Clinical Parameters and Epigenetic Biomarkers of Plaque Vulnerability in Patients with Carotid Stenosis.
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ABSTRACT:
SUBMITTER: Carballo-Perich L
PROVIDER: S-EPMC9101730 | biostudies-literature | 2022 May
REPOSITORIES: biostudies-literature
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Clinical Parameters and Epigenetic Biomarkers of Plaque Vulnerability in Patients with Carotid Stenosis.
Carballo-Perich Laia L Puigoriol-Illamola Dolors D Bashir Saima S Terceño Mikel M Silva Yolanda Y Gubern-Mérida Carme C Serena Joaquín J
International journal of molecular sciences 20220505 9
Atheromatous disease is the first cause of death and dependency in developed countries and carotid artery atherosclerosis is one of the main causes of severe ischaemic strokes. Current management strategies are mainly based on the degree of stenosis and patient selection has limited accuracy. This information could be complemented by the identification of biomarkers of plaque vulnerability, which would permit patients at greater and lesser risk of stroke to be distinguished, thus enabling a bett ...[more]
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Project description:PurposeWe explored the retinal microvascular changes in carotid artery stenosis (CAS) and their relationship with carotid plaque morphology.MethodsAll participants were diagnosed with carotid artery stenosis by a neurologist. Participants underwent digital subtraction angiography (DSA) and optical coherence tomography angiography (OCTA) imaging. The degree and length of carotid plaque were obtained from the DSA tool. OCTA tool measured the densities in the superficial vascular complex (SVC) and deep vascular complex (DVC).ResultsOne hundred seventeen patients with CAS patients were included in our data analysis. Eyes with ipsilateral stenosis had reduced retinal microvascular densities when compared to contralateral eyes in patients with CAS (P = 0.016 for SVC, and P = 0.004 for DVC). Microvascular densities correlated with the length of carotid plaque (P = 0.015 for SVC, and P = 0.022 for DVC) in our CAS cohort, although they did not correlate with the degree of carotid plaque (P = 0.264 for SVC, and P = 0.298 for DVC). However, when stratified into moderate and severe subgroups, the degree of carotid plaque correlated with microvascular densities in patients with severe stenosis (P = 0.045 for SVC, and P = 0.038 for DVC).ConclusionsOur study suggests that OCTA can noninvasively detect retinal microvascular changes in patients with CAS and that these changes correlated with the length of the stenosis, but future studies are required to confirm these findings.Translational relevanceNoninvasive and rapid acquisition of the OCTA image might have the potential to be used as a screening tool to detect microvascular changes in carotid artery stenosis.
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Project description:Carotid artery stenosis (CAS) develops from atherosclerotic lesions and plaques. Plaque rupture or stenosis may result in occlusion of the carotid artery. Accordingly, the asymptomatic disease becomes symptomatic, characterized by ischemic stroke or transient ischemic attacks, indicating an urgent need for better understanding of the underlying molecular mechanisms and eventually prevent symptomatic CAS. NOX4, a member of the NADPH oxidase family, has anti-atherosclerotic and anti-inflammatory properties in animal models of early atherosclerosis. We hypothesized that NOX4 mRNA expression is linked to protective mechanisms in CAS patients with advanced atherosclerotic lesions as well. Indeed, NOX4 mRNA expression is lower in patients with symptomatic CAS. A low NOX4 mRNA expression is associated with an increased risk of the development of clinical symptoms. In fact, NOX4 appears to be linked to plaque stability, apoptosis and plaque hemorrhage. This is supported by cleaved caspase-3 and glycophorin C and correlates inversely with plaque NOX4 mRNA expression. Even healing of a ruptured plaque appears to be connected to NOX4, as NOX4 mRNA expression correlates to fibrous cap collagen and is reciprocally related to MMP9 activity. In conclusion, low intra-plaque NOX4 mRNA expression is associated with an increased risk for symptomatic outcome and with reduced plaque stabilizing mechanisms suggesting protective effects of NOX4 in human advanced atherosclerosis.
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Project description:BackgroundResearch has shown that carotid intima-media thickness (CIMT) could help to predict carotid plaque (CP) progression in patients with mild carotid stenosis. However, the debate continues as to the value of carotid intima thickness (CIT) in monitoring the development of CP in patients with severe carotid stenosis. This study sought to evaluate the relationships between CIT and the ultrasonic characteristics of CP and to analyze the value of CIT and the ultrasonic parameters of CP in assessing plaque vulnerability in advanced human carotid atherosclerosis.MethodsA total of 55 individuals who underwent carotid endarterectomy (CEA) were included in the study (mean age: 65±7 years; female: 9.1%). CIMT and CIT were examined at the common carotid artery (CCA). Plaque textural features, such as the gray-scale median (GSM), superb microvascular imaging (SMI) level, and total plaque area (TPA), were also identified. A Spearman correlation coefficient analysis was performed to examine the relationship between CIT and the ultrasonic parameters of CP. The CIT of various plaque types was compared. Receiver operating characteristic (ROC) curves were used to analyze the diagnostic values of the ultrasound characteristics to evaluate CP vulnerability.ResultsThe mean CIT of all the participants was 0.382±0.095 mm, the mean CIT of the participants with stable plaques was 0.328±0.031 mm, and the mean CIT of participants with vulnerable plaques was 0.424±0.106 mm (P<0.001). CIT was associated with the SMI level (Spearman's correlation coefficient: r=0.392, P=0.005), TPA (Spearman's correlation coefficient: r=0.337, P=0.012). Patients with thicker CIT had larger lipid cores, higher levels of plaque vulnerability, and more intraplaque hemorrhages (IPHs). The areas under the ROCs (AUCs) with 95% confidence interval (CI) for CIMT, CIT, the SMI level, the GSM, the TPA, and the combined model for identifying vulnerable plaques were 0.673 (0.533-0.793), 0.849 (0.727-0.932), 0.771 (0.629-0.879), 0.669 (0.529-0.790), 0.858 (0.738-0.938), and 0.949 (0.854-0.990), respectively.ConclusionsCIT was associated with both the histology and ultrasonic features of CP. CIT may be helpful in the detection of severe CP development.
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