Analysis of Predictive Model of Coronary Vulnerable Plaque under Hemodynamic Numerical Simulation

Objective. Vulnerable plaque is considered to be the cause of most clinical coronary arteries, and linear cytokines are an important factor causing plaque instability. Early prediction of vulnerable plaque is of great significance in the treatment of cardiovascular diseases. Methods. Computational fluid dynamics (CFD) was used to simulate the hemodynamics around plaques, and the serum biochemical markers in 224 patients with low-risk acute coronary syndrome (ACS) were analyzed. Vulnerable plaques were predicted according to the distribution of biochemical markers in serum. Results. CFD can accurately capture the hemodynamic characteristics around the plaque. The patient’s age, history of hyperlipidemia, apolipoprotein B (apoB), adiponectin (ADP), and sE-Selection were risk factors for vulnerable plaque. Area under curve (AUC) values corresponding to the five biochemical markers were 0.601, 0.523, 0.562, 0.519, 0.539, and the AUC value after the combination of the five indicators was 0.826. Conclusion. The combination of multiple biochemical markers to predict vulnerable plaque was of high diagnostic value, and this method was convenient and noninvasive, which was worthy of clinical promotion.

Targeted Therapy of Atherosclerosis Vulnerable Plaque By ROS-Scavenging Nanoparticles And MR/Fluorescence Dual-Modality Imaging Tracing

Background: Cardiovascular diseases are currently the leading cause of death and disability worldwide, and the key pathological basis is atherosclerosis (AS). Especially, the rupture of vulnerable plaques is the main cause of acute cardiovascular and cerebrovascular events such as myocardial infarction and stroke. Thus, the early identifying and therapy of vulnerable plaques are necessary. Results: In this study, we developed a novel multimodal imaging platform (GPRD) based on Gd doped Prussian blue (GPB) and rhodamine (Rd) to specifically target and identify the vulnerable plaques with the help of dextran sulfate (DS), one of the excellent ligands of scavenger receptor class A (SR-A). It is more important that the nano-enzyme capacity of GPRD NPs realized the elimination of the excessive production of ROS in cells, and the following reduction of ROS-induced oxidative stress, inflammation, apoptosis, and the formation of macrophage-derived foam cells, presenting an inhibition of plaque progress eventually. Conclusions: The ROS-scavenging multimodal imaging nanoprobe provided a new avenue for the diagnosis and treatment of AS vulnerable plaques.

NR1D1 Deletion Induces Rupture-Prone Vulnerable Plaques by Regulating Macrophage Pyroptosis via the NF-κB/NLRP3 Inflammasome Pathway

Vulnerable plaque rupture is the main trigger of most acute cardiovascular events. But the underlying mechanisms responsible for the transition from stable to vulnerable plaque remain largely unknown. Nuclear receptor subfamily 1 group D member 1 (NR1D1), also known as REV-ERB α, is a nuclear receptor that has shown the protective role in cardiovascular system. However, the effect of NR1D1 on vulnerable plaque rupture and its underlying mechanisms are still unclear. By generating the rupture-prone vulnerable plaque model in hypercholesterolemic ApoE−/− mice and NR1D1−/−ApoE−/− mice, we demonstrated that NR1D1 deficiency significantly augmented plaque vulnerability/rupture, with higher incidence of intraplaque hemorrhage (78.26% vs. 47.82%, P = 0.0325 ) and spontaneous plaque rupture with intraluminal thrombus formation (65.21% vs. 39.13%, P = 0.1392 ). In vivo experiments indicated that NR1D1 exerted a protective role in the vasculature. Mechanically, NR1D1 deficiency aggravates macrophage infiltration, inflammation, and oxidative stress. Compared with the ApoE−/− mice, NR1D1−/−ApoE−/− mice exhibited a significantly higher expression level of pyroptosis-related genes in macrophages within the plaque. Further investigation based on mice bone marrow-derived macrophages (BMDMs) confirmed that NR1D1 exerted a protective effect by inhibiting macrophage pyroptosis in a NLRP3-inflammasome-dependent manner. Besides, pharmacological activation of NR1D1 by SR9009, a specific NR1D1 agonist, prevented plaque vulnerability/rupture. In general, our findings provide further evidences that NR1D1 plays a protective role in the vasculature, regulates inflammation and oxidative stress, and stabilizes rupture-prone vulnerable plaques.

Assessment of Carotid Plaque Stability Using Contrast-Enhanced Ultrasound and Its Correlation With the Expression of CD147 and MMP-9 in the Plaque

This study aims to investigate the correlation between the enhancement degree of contrast-enhanced ultrasound (CEUS) and the expression of CD147 and MMP-9 in carotid atherosclerotic plaques in patients with carotid endarterectomy and evaluate the diagnostic efficacy of CEUS using pathological results as the gold standard. Thirty-eight patients who underwent carotid endarterectomy (CEA) for carotid stenosis in the Department of Neurovascular Surgery of the Second People’s Hospital of Shenzhen from July 2019 to June 2020 were selected. Preoperatively, two-dimensional (2D) ultrasound scan was performed on all patients to assess the characteristics of the plaque and degree of stenosis, and CEUS was used to evaluate the surface morphology of the plaque and the distribution of neovascularization. Postoperatively, pathological sections and immunohistochemical analysis of CD147 and MMP-9 levels in the plaque were performed on the stripped plaque tissue, and the results were analyzed against the CEUS grading and pathological results. Among the 38 patients, pathological results showed that 10 and 28 were in the stable and vulnerable plaque groups, respectively. There were more smokers in the vulnerable plaque group than in the stable plaque group, with higher intraplaques CD147 and MMP-9. The difference in ultrasound plaque surface morphology grading and CEUS grading between the two groups was statistically significant. There was no significant difference in age, sex, incidence of complications such as hypertension, diabetes, and coronary heart disease between the two groups. CD147 was higher in the CEUS grade IV group than in the grades I (P = 0.040) and II (P = 0.010) groups. MMP-9 was higher in the CEUS grade IV group than in the grade II group (P = 0.017); MMP-9 was higher in the grade III group than in the grade II group (P = 0.015). Intraplaque contrast enhancement intensity was positively correlated with CD147 (r = 0.462, P = 0.003) and MMP-9 (r = 0.382, P = 0.018) levels. There was moderate consistency between the assessment of plaque vulnerability by 2D-ultrasound and by histopathological hematoxylin-eosin (HE) (kappa = 0.457, P > 0.05). 2D diagnosis of vulnerable plaque had a sensitivity of 85.7%, a specificity of 60.0%, a positive predictive value of 85.7%, a negative predictive value of 60.0%, and an accuracy of 78.0%. There was a strong consistency between the assessment of plaque vulnerability by CEUS and histopathological HE (kappa = 0.671, P < 0.01). CEUS had a sensitivity of 89.2%, a specificity of 80.0%, a positive predictive value of 92.6%, a negative predictive value of 72.7%, and an accuracy of 86.8% for the diagnosis of vulnerable plaques; CEUS is a reliable, non-invasive test that can show the distribution of neovascularization within vulnerable plaques, evaluate the vulnerability and risk of intraplaque hemorrhage, with a high consistency with pathological findings. The degree of intraplaque enhancement and the levels of CD147 and MMP-9 in the tissue were positively correlated.

246 Air pollution and coronary plaque vulnerability and instability: an optical coherence tomography study

Aims Air pollution is an emerging key player in determining the residual risk of coronary events. However, pathophysiological mechanisms linking air pollution and coronary events have been not adequately investigated. We aimed at assessing the relationship between exposure to air pollutants and mechanisms of coronary instability evaluated by optical coherence tomography (OCT) in patients with acute coronary syndrome (ACS). Methods and results ACS patients undergoing OCT imaging were retrospectively selected. Mechanism of culprit lesion instability was classified as plaque rupture (PR) or intact fibrous cap (IFC) by OCT, and the presence of macrophage infiltrates (MØI) and thin-cap fibroatheroma (TCFA) at the culprit site was also assessed. Based on each case’s home address, exposure to several pollutants was evaluated, including particulate matter 2.5 (PM2.5), particulate matter 10 (PM10), and carbon monoxide (CO). Only patients with >2 years of available data on air pollution exposure prior to ACS were enrolled. We included 126 patients [median age 67.0 years (55.5–76.0), 97 (77.0%) male]. Sixty-six patients (52.4%) had PR as mechanism of plaque instability. Patients with PR were exposed to significantly higher PM2.5 levels compared to IFC, and PM2.5 was independently associated with PR [odds ratio per unit = 1.194, 95% CI: (1.036–1.377), P = 0.015]. Moreover, exposure to higher levels of PM2.5 was independently associated with the presence of TCFA and of MØI at the culprit site. Interestingly, PM2.5, PM10, and CO levels were positively and significantly correlated with serum levels of C-reactive protein. ROC curves were constructed to assess the ability of PM2.5 to predict the presence of plaque rupture, TCFA or MØI. The AUC for PM2.5 to predict plaque rupture was 0.62 (95% CI: 0.52–0.71, P = 0.018), for TCFA was 0.71 (95% CI: 0.61–0.80, P <0.001) and for MØI was 0.80 (95% CI: 0.71–0.88, P <0.001). Using a PM2.5 cut-off value of 13.40 μg/m3, the sensitivity and specificity for MØI were 81% and 66%, respectively. Conclusions We provide novel insights into the missing link between air pollution and increased risk of coronary events. In particular, exposure to higher concentrations of air pollutants is a risk factor for vulnerable plaque features and for plaque rupture as mechanism of coronary instability mediated by systemic and local plaque inflammation. Of importance, the thresholds of air pollutants that predicted the presence of vulnerable plaque features are far lower than commonly accepted safety thresholds used to start preventive measures for public health, suggesting that further efforts are needed in order to reduce the adverse effects on the cardiovascular system.

Imaging Inflammation in Patients and Animals: Focus on PET Imaging the Vulnerable Plaque

Acute coronary syndrome (ACS) describes a range of conditions associated with the rupture of high-risk or vulnerable plaque. Vulnerable atherosclerotic plaque is associated with many changes in its microenvironment which could potentially cause rapid plaque progression. Present-day PET imaging presents a plethora of radiopharmaceuticals designed to image different characteristics throughout plaque progression. Improved knowledge of atherosclerotic disease pathways has facilitated a growing number of pathophysiological targets for more innovative radiotracer design aimed at identifying at-risk vulnerable plaque and earlier intervention opportunity. This paper reviews the efficacy of PET imaging radiotracers 18F-FDG, 18F-NaF, 68Ga-DOTATATE, 64Cu-DOTATATE and 68Ga-pentixafor in plaque characterisation and risk assessment, as well as the translational potential of novel radiotracers in animal studies. Finally, we discuss our murine PET imaging experience and the challenges encountered.

Carotid artery vulnerable plaque model for cerebrovascular events by conventional ultrasound & contrast-enhanced ultrasound: A preliminary study

BACKGROUND: Conventional ultrasound and contrast-enhanced ultrasound play an important role in the application of carotid plaque. AIMS: To establish carotid artery vulnerable plaques plaque model by conventional ultrasound combined with contrast-enhanced ultrasound, identify high-risk plaques that may lead to cerebrovascular events, and provide clinical risk warning of high-risk plaques of stroke. METHODS: 205 cases of patients selected in 5053 patients with symptoms from 2018 to 2019 who were verified carotid plaques by conventional ultrasound and contrast-enhanced ultrasound image characteristics, 147 cases as a training set, establishing the carotid artery plaque model, analyzing the characteristic of the plaques and the relationship between cerebrovascular event, with 58 cases as a test set, verify the model. Routine carotid ultrasound and contrast-enhanced carotid ultrasound were performed in all enrolled patients. RESULTS: The gray-level characteristics of conventional ultrasound in the training concentration showed statistical differences in plaque morphology, fibrous cap morphology, uniformity and calcification degree in cerebrovascular events. The contrast enhanced ultrasound characteristics of plaques showed statistical differences in neovascularization and perfusion mode in cerebrovascular events. In the test set, there were statistical differences in the above conventional gray scale features and CEUS features. CONCLUSION: The vulnerable plaque model established by conventional ultrasound combined with contrast-enhanced ultrasound has good diagnostic value for the characteristic plaque of carotid artery with cerebrovascular events.

Biomarkers in unstable carotid plaque: Physiopathology and Prediction

Aims: To study the role of cytokines and vascular inflammatory biomarkers in unstable carotid plaque. Background: Clinical studies showed that not only the degree of stenosis but also the type of carotid plaque can be responsible for ipsilateral ischemic stroke. Objective: The objective of this study is to suggest a role for vulnerable carotid atherosclerotic disease in the occurrence of ischemic stroke. Methods: PubMed, Embase, Cochrane library, and reference lists have been used to evaluate articles published until February 15, 2021. Results: Several factors may be involved in unstable plaque. Clinical studies support the involvement of brain inflammatory biomarkers as well as cytokines in the unstable carotid plaque. Conclusions: Biomarkers could help to stratify patients with a vulnerable carotid plaque and to personalize the drug treatment. In this review, we briefly discuss the characteristics of vulnerable plaque and the role of biomarkers in the vulnerable carotid plaque.