Clinical Application of Serum miRNA-126,miRNA-155 Detection in Evaluation of Plaque Property in the Carotid Atherosclerotic Desease / 现代检验医学杂志

Objective To investigate the clinical application of serum miRNA-126,miRNA-155 detection in evaluation of plaque property in the carotid atherosclerotic(CAS)desease.Methods A total of 75 patients with the CAS from May 2015 to May 2017 in the Xianyang Central Hospital and Shiquan Country Chinese Traditional Medicine was chosen,consisted of 35 cases of vulvernable plaque group and 40 cases of stable plaque group.Meanwhile,39 cases of healthy physical examines at the same time were regarded as the control group.The expression levels of serum miRNA-126,miRNA-155 in the groups were detected using the real-time reverse transcription-polymerase chain reaction technique.The largest carotid artery plaque thickness(MAPT)and intima-media thickness(IMT)in the groups were measured using the cervical enhancement CT.Re-sults The results of MAPT and IMT were(3.27±1.01 mm,1.93±0.51 mm)in the vulvernable plaque group and(2.50 ±0.79 mm,1.60±0.26 mm)in the stable plaque group.The carotid artery largest plaque thickness and intima-media thick-ness was higher in the vulvernable plaque group than in the stable plaque group(t=9.76,7.86,P<0.01),and there were significant differenes between the two groups.The expression levels of serum miRNA-126and miRNA-155 were(0.22 ± 0.06,0.87±0.18)in the vulvernable plaque group,(0.50±0.12,0.47±0.10)in the stable plaque group and(0.90±0.19, 0.19±0.05)in the control group.MiRNA-155 expression levels significantly increased in stable plaque group and vulvern-able plaque group compared with in the control group,which increased in the vulvernable plaque group compared with in the stable plaque group,and miRNA-126 expression levels markedly decreased,the differences were statistically significant(F=119.3,102.9,P<0.01).In the vulvernable plaque group,miRNA-126 expression negatively correlated with miRNA-155(r=0.912,P<0.01).miRNA-126 expression levels were inversely associated with the carotid artery largest plaque thickness and the intima-media thickness(r=-0.913,-0.893,P<0.01).While miRNA-155 expression levels were positively corre-lated with them(r=0.899,0.907,P<0.01).Conclusion Serum miRNA-155,miRNA-126 detection can be applied to pre-diction of CAS plaques rupture,and may become a useful warning marker of ischemic stroke events.

A novel mouse model of atherosclerotic plaque instability for drug testing and mechanistic/therapeutic discoveries using gene and microRNA expression profiling.

RATIONALE: The high morbidity/mortality of atherosclerosis is typically precipitated by plaque rupture and consequent thrombosis. However, research on underlying mechanisms and therapeutic approaches is limited by the lack of animal models that reproduce plaque instability observed in humans. OBJECTIVE: Development and use of a mouse model of plaque rupture that reflects the end stage of human atherosclerosis. METHODS AND RESULTS: On the basis of flow measurements and computational fluid dynamics, we applied a tandem stenosis to the carotid artery of apolipoprotein E-deficient mice on high-fat diet. At 7 weeks postoperatively, we observed intraplaque hemorrhage in ≈50% of mice, as well as disruption of fibrous caps, intraluminal thrombosis, neovascularization, and further characteristics typically seen in human unstable plaques. Administration of atorvastatin was associated with plaque stabilization and downregulation of monocyte chemoattractant protein-1 and ubiquitin. Microarray profiling of mRNA and microRNA (miR) and, in particular, its combined analysis demonstrated major differences in the hierarchical clustering of genes and miRs among nonatherosclerotic arteries, stable, and unstable plaques and allows the identification of distinct genes/miRs, potentially representing novel therapeutic targets for plaque stabilization. The feasibility of the described animal model as a discovery tool was established in a pilot approach, identifying a disintegrin and metalloprotease with thrombospondin motifs 4 (ADAMTS4) and miR-322 as potential pathogenic factors of plaque instability in mice and validated in human plaques. CONCLUSIONS: The newly described mouse model reflects human atherosclerotic plaque instability and represents a discovery tool toward the development and testing of therapeutic strategies aimed at preventing plaque rupture. Distinctly expressed genes and miRs can be linked to plaque instability.

Computational Flow Dynamics of the Severe M1 Stenosis Before and After Stenting / 신경중재치료의학

PURPOSE: Computational flow dynamic (CFD) study has not been widely applied in intracranial artery stenosis due to requirement of high resolution in identifying the small intracranial artery. We described a process in CFD study applied to symptomatic severe intracranial (M1) stenosis before and after stenting. MATERIALS AND METHODS: Reconstructed 3D angiography in STL format was transferred to Magics (Materialise NV, Leuven, Belgium) for smoothing of vessel surface and trimming of branch vessels and to HyperMesh (Altair Engineering Inc., Auckland, New Zealand) for generating tetra volume mesh from triangular surface-meshed 3D angiogram. Computational analysis of blood flow in the blood vessels was performed using the commercial finite element software ADINA Ver 8.5 (ADINA R & D, Inc., Lebanon, MA). The distribution of wall shear stress (WSS), peak velocity and pressure in a patient was analyzed before and after intracranial stenting. RESULTS: Computer simulation of wall shear stress, flow velocity and wall pressure before and after stenting could be demonstrated three dimensionally by video mode according to flow vs. time dimension. Such flow model was well correlated with angiographic finding related to maximum degree of stenosis. Change of WSS, peak velocity and pressure at the severe stenosis was demonstrated before and after stenting. There was no WSS after stenting in case without residual stenosis. CONCLUSION: Our study revealed that CFD analysis before and after intracranial stenting was feasible despite of limited vessel wall dimension and could reveal change of WSS as well as flow velocity and wall pressure.