The Role Of Renalase In Platelets Of Patients With Obstructive Sleep Apnea Syndrome

Obstructive sleep apnea hypopnea syndrome(OSAHS)is a sleep-breathing disease characterized by intermittent hypoxia,which can increase the risk of thrombotic diseases.Abnormal platelet number and activity,as one of the important pathological mechanisms of thrombosis,has not been well studied in OSAHS patients.Renalase(RNLS)is a secretory monoamine oxidase.It metabolizes catecholamines in circulation and closely relates to several thrombotic diseases such as coronary heart disease,and alleviate hypoxia-induced cell damage by inhibiting the production of reactive oxygen species(ROS).This thesis,mainly treating platelet as an entry point,studied the relationship between RNLS and the risk of thrombosis in patients with OSAHS.Firstly,we explored the platelet count and activation in patients with OSAHS using linear and nonlinear models in a large cross-sectional population of 903 patients.We found that the platelet counts in patients with OSAHS tended to increase.The apnea-hypopnea index(AHI)and oxygen desaturation index(ODI)of OSAHS,as risk factors for abnormal platelet distribution width PDW,were positively correlated with PDW,and the relationship was non-linear.These results suggested that OSAHS might be a risk factor for abnormal platelet count and activity,and thus the thrombotic diseases.Secondly,114 subjects with matched age,sex and blood pressure were selected from the large cross-sectional population.The relationship between serum RNLS level and hypoxia-related parameters of OSAHS(AHI and ODI)were analyzed.We found that RNLS were positively correlated with AHI and ODI,which might have protective effect on OSAHS and hypertension associated with OSAHS.These results suggested that RNLS,as a hypoxic stress factor,is associated with OSAHS disease.However,whether RNLS regulates platelet counts and activities remains unknown.Finally,RNLS knockout(KO)mice was used to investigate the role of RNLS in platelet counts and functions.We found that RNLS was expressed in platelets and were widely distributed in alpha granules.RNLS did not affect platelet count,production and metabolism,but regulated platelet functions of aggregation,release and contraction.Then,ROS probe,proteomics and bioinformatics analysis were used for further research.We found that RNLS knockout caused a significant increase in the level of endogenous ROS in platelets,suggesting that RNLS might regulate platelet function through ROS,and Rho GTPase family signals might participate in such process.Our study elucidates the correlation between RNLS and OSAHS,and preliminarily reveals the regulatory effects and potential mechanisms of RNLS on platelets,which help us understand the possible mechanism of thrombotic disease in OSAHS patients.