Repair Mechanisms Of Endothelial Progenitor Cell In Peripheral Blood Of Patients With Obstructive Sleep Apnea

Objective:There is closly relation between with the severity of obstruetive sleep apnea synd(OSA) and an increased risk of cardiovascular diseases. The heavier degree of hypoxia, the higher the incidence of cardiovascular events. Endothelial progenitor cells(EPCs) have the potential to maintain the balance between endothelial injury and endothelial repairment, and participate in vascular repair. The decrease of EPCs can predict the occurrence of future cardiovascular diseases. To explore the repair mechanisms of EPCs in patients with OSA, we measure the change of the levels of EPCs and pro-angiogenic factors, and culture MNCs in vitro to further detect proliferation, migration and angiogenesis ability of EPCs.Materials and Methods:90 patients with OSA and 30 healthy volunteers with matched gender and age were recruinted, who underwent polysomnography(PSG)and divided into 4 group resepectly according to sleep apnea-hypopnea index(AHI).Levels of hypoxia inducible factor-1 a(HIF-1 a), stromal cell derived factor-1 a(SDF-1a), vascular endothelial growth factor(VEGF) were determined by ELISA.Mononuclear cells were isolated by density gradient centrifugation. The levels of CD133+KDR+EPC, CD133+CD34+EPC, CD34+KDR+EPC and ALDHlo CD34+KDR+ EPC were detected by flow cytometry based on aldehyde dehydrogenase(ALDH) activity jointly CD133, CD34, containing the kinase insert domain receptor(KDR) corresponding EPC surface markers. Mononuclear cells(MNCs) from patients with OSA and healthy volunteers were cultured in a conditioned medium. The in vitro migration, proliferation were investigated.The effect on tube formation were also assessed in vivo. The data were analysed throught SPSS 17.0 software.Results:(1)There is no significantly difference in age and sex. BMI of patients with OSA is significantly higher comparing with control group, espationally the highest in severe OSA group. AHI is significantly increased while oxygen saturation is decreased in severe OSA group and moderate OSA group comparing with mild OSA group control group.(2)The levels of CD133+KDR+ EPC,CD133+CD34+ EPC and CD34+KDR+ EPC have statistically significant results described as the severe OSA group > moderate OSA group > mild OSA group > control group. While ALDHlo CD34+KDR+ EPC is highest in mild OSA group, the lowest is in severe OSA group when that is higher in control group than in the moderate OSA group.(3)The levels of HIF-1?, SDF-1? and VEGF have statistically significant results described as the severe OSA group > moderate OSA group > mild OSA group >control group.(4)The number of EC-CFU are significant increased in mild OSA group comparing with moderate and severe groups. The lowest is in severe OSA group when that is higher in control group than in the moderate OSA group.(5)The number of EPCs migration are significant increased in mild OSA group comparing with moderate and severe groups. The lowest is in severe OSA group when that is higher in control group than in the moderate OSA group.( 6) The level of CXCR4,VEGFR2 protein in surface of EPCs is significant increased in mild OSA group comparing with moderate and severe groups. The lowest is in severe OSA group when that is higher in control group than in the moderate OSA group.( 7) The length of tube formation are significant increased in mild OSA group comparing with moderate and severe groups. The lowest is in severe OSA group when that is higher in control group than in the moderate OSA group.Conclusion:(1)BMI is an independent risk factor for the onset of OSA, BMI can increase the morbidity of OSA and aggravate the severity of OSA.(2)Pro-angiogenesis factors are greatly increase in the patients with OSA, which promote the mobilization of a large number of EPCs. ALDHloEPC has a potential repair the injuried endothelial, whose number is higheset in the patients with mild OSA while that is the lowest in the patients with severe OSA results from continued depletion the ALDHlo EPC, which weaken the ability of repairing vessels.( 3) EPCs mobilization, proliferation, chemotaxis and angiogenesis capacity are enhancement in patients with mild OSA. With the degree of OSA is aggravating,endothelial function of EPC are correspondingly weakened, which may exacerbate endothelial dysfunction and needs further experimental study to verified.