Numerical simulation study of fracture mechanics of the atherosclerotic plaque / 生物医学工程学杂志

Atherosclerotic plaque rupture is the main cause of many cardiovascular diseases, and biomechanical factors play an important role in the process of plaque rupture. In the study of plaque biomechanics, there are relatively few studies based on fatigue fracture failure theory, and most of them mainly focus on the whole fatigue propagation process from crack initiation to plaque rupture, while there are few studies on the influence of crack on plaque rupture at a certain time in the process of fatigue propagation. In this paper, a two-dimensional plaque model with crack was established. Based on the theory of fracture mechanics and combined with the finite element numerical simulation method, the stress intensity factor (SIF) and related influencing factors at the crack tip in the plaque were studied. The SIF was used to measure the influence of crack on plaque rupture. The results show that the existence of crack can lead to local stress concentration, which increases the risk of plaque rupture. The SIF at the crack tip in the plaque was positively correlated with blood pressure, but negatively correlated with fibrous cap thickness and lipid pool stiffness. The effect of the thickness and angle of lipid pool on the SIF at the crack tip in the plaque was less than 4%, which could be ignored. This study provides a theoretical basis for the risk assessment of plaque rupture with cracks.

The value of circulating microRNA-1 in the early diagnosis of coronary atherosclerotic plaque rupture in patients with stable coronary heart disease / 中华危重病急救医学

Objective:To evaluate the diagnostic value of circulating microRNA-1 (miR-1) in early coronary artery plaque rupture in patients with stable coronary artery disease (SCAD).Methods:A prospective cohort study was conducted. Sixty-seven patients with SCAD admitted to the department of cardiology of the Third Affiliated Hospital of Soochow University from January to June in 2019 were enrolled. All patients had completed coronary angiography (CAG), percutaneous coronary intervention (PCI) single stent implantation or only CAG was performed according to the CAG results. Blood samples were collected before (0 hour) and 3 hours after the procedure. The expression of plasma miR-1 was detected by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR), and electrocardiogram was used to detect cardiac troponin I (cTnI) levels. The difference of miR-1 and cTnI levels in PCI or CAG patients before and after procedure were compared, and the value for early diagnosis of coronary artery plaque rupture in SCAD patients was evaluated. The diagnostic efficacy was evaluated by the receiver operating characteristic curve (ROC curve).Results:There were 38 CAG patients and 29 PCI patients. There were no significant differences in gender, age, previous history (without hypertension history) and baseline data of cardiac function between the two groups. The expression of miR-1 after PCI was significantly higher than that before PCI [2 -ΔΔCt: 2.11 (1.56, 2.73) vs. 1.26 (1.07, 1.92), P < 0.01], and there was no significant difference in cTnI level before and after PCI [μg/L: 0.00 (0.00, 0.02) vs. 0.00 (0.00, 0.02), P > 0.05]. There were no significant differences in miR-1 and cTnI levels before and after procedure in the CAG group [miR-1 (2 -ΔΔCt): 1.09 (1.00, 1.40) vs. 1.21 (1.00, 1.71), cTnI (μg/L): 0.00 (0.00, 0.02) vs. 0.00 (0.00, 0.02), both P > 0.05]. ROC curve analysis showed that the area under ROC curve (AUC) and 95% confidence interval (95% CI) of miR-1 in the diagnosis of coronary plaque rupture were 0.794 (0.687-0.900), P < 0.01, the sensitivity was 82.8%, the specificity was 68.4%, and the optimal cut-off value was 1.51. The AUC and 95% CI of the difference of miR-1 before and after operation (ΔmiR-1) were 0.704 (0.567-0.842), P = 0.004, the sensitivity was 62.1%, the specificity was 84.2%, and the optimal cut-off value was 0.39. The efficancy of miR-1 and ΔmiR-1 after procedure to diagnose coronary plaque rupture in patients with SCAD was similar ( Z = 1.287, P = 0.198). However, baseline miR-1 might not predict whether patients with SCAD need PCI or not (AUC = 0.630, P > 0.05). Multivariate binary Logistic regression analysis showed that increased postoperative miR-1 expression was an independent risk factor for coronary plaque rupture in SCAD patients [odds ratios ( OR) = 2.887, 95% CI was 1.044-7.978, P = 0.041]. Conclusion:Circulating miR-1 might have the value for early diagnosis of coronary artery plaque rupture in SCAD patients.

In Vivo Stress Analysis of an Atherosclerotic Plaque at Carotid Bifurcation / 医用生物力学

Objective To investigate the in vivo stress distribution of the atherosclerotic plaque at carotid bifurcation, so as to provide references for the mechanical mechanisms of plaque rupture at carotid bifurcation and the design for further medical treatment. Methods The three-dimensional geometric model of carotid bifurcation and plaque were established according to average geometric parameters of human carotid bifurcation. Residual stress of the carotid bifurcation and plague was reestablished with “thermal-structure” coupling method, and in vivo stresses of vessels with the plaque at carotid bifurcation under blood pressure and blood flow were calculated. Results Both the maximum principal stress and elastic shear stress concentrated on the shoulder of the plaque. Elastic shear stress increased with the increase of stenosis ratio and blood pressure. Wall shear stress in the upstream of the plaque was considerably higher than that of the downstream. The distribution of oscillatory shear index(OSI) was quite the opposite. The changing patterns of the elastic shear stress and flow shear stress were quite different with the change of stenosis ratios. Conclusions Tension grew gradually from the centrality to shoulder surface of the plaque. The centrality of the plaque might bear compression when the stenosis was very severe. The periodic variation of the structural stress might cause structural fatigue of the plaque, thus increasing the rupture risk. Distinction of the component and vulnerability of the plaque between upstream and downstream might be caused by differences in hemodynamic parameters of the plaque between upstream and downstream.

Association between optical coherence tomography characteristics and peripheral blood leukocyte count in patients with acute myocardial infarction / 中国介入心脏病学杂志

Objective To explore the relationship between optical coherence tomography (OCT) characteristics and peripheral blood leukocyte count in patients with acute myocardial infarction(AMI). Methods A total of 33 patients with AMI hospitalized in Fuwai Hospital for primary percutaneous coronary intervention were consecutively enrolled,and underwent intracoronary OCT procedures after manual aspiration of coronary thrombus. Demographic data, risk factors, procedural and OCT data, past medical history and perioperative laboratory findings were collected in all patients. Results The lymphocyte count,monocyte count and basophil count were significantly higher in the patients with fibrous cap thickness ≥ 65 μm than in those patients with fibrous cap thickness ≤ 65 μm. Patients presenting with cholesterol crystallization had lower eosinophil count than those patients with crystallization-free [(0.04±0.06)×109/L vs.(0.10±0.09) ×109/L,P =0.028]. In addition,the former had significantly higher to neutrophil lymphocyte ratio than the latter [(8.35±6.13)vs.(4.97±2.01), P =0.020]. Higher monocyte count was found in the patients with calcified plaque (P <0.05). Platelet to lymphocyte ratio was significantly increased in the patients with macrophage infiltration [(165.72±85.93)vs.(113.47±19.13),P <0.05]. The leukocyte count,neutrophil count and monocyte count showed the treat of elevation as the number of OCT characteristics increased,but only the elevation of monocyte count had statistical significant level (P = 0.014). Conclusions Peripheral blood leukocyte count seems to be associated with OCT characteristics of plaque rupture in patients with acute myocardial infarction,suggesting the potential role of inflammation in plaque rupture.

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.

To study other biomarkers that assess during myocardial infarction / Монголын Анагаах Ухаан

Background. When the coronary atherosclerotic plaque becomes vulnerable, a thrombus develops on that ruptured plaque and then occludes the coronary artery, which causes an acute blood defi ciency in the downstream myocardium. Furthermore oxLDL (oxidized Low Density Lipoprotein) is involved in the coronary atherosclerotic plaque pathogenesis, MMP-9 (Matrix Metalloproteinase-9) enzymes plays role during the plaque rupture and CPR (C Reactive Protein) has a prognostic value in myocardial infarction. Objective. To determine the involvement of oxLDL, MMP-9, CRP markers in the pathogenesis of myocardial infarction, to study their involvement in the injury of the myocardium and to evaluate the complications. Material and Methods. The study was conducted using case-control design. The main inclusion criteria of the 40 case groups are that the patient should have a ruptured coronary atherosclerotic plaque, confi rmed by clinical symptom, ECG, serum troponin I, and coronary angiography. Also 40 patients with coronary stenosis or chronic occlusion without ruptured plague were included in the control group. Serum MMP-9 enzyme and oxLDL titers were determined by ELISA according to the manufacturer’s recommended protocol. Additionally CRP was measured by full-automated analyzater. We used CIIS (cardiac infarction injury score) by ECG and Gensini score system (Coronary Angiographic Scoring System) for assessing the severity of coronary heart disease. Results. Serum MMP-9, oxLDL levels (p15, 0.376±0.132 ng/ ml) groups. MMP-9 levels were signifi cantly higher in the probable injury group patients (CIIS >15) compared to the possible injury group patients (CIIS 10-15) (p<0.001). ROC Curve analysis shows that MMP-9 enzyme levels variance (area=0.87, p<0.001) are more than other biomarkers making it a diagnostically benefi cial for the coronary atherosclerotic plaque rupture (CRP area=0,733, p<0.001, oxLDL area=0.635, p<0.05). Conclusion: Serum MMP-9, oxLDL and CRP are signifi cantly involved in the pathogenesis of coronary atherosclerotic plaque rupture in the myocardial infarction.

Perioperative Myocardial Infarction.

Myocardial infarction (MI) is defined by the World Health Organization Criteria, which includes typical ischemic chest pain, ECG criteria and raised cardiac enzymes. The perioperative period induces large, unpredictable and nonphysiological alterations in coronary plaque morphology, function and progression, and may trigger a mismatch of myocardial oxygen supply and demand. Perioperative MI (PMI) is one of the most important predictors of short- and long-term morbidity and mortality associated with noncardiac surgery. Inability to fulfil the criteria, different symptomatology and numerous differential diagnoses makes PMI our subject of detailed discussion.1

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.

High Shear Stress at the Surface of Enhancing Plaque in the Systolic Phase is Related to the Symptom Presentation of Severe M1 Stenosis

The computational fluid dynamics methods for the limited flow rate and the small dimensions of an intracranial artery stenosis may help demonstrate the stroke mechanism in intracranial atherosclerosis. We have modeled the high wall shear stress (WSS) in a severe M1 stenosis. The high WSS in the systolic phase of the cardiac cycle was well-correlated with a thick fibrous cap atheroma with enhancement, as was determined using high-resolution plaque imaging techniques in a severe stenosis of the middle cerebral artery.

Lesion Characteristics in Patients with Acute Coronary Syndrome: A Comparison with Lesion in Patients with Stable Angina by Intravascular Ultrasound

BACKGROUND AND OBJECTIVES: The pathophysiology of acute coronary syndrome (ACS) is plaque rupture with thrombus formation, which is different from that of stable angina pectoris (SA). Intravascular ultrasound (IVUS) prior to percutaneous coronary intervention provides information on the plaques and vessel wall itself. The purpose of this study was to evaluate the lesion characteristics of ACS prior to coronary intervention compared to those of SA lesions by IVUS. SUBJECTS AND METHODS: Pre-interventional IVUS was performed on 68 culprit lesions in 41 ACS and 25 SA patients. The plaque morphology, lumen and vessel sizes, and arterial remodeling pattern at the lesion segment were analyzed in both groups. A plaque rupture was defined as a plaque containing a cavity that communicated with the lumen, which was covered with a fibrous cap. RESULTS: Positive remodeling was more frequent in patients with ACS than those with SA (42 vs. 11%), whereas negative remodeling was more frequent in patients with SA (22 vs. 41%) (p=0.023). Plaque rupture/dissection and thrombus was more frequent (51 vs. 19%, p=0.006 and 39 vs. 4%, p=0.001) in patients with ACS. Lesions with ACS had significantly larger EEM CSA, plaque CSA and plaque burden (p<0.05). There were no significant differences in the clinical parameters, angiographic parameters and plaque morphologies. CONCLUSION: Positive remodeling, plaque rupture/dissection and thrombus were more frequently observed in patients with ACS. In addition, lesions with ACS had a larger vessel size and a higher plaque burden. The type of remodeling, plaque rupture or dissection, thrombus and amount of plaques might have an impact on the clinical presentation.

Study of aspirin on inhibiting the atherosclerotic plaque rupture and MMP-2 expression of abdominal aorta in atherosclerotic rabbits / 中国药理学通报

Aim To study the effects of aspirin on increasing the atherosclerotic plaque stability and its possible mechanisms.Methods The hyperlipidemic atherosclerotic model was generated in male New Zealand rabbits given high fat diet and endothelial abrasion of abdominal aorta.These rabbits were then treated with aspirin 5～20 mg?kg-1 for 4 weeks.At experimental end,the plaques were evoked into rupture by injection of Russell's viper venom and histamine.Areas of thrombosis on atherosclerotic aorta were determined by image analysis,morphologic character of plaque rupture was examined by light microscope,the protein expression of macrophages was detected by immunohistochemistry,and the mRNA expression of COX-2 and MMP-2 was determined by hybridization in situ,respectively.Results Aspirin at doses of 5～10 mg?kg-1 was able to inhibit thrombosis on atherosclerotic plaque(P

Effect of benapril on atherogenesis and plaque rupture in rabbits / 第二军医大学学报

Objective: To examine the effect of Benapril on atherogenesis and the plaque rupture in rabbits.Methods: Thirty four healthy male New Zealand white rabbits were randomly divided into 4 groups.Group C (control group) was fed normal diet for 10 weeks,group HL fed 1% cholesterol diet,group B fed 1% cholesterol diet and Benapril 5 mg/d.Ten rabbits of plaque rupture group were fed 1% cholesterol diet for 10 weeks with atherosclerosis induced by left carotid iliac damage.Ten weeks after the initiation of the diet,an angioplasty was performed.After angioplasty,the surviving rabbits( n =10) were randomized to receive benapril(5 mg/d,each) supplementation in drinking(B group, n =4) or no treatment(untreated group, n =4). The levels of CEC were measured by morphometrical counts at different periods(the 5th week,the 10th week).Before and 5,10 weeks after experiment,fasting blood samples were collected for serum total cholesterol(TC),high density lipoprotein cholesterol(HDL C),low density lipoprotein cholesterol(LDL C),and triglyceride(TG) assay.The levels of plasma circulating endothelial cells(CEC) were measured by morphometrical counts and the levels of plasma von Willebrand factor(vWF) were determined by ELISA.After sacrificing the separated, entire aortas were stained with oil red O and then processed for histological examination;planimetry was done with a computer system.Endothelial cells were confined by the presence of Factor Ⅷ related antigen as the specific cell marker.Results: The serum TC,TG,LDL C increased progressively in group B and group HL,but the levels of vWF in group HL were significantly higher than that in group B on the 5th and 10th respetively( P

Plaque Morphology in Acute Coronary Syndrome: An Intravascular Ultrasound Study

BACKGROUND: Plaque rupture of the atherosclerotic plaque is an important pathophysiologic mechanism of acute coronary syndrorne(acute myocardial infarction or unstable angina). Plaque rupture and resulting thrombus formation could be identified by intravascular ultrasound (IVUS), even though the sensitivity was variable in previous reports. We sought to know the morphologic characteristics, incidence of plaque rupture and thrombus formation by ultrasound in patients with acute coronary syndrome. METHOD: Between April and Septernber 1997, 23 admitted patients who was diagnosed as unstable angina or acute rnyocardial infarction was included. We performed coronary angiography with IVUS examination within 2 weeks. Atherosclerotic plaque was classified into soft, fibrous, calcific, and mixed plaque, and plaque rupture was defined as rupture of fibrous cap with discontinuity and / or backflow into plaque. Thrombus was defined as a scintillating, movable mass or layering materials that could be distinguished from underlying plaque. RESULTS: Most of the plaques were soft and mixed types(14 and 6, out of 23 cases). Plaque rupture could be identified only in small portion(6 cases, 26%) of the cases. Thrombus was noted in 12 cases(52%). 4 cases showed both plaque rupture and thrombus. CONCLUSION: Soft plaque is the most frequent plaque pye in acute coronary syndrome. IVUS is a useful tool to identify the morphologic features of the plaque such as rupture and thrombus formation.