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Mobilizing Effect Of Losartan On EPCs In Patients With CHD And Its Mechanism On Improving Endothelial Dysfunction

Posted on:2013-02-17Degree:MasterType:Thesis
Country:ChinaCandidate:W ChenFull Text:PDF
GTID:2234330395966094Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
ObjectiveThis study aimed to investigate the frequencies of CD34+/VEGFR+EPCsdetected by flow cytometry in peripheral blood and humeralflow-mediated-dilation(FMD) measured with high resolution ultrasonography inCHD patients confirmed by coronary angiography. At the same time,patientswithout CHD confirmed coronary angiography were selected as the controlgroup. Analyze the differences of EPCs and FMD between two groups, and thiskind of disease in patients with peripheral blood EPCs and FMD and healthyhuman, then, Analysis of correlation between EPCs number and FMD was done.After12weeks treatment, the frequencies of CD34+/VEGFR+EPCs weredetected in65patients with CHD and31patients without CHD by flow cytometry,and humeral FMD were measured with high resolution ultrasonography foreach patient.Then the correlation between the changes of EPCs and FMD wereanalyzed.Methods1.65patients with confirmed CHD by coronary angiography were recruitedrandomly. Meanwhile,31patients without CHD were choosed as normalcontrol group. The frequencies of CD34+/VEGFR+EPCs were detected in bothtwo group by flow cytometry, and humeral flow-mediated-dilation(FMD) weremeasured with high resolution ultrasonography also for each patient,thenhs-CRP and Ang II were determined in my hospital laboratory, enzymeimmunoassay method for the determination of SDF-1and ET-1, nitrate reductase assay for determination of NO.The difference between the two groupswere compared, and then analyze the correlation between EPCs and FMD. Atthe same time, analyze the correlation between endothelial function indicessuch as hs-CRP, Ang II, ET-1, NO and EPCs, FMD. the analyze effect of SDF-1on peripheral blood EPCs.2.65patients with confirmed CHD by coronary angiography were randomlydivided into two groups,33patients were treated with routine drugs and ARB asthe treatment group,32patients were treated with routine drugs as the standardtreatment group. After12weeks treatment, the frequencies of CD34+/VEGFR+EPCs were detected in65patients with CHD and31patients without CHD byflow cytometry, and humeral FMD were measured with high resolutionultrasonography for each patient.Then the correlation between the changes ofEPCs and FMD were analyzed. At the same time,other parameter such ashs-CRP, NO, Ang II, ET-1, and SDF-1were determined also, then analyze of theeffect of these parameter variation on FMD and the relationship with the numberof EPCs change.Results1. At the baseline, compared with patients without CHD, the endothelialfunction of CHD patients are significantly lower (5.63±1.92)%VS (8.68±2.25)%,and the number of EPCs are significantly reduced (0.040±0.017)%VS(0.072±0.018)%,hs-CRP increased,NO reduced (P<0.05).2. In the baseline, There is a significant positive relationship betweenendothelial function and the number of circulating EPCs, endothelial functionimproved with the increase in the number of EPCs (r=0.57,P<0.01),meanwhile,responses of endothelial function indices hs-CRP with FMD (r=-0.43, P<0.05) and EPCs (r=-0.50, P<0.05) were negatively correlated, NOwith FMD (r=0.54, P<0.05) and EPCs (r=0.45, P<0.05) were positively related.3. After12weeks, the endothelial function of two groups of CHD patientswere improved in varying degrees,but the treatment group is more notable,(P<0.05).4. Before treatment, the standard treatment group and ARB group therapy for patients with NO, hs-CRP, SDF-1, ET-1and Ang II comparison, thedifference was not statistically significant(P>0.05);12weeks after treatment,two groups of patients with NO content increased (P<0.05), ARB group inperipheral blood of patients with NO increased more significantly, the differencewas statistically significant (P<0.05);In two groups of patients with hs-CRPcontent were significantly reduced (P<0.05), ARB group therapy for patientswith peripheral blood decreased more obviously, the difference was statisticallysignificant (P<0.05); In two groups of patients with SDF-1increased to differentextents, but the standard treatment group after treatment had no significantdifference (P>0.05), but ARB treatment group (P<0.05);In two groups ofpatients with ET-1content were decreased, but there were no significantstatistically differences (P>0.05); The standard treatment group of patients withAng II content did not change significantly, while ARB treatment groupsignificantly increased (P<0.05).5. Before treatment the standard treatment group and ARB treatment groupFMD comparison, P>0.05;12weeks after the treatment, the number ofperipheral blood EPCs and FMD before and after the change of differencebefore and after the change of difference between ARB group patients changedobviously, the difference was statistically significant, P <0.05.6.12weeks after treatment, correlation analysis showed, the number ofEPCs and FMD before and after the changes were significantly correlated (r=0.52, P<0.01);Elevated NO and FMD improved (r=0.43, P<0.05) and EPCsincreased (r=0.34, P<0.05) were positively correlated;hs-CRP reduces withFMD improving (r=-0.43, P<0.05) and EPCs increased (r=-0.25, P<0.05) wasnegatively correlated; Group ARB elevated SDF-1and EPCs increased,andthere is of positive correlation (r=0.38, P<0.05); Group ARB there is no obviouscorrelation between Ang II increased and the increase of EPCs.Conclusions1. CHD patients compared with normal control group, baseline EPCsquantity and change rate of FMD decreased, NO decreased, hs-CRP increased, endothelial dysfunction is the result of inflammatory response and/or oxidativestress and other factors.2. The number of EPCs and NO with FMD rate was positively correlated,hs-CRP and FMD with EPCs increase were negatively correlated. Therefore,the number of endothelial progenitor cells change to a certain extent in theevaluation of vascular endothelial function, vascular lesion severity andprognosis, so,the EPCs is expected as the evaluation of endothelial function inbiological indicator.3.12weeks after administration of Losartan, the FMD of patients with CHDhave significantly improved, NO, SDF-1, Ang II increased significantly,hs-CRPsignificantly reduced. Compared with standard treatment, the administration oflosartan improved the endothelial function further.4. The number of EPCs was significantly increased in losartan treatmentgroup, SDF-1and NO increased with EPCs number was positively associated,hs-CRP decreased with EPCs increased was negatively correlated, therefore,we infer, clinical application of ARB drugs losartan has anti-inflammatory,inhibition of oxidative stress to improve endothelial function directly, could alsofurther improving endothelial function based on the EPCs mobilization.Therefore, we infer that the improvement of endothelial function was based onthe EPCs mobilization.
Keywords/Search Tags:Coronary heart disease, Endothelial progenitor cells, Endothelial diastolicdysfunction, Flow cytometry, Losartan
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