The Role of Magnetic Resonance Imaging and the Expression of MMP-9 Protein in the Analysis of Carotid Atherosclerotic Plaques in Patients Undergoing Carotid Endarterectomy: A Prospective Pilot Study

Components of carotid atherosclerotic plaque can be analysed preoperatively by non-invasive advanced imaging modalities such as magnetic resonance imaging (MRI). The expression of matrix metalloproteinase-9 protein (MMP-9), which has a potential role in remodelling of atherosclerotic plaques, can be analysed immunohistochemically. The aim of the present prospective pilot study is to analyse histological characteristics and expression of MMP-9 in carotid plaques of patients undergoing carotid endarterectomy (CEA) and to investigate the correlation with preoperative clinical symptoms and MRI features. Preoperative clinical assessment, MRI imaging, postoperative histological and immunohistochemical analyses were performed. Fifteen patients with symptomatic (7/15; 47%) and asymptomatic carotid artery stenosis undergoing CEA were included. Among symptomatic patients, 5 (71%) had recent stroke and 2 (29%) had recent transient ischaemic attack with a median timing of 6 weeks (IQR:1, 18) before the surgery. Both groups did not significantly differ in respect to preoperative characteristics. Prevalence of unstable plaque was higher in symptomatic than asymptomatic patients, although it was not significant (63% vs. 37%, p=0.077). The expression of MMP-9 in CD68 cells within the plaque by semiquantitative analysis was found to be significantly higher in symptomatic as compared to asymptomatic patients (86% vs. 25% with the highest expression, p=0.014). The average microvascular density was found to be higher and lipid core area larger among both symptomatic patients and unstable carotid plaque specimens, although this did not reach statistical significance (p=0.064 and p=0.132, p=0.360 and p=0.569, respectively). Our results demonstrate that MRI is reliable in classifying carotid lesions and differentiating unstable from stable plaques. We have also shown that the expression of MMP-9 is significantly higher among symptomatic patients undergoing CEA. Trial Registration: This study has been registered at the ISRCTN registry (ID ISRCTN46536832), isrctn.org Identifier: https://www.isrctn.com/ISRCTN46536832 Keywords: atherosclerosis, carotid endarterectomy, unstable plaque, magnetic resonance imaging, matrix metalloproteinase.

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.

Clinical Implications of IL-32, IL-34 and IL-37 in Atherosclerosis: Speculative Role in Cardiovascular Manifestations of COVID-19

Atherosclerosis, which is a primary cause of cardiovascular disease (CVD) deaths around the world, is a chronic inflammatory disease that is characterised by the accumulation of lipid plaques in the arterial wall, triggering inflammation that is regulated by cytokines/chemokines that mediate innate and adaptive immunity. This review focuses on IL-32, -34 and -37 in the stable vs. unstable plaques from atherosclerotic patients. Dysregulation of the novel cytokines IL-32, -34 and -37 has been discovered in atherosclerotic plaques. IL-32 and -34 are pro-atherogenic and associated with an unstable plaque phenotype; whereas IL-37 is anti-atherogenic and maintains plaque stability. It is speculated that these cytokines may contribute to the explanation for the increased occurrence of atherosclerotic plaque rupture seen in patients with COVID-19 infection. Understanding the roles of these cytokines in atherogenesis may provide future therapeutic perspectives, both in the management of unstable plaque and acute coronary syndrome, and may contribute to our understanding of the COVID-19 cytokine storm.

Association between carotid plaque vulnerability and high mobility group box-1 serum levels in a diabetic population

Background Carotid atherosclerosis represents one of the complications of diabetes mellitus. In particular, plaque instability contributes to disease progression and stroke incidence. High mobility group box-1 (HMGB1) is a nuclear protein involved in promotion and progression of atherosclerosis and cardiovascular diseases. The aim of this study was to analyze the relationship between HMGB1 serum levels, main inflammatory cytokines, the presence of internal carotid stenosis and unstable plaque in a diabetic population. Research design and methods We studied 873 diabetic patients, including 347 patients with internal carotid artery stenosis (ICAS) who underwent carotid endarterectomy and 526 diabetic patients without internal carotid artery stenosis (WICAS). At baseline, HMGB1 and the main inflammatory cytokines serum levels were evaluated. For ICAS patients, the histological features of carotid plaque were also collected to differentiate them in patients with stable or unstable atherosclerotic lesions. Results We found that HMGB1 serum levels, osteoprotegerin, high-sensitivity C-reactive protein, tumor necrosis factor-alpha and interleukin-6, were significantly higher in diabetic ICAS patients compared to diabetic WICAS patients. Among ICAS patients, individuals with unstable plaque had higher levels of these cytokines, compared to patients with stable plaque. A multivariable stepwise logistic regression analysis showed that HMGB1 and osteoprotegerin remained independently associated with unstable plaque in ICAS patients. Conclusions The present study demonstrated that HMGB1 is an independent risk factor for carotid plaque vulnerability in an Italian population with diabetes mellitus, representing a promising biomarker of carotid plaque instability and a possible molecular target to treat unstable carotid plaques and to prevent stroke.

Association Between Carotid Plaque Vulnerability and High Mobility Group Box-1 Serum Levels in a Diabetic Population

Background: Carotid atherosclerosis represents one of the complications of diabetes mellitus. In particular, plaque instability contributes to disease progression and stroke incidence. High mobility group box-1 (HMGB1) is a nuclear protein involved in promotion and progression of atherosclerosis and cardiovascular diseases. The aim of this study was to analyze the relationship between HMGB1 serum levels, main inflammatory cytokines, the presence of internal carotid stenosis and unstable plaque in a diabetic population.Research Design and Methods: We studied 873 diabetic patients, including 347 patients with internal carotid artery stenosis (ICAS) who underwent carotid endarterectomy and 526 diabetic patients without internal carotid artery stenosis (WICAS). At baseline, HMGB1 and the main inflammatory cytokines serum levels were evaluated. For ICAS patients, the histological features of carotid plaque were also collected to differentiate them in patients with stable or unstable atherosclerotic lesions.Results: We found that HMGB1 serum levels, osteoprotegerin, high-sensitivity C-reactive protein, tumor necrosis factor-alpha and interleukin-6, were significantly higher in diabetic ICAS patients compared to diabetic WICAS patients. Among ICAS patients, individuals with unstable plaque had higher levels of these cytokines, compared to patients with stable plaque. A multivariable stepwise logistic regression analysis showed that HMGB1 and osteoprotegerin remained independently associated with unstable plaque in ICAS patients.Conclusions: The present study demonstrated that HMGB1 is an independent risk factor for carotid plaque vulnerability in an Italian population with diabetes mellitus, representing a promising biomarker of carotid plaque instability and a possible molecular target to treat unstable carotid plaques and to prevent stroke.

THROMBUS ASPIRATION WITHOUT STENTING IN A PATIENT WITH ANTERIOR STEMI (REGRESSION AND HEALING OF AN UNSTABLE PLAQUE 24 MONTHS LATER AFTER PCI ASSESSED BY OCT)

We report a case of natural healing of a ruptured unstable coronary plaque using serial OCT examination. Stenting procedure was deferred based on the angiographic and mainly OCT findings. A healing process of ruptured plaque without foreign body was studied using OCT at 3, 14 and 24 months after PCI.

Early identification of carotid vulnerable plaque in asymptomatic patients

Background This study was to explore the influencing factors of atherosclerotic plaque formation and stability in patients with asymptomatic carotid atherosclerotic plaques, so as to identify the vulnerable plaques at early stage, and then find high-risk group of cardio-cerebrovascular events for early clinical intervention to reduce related mortality and disability. Methods A total of 302 enrolled patients with asymptomatic carotid atherosclerotic plaques were divided into 3 groups based on the results of carotid artery color Doppler ultrasound: atherosclerotic unstable plaque (UP) group, atherosclerotic stable plaque (SP) group, and control group without plaques. Serum markers were measured by ELISA. χ2 test, t test, Pearson correlation analysis, and Logistic multivariate regression analysis were used in the analysis, and P < 0.05 was considered statistically significant. Results It revealed that high MMP-9, LOX-1and YKL-40 were independent risk factors for unstable plaque formation. The area under the curve (AUC) of serum markers combined with MMP-9, LOX-1 and YKL-40 was 0.850, with sensitivity 87.67%, specificity 81.13%, and diagnostic accuracy 84.92%, which was significantly better than the individual diagnostic efficacy of other three factors. The accuracy rate of Crouse Plaque Score (CPS) in the diagnosis of vulnerable plaques was 61.90%, the 10-year ICVD diagnosis accuracy rate was 56.75%, and the diagnostic accuracy of serum markers was significantly better than CPS and 10-year ICVD. Conclusion Noninvasive cervical color Doppler ultrasound combined with serum markers MMP-9, LOX-1 and YKL-40 have significant early recognition effect on asymptomatic carotid vulnerable plaque patients.