Expression Of Zinc Finger Protein A20in Peripheral Blood Monocytes From Patients With Acute Coronary Syndrome And Its Intervention With Atorvastatin

Background:Acute coronary syndrome is a clinical syndrome attributed to thecorresponding myocardial cells with serious and lasting acute ischemic and localmyocardial necrosis. It is a result of the rupture of unstable atherosclerotic plaquesand the formation of thrombosis which are based on atherosclerosis，and cause thecoronary incomplete or complete occlusion and then a sharp reduction or interruptionof the distal blood supply.The unstable plaque rupture, intraplaque hemorrhage, andsecondary thrombosis are the key factors of the ACS. Inflammatory Response playsan important role in the formation and rupture of unstable plaque, and thrombosis.Zinc finger protein A20(A20),which has been one of the most popular cytoprotectiveproteins in researched in recent years, was confirmed to play an important role ina variety of immune and inflammatory diseases. The study of A20with coronary heartdisease, particularly with acute coronary inflammation, has not been reported.A20, anendogenous protective factor, remains to be depth in the effect of A20and itsregulating mechanism in coronary inflammation.Objectives:Measure the expression of A20in peripheral blood monocytes frompatients with acute coronary syndrome,and analysis the correlation between A20andhs-CRP/TNF-ɑ,to determine the effect of A20in patients with acute coronarysyndrome.Observe the change of the supernatant TNF-ɑ and A20in peripheral bloodmonocytes cultured with different concentrations of atorvastatin outside of thepatients with acute coronary syndrome.To investigate the impact of A20expressionwith atorvastatin.Methods:Enroll40patients with acute coronary in Department of Cardiology ofChangsha Central Hospital from January to March in year of2012,as ACS group.Enroll20healthy people in Department of physical examination in the samehospital,as control group.the two groups are matched with age and sex.Test the liverand kidney function, fasting blood-glucose, blood lipids and blood routine.Atbaseline,peripheral blood was drawn from all patients.The Ficoll separating mediumwas used to separate the single nuclear cell from peripheral blood anticoagulant byheparin sodium.Get monocytes sticking wall after cultured the single nuclearcell.Adjustment the concentration of monocytes for2x106/ml.Set the monocytesof the ACS group into4culture holes with atorvastatin in different concentration.Thecontrol group was blank control.Get the supernatant and monocytes after24hourscultured.Hs-CRP expression in plasma and TNF-ɑ expression in the supernatant ofmonocytes were measured by enzyme-linked immunosorbent assays（ELISA).A20expression in monocytes was measured by immunohistochemical.Results:1.ACS group compared with controls, there’s no obvious difference ingender, age, body mass index, blood pressure, blood sugar, and triglyceride.TC andLDL-C were significantly increased in the ACS group compared with the controlgroup（5.69±1.68vs4.98±0.91,3.28±1.13vs2.55±0.76，both P＜0.05).HDL-Cwas significantly increased in the control group compared with the ACS group（1.39±0.36vs1.03±0.61,P＜0.05).White blood cell counts was increased in theACS group compared with the control group(8.6±2.4vs5.6±1.7,P＜0.05).2.Hs-CRP expression in plasma in the ACS group（20.15±9.10mg/L）wassignificantly higher than that in the control group(1.63±0.77mg/L,P＜0.05).3.TNF-ɑexpression in the supernatant in the ACS group（36.03±6.14pg/mL)was significantly higher than that in the control group（6.15±3.18）pg/mL,(P＜0.05).4.Hs-CRP expression in plasma in the ACS group was positively correlatedwith TNF-ɑ expression in the supernatant of monocytes（r=0.636，P＜0.05).5.A20expression in monocytes in the ACS group（7.78±3.42) wassignificantly higher than that in the control group(0.79±0.41，P＜0.05).6.A20expression in monocytes in the ACS group was positively correlated with both TNF-ɑ expression in the supernatant and hs-CRP expression in plasma inACS group(r=0.740and0.664，both P＜0.05).7.A20expression in monocytes in the ACS group was positively correlatedwith the white blood cell count(（r=0.546,P＜0.05).8.In ACS group,after cultured with atorvastatin in different concentration(0,0.1,1,10μmol/L),A20expression （7.78±2.72,8.63±2.94,10.19±3.29,13.13±4.09） in monocytes was gradually increasing(P＜0.05);TNF-ɑexpression（36.03±6.14，32.15±6.10，27.89±5.18，19.08±4.01）was gradually decreasing(＜0.05).Conclusions:1.There is an inflammatory activation in peripheral blood in acutecoronary syndrome,and monocytes activation may paly a important role ininflammatory activation of acute coronary syndrome.2. A20expression in monocytes in the ACS group was positivelycorrelated with secretion TNF-α、plasma hs-CRP and the white blood cell count.Itshow that A20palys an important role in acute coronary inflammation.3. When atorvastatin suppressed TNF-a expression, A20expressionis promoted,and that show atorvastatin can through promote the A20expression toplay inflammation.A20may be an important endogenous protective factor in acutecoronary syndrome.