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Journal of Internal Medicine Nov 2015
Topics: Adaptive Immunity; Cardiovascular Diseases; Humans; Immunity, Cellular; Inflammation; Lipid Metabolism; Plaque, Atherosclerotic; Therapies, Investigational
PubMed: 26477594
DOI: 10.1111/joim.12403 -
European Journal of Clinical... Jan 2015Atherosclerosis is a chronic inflammatory disease of large- to medium-sized arteries and is the main underlying cause of death worldwide. The lymphatic vasculature is... (Review)
Review
BACKGROUND
Atherosclerosis is a chronic inflammatory disease of large- to medium-sized arteries and is the main underlying cause of death worldwide. The lymphatic vasculature is critical for processes that are intimately linked to atherogenesis such as the immune response and cholesterol metabolism. However, whether lymphatic vessels truly contribute to the pathogenesis of atherosclerosis is less clear despite increasing research efforts in this field.
DESIGN
PubMed and Ovid MEDLINE databases were searched. In addition, key review articles were screened for relevant original publications.
RESULTS
Current knowledge about lymphatic vessels in the arterial wall came from studies that examined the presence and location of such vessels in human atherosclerotic plaque specimens, as well as in a variety of arteries in animal models for atherosclerosis (e.g. rabbits, dogs, rats and mice). Generally, three experimental approaches have been used to investigate the functional role of plaque-associated lymphatic vessels; experimental lymphostasis was used to investigate lymphatic drainage of the arterial wall, and more recently, studies with genetic interventions and/or surgical transplantation have been performed.
CONCLUSIONS
Lymphatic vessels seem to be mostly present in the adventitial layer of the arterial walls of animals and humans. They are involved in reverse cholesterol transport from atherosclerotic lesions, and arteries with a dense lymphatic network seem naturally protected against atherosclerosis. Lymphangiogenesis is a process that is an important part of the inflammatory loop in atherosclerosis. However, how augmenting or impeding the distribution of lymphatic vessels impacts disease progression remains to be investigated in future studies.
Topics: Animals; Atherosclerosis; Disease Progression; Dogs; Humans; Lymphangiogenesis; Lymphatic Vessels; Mice; Microvessels; Plaque, Atherosclerotic; Rabbits; Rats
PubMed: 25388153
DOI: 10.1111/eci.12372 -
European Journal of Pharmacology Dec 2017Acute cardiovascular events, due to rupture or erosion of an atherosclerotic plaque, represent the major cause of morbidity and mortality in patients. Growing evidence... (Review)
Review
Acute cardiovascular events, due to rupture or erosion of an atherosclerotic plaque, represent the major cause of morbidity and mortality in patients. Growing evidence suggests that plaque neovascularization is an important contributor to plaque growth and instability. The vessels' immaturity, with profound structural and functional abnormalities, leads to recurrent intraplaque hemorrhage. This review discusses new insights of atherosclerotic neovascularization, including the effects of leaky neovessels on intraplaque hemorrhage, both in experimental models and humans. Furthermore, modalities for in vivo imaging and therapeutic interventions to target plaque angiogenesis will be discussed.
Topics: Animals; Hemorrhage; Humans; Molecular Imaging; Neovascularization, Pathologic; Plaque, Atherosclerotic
PubMed: 28435093
DOI: 10.1016/j.ejphar.2017.04.028 -
Biochemical and Biophysical Research... Feb 2019Atherosclerosis and cancer are the leading causes of mortality around the world that share common pathogenic pathways. The aim of this study is the investigation of the...
Atherosclerosis and cancer are the leading causes of mortality around the world that share common pathogenic pathways. The aim of this study is the investigation of the protein profile of atherosclerotic plaque in order to find similar biomarker between cancer and atherosclerosis. The small pieces of human coronary artery containing advanced atherosclerotic plaque is obtained from patients during bypass surgery. Structural characterization of type V plaque, including fibrous connective tissue, necrotic lipid core, cholesterol clefts and calcium deposits are performed using high resolution transmission electron microscopy (HR-TEM). The protein profile of atherosclerosis plaque is also analyzed using 2-dimensional electrophoresis and matrix-assisted laser desorption-ionization time-of-flight (MALDI-TOF). TEM analysis shows that vascular smooth muscle cells (VSMCs) exhibit different and uncommon morphologies in atherosclerotic plaque which is correlated to the proliferative state of the cells. The proteomics analysis reveals proteins related to atherosclerosis formation including Mimecan, Ras Suppressor Protein-1 (RSUP-1) and Cathepsin D which identified as biomarker of cancerous tumors. The expression of Mimecan and RSUP-1 is down-regulated in atherosclerotic plaque while the expression of Cathepsin D is up-regulated. These data support that atherosclerotic plaque presents some degree of tumorgenesis with the significant activity of VSMCs as the key player in atherogenesis.
Topics: Biomarkers, Tumor; Cathepsin D; Electrophoresis, Gel, Two-Dimensional; Humans; Intercellular Signaling Peptides and Proteins; Neoplasms; Plaque, Atherosclerotic; Proteome; Proteomics; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Transcription Factors
PubMed: 30616890
DOI: 10.1016/j.bbrc.2018.12.160 -
The American Journal of Cardiology Oct 2023Acute coronary syndromes and, in particular, ST-elevation myocardial infarction are usually caused by coronary thrombosis in which the thrombus develops either on a... (Review)
Review
Acute coronary syndromes and, in particular, ST-elevation myocardial infarction are usually caused by coronary thrombosis in which the thrombus develops either on a disrupted plaque (usually a thin-capped fibroatheroma) or an eroded atherosclerotic plaque. These thrombus-prone plaques are vulnerable or high-risk. Although, traditionally, cardiologists have concentrated on treating significant coronary obstruction, there has been great interest over the last 2 decades in possibly preventing the thrombotic causes of myocardial infarction/sudden coronary death by mostly identifying and stabilizing these asymptomatic vulnerable or high-risk plaques, which, at least on invasive angiography, are mostly nonobstructive. Computed tomographic angiography and intravascular imaging during invasive coronary angiography have now been shown to identify a majority of these vulnerable or high-risk plaques before symptoms, thus opening up new preventive strategies. In conclusion, this article discusses the identification and management of these thrombus-prone lesions and patients with these lesions either with noninvasive techniques and systemic therapies or possibly through a new and bold interventional paradigm.
Topics: Humans; Plaque, Atherosclerotic; Coronary Thrombosis; Acute Coronary Syndrome; Cardiologists; Coronary Angiography
PubMed: 37611413
DOI: 10.1016/j.amjcard.2023.07.121 -
European Radiology Mar 2023This study aimed to demonstrate the effectiveness of spectral photon-counting CT (SPCCT) in quantifying fibrous cap (FC) thickness, FC area, and lipid-rich necrotic core... (Observational Study)
Observational Study
OBJECTIVES
This study aimed to demonstrate the effectiveness of spectral photon-counting CT (SPCCT) in quantifying fibrous cap (FC) thickness, FC area, and lipid-rich necrotic core (LRNC) area, in excised carotid atherosclerotic plaques by comparing it with histopathological measurements.
METHODS
This is a single-center ex vivo cross-sectional observational study. Excised plaques of 20 patients (71 +/- 6 years; 13 men), obtained from carotid endarterectomy were scanned with SPCCT using standardized acquisition settings (120k Vp/19 μA; 7-18 keV, 18-30 keV, 30-45 keV, 45-75 keV, and 75-118 keV). FC thickness, FC area, and LRNC area were quantified and compared between high-resolution 3D multi-energy CT images and histopathology using the Wilcoxon signed-ranks test and Bland-Altman analysis. Images were interpreted twice by two radiologists separately, blinded to the histopathology; inter- and intra-rater reliability were assessed with the intra-class correlation coefficients (ICC).
RESULTS
FC thickness and FC area did not show significant differences between the SPCCT-derived radiological measurements versus the histopathological measurements (p value range 0.15-0.51 for FC thickness and 0.053-0.30 for FC area). For the LRNC area, the p value was statistically non-significant for reader 1 (range 0.36-0.81). The Bland-Altman analysis showed mean difference and 95% confidence interval for FC thickness, FC area, and LRNC area, 0.04 (-0.36 to 0.12) square root mm, -0.18 (-0.34 to -0.02) log mm and 0.10 (-0.088. to 0.009) log mm respectively.
CONCLUSION
The result demonstrated a viable technique for quantifying FC thickness, FC area, and LRNC area due to the combined effect of high spatial and energy resolution of SPCCT.
KEY POINTS
• SPCCT can identify and quantify different components of carotid atherosclerotic plaque in ex vivo study. • Components of atherosclerotic plaque did not show significant differences between the SPCCT-derived radiological measurements versus the histopathological measurements.
Topics: Male; Humans; Plaque, Atherosclerotic; Reproducibility of Results; Cross-Sectional Studies; Carotid Arteries; Tomography, X-Ray Computed; Fibrosis
PubMed: 36205768
DOI: 10.1007/s00330-022-09155-x -
ACS Nano Feb 2020The past several decades have brought significant advances in the application of clinical and preclinical nanoparticulate drugs in the field of cancer, but nanodrug... (Review)
Review
The past several decades have brought significant advances in the application of clinical and preclinical nanoparticulate drugs in the field of cancer, but nanodrug development in cardiovascular disease has lagged in comparison. Improved understanding of the spatiotemporal kinetics of nanoparticle delivery to atherosclerotic plaques is required to optimize preclinical nanodrug delivery and to drive their clinical translation. Mechanistic studies using super-resolution and correlative light microscopy/electron microscopy permit a broad, ultra-high-resolution picture of how endothelial barrier integrity impacts the enhanced permeation and retention (EPR) effect for nanoparticles as a function of both atherosclerosis progression and metabolic therapy. Studies by Beldman in the December issue of suggest atherosclerotic plaque progression supports endothelial junction stabilization, which can reduce nanoparticle entry into plaques, and metabolic therapy may induce similar effects. Herein, we examine the potential for advanced dynamic intravital microscopy-based mechanistic studies of nanoparticle entry into atherosclerotic plaques to shed light on the advantages of free extravasation immune-mediated nanoparticle uptake for effective clinical translation. We further explore the potential combination of metabolic therapy with another emerging cardiovascular disease treatment paradigm-efferocytosis stimulation-to enhance atherosclerotic plaque regression.
Topics: Animals; Drug Delivery Systems; Humans; Nanoparticles; Nanotechnology; Particle Size; Plaque, Atherosclerotic; Surface Properties
PubMed: 31986012
DOI: 10.1021/acsnano.0c00245 -
Molecules (Basel, Switzerland) Aug 2023Atherosclerosis is a multifactorial, progressive, chronic inflammatory disease. Ultrasound and magnetic resonance imaging are the most accurate predictors of...
Atherosclerosis is a multifactorial, progressive, chronic inflammatory disease. Ultrasound and magnetic resonance imaging are the most accurate predictors of atherosclerotic plaque instability (MRI). Cytokines such as osteopontin, osteoprotegerin, and metalloproteinase 9 could be used as the most recent markers to identify and track the efficacy of anti-atherosclerotic therapy. Patients with USG and MRI-verified unstable atherosclerotic plaque were included in the study. Biomarker concentrations were measured and compared before and after PCSK9 inhibitor therapy. Additionally, concentrations prior to treatment were correlated with MRI images of the carotid artery. After treatment with alirocumab, the concentrations of MMP-9 ( < 0.01) and OPN, OPG ( < 0.05) decreased significantly. Furthermore, the results of OPN, OPG, and MMP 9 varied significantly depending on the type of atherosclerotic plaque in the MRI assay. In stable atherosclerotic plaques, the concentrations of OPN and OPG were greater ( < 0.01), whereas the concentration of MMP9 correlated with the instability of the plaque ( < 0.05). We demonstrated, probably for the first time, that alirocumab therapy significantly decreased the serum concentration of atherosclerotic plaque markers. In addition, we demonstrated the relationship between the type of atherosclerotic plaque as determined by carotid MRI and the concentration of these markers.
Topics: Humans; Plaque, Atherosclerotic; Proprotein Convertase 9; Atherosclerosis; Ultrasonography
PubMed: 37570897
DOI: 10.3390/molecules28155928 -
Advanced Science (Weinheim,... Oct 2021Pathological angiogenesis is a crucial factor that causes atherosclerotic plaque rupture. Sinoporphyrin sodium-mediated sonodynamic therapy (DVDMS-SDT) induces...
Pathological angiogenesis is a crucial factor that causes atherosclerotic plaque rupture. Sinoporphyrin sodium-mediated sonodynamic therapy (DVDMS-SDT) induces regression of plaque neovascularization in humans without causing obvious side effects. However, a clinical noninvasive theranostic strategy for atherosclerotic plaque neovascularization is urgently needed. A nanoplatform designed for multimodality imaging-guided SDT in plaque angiogenesis theranostics, termed PFP-HMME@PLGA/MnFe O -ramucirumab nanoparticles (PHPMR NPs), is fabricated. It encapsulates manganese ferrite (MnFe O ), hematoporphyrin monomethyl ether (HMME), and perfluoropentane (PFP) stabilized by polylactic acid-glycolic acid (PLGA) shells and is conjugated to an anti-VEGFR-2 antibody. With excellent magnetic resonance imaging (MRI)/photoacoustic/ultrasound imaging ability, the distribution of PHPMR NPs in plaque can be observed in real time. Additionally, they actively accumulate in the mitochondria of rabbit aortic endothelial cells (RAECs), and the PHPMR NP-mediated SDT promotes mitochondrial-caspase apoptosis via the production of reactive oxygen species and inhibits the proliferation, migration, and tubulogenesis of RAECs. On day 3, PHPMR NP-mediated SDT induces apoptosis in neovessel endothelial cells and improves hypoxia in the rabbit advanced plaque. On day 28, PHPMR NP-mediated SDT reduces the density of neovessels, subsequently inhibiting intraplaque hemorrhage and inflammation and eventually stabilizing the plaque. Collectively, PHPMR NP-mediated SDT presents a safe and effective theranostic strategy for inhibiting plaque angiogenesis.
Topics: Animals; Disease Models, Animal; Ferric Compounds; Male; Manganese Compounds; Nanoparticles; Neovascularization, Pathologic; Plaque, Atherosclerotic; Rabbits; Theranostic Nanomedicine; Ultrasonic Therapy
PubMed: 34382370
DOI: 10.1002/advs.202100850 -
Journal of Cardiovascular Pharmacology... May 2015Coronary atherosclerosis progresses both as slow, gradual enlargement of focal plaque and also as a more dynamic process with periodic abrupt changes in plaque geometry,... (Review)
Review
How do we prevent the vulnerable atherosclerotic plaque from rupturing? Insights from in vivo assessments of plaque, vascular remodeling, and local endothelial shear stress.
Coronary atherosclerosis progresses both as slow, gradual enlargement of focal plaque and also as a more dynamic process with periodic abrupt changes in plaque geometry, size, and morphology. Systemic vasculoprotective therapies such as statins, angiotensin-converting enzyme inhibitors, and antiplatelet agents are the cornerstone of prevention of plaque rupture and new adverse clinical outcomes, but such systemic therapies are insufficient to prevent the majority of new cardiac events. Invasive imaging methods have been able to identify both the anatomic features of high-risk plaque and the ongoing pathobiological stimuli responsible for progressive plaque inflammation and instability and may provide sufficient information to formulate preventive local mechanical strategies (eg, preemptive percutaneous coronary interventions) to avert cardiac events. Local endothelial shear stress (ESS) triggers vascular phenomena that synergistically exacerbate atherosclerosis toward an unstable phenotype. Specifically, low ESS augments lipid uptake and catabolism, induces plaque inflammation and oxidation, downregulates the production, upregulates the degradation of extracellular matrix, and increases cellular apoptosis ultimately leading to thin-cap fibroatheromas and/or endothelial erosions. Increases in blood thrombogenicity that result from either high or low ESS also contribute to plaque destabilization. An understanding of the actively evolving vascular phenomena, as well as the development of in vivo imaging methodologies to identify the presence and severity of the different processes, may enable early identification of a coronary plaque destined to acquire a high-risk state and allow for highly selective, focal preventive interventions to avert the adverse natural history of that particular plaque. In this review, we focus on the role of ESS in the pathobiologic processes responsible for plaque destabilization, leading either to accelerated plaque growth or to acute coronary events, and emphasize the potential to utilize in vivo risk stratification of individual coronary plaques to optimize prevention strategies to preclude new cardiac events.
Topics: Endothelium, Vascular; Extracellular Matrix; Humans; Lipoproteins, LDL; Oxidative Stress; Plaque, Atherosclerotic; Receptor for Advanced Glycation End Products; Stress, Mechanical; Vascular Remodeling
PubMed: 25336461
DOI: 10.1177/1074248414555005