Study of endothelial dysfunction and vascular inflammation in sleep apnea, obesity and aged humans

Abstract

Background Obstructive sleep apnea (OSA) has been associated with cardiovascular complications. The overnight repetitive hypoxia represents a form of oxidative stress in the vasculature which may activate the oxidant-sensitive, proinflammatory transcription factor nuclear factor κB (NF-κB), affecting endothelial function and atherosclerosis. Aim We investigated whether the endothelial alterations attributed to OSA rather than to other confounding factors. Also, the production of inflammatory cytokine nuclear factor-kappa β (NF-Kβ) was investigated as the molecular mechanism involved in vascular endothelial dysfunction with OSA. Material and methods Sixty subjects underwent attended nocturnal polysomnography were grouped by apnea hypopnea index: control (AHI<5/h) and OSA cases (AHI>5/h) the cases were further classified according to age and BMI into subgroup IIA: OSA, non-obese, middle age (35–52 y), subgroup IIB: OSA, non-obese, older age group (55–68 y), subgroup IIIA: OSA, obese, middle age group (35–52 y) and subgroup IIIB: OSA, obese, older age group (55–68 y). A morning venous blood sample was obtained. Neutrophils were isolated, and NF-κB activity was determined. Plasma sVCAM-1 was assayed by enzyme-linked immunosorbent assay and flow-mediated dilation (FMD) was performed. Results NF-κB activation and plasma level of sVCAM-1 were significantly increased in OSA patients as compared to the control group and there was no significant difference between the obese and non-obese cases also no significant difference between the middle and old age cases. The degree of NF-κB activation was positively correlated with indices of apnea severity(r = 0.938; p < 0.001). FMD was significantly decreased in OSA patients as compared to the control group. Conclusion These findings suggested that OSA is an independent risk factor for cardiovascular morbidity also that OSA leads to NF-κB activation, which may constitute an important pathway linking OSA with systemic inflammation and cardiovascular disease. Keywords Obstructive sleep apnea; Nuclear factor κB; Cardiovascular diseases; Endothelial dysfunction; Inflammation Abbreviations OSA, Obstructive sleep apnea; AHI, Apnea hypopnea index; BMI, body mass index; NF-κB, Nuclear factor κB; sVCAM-1, soluble Vascular cell adhesion molecule; FMD, Flow mediated dilatation