Clinical Monitoring Of The Vulnerable Plaque In The Coronary Arteries

PartⅠStudy the threshold of the thickness of fibroma and the level of serum inflammation markers in CAD patients with unstable plaquesBackground There are robust correlations between acute coronary syndrome and the stability of atherosclerotic plaque.However,the thickness of cap fibroatheroma is the critical factor affects the stability of atherosclerotic plaque.A vulnerable plaque was defined as the thin cap fibroatheroma(TCFA,＜65μm).Intravascular optical coherence tomography(OCT) provides high-resolution(~10μm),cross-sectional images of tissue in situ.The resolution of OCT is appropriate for measuring the cap thickness of a vulnerable plaque.There are robust correlations between clinical cardiovascular events and the leverls of serum inflammatory markers.Data from large-scale population-based studies have demonstrated that increased circulating levels of numerous markers of inflammation predict future cardiovascular events.The cut-off value and the correlation of the thickness of cap fibroatheroma and the levels of inflammatory markers are still need to be clarified.Aims To evaluate the correlation between fibrous cap thickness and levels of plasma inflammatory factors,and search those thresholds for predicting vulnerable plaques in patients with coronary artery diseases.Methods and results A comparative study was performed in patients with acute myocardial infarct(AMI),unstable angina pectoris(UAP),stable angina pectoris(SAP) and chest pain syndrome(CPS).Intravascular optical coherence tomography was used to measure the fibrous cap thickness of coronary artery atherosclerotic plaques.Enzyme linked immunosorbent assay was used to detect plasma levels of highly sensitive C-reacting proteins(hs-CRP),interleukin 18(IL-18) and tumor necrosis factor alpha(TNF-α).With increases of coronary artery event risks,plaque fibrous cap thickness decreased and plasma hs-CRP,IL-18 and TNF-αlevels increased considerably(P＜0.05).There were significant correlations between fibrous cap thickness and plasma levels of inflammatory factors (P＜0.05).Cap thickness＜65βm correlated with threshold levels of plasma inflammatory factors as follows:hs-CRP 0.75 mg/L,IL-18 75μg/L and TNF-α35μg/L.Conclusion Results show that cut-off value of hs-CRP≥0.75mg/L,IL-18＜75μg/L and TNF-α≥35μg/L could be the threshold to predict instability of atherosclerotic plaques. It may provide an easy way to identify vulnerable patients in future clinical practice.PartⅡCorrelation between inflammatory factors and different state of coronary artery diseaseBackground Abundant data link hypercholesterolaemia to atherogenesis.However, only recently have we appreciated that inflammatory mechanisms couple dyslipidaemia to atheroma formation.Leukocyte recruitment and expression of pro-inflammatory cytokines characterize early atherogenesis,and malfunction of inflammatory mediators mutes atheroma formation.Moreover,inflammatory pathways promote thrombosis,a late and dreaded complication of atherosclerosis responsible for myocardial infarctions and most strokes.Dependend these data,the new appreciation of the correlation between inflammation and coronary artery disease has been paid close attention to.Therefore, unrevalling the levels of serum inflammatory factors and identifying the correlation between inflammatory factors and different state of coronary artery disease may eventually furnish the discrimination of dangerous CAD patients.Objective To detecte the diversity of serum levels of interleukin-10(IL-10), intedeukin-17(IL-17),interleukin-18(IL-18),C reactive protein(CRP) and TNF-αin the process of coronary artery disease(CAD).and to identify the correlation between inflammatory factors and different state of CAD.Methods The levels of plasma IL-10,IL-17,IL-18,hs-CRP and TNF-αin 160 patients(AMI50,UAP68,and SAP42) with CAD and 40 CPS were determined by enzyme linked immunoadsorbent assay(ELISA).Results The plasma levels of IL-17,IL-18,hs-CRP and TNF-αin patients with CAD wre increased significantly than that in CPS patients(P＜0.05).The concentration of IL-10 in patients with CAD was increased significantly than that in CPS patients(P＜0.05), however,the serum level of IL-10 in UAP patients was lower than that in SAP group,there may be some mechanism need to be unrevlled to clarify this phenomenon.Conclutiou The findings suggest that IL-10,IL-17,IL-18,hs-CRP and TNF-αmay co-participate the pathogenesis and progression of CAD.The serum levels of IL-10,IL-17, IL-18,hs-CRP and TNF-αwill contribute to the assement of the pathogenetic condition with CAD.The levels of these inflammatory markers could be one of the references in discriminating the dangerous patients.PartⅢEffects of the c-myc and PCNA on the multiplication of VSMCBackground Smooth muscle cells in the intima divide,other smooth muscle cells that migrate into the intima from the media.Smooth muscle cells can then divide and elaborate extracellular matrix,promoting extracellular matrix accumulation in the growing atherosclerotic plaque.In this manner,the fatty streak can evolve into a fibrofatty lesion.In addition to smooth muscle cell replication,death of these cells can also participate in the complication of the atherosclerotic plaque.Thin cap fibroatheroma in the growing atherosclerotic plaque probably results from a tug-of-war between cell replication and cell death.Thus,inhibiting the multiplication of VSMC may be important to retard the development of atherosclerosis.Chuanxiong is the major component of general complex prescription of traditional Chinese herbal in treating atherosclerosis.Some data indicated that chuanxiongzine,the major active ingredient,may inhibit the proliferation of VSMC, however,the mechanism of this effectiveness is still unkown.C-myc protein as the expression product of c-myc proto-oncogene has been shown to be a "compentence factor", which could promote the related gene patency,brings about a great deal of GH-like substance,precipitate VSMC into vegetative state.PCNA is the critical link of signal conduction during the process of DNA duplication,cell cycle and fission.The VSMC gene expression would increase quickly,when the cell proliferate vigorously.Therefore,the mechanism of chuanxiongzine in inhibiting the proliferation of VSMC and the role of c-myc and PCNA in this process need to be unrevelled.Objective To study the depressive effect of the antisense oligonuceotides(ASODN) of c-myc and proliferating cell nuclear antigen(PCNA) on the proliferation of VSMC. Detecting the inhibitory effect of chuanxiongzine on vascular smooth muscle cell(VSMC) proliferation and exploring its molecular biology basis.Methods Taking the VSMC obtained from rat aorta thoracalis cultured 4～8 generation as research object.The objects were divided into three groups to carry out control study: control group;PCNA ASODN group and c-myc ASODN group.The ASODNs' working concentration all were 1:50.The depressive effect of ASODN on VSMC proliferation was investigated by cell counting,MTT and ~3H-TdR incorporation assay;PCNA and c-myc expression were detected by immunohistochemical method after transferring PCNA and c-myc ASODN into VSMC.Taking the VSMC obtained from rat aorta thoracalis cultured 4～8 generation as research object.The objects were divided into four groups to carry out control study:(Ⅰ) control group,(Ⅱ) chuanxiongzine(50μg/ml) group,(Ⅲ) chuanxiongzine(100μg/ml) group and(Ⅳ) chuanxiongzine(200μg/ml) group.The inhibitory effect of chuanxiongzine on VSMC proliferation was investigated by cell counting,MTT and ~3H-TdR incorporation assay.In order to illuminate the molecular biology mechanism of chuanxiongzine,the expression of proliferating cell nuclear antigen (PCNA) and c-myc were detected.Results PCNA and c-myc ASODN could inhibit the proliferation of VSMC significantly,compared with control group(P＜0.05);Transferring PCNA and c-myc ASODN into VSMC obtained successfully;the corresponding gene was inhibited obviously; compared with control group(P＜0.05);Chuanxiongzine could inhibit the proliferation of VSMC significantly in a dose- and time-dependent manner,compared with control group (P＜0.05).The expression of PCNA and c-myc were inhibited obviously by chuanxiongzine and was correlated with the concentration of chuanxiongzine(P＜0.05).Conclusion PCNA and c-myc might play a considerable role in the VSMC proliferation process.The corresponding gene could be depressed successfully after transferring PCNA and c-myc ASODN into VSMC,and then the proliferation of VSMC was retarded;Chuanxiongzine may play a considerable role in the VSMC proliferation process.The inhibitory effect of chuanxiongzine in a dose- and time-dependent manner could be realized via down regulating the expression of PCNA and c-myc.In this study, great theoretical fundament about Chinese medicine,which is used to treat atherosclerosis (AS),has been obtained.