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Journal of the American College of... Sep 2021Plaque erosion, a distinct histopathological and clinical entity, accounts for over 30% of acute coronary syndromes (ACS). Optical coherence tomography allows in vivo... (Review)
Review
Plaque erosion, a distinct histopathological and clinical entity, accounts for over 30% of acute coronary syndromes (ACS). Optical coherence tomography allows in vivo diagnosis of plaque erosion. Local flow perturbation with activation of Toll-like receptor 2 and CD8 T cells and subsequent desquamation of endothelium and neutrophil extracellular trap formation contribute to mechanisms of plaque erosion. Compared with ACS patients with plaque rupture, those with plaque erosion are younger, have fewer traditional cardiovascular risk factors, have lower plaque burden, and are more likely to present with non-ST-segment elevation ACS. Early evidence suggests that in patients with ACS caused by plaque erosion, antithrombotic therapy without stenting may be a safe and effective option. Future randomized trials are needed to validate these findings. Clinical studies to develop noninvasive point-of-care biomarkers that distinguish plaque rupture from erosion, and to test novel therapies that target molecular pathways involved in plaque erosion are needed.
Topics: Acute Coronary Syndrome; Cardiac Imaging Techniques; Coronary Vessels; Humans; Plaque, Atherosclerotic; Tomography, Optical Coherence
PubMed: 34531028
DOI: 10.1016/j.jacc.2021.07.030 -
European Journal of Echocardiography :... Apr 2011This manuscript reviews the use of serial intravascular ultrasound (IVUS) examination of coronary atherosclerosis in recent observational studies and randomized trials... (Review)
Review
This manuscript reviews the use of serial intravascular ultrasound (IVUS) examination of coronary atherosclerosis in recent observational studies and randomized trials that revealed the effects of cholesterol-lowering and lipid-modifying therapies and offered novel insight into plaque progression and regression. We discuss the value of plaque progression-regression as complementary imaging endpoint and potential surrogate marker of cardiovascular event risk. In addition, the progress in serial assessment of coronary plaque composition and plaque vulnerability by radiofrequency-based analyses is reviewed. Finally, we report on the evaluation of true vessel remodelling in recent serial IVUS trials and discuss the future perspective of serial invasive imaging of coronary atherosclerosis.
Topics: Anticholesteremic Agents; Clinical Trials as Topic; Coronary Artery Disease; Disease Progression; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Plaque, Atherosclerotic; Risk Assessment; Ultrasonography, Interventional
PubMed: 21421584
DOI: 10.1093/ejechocard/jer017 -
Biomechanics and Modeling in... Jun 2021Atherosclerosis is initiated by endothelial injury that is related to abnormal values of hemodynamic parameters such as wall shear stress (WSS), oscillatory shear index...
Atherosclerosis is initiated by endothelial injury that is related to abnormal values of hemodynamic parameters such as wall shear stress (WSS), oscillatory shear index (OSI) and stress phase angle (SPA), which are more common in arterial bifurcations due to the complex structure. An experimental model of human carotid bifurcation with accurate geometrical and mechanical features was set up, and using realistic pulsatile flow rates, the inlet and outlet pressure pulses were measured for normal and stenosed models with 40% and 80% severities at common carotid (CCA), internal carotid (ICA) and external carotid (ECA) arteries. Based on the obtained experimental data, fluid-structure models were developed to obtain WSS, OSI, and SPA and evaluate pathological consequences at different locations. Mild severity had minor impact, however, inducing severe 80% stenosis in each branch led to considerable localized changes of hemodynamic parameters both in the stenosis site and other locations. This included sharp increases in WSS values accompanied by very low values close to zero before and after the peaks. Severe stenosis not only caused significant changes in the local artery, but also in other branches. OSI and SPA were less sensitive to stenosis, although high peaks were observed on bifurcation site for the stenosis at ECA. The interconnection of arteries at carotid bifurcation results in altered pressure/flow patterns in all branches when a stenosis is applied in any site. Such effect confirms pathological findings that atherosclerotic plaques are observed simultaneously in different carotid branches, although with different degrees of plaque growth and severity.
Topics: Biomechanical Phenomena; Carotid Arteries; Computer Simulation; Hemodynamics; Hemorheology; Humans; Models, Cardiovascular; Plaque, Atherosclerotic; Pressure; Shear Strength; Stress, Mechanical; Time Factors
PubMed: 33609192
DOI: 10.1007/s10237-021-01431-x -
Journal of Visualized Experiments : JoVE Nov 2022The rupture of atherosclerotic plaques in coronary and carotid arteries is the primary cause of fatal cardiovascular events. However, the rupture mechanics of the...
The rupture of atherosclerotic plaques in coronary and carotid arteries is the primary cause of fatal cardiovascular events. However, the rupture mechanics of the heterogeneous, highly collagenous plaque tissue, and how this is related to the tissue's fibrous structure, are not known yet. Existing pipelines to study plaque mechanics are limited to obtaining only gross mechanical characteristics of the plaque tissue, based on the assumption of structural homogeneity of the tissue. However, fibrous plaque tissue is structurally heterogeneous, arguably mainly due to local variation in the collagen fiber architecture. The mechano-imaging pipeline described here has been developed to study the heterogeneous structural and mechanical plaque properties. In this pipeline, the tissue's local collagen architecture is characterized using multiphoton microscopy (MPM) with second-harmonic generation (SHG), and the tissue's failure behavior is characterized under uniaxial tensile testing conditions using digital image correlation (DIC) analysis. This experimental pipeline enables correlation of the local predominant angle and dispersion of collagen fiber orientation, the rupture behavior, and the strain fingerprints of the fibrous plaque tissue. The obtained knowledge is key to better understand, predict, and prevent atherosclerotic plaque rupture events.
Topics: Humans; Plaque, Atherosclerotic; Carotid Arteries; Collagen; Fibrosis; Microscopy
PubMed: 36440849
DOI: 10.3791/64334 -
Journal of Structural Biology Apr 2011Several studies have suggested that evolving mechanical stresses and strains drive atherosclerotic plaque development and vulnerability. Especially, stress distribution...
Several studies have suggested that evolving mechanical stresses and strains drive atherosclerotic plaque development and vulnerability. Especially, stress distribution in the plaque fibrous capsule is an important determinant for the risk of vulnerable plaque rupture. Knowledge of the stiffness of atherosclerotic plaque components is therefore of critical importance. In this work, force mapping experiments using atomic force microscopy (AFM) were conducted in apolipoprotein E-deficient (ApoE(-/-)) mouse, which represents the most widely used experimental model for studying mechanisms underlying the development of atherosclerotic lesions. To obtain the elastic material properties of fibrous caps and lipidic cores of atherosclerotic plaques, serial cross-sections of aortic arch lesions were probed at different sites. Atherosclerotic plaque sub-structures were subdivided into cellular fibrotic, hypocellular fibrotic and lipidic rich areas according to histological staining. Hertz's contact mechanics were used to determine elasticity (Young's) moduli that were related to the underlying histological plaque structure. Cellular fibrotic regions exhibit a mean Young modulus of 10.4±5.7kPa. Hypocellular fibrous caps were almost six-times stiffer, with average modulus value of 59.4±47.4kPa, locally rising up to ∼250kPa. Lipid rich areas exhibit a rather large range of Young's moduli, with average value of 5.5±3.5kPa. Such precise quantification of plaque stiffness heterogeneity will allow investigators to have prospectively a better monitoring of atherosclerotic disease evolution, including arterial wall remodeling and plaque rupture, in response to mechanical constraints imposed by vascular shear stress and blood pressure.
Topics: Animals; Apolipoproteins E; Elastic Modulus; Female; In Vitro Techniques; Mice; Mice, Mutant Strains; Microscopy, Atomic Force; Plaque, Atherosclerotic
PubMed: 21296163
DOI: 10.1016/j.jsb.2011.01.010 -
The American Journal of Pathology Apr 2024Atherosclerosis is a chronic inflammatory disease of the arterial wall, characterized by the buildup of plaques with the accumulation and transformation of lipids,... (Review)
Review
Atherosclerosis is a chronic inflammatory disease of the arterial wall, characterized by the buildup of plaques with the accumulation and transformation of lipids, immune cells, vascular smooth muscle cells, and necrotic cell debris. Plaques with collagen-poor thin fibrous caps infiltrated by macrophages and lymphocytes are considered unstable because they are at the greatest risk of rupture and clinical events. However, the current histologic definition of plaque types may not fully capture the complex molecular nature of atherosclerotic plaque biology and the underlying mechanisms contributing to plaque progression, rupture, and erosion. The advances in omics technologies have changed the understanding of atherosclerosis plaque biology, offering new possibilities to improve risk prediction and discover novel therapeutic targets. Genomic studies have shed light on the genetic predisposition to atherosclerosis, and integrative genomic analyses expedite the translation of genomic discoveries. Transcriptomic, proteomic, metabolomic, and lipidomic studies have refined the understanding of the molecular signature of atherosclerotic plaques, aiding in data-driven hypothesis generation for mechanistic studies and offering new prospects for biomarker discovery. Furthermore, advancements in single-cell technologies and emerging spatial analysis techniques have unveiled the heterogeneity and plasticity of plaque cells. This review discusses key omics-based discoveries that have advanced the understanding of human atherosclerotic plaque biology, focusing on insights derived from omics profiling of human atherosclerotic vascular specimens.
Topics: Humans; Plaque, Atherosclerotic; Proteomics; Atherosclerosis; Macrophages; Extracellular Matrix
PubMed: 38280419
DOI: 10.1016/j.ajpath.2023.12.007 -
BMC Medical Genomics May 2022The clinical consequences of atherosclerosis are significant source of morbidity and mortality throughout the world, while the molecular mechanisms of the pathogenesis...
Integrated investigation of DNA methylation, gene expression and immune cell population revealed immune cell infiltration associated with atherosclerotic plaque formation.
BACKGROUND
The clinical consequences of atherosclerosis are significant source of morbidity and mortality throughout the world, while the molecular mechanisms of the pathogenesis of atherosclerosis are largely unknown.
METHODS
In this study, we integrated the DNA methylation and gene expression data in atherosclerotic plaque samples to decipher the underlying association between epigenetic and transcriptional regulation. Immune cell classification was performed on the basis of the expression pattern of detected genes. Finally, we selected ten genes with dysregulated methylation and expression levels for RT-qPCR validation.
RESULTS
Global DNA methylation profile showed obvious changes between normal aortic and atherosclerotic lesion tissues. We found that differentially methylated genes (DMGs) and differentially expressed genes (DEGs) were highly associated with atherosclerosis by being enriched in atherosclerotic plaque formation-related pathways, including cell adhesion and extracellular matrix organization. Immune cell fraction analysis revealed that a large number of immune cells, especially macrophages, activated mast cells, NK cells, and Tfh cells, were specifically enriched in the plaque. DEGs associated with immune cell fraction change showed that they were mainly related to the level of macrophages, monocytes, resting NK cells, activated CD4 memory T cells, and gamma delta T cells. These genes were highly enriched in multiple pathways of atherosclerotic plaque formation, including blood vessel remodeling, collagen fiber organization, cell adhesion, collagen catalogic process, extractable matrix assembly, and platelet activation. We also validated the expression alteration of ten genes associated with infiltrating immune cells in atherosclerosis.
CONCLUSIONS
In conclusion, these findings provide new evidence for understanding the mechanisms of atherosclerotic plaque formation, and provide a new and valuable research direction based on immune cell infiltration.
Topics: Atherosclerosis; DNA Methylation; Gene Expression; Humans; Macrophages; Plaque, Atherosclerotic
PubMed: 35534881
DOI: 10.1186/s12920-022-01259-z -
The Biochemical Journal May 2016The formation of atherosclerotic plaques in the large and medium sized arteries is classically driven by systemic factors, such as elevated cholesterol and blood... (Review)
Review
The formation of atherosclerotic plaques in the large and medium sized arteries is classically driven by systemic factors, such as elevated cholesterol and blood pressure. However, work over the past several decades has established that atherosclerotic plaque development involves a complex coordination of both systemic and local cues that ultimately determine where plaques form and how plaques progress. Although current therapeutics for atherosclerotic cardiovascular disease primarily target the systemic risk factors, a large array of studies suggest that the local microenvironment, including arterial mechanics, matrix remodelling and lipid deposition, plays a vital role in regulating the local susceptibility to plaque development through the regulation of vascular cell function. Additionally, these microenvironmental stimuli are capable of tuning other aspects of the microenvironment through collective adaptation. In this review, we will discuss the components of the arterial microenvironment, how these components cross-talk to shape the local microenvironment, and the effect of microenvironmental stimuli on vascular cell function during atherosclerotic plaque formation.
Topics: Animals; Atherosclerosis; Endothelium, Vascular; Humans; Models, Biological; Plaque, Atherosclerotic; Risk Factors
PubMed: 27208212
DOI: 10.1042/BJ20150844 -
European Heart Journal. Cardiovascular... Nov 2014Atherosclerosis is an inflammatory disorder that can evolve into an acute clinical event by plaque development, rupture, and thrombosis. Plaque vulnerability represents... (Review)
Review
Atherosclerosis is an inflammatory disorder that can evolve into an acute clinical event by plaque development, rupture, and thrombosis. Plaque vulnerability represents the susceptibility of a plaque to rupture and to result in an acute cardiovascular event. Nevertheless, plaque vulnerability is not an established medical diagnosis, but rather an evolving concept that has gained attention to improve risk prediction. The availability of high-resolution imaging modalities has significantly facilitated the possibility of performing in vivo regression studies and documenting serial changes in plaque stability. This review summarizes the currently available non-invasive methods to identify vulnerable plaques and to evaluate the effects of the current cardiovascular treatments on plaque evolution.
Topics: Coronary Artery Disease; Diagnostic Imaging; Humans; Plaque, Atherosclerotic; Risk Assessment
PubMed: 24876097
DOI: 10.1093/ehjci/jeu097 -
Journal of Atherosclerosis and... 2015Atherosclerosis is a progressive disease characterized by the accumulation of lipids in medium to large sized arteries. Atherothrombosis is a term used to describe... (Review)
Review
Atherosclerosis is a progressive disease characterized by the accumulation of lipids in medium to large sized arteries. Atherothrombosis is a term used to describe formation of a thrombus after rupture of an atherosclerotic plaque. Thrombosis can lead to myocardial infarction and stroke. Risk factors for atherosclerosis include hyperlipidemia, diabetes, smoking and hypertension all of which increase tissue factor (TF) expression. High levels of TF are present in atherosclerotic plaques due to expression by macrophages and vascular smooth muscle cells and the presence of cell-derived TF-positive microvesicles (MVs). In addition, hyperlipidemia leads to the formation of oxidized LDL, which induces TF expression in circulating monocytes and the release of TF-positive MVs. The major source of TF that drives thrombosis after plaque rupture is TF within the plaque. However, TF in the blood on monocytes and MVs may also contribute the thrombosis. Inhibition of the TF/factor VIIa complex is unlikely to be an effective strategy to reduce atherothrombosis due the essential role of the complex in hemostasis. However, selective blockade of pathologic TF without affecting protective TF may be effective in reducing atherothrombosis. For instance, statins have been shown to reduce TF expression in the plaque and in circulating monocytes, which would be expected to reduce thrombosis. Further studies are needed to determine safe strategies to reduce pathologic TF expression and atherothrombosis.
Topics: Animals; Humans; Plaque, Atherosclerotic; Thromboplastin; Thrombosis
PubMed: 26016513
DOI: 10.5551/jat.30940