MicroRNAs as sentinels and protagonists of carotid artery thromboembolism

2020 ◽  
Vol 134 (2) ◽  
pp. 169-192
Author(s):  
Sneha Raju ◽  
Jason E. Fish ◽  
Kathryn L. Howe
Keyword(s):  
Carotid Artery ◽  
Atherosclerotic Plaque ◽  
Carotid Plaque ◽  
Molecular Mechanisms ◽  
Clinical Decision Making ◽  
Plaque Rupture ◽  
Cell Communication ◽  
Clinical Decision ◽  
Plaque Instability

Abstract Stroke is the leading cause of serious disability in the world and a large number of ischemic strokes are due to thromboembolism from unstable carotid artery atherosclerotic plaque. As it is difficult to predict plaque rupture and surgical treatment of asymptomatic disease carries a risk of stroke, carotid disease continues to present major challenges with regard to clinical decision-making and revascularization. There is therefore an imminent need to better understand the molecular mechanisms governing plaque instability and rupture, as this would allow for the development of biomarkers to identify at-risk asymptomatic carotid plaque prior to disease progression and stroke. Further, it would aid in creation of therapeutics to stabilize carotid plaque. MicroRNAs (miRNAs) have been implicated as key protagonists in various stages of atherosclerotic plaque initiation, development and rupture. Notably, they appear to play a crucial role in carotid artery thromboembolism. As the molecular pathways governing the role of miRNAs are being uncovered, we are learning that their involvement is complex, tissue- and stage-specific, and highly selective. Notably, miRNAs can be packaged and secreted in extracellular vesicles (EVs), where they participate in cell–cell communication. The measurement of EV-encapsulated miRNAs in the circulation may inform disease mechanisms occurring in the plaque itself, and therefore may serve as sentinels of unstable plaque as well as therapeutic targets.

ILF3 Mediated BMP2 and STAT1 Transcription Is Responsible for Hyperlipidemia-Induced Arteriosclerotic Calcification

2020 ◽  
Author(s):  
Fei Xie ◽  
Zhao-yang Wang ◽  
Bin Liu ◽  
Wen Qiao ◽  
Na Li ◽  
...  
Keyword(s):  
Atherosclerotic Plaque ◽  
Molecular Mechanisms ◽  
Plaque Rupture ◽  
Bone Morphogenetic Protein 2 ◽  
Signal Transducer ◽  
Promoter Regions ◽  
Morphogenetic Protein ◽  
Binding Factor ◽  
Precise Role

Abstract Calcification is common in atherosclerotic plaque and can induce vulnerability, which further leads to myocardial infarction, plaque rupture and stroke. The mechanisms of atherosclerotic calcification are poorly characterized. Interleukin enhancer binding factor 3 (ILF3) has been identified as a novel factor affecting dyslipidemia and stroke subtypes. However, the precise role of ILF3 in atherosclerotic calcification remains unclear. Here we showed that ILF3 expression is increased in calcified human aortic vascular smooth muscle cells (HAVSMCs) and calcified atherosclerotic plaque in humans and mice. We then found that hyperlipidemia increases ILF3 expression and exacerbates calcification of VSMCs and macrophages by regulating bone morphogenetic protein 2 (BMP2) and signal transducer and activator of transcription 1 (STAT1) transcription. We further explored the molecular mechanisms of ILF3 in atherosclerotic calcification and revealed that ILF3 acts on the promoter regions of BMP2 and STAT1 and mediates BMP2 upregulation and STAT1 downregulation, which promotes atherosclerotic calcification. Our results demonstrate the effect of ILF3 in atherosclerotic calcification. Inhibition of ILF3 may be a useful therapy for preventing and even reversing atherosclerotic calcification.

scholarly journals In-depth blood proteome profiling analysis revealed distinct functional characteristics of plasma proteins between severe and non-severe COVID-19 patients

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Joonho Park ◽  
Hyeyoon Kim ◽  
So Yeon Kim ◽  
Yeonjae Kim ◽  
Jee-Soo Lee ◽  
...  
Keyword(s):  
Clinical Decision Making ◽  
Clinical Decision ◽  
Good Prognosis ◽  
Severe Illness ◽  
Proteome Profiling ◽  
T Cell Suppression ◽  
Cell Suppression ◽  
Profiling Analysis ◽  
Necrosis Factor

AbstractThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over forty million patients worldwide. Although most coronavirus disease 2019 (COVID-19) patients have a good prognosis, some develop severe illness. Markers that define disease severity or predict clinical outcome need to be urgently developed as the mortality rate in critical cases is approximately 61.5%. In the present study, we performed in-depth proteome profiling of undepleted plasma from eight COVID-19 patients. Quantitative proteomic analysis using the BoxCar method revealed that 91 out of 1222 quantified proteins were differentially expressed depending on the severity of COVID-19. Importantly, we found 76 proteins, previously not reported, which could be novel prognostic biomarker candidates. Our plasma proteome signatures captured the host response to SARS-CoV-2 infection, thereby highlighting the role of neutrophil activation, complement activation, platelet function, and T cell suppression as well as proinflammatory factors upstream and downstream of interleukin-6, interleukin-1B, and tumor necrosis factor. Consequently, this study supports the development of blood biomarkers and potential therapeutic targets to aid clinical decision-making and subsequently improve prognosis of COVID-19.

scholarly journals Role of KCa3.1 Channels in Macrophage Polarization and Its Relevance in Atherosclerotic Plaque Instability

2017 ◽  
Vol 37 (2) ◽  
pp. 226-236 ◽  
Author(s):  
Rende Xu ◽  
Chenguang Li ◽  
Yizhe Wu ◽  
Li Shen ◽  
Jianying Ma ◽  
...  
Keyword(s):  
Atherosclerotic Plaque ◽  
Macrophage Polarization ◽  
Plaque Instability

scholarly journals Clinical decision making and research in hepatocellular carcinoma: Pivotal role of imaging techniques

Hepatology ◽  
2011 ◽  
Vol 54 (6) ◽  
pp. 2238-2244 ◽  
Author(s):  
Jordi Bruix ◽  
Maria Reig ◽  
Jordi Rimola ◽  
Alejandro Forner ◽  
Marta Burrel ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Decision Making ◽  
Clinical Decision Making ◽  
Imaging Techniques ◽  
Clinical Decision ◽  
Pivotal Role

Abstract 110: Carotid Plaque Instability is Associated with an Increase in the Serum Ratio of circularRNA-284 to microRNA-221

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Hernan Bazan ◽  
Ashton Brooks ◽  
Daniel Lightell ◽  
T. Cooper Woods
Keyword(s):  
Ischemic Stroke ◽  
Sensitivity And Specificity ◽  
Carotid Plaque ◽  
Plaque Rupture ◽  
Serum Levels ◽  
Circular Rna ◽  
Cerebrovascular Event ◽  
Asymptomatic Group ◽  
Plaque Instability ◽  
Non Coding Rnas

Introduction: Atherosclerotic cap thinning and plaque instability occur as a result of a decrease in vascular smooth muscle cell proliferation, which is partly regulated by alterations in the expression of non-coding RNAs in the arterial wall. We recently reported that miR-221 expression in the carotid plaque shoulder is reduced immediately following a carotid-related ischemic cerebrovascular event and returns to normal levels after seven days. We hypothesized that changes in the expression of non-coding RNAs within carotid plaques are reflected in the serum of asymptomatic and acutely symptomatic patients with carotid disease. Methods: Serum levels of microRNA (miR) -221 and a circular RNA with potential binding sites for miR-221 (circR-284), were measured using real-time polymerase chain reaction in 41 patients undergoing carotid endarterectomy. Patients were grouped into those who were asymptomatic and those with an acute ischemic cerebrovascular event within the previous 5 days (urgent). Results: miR-221 was significantly lower (0.25 ± 0.11 vs. 1.00 ± 0.31, p = 0.01) while circR-284 was significantly elevated (2.96 ± 1.16 vs. 1.00 ± 0.37, p = 0.06) in the serum of the urgent compared to the asymptomatic group. Serum levels of these RNAs alone did not exhibit favorable sensitivity and specificity for use as a biomarker indicative of carotid-related ischemic stroke. The ratio of serum circR-284:miR-221, however, was significantly elevated in the urgent group [11.7 ± 0.48 vs. 1.0 ± 0.6, p = 0.0002 (Figure, A)]. Furthermore, receiver operator curve analysis of circR-284:miR-221 ratio demonstrated favorable sensitivity and specificity (Figure, B) for detecting carotid plaque rupture and ischemic stroke. Conclusions: Increases in the ratio of serum circR-284:miR-221 has potential as a diagnostic biomarker of carotid-related ischemic stroke. This data also supports the use and development of functionally related pairs of circulating non-coding RNAs as biomarkers.

Differentiation of Vulnerable Carotid Plaques by Analysis of Calcium Content and Spectral Curve Slope using Gemstone Spectral Imaging

2021 ◽  
Author(s):  
Ze-Xin Fan ◽  
Xiao-Qing Li ◽  
Ting-Ting Yang ◽  
Shao-Jie Yuan ◽  
Tian-Tong Niu ◽  
...  
Keyword(s):  
Atherosclerotic Plaque ◽  
Carotid Plaque ◽  
Spectral Curve ◽  
Plaque Rupture ◽  
Spectral Imaging ◽  
Calcium Content ◽  
Carotid Atherosclerotic Plaque ◽  
Close Link ◽  
Gemstone Spectral Imaging ◽  
Hs Crp

Abstract Growing evidence indicates that vulnerable carotid plaque rupture is an important cause of stroke. However, fewer studies have been conducted to investigate the role of a novel gemstone spectral imaging (GSI) in assessment of vulnerable carotid plaque. In this study, we analyzed GSI data including calcium content of carotid atherosclerotic plaque and spectral curve slope, as well as serum high-sensitivity C-reactive protein (Hs-CRP), monocyte chemotactic protein-1 (MCP-1) levels in patients with carotid atherosclerotic plaque using the GSI-computed tomographic angiography (CTA) and immunoturbidimetry. The patients with unstable plaques demonstrated a significantly lower calcium content and higher spectral curve slope than the stable plaques group. In addition, the patients with unstable plaque showed an increase in Hs-CRP levels and MCP-1 levels compared with the stable plaque and normal controls (NC) group. The alternation in GSI calcium content and spectral curve slope reflects a close link between calcification and plaque instability, while derangement of Hs-CRP and MCP-1 is involved in the formation or development of vulnerable plaques. Taken together, our results strongly support the feasibility of using these serological and newly discovered imaging parameters as multiple potential biomarkers relevant to plaque vulnerability or stroke progression.

Practice Guidelines for the Diagnosis of COVID-19-Associated Pulmonary Aspergillosis in an Intensive Care Setting

2021 ◽  
pp. 088506662110471
Author(s):  
Zia Hashim ◽  
Zafar Neyaz ◽  
Rungmei S.K. Marak ◽  
Alok Nath ◽  
Soniya Nityanand ◽  
...  
Keyword(s):  
Intensive Care ◽  
Practice Guidelines ◽  
Clinical Management ◽  
Care Setting ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Third Wave ◽  
Intensive Care Setting ◽  
Pulmonary Aspergillosis

Coronavirus disease-2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) is a new disease characterized by secondary Aspergillus mold infection in patients with COVID-19. It primarily affects patients with COVID-19 in critical state with acute respiratory distress syndrome, requiring intensive care and mechanical ventilation. CAPA has a higher mortality rate than COVID-19, posing a serious threat to affected individuals. COVID-19 is a potential risk factor for CAPA and has already claimed a massive death toll worldwide since its outbreak in December 2019. Its second wave is currently progressing towards a peak, while the third wave of this devastating pandemic is expected to follow. Therefore, an early and accurate diagnosis of CAPA is of utmost importance for effective clinical management of this highly fatal disease. However, there are no uniform criteria for diagnosing CAPA in an intensive care setting. Therefore, based on a review of existing information and our own experience, we have proposed new criteria in the form of practice guidelines for diagnosing CAPA, focusing on the points relevant for intensivists and pulmonary and critical care physicians. The main highlights of these guidelines include the role of CAPA-appropriate test specimens, clinical risk factors, computed tomography of the thorax, and non-culture-based indirect and direct mycological evidence for diagnosing CAPA in the intensive care unit. These guidelines classify the diagnosis of CAPA into suspected, possible, and probable categories to facilitate clinical decision-making. We hope that these practice guidelines will adequately address the diagnostic challenges of CAPA, providing an easy-to-use and practical algorithm to clinicians for rapid diagnosis and clinical management of the disease.

scholarly journals Single-Cell Transcriptomic Analysis Revealed a Critical Role of SPP1/CD44-Mediated Crosstalk Between Macrophages and Cancer Cells in Glioma

2021 ◽  
Vol 9 ◽  
Author(s):  
Cong He ◽  
Luoyan Sheng ◽  
Deshen Pan ◽  
Shuai Jiang ◽  
Li Ding ◽  
...  
Keyword(s):  
Single Cell ◽  
Tumor Heterogeneity ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Cell Communication ◽  
High Grade Glioma ◽  
Sequencing Analysis ◽  
High Grade ◽  
Cellular Components

High-grade glioma is one of the most lethal human cancers characterized by extensive tumor heterogeneity. In order to identify cellular and molecular mechanisms that drive tumor heterogeneity of this lethal disease, we performed single-cell RNA sequencing analysis of one high-grade glioma. Accordingly, we analyzed the individual cellular components in the ecosystem of this tumor. We found that tumor-associated macrophages are predominant in the immune microenvironment. Furthermore, we identified five distinct subpopulations of tumor cells, including one cycling, two OPC/NPC-like and two MES-like cell subpopulations. Moreover, we revealed the evolutionary transition from the cycling to OPC/NPC-like and MES-like cells by trajectory analysis. Importantly, we found that SPP1/CD44 interaction plays a critical role in macrophage-mediated activation of MES-like cells by exploring the cell-cell communication among all cellular components in the tumor ecosystem. Finally, we showed that high expression levels of both SPP1 and CD44 correlate with an increased infiltration of macrophages and poor prognosis of glioma patients. Taken together, this study provided a single-cell atlas of one high-grade glioma and revealed a critical role of macrophage-mediated SPP1/CD44 signaling in glioma progression, indicating that the SPP1/CD44 axis is a potential target for glioma treatment.

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