Research On The Correlation Among CDK,Phosphorylation Of PPAR? And PASP In PH Secondary To COPD

Chronic obstructive pulmonary disease(COPD)is a respiratory disease with high morbidity,hospitalization,disability and mortality,which is characterized by incomplete reversible airflow limitation which is usually progressive.Pulmonary hypertension(PH)secondary to COPD could lead to right ventricular dysfunction and chronic pulmonary heart disease(CPHD),and affect the quality of life and survival period of patients seriously,and bring heavy economic burden to family and society.However,the mechanism of PH secondary to COPD is not clear,and there is no satisfactory drug to treat it in clinic.Therefore,studding the mechanism of PH secondary to COPD could provide a new target for the treatment of COPD.In addition,the detection of pulmonary arterial systolic pressure(PASP)is helpful to evaluate the severity of PH secondary to COPD,and to guide the clinical treatment.However,right heart catheterization as the gold standard for the diagnosis and evaluation of PH is restricted greatly in clinical application because of its invasiveness.Therefore,it is very important to study the biological markers for identifying PH and assess the PH severity in clinic.Purpose:(1)To confirm upregulation of plasma cyclin-dependent kinase 5(CDK5),downregulation of plasma cyclin-dependent kinase 7(CDK7)and phosphorylation of peroxisome proliferators-activated receptors ?(P-PPAR?)are the important pathologic changes in PH secondary to COPD to provide new targets and basis for the treatment of COPD.(2)To verify plasma contents of CDK5?CDK7 and phosphorylated-PPAR?(P-PPAR?)are closely related to PASP in COPD patients with PH and these biological markers could identify PH and assess the PH severity in clinic.Methods:A total of 60 COPD patients with PH and 20 COPD patients without PH were enrolled in this study,with 20 volunteers with normal pulmonary function as controls.These subjects were divided into control and COPD groups,and mild,moderate and severe PH groups.PASP was determined by Doppler echocardiograph and the severity(mild,moderate and severe)of PH secondary to COPD was evaluated.The plasma contents of CDK5 ? CDK7 ?Ser273-P-PPAR? ? Ser112-P-PPAR? in subjects were determined using ELISA kits.Correlation among plasma contents of CDK5,CDK7,Ser273-P-PPAR? and Ser112-P-PPAR? and PASP was analyzed using Pearson's correlation.ROC curve was drawn to assess the diagnostic accuracy of these plasma biological markers in PH.Results:(1)The comparison of plasma CDK5 and Ser273-P-PPAR? among these groups showed that the plasma contents of CDK5 and Ser273-P-PPAR? in COPD patients with PH were higher than those in the control subjects and COPD patients without PH respectively(P<0.05,respectively).The plasma contents of the two markers were the highest in the severe PH group,lower in the moderate PH group.(2)The plasma contents of CDK7 and Ser112-P-PPAR? in COPD patients with PH were lower than those in the control subjects and COPD patients without PH respectively(P<0.05).Among PH groups,the plasma contents of the two markers were the lowest in the severe PH group,lower in the moderate PH group.(3)The Pearson's correlation analysis showed the moderate positive correlations between plasma CDK5 and PASP(r=0.789,P<0.05)and between plasma CDK5 and Ser273-P-PPAR?(r=0.674,P<0.05).In addition,negative correlation was found between plasma CDK7 and PASP(r=-0.690,P<0.05),whereas positive correlation between plasma CDK7 and Ser112-P-PPAR?(r=0.763,P < 0.05)was found.Furthermore,plasma Ser273-P-PPAR? was correlated positively with PASP(r=0.649,P<0.05),whereas plasma Ser112-P-PPAR? was correlated negatively with PASP(r=-0.709,P<0.05).(4)The areas under ROC curve of diagnosing PH using plasma CDK5?CDK7?Ser273-P-PPAR??Ser112-P-PPAR? were 0.762,0.806,0.836,0.865 respectively.Plasma content of CDK5?115.91 ng/ml was found to be 60.0% sensitive and 87.5% specific for diagnosing PH,and plasma content of CDK7?168.35 ng/L was found to be 81.70 % sensitive and 72.50 % specific for diagnosing PH,and plasma content of Ser273-P-PPAR??95.34 ng/ml was found to be 80.0% sensitive and 75.0% specific for diagnosing PH,and plasma content of Ser112-P-PPAR??128.57 ng/L was found to be 73.30% sensitive and 85.00% specific for diagnosing PH.Conclusions:(1)Upregulation of plasma CDK5,downregulation of plasma CDK7,increase of phosphorylation of PPAR? on Ser273 site and inhibititon of phosphorylation of PPAR? on Ser112 site could be the important pathologic changes in PH secondary to COPD.The result could provide new targets for the treatment of COPD in clinic.(2)The plasma contents of CDK5?CDK7?Ser273-P-PPAR??Ser112-P-PPAR? are closely related with PASP.These biological markers could help to identify PH and assess the PH severity in clinic in the future.