-
Arteriosclerosis, Thrombosis, and... Mar 2022The development of innovative single-cell technologies has allowed the high-dimensional transcriptomic and proteomic profiling of individual blood and tissue cells.... (Review)
Review
The development of innovative single-cell technologies has allowed the high-dimensional transcriptomic and proteomic profiling of individual blood and tissue cells. Recent single-cell studies revealed a new cellular heterogeneity of atherosclerotic plaque tissue and allowed a better understanding of distinct immune functional states in the context of atherosclerosis. In this brief review, we describe how single-cell technologies have shed a new light on the cellular composition of atherosclerotic plaques, and their response to diet perturbations or genetic manipulation in mouse models of atherosclerosis. We discuss how single-cell RNA sequencing, cellular indexing of transcriptomes and epitopes by sequencing, transposase-accessible chromatin with high-throughput sequencing, and cytometry by time-of-flight platforms have empowered the identification of discrete immune, endothelial, and smooth muscle cell alterations in atherosclerosis progression and regression. Finally, we review how single-cell approaches have allowed mapping the cellular and molecular composition of human atherosclerotic plaques and the discovery of new immune alterations in plaques from patients with stroke.
Topics: Animals; Atherosclerosis; Disease Models, Animal; Disease Progression; Gene Expression Profiling; Humans; Mice; Mice, Transgenic; Plaque, Atherosclerotic; Precision Medicine; RNA-Seq; Single-Cell Analysis
PubMed: 35109673
DOI: 10.1161/ATVBAHA.121.315849 -
Vascular Health and Risk Management 2015Identifying the mechanisms that convert a healthy vascular wall to an atherosclerotic wall is of major importance since the consequences may lead to a shortened... (Review)
Review
Identifying the mechanisms that convert a healthy vascular wall to an atherosclerotic wall is of major importance since the consequences may lead to a shortened lifespan. Classical risk factors (age, smoking, obesity, diabetes mellitus, hypertension, and dyslipidemia) may result in the progression of atherosclerotic lesions by processes including inflammation and lipid accumulation. Thus, the evaluation of blood lipids and the full lipid complement produced by cells, organisms, or tissues (lipidomics) is an issue of importance. In this review, we shall describe the recent progress in vascular health research using lipidomic advances. We will begin with an overview of vascular wall biology and lipids, followed by a short analysis of lipidomics. Finally, we shall focus on the clinical implications of lipidomics and studies that have examined lipidomic approaches and vascular health.
Topics: Atherosclerosis; Biomarkers; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipid Metabolism; Lipids; Lipoproteins; Plaque, Atherosclerotic; Risk Factors
PubMed: 26109865
DOI: 10.2147/VHRM.S54874 -
The Journal of Clinical Investigation Jul 2018Non-resolving inflammation drives the development of clinically dangerous atherosclerotic lesions by promoting sustained plaque inflammation, large necrotic cores, thin... (Review)
Review
Non-resolving inflammation drives the development of clinically dangerous atherosclerotic lesions by promoting sustained plaque inflammation, large necrotic cores, thin fibrous caps, and thrombosis. Resolution of inflammation is not merely a passive return to homeostasis, but rather an active process mediated by specific molecules, including fatty acid-derived specialized pro-resolving mediators (SPMs). In advanced atherosclerosis, there is an imbalance between levels of SPMs and proinflammatory lipid mediators, which results in sustained leukocyte influx into lesions, inflammatory macrophage polarization, and impaired efferocytosis. In animal models of advanced atherosclerosis, restoration of SPMs limits plaque progression by suppressing inflammation, enhancing efferocytosis, and promoting an increase in collagen cap thickness. This Review discusses the roles of non-resolving inflammation in atherosclerosis and highlights the unique therapeutic potential of SPMs in blocking the progression of clinically dangerous plaques.
Topics: Animals; Atherosclerosis; Disease Progression; Humans; Inflammation; Inflammation Mediators; Lipid Metabolism; Lipoxygenases; Models, Cardiovascular; Plaque, Atherosclerotic; Signal Transduction
PubMed: 30108191
DOI: 10.1172/JCI97950 -
International Journal of Molecular... Mar 2022Atherosclerosis is a chronic and progressive inflammatory disease of the arteries initiated by the functional and structural alteration of the endothelial layer...
Atherosclerosis is a chronic and progressive inflammatory disease of the arteries initiated by the functional and structural alteration of the endothelial layer responsible for promoting the subendothelial retention of modified low-density lipoproteins (LDL), which in turn generate an active proinflammatory state in which environmental factors, such as oxidizing agents, growth factors, cytokines, monocyte-macrophages and smooth muscle cells (SMCs), work in cooperation to promote the formation of plaque [...].
Topics: Atherosclerosis; Humans; Lipoproteins, LDL; Molecular Biology; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Plaque, Atherosclerotic
PubMed: 35408804
DOI: 10.3390/ijms23073444 -
Cell Communication and Signaling : CCS Nov 2023Atherosclerosis, which is a vascular pathology characterized by inflammation and plaque build-up within arterial vessel walls, acts as the important cause of most... (Review)
Review
Atherosclerosis, which is a vascular pathology characterized by inflammation and plaque build-up within arterial vessel walls, acts as the important cause of most cardiovascular diseases. Except for a lipid-depository and chronic inflammatory, increasing evidences propose that epigenetic modifications are increasingly associated with atherosclerosis and are of interest from both therapeutic and biomarker perspectives. The chronic progressive nature of atherosclerosis has highlighted atherosclerosis heterogeneity and the fact that specific cell types in the complex milieu of the plaque are, by far, not the only initiators and drivers of atherosclerosis. Instead, the ubiquitous effects of cell type are tightly controlled and directed by the epigenetic signature, which, in turn, is affected by many proatherogenic stimuli, including low-density lipoprotein, proinflammatory, and physical forces of blood circulation. In this review, we summarize the role of DNA methylation and histone post-translational modifications in atherosclerosis. The future research directions and potential therapy for the management of atherosclerosis are also discussed. Video Abstract.
Topics: Humans; DNA Methylation; Histones; Atherosclerosis; Plaque, Atherosclerotic; Epigenesis, Genetic; Protein Processing, Post-Translational; Inflammation
PubMed: 38031118
DOI: 10.1186/s12964-023-01298-8 -
Current Opinion in Lipidology Oct 2021Cardiovascular calcification, a common feature of atherosclerotic lesions, has long been known to associate with cardiovascular risk. The roles of lipoproteins in... (Review)
Review
PURPOSE OF REVIEW
Cardiovascular calcification, a common feature of atherosclerotic lesions, has long been known to associate with cardiovascular risk. The roles of lipoproteins in atherosclerosis are also established, and lipid-modifying therapies have shown capacity for plaque regression. However, the association of lipid-modifying therapies with calcification is more complex, and currently no medical therapies have been found to reverse or attenuate calcification in patients. In this review, we summarize recent developments in our understanding of the interplay between lipids and cardiovascular calcification, as well as new imaging modalities for assessing calcified atherosclerotic plaque vulnerability.
RECENT FINDINGS
Recent clinical studies have highlighted the associations of lipoprotein subtypes, such as low-density and high-density lipoprotein particles, as well as lipoprotein (a) [Lp(a)], with coronary calcification and calcific aortic valve disease. Further, evidence continues to emerge for the utility of fused 18F-sodium fluoride positron-emission tomographic and computed tomographic (18F-NaF PET/CT) imaging in characterizing the microarchitecture and vulnerability of atherosclerotic plaque, in both humans and animal models.
SUMMARY
The relationship between lipids and cardiovascular calcification is complex, and new imaging techniques, such as 18F-NaF PET/CT imaging, may allow for better identification of disease-modifying therapies and prediction of calcified plaque progression and stability to help guide clinical management.
Topics: Animals; Humans; Lipids; Plaque, Atherosclerotic; Positron Emission Tomography Computed Tomography; Radiopharmaceuticals; Sodium Fluoride
PubMed: 34320564
DOI: 10.1097/MOL.0000000000000777 -
Ugeskrift For Laeger May 2016Acute aortic syndrome is a group of pathogenic conditions including aortic dissection, intramural haematoma, penetrating ulcer and aortic aneurysm. The syndrome is a... (Review)
Review
Acute aortic syndrome is a group of pathogenic conditions including aortic dissection, intramural haematoma, penetrating ulcer and aortic aneurysm. The syndrome is a challenging clinical diagnosis because the symptoms are numerous and diverse with similarity to other more common conditions. Delayed diagnosis and treatment can be fatal. Computed tomography angiography is the most important diagnostic tool and is the first choice when acute aortic syndrome is suspected. With this article, we wish to raise awareness of the incidence of acute aortic syndrome and the clinical features of the syndrome.
Topics: Acute Disease; Aortic Dissection; Aortic Aneurysm; Aortic Diseases; Aortography; Hematoma; Humans; Plaque, Atherosclerotic; Syndrome; Tomography, X-Ray Computed; Ulcer
PubMed: 27188992
DOI: No ID Found -
International Journal of Molecular... May 2015A thrombotic occlusion of the vessel fed by ruptured coronary atherosclerotic plaque may result in unstable angina, myocardial infarction or death, whereas embolization... (Review)
Review
A thrombotic occlusion of the vessel fed by ruptured coronary atherosclerotic plaque may result in unstable angina, myocardial infarction or death, whereas embolization from a plaque in carotid arteries may result in transient ischemic attack or stroke. The atherosclerotic plaque prone to such clinical events is termed high-risk or vulnerable plaque, and its identification in humans before it becomes symptomatic has been elusive to date. Ultrasonic tissue characterization of the atherosclerotic plaque is possible with different techniques--such as vascular, transesophageal, and intravascular ultrasound--on a variety of arterial segments, including carotid, aorta, and coronary districts. The image analysis can be based on visual, video-densitometric or radiofrequency methods and identifies three distinct textural patterns: hypo-echoic (corresponding to lipid- and hemorrhage-rich plaque), iso- or moderately hyper-echoic (fibrotic or fibro-fatty plaque), and markedly hyperechoic with shadowing (calcific plaque). Hypoechoic or dishomogeneous plaques, with spotty microcalcification and large plaque burden, with plaque neovascularization and surface irregularities by contrast-enhanced ultrasound, are more prone to clinical complications than hyperechoic, extensively calcified, homogeneous plaques with limited plaque burden, smooth luminal plaque surface and absence of neovascularization. Plaque ultrasound morphology is important, along with plaque geometry, in determining the atherosclerotic prognostic burden in the individual patient. New quantitative methods beyond backscatter (to include speed of sound, attenuation, strain, temperature, and high order statistics) are under development to evaluate vascular tissues. Although not yet ready for widespread clinical use, tissue characterization is listed by the American Society of Echocardiography roadmap to 2020 as one of the most promising fields of application in cardiovascular ultrasound imaging, offering unique opportunities for the early detection and treatment of atherosclerotic disease.
Topics: Animals; Echocardiography; Endosonography; Humans; Plaque, Atherosclerotic; Ultrasonography, Interventional
PubMed: 25950760
DOI: 10.3390/ijms160510121 -
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 -
The Journal of Pathology Apr 2020Macrophages play a major role in the pathogenesis of atherosclerosis. Many studies have shone light on the different phenotypes and functions that macrophages can... (Review)
Review
Macrophages play a major role in the pathogenesis of atherosclerosis. Many studies have shone light on the different phenotypes and functions that macrophages can acquire upon exposure to local cues. The microenvironment of the atherosclerotic plaque contains a plethora of macrophage-controlling factors, such as cytokines, oxidised low-density lipoproteins and cell debris. Previous research has determined macrophage function within the plaque mainly by using immunohistochemistry and bulk analysis. The recent development and rapid progress of single-cell technologies, such as cytometry by time of flight and single-cell RNA sequencing, now enable comprehensive mapping of the wide range of cell types and their phenotypes present in atherosclerotic plaques. In this review we discuss recent advances applying these technologies in defining macrophage subsets residing in the atherosclerotic arterial wall of mice and men. Resulting from these studies, we describe three main macrophage subsets: resident-like, pro-inflammatory and anti-inflammatory foamy TREM2 macrophages, which are found in both mouse and human atherosclerotic plaques. Furthermore, we discuss macrophage subset-specific markers and functions. More insights into the characteristics and phenotype of immune cells within the atherosclerotic plaque may guide future clinical approaches to treat disease. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
Topics: Atherosclerosis; Biomarkers; Cytokines; Humans; Macrophages; Plaque, Atherosclerotic; Sequence Analysis, RNA; Single-Cell Analysis
PubMed: 32003464
DOI: 10.1002/path.5392