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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 -
Current Opinion in Lipidology Oct 2014Atherosclerotic plaque rupture and subsequent acute events, such as myocardial infarction and stroke, contribute to the majority of cardiovascular-related deaths.... (Review)
Review
PURPOSE OF REVIEW
Atherosclerotic plaque rupture and subsequent acute events, such as myocardial infarction and stroke, contribute to the majority of cardiovascular-related deaths. Calcification has emerged as a significant predictor of cardiovascular morbidity and mortality, challenging previously held notions that calcifications stabilize atherosclerotic plaques. In this review, we address this discrepancy through recent findings that not all calcifications are equivalent in determining plaque stability.
RECENT FINDINGS
The risk associated with calcification is inversely associated with calcification density. As opposed to large calcifications that potentially stabilize the plaque, biomechanical modeling indicates that small microcalcifications within the plaque fibrous cap can lead to sufficient stress accumulation to cause plaque rupture. Microcalcifications appear to derive from matrix vesicles enriched in calcium-binding proteins that are released by cells within the plaque. Clinical detection of microcalcifications has been hampered by the lack of imaging resolution required for in-vivo visualization; however, recent studies have demonstrated promising new techniques to predict the presence of microcalcifications.
SUMMARY
Microcalcifications play a major role in destabilizing atherosclerotic plaques. The identification of critical characteristics that lead to instability along with new imaging modalities to detect their presence in vivo may allow early identification and prevention of acute cardiovascular events.
Topics: Calcinosis; Humans; Myocardial Infarction; Plaque, Atherosclerotic; Stroke
PubMed: 25188916
DOI: 10.1097/MOL.0000000000000105 -
European Journal of Pharmacology Dec 2017Macrophages are key players in atherosclerotic lesions, regulating the local inflammatory milieu and plaque stability by the secretion of many inflammatory molecules,... (Review)
Review
Macrophages are key players in atherosclerotic lesions, regulating the local inflammatory milieu and plaque stability by the secretion of many inflammatory molecules, growth factors and cytokines. Monocytes have long been considered to be the main source of plaque macrophages. However, recent findings provide evidence for proliferation of local macrophages or transdifferentiation from other vascular cells as alternative sources. Recent years of research focused on the further identification and characterisation of macrophage phenotypes and functions. In this review we describe the advances in our understanding of monocyte and macrophage heterogeneity and its implications for specific therapeutic interventions, aiming to reduce the ever growing significant risk of cardiovascular events without any detrimental side effects on the patient's immune response.
Topics: Animals; Humans; Macrophages; Molecular Targeted Therapy; Monocytes; Phenotype; Plaque, Atherosclerotic
PubMed: 28989084
DOI: 10.1016/j.ejphar.2017.10.005 -
Journal of Drug Targeting Dec 2024Atherosclerosis is one of the major causes of death worldwide, and it is closely related to many cardiovascular diseases, such as stroke, myocardial infraction and... (Review)
Review
Atherosclerosis is one of the major causes of death worldwide, and it is closely related to many cardiovascular diseases, such as stroke, myocardial infraction and angina. Although traditional surgical and pharmacological interventions can effectively retard or slow down the progression of atherosclerosis, it is very difficult to prevent or even reverse this disease. In recent years, with the rapid development of nanotechnology, various nanoagents have been designed and applied to different diseases including atherosclerosis. The unique atherosclerotic microenvironment with signature biological components allows nanoplatforms to distinguish atherosclerotic lesions from normal tissue and to approach plaques specifically. Based on the process of atherosclerotic plaque formation, this review summarises the nanodrug delivery strategies for atherosclerotic therapy, trying to provide help for researchers to understand the existing atherosclerosis management approaches as well as challenges and to reasonably design anti-atherosclerotic nanoplatforms.
Topics: Humans; Atherosclerosis; Plaque, Atherosclerotic; Drug Delivery Systems; Nanotechnology
PubMed: 38217526
DOI: 10.1080/1061186X.2023.2300694 -
Ultrasound in Medicine & Biology Jan 2016Stroke is a leading cause of morbidity and mortality worldwide, and characterization of vulnerable carotid plaque remains the spearhead of scientific research. Plaque... (Review)
Review
Stroke is a leading cause of morbidity and mortality worldwide, and characterization of vulnerable carotid plaque remains the spearhead of scientific research. Plaque destabilization, the key factor that induces the series of events leading to the clinical symptoms of carotid artery disease, is a consequence of complex mechanical, structural and biochemical processes. Novel imaging and molecular markers have been studied as predictors of disease outcome with promising results. The aim of this review is to present the current state of research on the association between ultrasound-derived echogenicity indices and blood parameters indicative of carotid plaque stability and activity. Bibliographic research revealed that there are limited available data. Among the biomarkers studied, those related to oxidative stress, lipoproteins and diabetes/insulin resistance are associated with echolucent plaques, whereas adipokines are associated with echogenic plaques. Biomarkers of inflammation and coagulation have not exhibited any conclusive relationship with plaque echogenicity, and it is not possible to come to any conclusion regarding calcification-, apoptosis- and neo-angiogenesis-related parameters because of the extremely limited bibliographic data.
Topics: Carotid Artery Diseases; Humans; Inflammation; Plaque, Atherosclerotic; Risk Factors; Ultrasonography
PubMed: 26493239
DOI: 10.1016/j.ultrasmedbio.2015.09.003 -
Advanced Healthcare Materials Jun 2024Atherosclerotic plaque formation is considered the primary pathological mechanism underlying atherosclerotic cardiovascular diseases, leading to severe cardiovascular... (Review)
Review
Atherosclerotic plaque formation is considered the primary pathological mechanism underlying atherosclerotic cardiovascular diseases, leading to severe cardiovascular events such as stroke, acute coronary syndromes, and even sudden cardiac death. Early detection and timely intervention of plaques are challenging due to the lack of typical symptoms in the initial stages. Therefore, precise early detection and intervention play a crucial role in risk stratification of atherosclerotic plaques and achieving favorable post-interventional outcomes. The continuously advancing nanoplatforms have demonstrated numerous advantages including high signal-to-noise ratio, enhanced bioavailability, and specific targeting capabilities for imaging agents and therapeutic drugs, enabling effective visualization and management of atherosclerotic plaques. Motivated by these superior properties, various noninvasive imaging modalities for early recognition of plaques in the preliminary stage of atherosclerosis are comprehensively summarized. Additionally, several therapeutic strategies are proposed to enhance the efficacy of treating atherosclerotic plaques. Finally, existing challenges and promising prospects for accelerating clinical translation of nanoplatform-based molecular imaging and therapy for atherosclerotic plaques are discussed. In conclusion, this review provides an insightful perspective on the diagnosis and therapy of atherosclerotic plaques.
Topics: Humans; Plaque, Atherosclerotic; Animals; Theranostic Nanomedicine; Nanoparticles
PubMed: 38564883
DOI: 10.1002/adhm.202303612 -
Polski Merkuriusz Lekarski : Organ... Mar 2017Atherogenesis is the process of atherosclerotic plaque formation, leading to coronary artery heart disease. This process involves immune cells, mainly T and B cells,... (Review)
Review
Atherogenesis is the process of atherosclerotic plaque formation, leading to coronary artery heart disease. This process involves immune cells, mainly T and B cells, monocytes and macrophages. The process of atherogenesis is induced by inflammatory damage of endothelial cells. The characteristic construction features of the atherosclerotic plaque is a predisposing factor for acute coronary syndromes. The accumulation of inflammatory cells in the artery inner membrane enhances the local inflammatory process due to the secretion of reactive oxygen species, inflammatory cytokines and metalloproteinases, which accelerate the development of atherosclerotic lesions in the arteries. In chronic inflammation of endothelial cells, which is atherosclerosis, there is a decrease in the concentration of elastin and collagen as a result of the increased apoptosis of smooth muscle cells of the intima. This reduces the integrity and strength of the fibrous cap that covers a layer of thrombogenic plaque from contact with blood elements. Permanent inflammation promotes the formation of necrotic core, composed of dead smooth muscle cells, macrophages and foam cells formed by phagocytosis of oxidized lipid molecules. The thin fibrous cap and a large necrotic core are the cause of plaque rupture and thrombus formation within the coronary artery.
Topics: Atherosclerosis; Humans; Immune System; Inflammation; Plaque, Atherosclerotic
PubMed: 28333905
DOI: No ID Found -
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 -
Journal of the American Heart... Mar 2017
Review
Topics: Coronary Artery Disease; Coronary Vessels; Global Health; Humans; Morbidity; Plaque, Atherosclerotic
PubMed: 28314799
DOI: 10.1161/JAHA.117.005543 -
European Journal of Pharmacology Sep 2015Atherosclerosis is a disease of the vascular wall that forms the basis for a large spectrum of pathologies of various organs and tissues. Although massive research... (Review)
Review
Atherosclerosis is a disease of the vascular wall that forms the basis for a large spectrum of pathologies of various organs and tissues. Although massive research efforts in the last decades have yielded valuable information about its underlying molecular mechanisms, this has not led to a translation into effective therapeutic interventions that can stop the progression or even can induce regression of atherosclerosis. This underscores the importance of investigations on the involvement of novel signaling pathways in the development and progression of this condition. In this review we focus on the role of Wnt signaling in atherosclerosis. Experimental evidence is presented that Wnt signaling is involved in many aspects of the development and progression of vascular lesions including endothelial dysfunction, macrophage activation and the proliferation and migration of vascular smooth muscle cells. Subsequently, we will discuss the role of Wnt signaling in myocardial infarction and stroke, two common pathologies resulting from the progression of atherosclerotic lesions towards an unstable phenotype. Despite the fact that the published data sometimes are ambiguous or even conflicting, a picture is emerging that an attenuation of Wnt signaling is beneficial for the cardiovascular system that is compromised by atherosclerosis.
Topics: Animals; Atherosclerosis; Humans; Plaque, Atherosclerotic; Wnt Signaling Pathway
PubMed: 25987418
DOI: 10.1016/j.ejphar.2015.05.023