|M.Sc Student||Eyal Inbal|
|Subject||Vascular Endothelial Growth Factor (VEGF), Heat Shock|
Proteins and Adhesion Molecules Levels in
Obstructive Sleep Apnea Syndrome (OSAS)
|Department||Department of Medicine||Supervisors||Dr. Lena Lavie|
|Professor Emeritus Peretz Lavie|
|Full Thesis text - in Hebrew|
Background: Obstructive Sleep Apnea Syndrome (OSAS) is characterized by frequent episodes of cessation of breathing (apneas) and hypoxemic events during sleep. OSAS has emerged in recent years as an important risk factor for cardiovascular morbidity. It has been suggested that repeated apnea-related hypoxic event, initiate oxidative stress, which increases reactive oxygen species production in OSAS patients. These radicals cause both direct and indirect injury to the endothelial cells, which results in endothelial dysfunction. Oxidant molecules also have an essential role in the activation of redox sensitive signaling pathways. This may initiate adaptive responses to hypoxia by increased expression of sets of genes that encode proteins essential to adaptation to hypoxia, such as Vascular Endothelial Growth Factor (VEGF) and Heat Shock Proteins (HSP).
methods: Male OSAS patients and control subjects were recruited from the population referred to the Technion Sleep Medicine Center. A diagnosis of OSAS was based on at least one night of polysomnographic recording. Blood samples were taken after an overnight fasting in the sleep laboratory.
Results and Conclusions: VEGF and HSP levels were measured, in the plasma of 228 and 248 male subjects, respectively, which were divided by smoking status into non-smokers, ex-smokers and current-smokers. No significant differences were found between the levels of VEGF and HSP in the plasma of OSAS patients compared with control subjects. Contradictory results were reported in the literature on the effects of systematic hypoxemia on plasma VEGF in OSAS patients. This could attest to the existence of large inter-individual differences in the response of VEGF to a given hypoxic stimulus. HSP expression levels were not investigated systematically in the plasma of OSAS patients. Our results may suggest that measurement of plasma HSP levels in OSAS patients is not sensitive enough, and that a more sensitive methodology should be used. Additionally, In OSAS patients there was a significant correlation between plasma VEGF levels and sP-selectin levels, in all of the smoking groups. This suggests an association between angiogenesis and platelet activation in OSAS. Similarly, a significant correlation was found between plasma HSP levels and sP-selectin, in non-smokers and ex-smokers. Also, we found significant correlations between the number of cigarettes smoked and both plasma VEGF and HSP levels. It is suggested that cigarette smoking exaggerates the oxidative stress already experienced by OSAS patients, and that the increase in VEGF and HSP levels is a part of the adaptive mechanism against that stress.