.25 (IQR 0.15-0.56); p = 0.052]. Conclusions: Relaxin-2 in male subjects was not related to OSA severity, but it was associated with lower TIMP-1. As it was often undetectable, even when BP values were normal, it is unlikely that it plays a role as a major factor protecting from hypertension in OSA.

Elevation of CD40/CD40L Inflammatory Pathway Molecules in Carotid Plaques from Moderate-and-Severe Obstructive Sleep Apnea Patients

“…On the contrary, at least three studies showed no significant differences in MMP-9 values in OSA versus non-OSA subjects. One was performed in the paediatric population [ 33 ] and two others in adults [ 34 , 35 ]. The roles of MMPs in the inflammatory process associated with OSA were reviewed recently by two papers [ 36 , 37 ].…”

Matrix Metalloproteinase-9 Is a Predictive Factor for Systematic Hypertension and Heart Dysfunction in Patients with Obstructive Sleep Apnea Syndrome

“…Thirdly, OSAS therapy and drug administration during follow-up may also affect the final results. In addition, the up-stream signaling of MMP-9 in hypoxia condition was not investigated in this study; previous data suggested that HIF-1 α [ 36 ], MMP-9 tissue inhibitor [ 37 ], and other cytokines [ 38 , 39 ] may regulate MMP-9 expression. Similarly, since hypoxia and OSAS will cause alterations of multiple biomarkers [ 5 ], parallelly analyzing other molecule would be better to predict disease progression.…”

Matrix metalloproteinase-9 as a messenger in the cross talk between obstructive sleep apnea and comorbid systemic hypertension, cardiac remodeling, and ischemic stroke: a literature review

“…Because there is a cross-reactivity between MMP-9 and other MMPs, some studies evaluated the levels of other MMPs in addition to MMP-9. Bonanno et al 52 showed that MMP-2 levels were lower in patients with severe OSA. However, all other MMP levels did not show any significant correlation with OSA severity.…”