Plasma Vascular Endothelial Growth Factor in Sleep Apnea Syndrome

Abstract

Sleep apnea syndrome is associated with recurrent episodic hypoxia during sleep, which has been implicated in the development of cardiovascular morbidity. Hypoxia is the major stimulus of vascular endothelial growth factor (VEGF), which is a potent angiogenic cytokine. In the present article we describe the results of three experiments in which plasma concentrations of VEGF were measured in patients with sleep apnea. In Experiment 1, apnea-hypopnea index was found to be a significant independent predictor of morning VEGF concentrations in 85 male subjects investigated in the sleep laboratory, of whom 47 had an apnea-hypopnea index greater than 20. In Experiment 2, VEGF concentrations measured hourly during the sleep period were found to be significantly higher in a group of five sleep apnea patients compared with six age-similar snorers and six normal young adults (129.1 +/- 43.4 versus 74.6 +/- 11.5 and 32.5 +/- 12.8 pg/ml, respectively [p < 0.007]). In Experiment 3, VEGF concentrations were compared in patients with sleep apnea before and 1 year after nasal continuous positive airway pressure treatment. A significant decrease in VEGF concentrations was found only in patients in whom nocturnal hypoxia improved after treatment (57.1 +/- 62.5 versus 39.6 +/- 46.9 pg/ml, p < 0.01). There was no comparable improvement in patients who did not accept treatment (53.9 +/- 23.6 versus 54.0 +/- 21.5 pg/ml, ns). These results raise the possibility that VEGF may contribute to the long-term adaptation of sleep apnea syndrome to recurrent nocturnal hypoxia.

Sleep Apnea and Heart Failure

“…In addition, VEGF concentrations fall in response to reversal of OSA by CPAP. 58,59 As of yet, however, there is no direct evidence of enhanced VEGF-induced angiogenesis in OSA. Nevertheless, variations in the VEGF response to nocturnal hypoxia may influence the cardiovascular system's response to tissue hypoxia.…”

Deleterious Effects of Sleep-Disordered Breathing on the Heart and Vascular System

“…A possible mechanism is thought to be secondary to hypoxemia-induced endothelial cell dysfunction and pulmonary artery remodeling [81]. This may be related to hypoxia upregulation vascular endothelial growth factor, which is a mediator in angiogenesis, resulting in vascular remodeling [82, 83]. Most experts feel that OSA may modestly increase pulmonary arterial pressures, and evaluation for OSA should be part of the initial work-up in patients with pulmonary hypertension [84].…”

Association of Elevated Levels of Vascular Endothelial Growth Factor in Obstructive Sleep Apnea Syndrome with Patient Age rather than with Obstructive Sleep Apnea Syndrome Severity

“…The synthesis of VEGF is stimulated by hypoxia-inducible factor 1α and by other GF such as platelet-derived GF, transforming GF α and β, insulin GF, fibroblast GF and keratinocyte GF [12]. Recent studies have reported high VEGF levels in patients with the sleep apnea syndrome, which decrease after treatment with continuous positive airway pressure [13, 14]. However, others did not find an association [15,16,17] or found that this was not a true association because of the presence of thrombocytosis in OSAS [18], which increases the VEGF level due to a high content of VEGF in platelets [19, 20].…”