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International Journal of Molecular... Mar 2021Atherosclerotic plaque is the pathophysiological basis of important and life-threatening diseases such as myocardial infarction. Although key aspects of the process of... (Review)
Review
Atherosclerotic plaque is the pathophysiological basis of important and life-threatening diseases such as myocardial infarction. Although key aspects of the process of atherosclerotic plaque development and progression such as local inflammation, LDL oxidation, macrophage activation, and necrotic core formation have already been discovered, many molecular mechanisms affecting this process are still to be revealed. This minireview aims to describe the current directions in research on atherogenesis and to summarize selected studies published in recent years-in particular, studies on novel cellular pathways, epigenetic regulations, the influence of hemodynamic parameters, as well as tissue and microorganism (microbiome) influence on atherosclerotic plaque development. Finally, some new and interesting ideas are proposed (immune cellular heterogeneity, non-coding RNAs, and immunometabolism) which will hopefully bring new discoveries in this area of investigation.
Topics: Animals; Atherosclerosis; Epigenesis, Genetic; Humans; Inflammation; Lipoproteins, LDL; Macrophage Activation; Plaque, Atherosclerotic
PubMed: 33805303
DOI: 10.3390/ijms22073513 -
Current Atherosclerosis Reports Oct 2020Inflammatory cytokines play a major role in atherosclerotic plaque progression. This review summarizes the rationale for personalized anti-inflammatory therapy. (Review)
Review
PURPOSE OF THE REVIEW
Inflammatory cytokines play a major role in atherosclerotic plaque progression. This review summarizes the rationale for personalized anti-inflammatory therapy.
RECENT FINDINGS
Systemic inflammatory parameters may be used to follow the clinical outcome in primary and secondary prevention. Medical therapy, both in patients with stable cardiovascular disease, or with acute events, may be tailored taking into consideration the level and course of systemic inflammatory mediators. There is significant space for improvement in primary prevention and in the treatment of patients who have suffered from severe cardiovascular events, paying attention to not only blood pressure and cholesterol levels but also including inflammatory parameters in our clinical analysis. The potential exists to alter the course of atherosclerosis with anti-inflammatory drugs. With increased understanding of the specific mechanisms that regulate the relationship between inflammation and atherosclerosis, new, more effective and specific anti-inflammatory treatment may become available.
Topics: Animals; Anti-Inflammatory Agents; Atherosclerosis; Cytokines; Disease Progression; Humans; Inflammation; Inflammation Mediators; Mice; Plaque, Atherosclerotic; Secondary Prevention; Treatment Outcome
PubMed: 33025148
DOI: 10.1007/s11883-020-00891-3 -
Redox Biology Aug 2017Atherosclerosis is a multifocal alteration of the vascular wall of medium and large arteries characterized by a local accumulation of cholesterol and non-resolving... (Review)
Review
Atherosclerosis is a multifocal alteration of the vascular wall of medium and large arteries characterized by a local accumulation of cholesterol and non-resolving inflammation. Atherothrombotic complications are the leading cause of disability and mortality in western countries. Neovascularization in atherosclerotic lesions plays a major role in plaque growth and instability. The angiogenic process is mediated by classical angiogenic factors and by additional factors specific to atherosclerotic angiogenesis. In addition to its role in plaque progression, neovascularization may take part in plaque destabilization and thromboembolic events. Anti-angiogenic agents are effective to reduce atherosclerosis progression in various animal models. However, clinical trials with anti-angiogenic drugs, mainly anti-VEGF/VEGFR, used in anti-cancer therapy show cardiovascular adverse effects, and require additional investigations.
Topics: Angiogenesis Inhibitors; Animals; Clinical Trials as Topic; Disease Progression; Humans; Neovascularization, Pathologic; Oxidative Stress; Plaque, Atherosclerotic
PubMed: 28212521
DOI: 10.1016/j.redox.2017.01.007 -
Annals of Biomedical Engineering Feb 2014Coronary atheroma develop in local sites that are widely variable among patients and are considerably variable in their vulnerability for rupture. This article... (Review)
Review
Coronary atheroma develop in local sites that are widely variable among patients and are considerably variable in their vulnerability for rupture. This article summarizes studies conducted by our collaborative laboratories on predictive biomechanical modeling of coronary plaques. It aims to give insights into the role of biomechanics in the development and localization of atherosclerosis, the morphologic features that determine vulnerable plaque stability, and emerging in vivo imaging techniques that may detect and characterize vulnerable plaque. Composite biomechanical and hemodynamic factors that influence the actual site of development of plaques have been studied. Plaque vulnerability, in vivo, is more challenging to assess. Important steps have been made in defining the biomechanical factors that are predictive of plaque rupture and the likelihood of this occurring if characteristic features are known. A critical key in defining plaque vulnerability is the accurate quantification of both the morphology and the mechanical properties of the diseased arteries. Recently, an early IVUS based palpography technique developed to assess local strain, elasticity and mechanical instabilities has been successfully revisited and improved to account for complex plaque geometries. This is based on an initial best estimation of the plaque components' contours, allowing subsequent iteration for elastic modulus assessment as a basis for plaque stability determination. The improved method has also been preliminarily evaluated in patients with successful histologic correlation. Further clinical evaluation and refinement are on the horizon.
Topics: Biomechanical Phenomena; Coronary Artery Disease; Elasticity; Hemodynamics; Humans; Models, Cardiovascular; Plaque, Atherosclerotic
PubMed: 24043605
DOI: 10.1007/s10439-013-0888-1 -
Theranostics 2024Smooth muscle cell (SMC) remodeling poses a critical feature in the development and progression of atherosclerosis. Although fate mapping and in silicon approaches have...
Smooth muscle cell (SMC) remodeling poses a critical feature in the development and progression of atherosclerosis. Although fate mapping and in silicon approaches have expanded SMC phenotypes in atherosclerosis, it still remains elusive about the contributions of individual SMC phenotypes and molecular dynamics to advanced atherosclerotic plaque. Using single-cell transcriptome, we investigated cellular compositions of human carotid plaque laden with atherosclerotic core, followed by in vivo experiments utilizing SMC-lineage tracing technology, bulk RNA sequencing (RNA-seq) and both in vivo and in vitro validation of the underlying molecular mechanism. 5 functionally distinct SMC subtypes were uncovered based on transcriptional features (described as contractile, fibroblast-like, osteogenic, synthetic and macrophage-like) within the niche. A proinflammatory, macrophage-like SMC subtype displaying an intermediary phenotype between SMC and macrophage, exhibits prominent potential in destabilizing plaque. At the molecular level, we explored cluster-specific master regulons by algorithm, and identified interferon regulatory factor-8 (IRF8) as a potential stimulator of SMC-to-macrophage transdifferentiation via activating nuclear factor-κB (NF-κB) signaling. Our study illustrates a comprehensive cell atlas and molecular landscape of advanced atherosclerotic lesion, which might renovate current understanding of SMC biology in atherosclerosis.
Topics: Humans; Plaque, Atherosclerotic; Atherosclerosis; Gene Expression Profiling; Myocytes, Smooth Muscle; Macrophages
PubMed: 38389849
DOI: 10.7150/thno.87201 -
Journal of Internal Medicine Nov 2015Atherosclerosis is a maladaptive, nonresolving chronic inflammatory disease that occurs at sites of blood flow disturbance. The disease usually remains silent until a... (Review)
Review
Atherosclerosis is a maladaptive, nonresolving chronic inflammatory disease that occurs at sites of blood flow disturbance. The disease usually remains silent until a breakdown of integrity at the arterial surface triggers the formation of a thrombus. By occluding the lumen, the thrombus or emboli detaching from it elicits ischaemic symptoms that may be life-threatening. Two types of surface damage can cause atherothrombosis: plaque rupture and endothelial erosion. Plaque rupture is thought to be caused by loss of mechanical stability, often due to reduced tensile strength of the collagen cap surrounding the plaque. Therefore, plaques with reduced collagen content are thought to be more vulnerable than those with a thick collagen cap. Endothelial erosion, on the other hand, may occur after injurious insults to the endothelium instigated by metabolic disturbance or immune insults. This review discusses the molecular mechanisms involved in plaque vulnerability and the development of atherothrombosis.
Topics: Animals; Cysteine Proteases; Endothelium, Vascular; Humans; Inflammation; Matrix Metalloproteinases; Plaque, Atherosclerotic; Rupture, Spontaneous; Thromboembolism
PubMed: 26260307
DOI: 10.1111/joim.12406 -
Biomedical Papers of the Medical... Mar 2018Atherosclerosis is the most common cause of both carotid and coronary steno-occlusive disease. Rupture of an atherosclerotic plaque may lead to the formation of an... (Review)
Review
Atherosclerosis is the most common cause of both carotid and coronary steno-occlusive disease. Rupture of an atherosclerotic plaque may lead to the formation of an overlying thrombosis resulting in complete arterial occlusion or downstream embolism. Clinically, this may manifest as a stroke or acute myocardial infarction, the overall leading causes of mortality and disability in developed countries. In this article, we summarize current concepts of the development of vulnerable plaque and provide an overview of commonly used imaging methods that may suggest/indicate atherosclerotic plaque vulnerability.
Topics: Atherosclerosis; Carotid Arteries; Coronary Angiography; Disease Progression; Embolism; Humans; Myocardial Infarction; Plaque, Atherosclerotic; Stroke
PubMed: 29467545
DOI: 10.5507/bp.2018.004 -
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 -
ACS Nano Jul 2023Atherosclerosis is a complex disease that can lead to life-threatening events, such as myocardial infarction and ischemic stroke. Despite the severity of this disease,...
Atherosclerosis is a complex disease that can lead to life-threatening events, such as myocardial infarction and ischemic stroke. Despite the severity of this disease, diagnosing plaque vulnerability remains challenging due to the lack of effective diagnostic tools. Conventional diagnostic protocols lack specificity and fail to predict the type of atherosclerotic lesion and the risk of plaque rupture. To address this issue, technologies are emerging, such as noninvasive medical imaging of atherosclerotic plaque with customized nanotechnological solutions. Modulating the biological interactions and contrast of nanoparticles in various imaging techniques, including magnetic resonance imaging, is possible through the careful design of their physicochemical properties. However, few examples of comparative studies between nanoparticles targeting different hallmarks of atherosclerosis exist to provide information about the plaque development stage. Our work demonstrates that Gd (III)-doped amorphous calcium carbonate nanoparticles are an effective tool for these comparative studies due to their high magnetic resonance contrast and physicochemical properties. In an animal model of atherosclerosis, we compare the imaging performance of three types of nanoparticles: bare amorphous calcium carbonate and those functionalized with the ligands alendronate (for microcalcification targeting) and trimannose (for inflammation targeting). Our study provides useful insights into ligand-mediated targeted imaging of atherosclerosis through a combination of imaging, tissue analysis, and targeting experiments.
Topics: Animals; Plaque, Atherosclerotic; Atherosclerosis; Magnetic Resonance Imaging; Nanoparticles
PubMed: 37399106
DOI: 10.1021/acsnano.3c03523 -
Scientific Reports Dec 2020Complications of atherosclerosis are the leading cause of morbidity and mortality worldwide. Various genetically modified mouse models are used to investigate disease...
Complications of atherosclerosis are the leading cause of morbidity and mortality worldwide. Various genetically modified mouse models are used to investigate disease trajectory with classical histology, currently the preferred methodology to elucidate plaque composition. Here, we show the strength of light-sheet fluorescence microscopy combined with deep learning image analysis for characterising and quantifying plaque burden and composition in whole aorta specimens. 3D imaging is a non-destructive method that requires minimal ex vivo handling and can be up-scaled to large sample sizes. Combined with deep learning, atherosclerotic plaque in mice can be identified without any ex vivo staining due to the autofluorescent nature of the tissue. The aorta and its branches can subsequently be segmented to determine how anatomical position affects plaque composition and progression. Here, we find the highest plaque accumulation in the aortic arch and brachiocephalic artery. Simultaneously, aortas can be stained for markers of interest (for example the pan immune cell marker CD45) and quantified. In ApoE-/- mice we observe that levels of CD45 reach a plateau after which increases in plaque volume no longer correlate to immune cell infiltration. All underlying code is made publicly available to ease adaption of the method.
Topics: Animals; Aorta; Aortic Diseases; Apolipoproteins E; Atherosclerosis; Deep Learning; Disease Models, Animal; Female; Image Processing, Computer-Assisted; Imaging, Three-Dimensional; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Microscopy, Fluorescence; Plaque, Atherosclerotic; Receptors, LDL
PubMed: 33299076
DOI: 10.1038/s41598-020-78632-4