plaque disruption
Recently Published Documents


TOTAL DOCUMENTS

143
(FIVE YEARS 26)

H-INDEX

29
(FIVE YEARS 1)

2022 ◽  
Vol 8 ◽  
Author(s):  
Teresa Gerhardt ◽  
Arash Haghikia ◽  
Philip Stapmanns ◽  
David Manuel Leistner

Inflammation crucially drives atherosclerosis from disease initiation to the emergence of clinical complications. Targeting pivotal inflammatory pathways without compromising the host defense could compliment therapy with lipid-lowering agents, anti-hypertensive treatment, and lifestyle interventions to address the substantial residual cardiovascular risk that remains beyond classical risk factor control. Detailed understanding of the intricate immune mechanisms that propel plaque instability and disruption is indispensable for the development of novel therapeutic concepts. In this review, we provide an overview on the role of key immune cells in plaque inception and progression, and discuss recently identified maladaptive immune phenomena that contribute to plaque destabilization, including epigenetically programmed trained immunity in myeloid cells, pathogenic conversion of autoreactive regulatory T-cells and expansion of altered leukocytes due to clonal hematopoiesis. From a more global perspective, the article discusses how systemic crises such as acute mental stress or infection abruptly raise plaque vulnerability and summarizes recent advances in understanding the increased cardiovascular risk associated with COVID-19 disease. Stepping outside the box, we highlight the role of gut dysbiosis in atherosclerosis progression and plaque vulnerability. The emerging differential role of the immune system in plaque rupture and plaque erosion as well as the limitations of animal models in studying plaque disruption are reviewed.


Author(s):  
Brent Gudenkauf ◽  
Allison G. Hays ◽  
Jacqueline Tamis‐Holland ◽  
Jeffrey Trost ◽  
Daniel I. Ambinder ◽  
...  

Abstract Myocardial infarction with nonobstructive coronary arteries (MINOCA) is a heterogeneous clinical entity, encompassing multiple different causes, and a cause of substantial morbidity and mortality. Current guidelines suggest a multimodality imaging approach in establishing the underlying cause for MINOCA, which is considered a working diagnosis. Recent studies have suggested that an initial workup consisting of cardiac magnetic resonance and invasive coronary imaging can yield the diagnosis in most patients. Cardiac magnetic resonance is particularly helpful in excluding nonischemic causes that can mimic MINOCA including myocarditis and Takotsubo cardiomyopathy, as well as for long‐term prognostication. Additionally, intracoronary imaging with intravascular ultrasound or optical coherence tomography may be warranted to evaluate plaque composition, or evaluate for plaque disruption or spontaneous coronary dissection. The role of noninvasive imaging modalities such as coronary computed tomography angiography is currently being investigated in the diagnostic approach and follow‐up of MINOCA and may be appropriate in lieu of invasive coronary angiography in select patients. In recent years, many strides have been made in the workup of MINOCA; however, significant knowledge gaps remain in the field, particularly in terms of treatment strategies. In this review, we summarize recent society guideline recommendations and consensus statements on the initial evaluation of MINOCA, review contemporary multimodality imaging approaches, and discuss treatment strategies including an ongoing clinical trial.


Stroke ◽  
2021 ◽  
Author(s):  
David Izquierdo-Garcia ◽  
Himashinie Diyabalanage ◽  
Ian A. Ramsay ◽  
Nicholas J. Rotile ◽  
Adam Mauskapf ◽  
...  

Background and Purpose: High-risk atherosclerosis is an underlying cause of cardiovascular events, yet identifying the specific patient population at immediate risk is still challenging. Here, we used a rabbit model of atherosclerotic plaque rupture and human carotid endarterectomy specimens to describe the potential of molecular fibrin imaging as a tool to identify thrombotic plaques. Methods: Atherosclerotic plaques in rabbits were induced using a high-cholesterol diet and aortic balloon injury (N=13). Pharmacological triggering was used in a group of rabbits (n=9) to induce plaque disruption. Animals were grouped into thrombotic and nonthrombotic plaque groups based on gross pathology (gold standard). All animals were injected with a novel fibrin-specific probe 68 Ga-CM246 followed by positron emission tomography (PET)/magnetic resonance imaging 90 minutes later. 68 Ga-CM246 was quantified on the PET images using tissue-to-background (back muscle) ratios and standardized uptake value. Results: Both tissue-to-background (back muscle) ratios and standardized uptake value were significantly higher in the thrombotic versus nonthrombotic group ( P <0.05). Ex vivo PET and autoradiography of the abdominal aorta correlated positively with in vivo PET measurements. Plaque disruption identified by 68 Ga-CM246 PET agreed with gross pathology assessment (85%). In ex vivo surgical specimens obtained from patients undergoing elective carotid endarterectomy (N=12), 68 Ga-CM246 showed significantly higher binding to carotid plaques compared to a D-cysteine nonbinding control probe. Conclusions: We demonstrated that molecular fibrin PET imaging using 68 Ga-CM246 could be a useful tool to diagnose experimental and clinical atherothrombosis. Based on our initial results using human carotid plaque specimens, in vivo molecular imaging studies are warranted to test 68 Ga-CM246 PET as a tool to stratify risk in atherosclerotic patients.


Author(s):  
M. F. A. Karel ◽  
T. P. Lemmens ◽  
B. M. E. Tullemans ◽  
S. J. H. Wielders ◽  
E. Gubbins ◽  
...  

Abstract Introduction Studying arterial thrombus formation by in vitro flow assays is a widely used approach. Incorporating human atherosclerotic plaque material as a thrombogenic surface in these assays represents a method to model the pathophysiological environment of thrombus formation upon plaque disruption. Up until now, achieving a homogeneous coating of plaque material and subsequent reproducible platelet adhesion has been challenging. Here, we characterized a novel method for coating of plaque material on glass coverslips for use in thrombosis microfluidic assays. Methods A homogenate of human atherosclerotic plaques was coated on glass coverslips by conventional manual droplet coating or by spin coating. Prior to coating, a subset of coverslips was plasma treated. Water contact angle measurements were performed as an indicator for the hydrophilicity of the coverslips. Homogeneity of plaque coatings was determined using profilometric analysis and scanning electron microscopy. Thrombogenicity of the plaque material was assessed in real time by microscopic imaging while perfusing whole blood at a shear rate of 1500 s−1 over the plaque material. Results Plasma treatment of glass coverslips, prior to spin coating with plaque material, increased the hydrophilicity of the coverslip compared to no plasma treatment. The most homogeneous plaque coating and highest platelet adhesion was obtained upon plasma treatment followed by spin coating of the plaque material. Manual plaque coating on non-plasma treated coverslips yielded lowest coating homogeneity and platelet adhesion and activation. Conclusion Spin coating of atherosclerotic plaque material on plasma treated coverslips leads to a more homogenous coating and improved platelet adhesion to the plaque when compared to conventional droplet coating on non-plasma treated coverslips. These properties are beneficial in ensuring the quality and reproducibility of flow experiments.


2021 ◽  
Vol 10 (19) ◽  
Author(s):  
Audrey Hemadou ◽  
Alexandre Fontayne ◽  
Jeanny Laroche‐Traineau ◽  
Florence Ottones ◽  
Philippe Mondon ◽  
...  

Background Atherosclerosis is a complex pathology in which dysfunctional endothelium, activated leucocytes, macrophages, and lipid‐laden foam cells are implicated, and in which plaque disruption is driven by many putative actors. This study aimed to identify accurate targetable biomarkers using new in vivo approaches to propose tools for improved diagnosis and treatment. Methods and Results Human scFv (single‐chain fragment variable) selected by in vivo phage display in a rabbit model of atherosclerosis was reformatted as scFv fused to the scFv‐Fc (single‐chain fragment variable fused to the crystallizable fragment of immunoglobulin G format) antibodies. Their reactivity was tested using flow cytometry and immunoassays, and aorta sections from animal models and human carotid and coronary artery specimens. A pool of atherosclerotic proteins from human endarterectomies was co‐immunoprecipitated with the selected scFv‐Fc followed by mass spectrometry for target identification. Near‐infrared fluorescence imaging was performed in Apoe −/− mice after injection of an Alexa Fluor 647–labeled scFv‐Fc‐2c antibody produced in a baculovirus system with 2 additional cysteine residues (ie, 2c) for future coupling to nano‐objects for theranostic applications. One scFv‐Fc clone (P3) displayed the highest cross‐reactivity against atherosclerotic lesion sections (rabbit, mouse, and human) and was chosen for translational development. Mass spectrometry identified galectin‐3, a β‐galactoside‐binding lectin, as the leader target. ELISA and immunofluorescence assays with a commercial anti‐galectin‐3 antibody confirmed this specificity. P3 scFv‐Fc‐2c specifically targeted atherosclerotic plaques in the Apoe −/− mouse model. Conclusions These results provide evidence that the P3 antibody holds great promise for molecular imaging of atherosclerosis and other inflammatory pathologies involving macrophages. Recently, galectin‐3 was proposed as a high‐value biomarker for the assessment of coronary and carotid atherosclerosis.


2021 ◽  
Author(s):  
Peter Libby

Abstract Inflammation orchestrates each stage of the life cycle of atherosclerotic plaques. Indeed, inflammatory mediators likely link many traditional and emerging risk factors with atherogenesis. Atheroma initiation involves endothelial activation with recruitment of leucocytes to the arterial intima, where they interact with lipoproteins or their derivatives that have accumulated in this layer. The prolonged and usually clinically silent progression of atherosclerosis involves periods of smouldering inflammation, punctuated by episodes of acute activation that may arise from inflammatory mediators released from sites of extravascular injury or infection or from subclinical disruptions of the plaque. Smooth muscle cells and infiltrating leucocytes can proliferate but also undergo various forms of cell death that typically lead to formation of a lipid-rich ‘necrotic’ core within the evolving intimal lesion. Extracellular matrix synthesized by smooth muscle cells can form a fibrous cap that overlies the lesion’s core. Thus, during progression of atheroma, cells not only procreate but perish. Inflammatory mediators participate in both processes. The ultimate clinical complication of atherosclerotic plaques involves disruption that provokes thrombosis, either by fracture of the plaque’s fibrous cap or superficial erosion. The consequent clots can cause acute ischaemic syndromes if they embarrass perfusion. Incorporation of the thrombi can promote plaque healing and progressive intimal thickening that can aggravate stenosis and further limit downstream blood flow. Inflammatory mediators regulate many aspects of both plaque disruption and healing process. Thus, inflammatory processes contribute to all phases of the life cycle of atherosclerotic plaques, and represent ripe targets for mitigating the disease.


2021 ◽  
Vol 8 ◽  
Author(s):  
Runjianya Ling ◽  
Lihua Yu ◽  
Zhigang Lu ◽  
Yuehua Li ◽  
Jiayin Zhang

Objective: This study sought to investigate the diagnostic value of dynamic CT myocardial perfusion imaging (CT-MPI) combined with coronary CT angiography (CCTA) in acute coronary syndrome (ACS) patients without obstructive coronary angiography.Methods: Consecutive ACS patients with normal or non-obstructive coronary angiography findings who had cardiac magnetic resonance (CMR) contraindications or inability to cooperate with CMR examinations were prospectively enrolled and referred for dynamic CT-MPI + CCTA + late iodine enhancement (LIE). ACS etiology was determined according to combined assessment of coronary vasculature by CCTA, quantified myocardial blood flow (MBF) and presence of LIE.Results: Twenty two patients were included in the final analysis. CCTA revealed two cases of side branch occlusion and one case of intramural hematoma which were overlooked by invasive angiography. High risk plaques were observed in 6 (27.3%) patients whereas myocardial ischemia was presented in 19 (86.4%) patients with varied extent and severity. LIE was positive in 13 (59.1%) patients and microvascular obstruction was presented in three cases with side branch occlusion or spontaneous intramural hematoma. The specific etiology was identified in 20 (90.9%) patients, of which the most common cause was cardiomyopathies (41%), followed by microvascular dysfunction (14%) and plaque disruption (14%).Conclusion: Dynamic CT-MPI + CCTA was able to reveal the potential etiologies in majority of patients with ACS and non-obstructive coronary angiography. It may be a useful alternative to CMR for accurate etiology evaluation.


Medicina ◽  
2021 ◽  
Vol 57 (8) ◽  
pp. 833
Author(s):  
Christopher Dayaramani ◽  
Joshua De Leon ◽  
Allison B. Reiss

SARS-CoV-2, a single-stranded RNA coronavirus, causes an illness known as coronavirus disease 2019 (COVID-19). The highly transmissible virus gains entry into human cells primarily by the binding of its spike protein to the angiotensin-converting enzyme 2 receptor, which is expressed not only in lung tissue but also in cardiac myocytes and the vascular endothelium. Cardiovascular complications are frequent in patients with COVID-19 and may be a result of viral-associated systemic and cardiac inflammation or may arise from a virus-induced hypercoagulable state. This prothrombotic state is marked by endothelial dysfunction and platelet activation in both macrovasculature and microvasculature. In patients with subclinical atherosclerosis, COVID-19 may incite atherosclerotic plaque disruption and coronary thrombosis. Hypertension and obesity are common comorbidities in COVID-19 patients that may significantly raise the risk of mortality. Sedentary behaviors, poor diet, and increased use of tobacco and alcohol, associated with prolonged stay-at-home restrictions, may promote thrombosis, while depressed mood due to social isolation can exacerbate poor self-care. Telehealth interventions via smartphone applications and other technologies that document nutrition and offer exercise programs and social connections can be used to mitigate some of the potential damage to heart health.


2021 ◽  
pp. 153857442110320
Author(s):  
Steven G. Dolan ◽  
Douglas Mulholland ◽  
Narayanan Thulasidasan ◽  
Athanasios Diamantopoulos

The Mynx Control device (Cardinal Healthcare, Dublin, Ohio, USA) was recently licensed and allows for entirely extravascular arteriotomy closure. It uses a polyethylene glycol sealant plug which is absorbed fully within 30 days, alleviating concerns around difficulties with regaining access in future. The Mynx device uses a balloon, inflated within the artery and retracted against the arteriotomy to achieve haemostasis, with the extravascular sealant plug then deployed outside the vessel wall. While the manufacturer’s instructions for use do not include utilisation of imaging guidance, we routinely employ fluoroscopic and/or ultrasound to ensure safe use of the device. These techniques allow confirmation of balloon position against the arteriotomy, hence avoiding inadvertent deployment of the plug partially or fully intraluminally. Visualisation of the balloon within the lumen also eliminates risk of plaque disruption in diseased vessels on retraction of the device. Image guidance adds little time to device deployment, and the safety benefits are such that we recommend that practitioners elsewhere consider adopting our techniques. Here, we describe the process involved in both techniques.


2021 ◽  
Vol 10 (13) ◽  
pp. 2759
Author(s):  
Krzysztof Bryniarski ◽  
Pawel Gasior ◽  
Jacek Legutko ◽  
Dawid Makowicz ◽  
Anna Kedziora ◽  
...  

Myocardial infarction with non-obstructive coronary artery disease (MINOCA) is a working diagnosis for patients presenting with acute myocardial infarction without obstructive coronary artery disease on coronary angiography. It is a heterogenous entity with a number of possible etiologies that can be determined through the use of appropriate diagnostic algorithms. Common causes of a MINOCA may include plaque disruption, spontaneous coronary artery dissection, coronary artery spasm, and coronary thromboembolism. Optical coherence tomography (OCT) is an intravascular imaging modality which allows the differentiation of coronary tissue morphological characteristics including the identification of thin cap fibroatheroma and the differentiation between plaque rupture or erosion, due to its high resolution. In this narrative review we will discuss the role of OCT in patients presenting with MINOCA. In this group of patients OCT has been shown to reveal abnormal findings in almost half of the cases. Moreover, combining OCT with cardiac magnetic resonance (CMR) was shown to allow the identification of most of the underlying mechanisms of MINOCA. Hence, it is recommended that both OCT and CMR can be used in patients with a working diagnosis of MINOCA. Well-designed prospective studies are needed in order to gain a better understanding of this condition and to provide optimal management while reducing morbidity and mortality in that subset patients.


Sign in / Sign up

Export Citation Format

Share Document