Advanced atherosclerotic plaques in animal models versus human lesions: Key elements to translation

2021 ◽  
pp. 85-105
Author(s):  
Emmanuelle Canet Soulas ◽  
Saami K. Yazdani
Keyword(s):  
Animal Models ◽  
Atherosclerotic Plaques

scholarly journals Discoidin Domain-Containing Receptor 2 Is Present in Human Atherosclerotic Plaques and Involved in the Expression and Activity of MMP-2

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Qi Yu ◽  
Ruihan Liu ◽  
Ying Chen ◽  
Ahmed Bilal Waqar ◽  
Fuqiang Liu ◽  
...  
Keyword(s):  
Animal Models ◽  
Matrix Metalloproteinases ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Atherosclerotic Plaques ◽  
Clinical Role ◽  
Induced Expression ◽  
Unstable Plaques ◽  
Expression And Activity

Discoidin domain-containing receptor 2 (DDR2) has been suggested to be involved in atherosclerotic progression, but its pathological role remains unknown. Using immunochemical staining, we located and compared the expression of DDR2 in the atherosclerotic plaques of humans and various animal models. Then, siRNA was applied to knock down the expression of DDR2 in vascular smooth muscle cells (VSMCs), and the migration, proliferation, and collagen Ι-induced expression of matrix metalloproteinases (MMPs) were evaluated. We found that an abundance of DDR2 was present in the atherosclerotic plaques of humans and various animal models and was distributed around fatty and necrotic cores. After incubation of oxidized low-density lipoprotein (ox-LDL), DDR2 was upregulated in VSMCs in response to such a proatherosclerotic condition. Next, we found that decreased DDR2 expression in VSMCs inhibited the migration, proliferation, and collagen Ι-induced expression of matrix metalloproteinases (MMPs). Moreover, we found that DDR2 is strongly associated with the protein expression and activity of MMP-2, suggesting that DDR2 might play a role in the etiology of unstable plaques. Considering that DDR2 is present in the atherosclerotic plaques of humans and is associated with collagen Ι-induced secretion of MMP-2, the clinical role of DDR2 in cardiovascular disease should be elucidated in further experiments.

scholarly journals Discoidin domain-containing receptor 2 is present in human atherosclerotic plaques and involved in the expression and activity of MMP-2

2020 ◽  
Author(s):  
Yu Qi ◽  
Ruihan Liu ◽  
Ying Chen ◽  
Ahmed Bilal Waqar ◽  
Fuqiang Liu ◽  
...  
Keyword(s):  
Animal Models ◽  
Matrix Metalloproteinases ◽  
Collagen I ◽  
Atherosclerotic Plaques ◽  
Clinical Role ◽  
Induced Expression ◽  
Immunochemical Staining ◽  
Unstable Plaques ◽  
Expression And Activity

Abstract Background: DDR2 has been suggested to be involved in atherosclerotic progression, but its pathological role remains unknown. Methods: Using immunochemical staining, we located and compared the expression of DDR2 in the atherosclerotic plaques of humans and various animal models. Then, siRNA was applied to knockdown the expression of DDR2 in smooth muscle cells (VSMCs), and the migration, proliferation and collagen I-induced expression of matrix metalloproteinases (MMPs) were evaluated. Results: We found that an abundance of DDR2 was present in the atherosclerotic plaques of humans and various animal models and was distributed around fatty and necrotic cores. After incubation of ox-LDL, DDR2 was upregulated in VSMCs in response to such a pro-atherosclerotic condition. Next, we found that decreased DDR2 expression in VSMCs inhibited the migration, proliferation and collagen I-induced expression of matrix metalloproteinases (MMPs). Moreover, we found that DDR2 strongly associated with the protein expression and activity of MMP-2, suggesting that DDR2 might play a role in the etiology of unstable plaques. Conclusion: Considering that DDR2 is present in the atherosclerotic plaques of humans and is associated with collagen I-induced secretion of MMP-2, the clinical role of DDR2 in cardiovascular disease should be elucidated in further experiments.

scholarly journals Molecular Imaging of Vulnerable Atherosclerotic Plaques in Animal Models

2016 ◽  
Vol 17 (9) ◽  
pp. 1511 ◽  
Author(s):  
Sara Gargiulo ◽  
Matteo Gramanzini ◽  
Marcello Mancini
Keyword(s):  
Molecular Imaging ◽  
Animal Models ◽  
Atherosclerotic Plaques

Animal models for plaque rupture: a biomechanical assessment

2016 ◽  
Vol 115 (03) ◽  
pp. 501-508 ◽  
Author(s):  
Mat J. Daemen ◽  
Frank J. H. Gijsen ◽  
Kim Van der Heiden ◽  
Ayla Hoogendoorn
Keyword(s):  
Animal Models ◽  
Animal Studies ◽  
Plaque Rupture ◽  
Treatment Strategies ◽  
Strength Distribution ◽  
Atherosclerotic Plaques ◽  
Biomechanical Assessment ◽  
Inflammatory State ◽  
New Treatment ◽  
Patient At Risk

SummaryRupture of atherosclerotic plaques is the main cause of acute cardiovascular events. Animal models of plaque rupture are rare but essential for testing new imaging modalities to enable diagnosis of the patient at risk. Moreover, they enable the design of new treatment strategies to prevent plaque rupture. Several animal models for the study of atherosclerosis are available. Plaque rupture in these models only occurs following severe surgical or pharmaceutical intervention. In the process of plaque rupture, composition, biology and mechanics each play a role, but the latter has been disregarded in many animal studies. The biomechanical environment for atherosclerotic plaques is comprised of two parts, the pressure-induced stress distribution, mainly - but not exclusively – influenced by plaque composition, and the strength distribution throughout the plaque, largely determined by the inflammatory state. This environment differs considerably between humans and most animals, resulting in suboptimal conditions for plaque rupture. In this review we describe the role of the biomechanical environment in plaque rupture and assess this environment in animal models that present with plaque rupture.

Abstract 493: Antiatherosclerotic Activity of a New P2y13 Receptor Agonist (ct1007900) in Animal Models

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Ronald Barbaras ◽  
Rudi Baron ◽  
Marine Goffinet ◽  
Claudine Tardy ◽  
Nadia Boubekeur ◽  
...  
Keyword(s):  
Animal Models ◽  
High Fat Diet ◽  
Receptor Agonist ◽  
Positive Impact ◽  
Cholesterol Content ◽  
Cholesterol Concentration ◽  
Atherosclerotic Plaques ◽  
Mrna Levels ◽  
High Fat ◽  
Vitro Assay

The F1-ATPase/P2Y13 receptor pathway has been involved in the regulation of the HDL uptake liver and disposition via the reverse cholesterol transport. CT1007900 is a novel selective P2Y13 receptor agonist that has been shown to enhance the HDL uptake that results in the increased secretion of the bile acid, bile cholesterol and bile phospholipid into the gallbladder in mice. In the present study, CT1007900 has been evaluated in three different animal models of atherosclerosis. In ApoE -/- flow cessation model, the administration of the drug decreased the cholesterol concentration in atherosclerotic plaques. In a high fat diet fed ApoE -/- mouse model, the prevention of the progression of the plaque in aorta was further evaluated after 4-week treatment with CT1007900. The treated animals had significant decreases in plaque area, cholesterol content, VCAM1 expression and macrophage content. In the high fat diet fed rabbits, 4-week treatment reduced the cholesterol content by about 30% and also decreased the thickness of the plaques. The ApoA1 mRNA levels in the liver and ApoA1 protein concentration in the plasma increased in the drug-treated animals. The HDL content of the treated animals showed a very consistent pattern with a specific decrease in large HDL and an increase of the “intermediate” size HDL particles as compared to control animals. These intermediate HDL particles seem to be more efficient particles for the removal of cholesterol from atherosclerotic plaques by increasing efflux of cholesterol from the macrophages present in the lesions. The plasma samples from drug treated rabbits showed a dose-dependent increase in the cholesterol efflux in an in vitro assay using J774 cells. These results clearly demonstrate that improving functionality of HDL rather than the levels of HDL could have a positive impact on the atherosclerotic pathology. These data also support that P2Y13 receptor agonists could be useful pharmacological therapeutics for the treatment of complications due to atherosclerotic disease.

Animal models of atherosclerosis and magnetic resonance imaging for monitoring plaque progression

Vascular ◽  
2014 ◽  
Vol 22 (3) ◽  
pp. 221-237 ◽  
Author(s):  
Antoine Millon ◽  
Emmanuelle Canet-Soulas ◽  
Loic Boussel ◽  
Zahi Fayad ◽  
Philippe Douek
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Animal Models ◽  
Atherosclerotic Plaque ◽  
Atherosclerotic Plaques ◽  
Resonance Imaging ◽  
Human Atherosclerotic Plaque ◽  
Clinical Events ◽  
Vulnerable Plaques

Atherosclerosis, the main cause of heart attack and stroke, is the leading cause of death in most modern countries. Preventing clinical events depends on a better understanding of the mechanism of atherosclerotic plaque destabilization. Our knowledge on the characteristics of vulnerable plaques in humans has grown past decades. Histological studies have provided a precise definition of high-risk lesions and novel imaging methods for human atherosclerotic plaque characterization have made significant progress. However the pathological mechanisms leading from stable lesions to the formation of vulnerable plaques remain uncertain and the related clinical events are unpredictable. An animal model mimicking human plaque destablization is required as well as an in vivo imaging method to assess and monitor atherosclerosis progression. Magnetic resonance imaging (MRI) is increasingly used for in vivo assessment of atherosclerotic plaques in the human carotids. MRI provides well-characterized morphological and functional features of human atherosclerotic plaque which can be also assessed in animal models. This review summarizes the most common species used as animal models for experimental atherosclerosis, the techniques to induce atherosclerosis and to obtain vulnerable plaques, together with the role of MRI for monitoring atherosclerotic plaques in animals.

Reductionist thinking and animal models in neuropsychiatric research

2019 ◽  
Vol 42 ◽  
Author(s):  
Nicole M. Baran
Keyword(s):  
Animal Models ◽  
Mental Disorders ◽  
Environmental Factors ◽  
Neuropsychiatric Disorders ◽  
Model Organisms ◽  
Developmental Genetic ◽  
Term Study ◽  
Genetic And Environmental Factors ◽  
Mechanisms Of Plasticity

AbstractReductionist thinking in neuroscience is manifest in the widespread use of animal models of neuropsychiatric disorders. Broader investigations of diverse behaviors in non-model organisms and longer-term study of the mechanisms of plasticity will yield fundamental insights into the neurobiological, developmental, genetic, and environmental factors contributing to the “massively multifactorial system networks” which go awry in mental disorders.

A Cytochemical Study of Glucose-6-Phosphatase (G-6-PASE) in Cells Participating in Atherogenesis of Rabbit Aorta

1975 ◽  
Vol 33 ◽  
pp. 460-461
Author(s):  
Sidney D. Kobernick ◽  
Edna A. Elfont ◽  
Neddra L. Brooks
Keyword(s):  
Lipid Metabolism ◽  
New Zealand ◽  
Aortic Wall ◽  
Rabbit Aorta ◽  
Plaque Formation ◽  
Metabolic Changes ◽  
Atherosclerotic Plaques ◽  
Cytochemical Study ◽  
Cellular Alteration ◽  
New Zealand White Rabbits

This cytochemical study was designed to investigate early metabolic changes in the aortic wall that might lead to or accompany development of atherosclerotic plaques in rabbits. The hypothesis that the primary cellular alteration leading to plaque formation might be due to changes in either carbohydrate or lipid metabolism led to histochemical studies that showed elevation of G-6-Pase in atherosclerotic plaques of rabbit aorta. This observation initiated the present investigation to determine how early in plaque formation and in which cells this change could be observed.Male New Zealand white rabbits of approximately 2000 kg consumed normal diets or diets containing 0.25 or 1.0 gm of cholesterol per day for 10, 50 and 90 days. Aortas were injected jin situ with glutaraldehyde fixative and dissected out. The plaques were identified, isolated, minced and fixed for not more than 10 minutes. Incubation and postfixation proceeded as described by Leskes and co-workers.

Inflammational Animal Models for Schizophrenia

2015 ◽  
Vol 223 (3) ◽  
pp. 157-164 ◽  
Author(s):  
Georg Juckel
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
Immune Activation ◽  
Microglial Activation ◽  
Treatment Options ◽  
Early Adulthood ◽  
Brain Regions ◽  
Synaptic Connections ◽  
Preventive Interventions ◽  
Immunological System

Abstract. Inflammational-immunological processes within the pathophysiology of schizophrenia seem to play an important role. Early signals of neurobiological changes in the embryonal phase of brain in later patients with schizophrenia might lead to activation of the immunological system, for example, of cytokines and microglial cells. Microglia then induces – via the neurotoxic activities of these cells as an overreaction – a rarification of synaptic connections in frontal and temporal brain regions, that is, reduction of the neuropil. Promising inflammational animal models for schizophrenia with high validity can be used today to mimic behavioral as well as neurobiological findings in patients, for example, the well-known neurochemical alterations of dopaminergic, glutamatergic, serotonergic, and other neurotransmitter systems. Also the microglial activation can be modeled well within one of this models, that is, the inflammational PolyI:C animal model of schizophrenia, showing a time peak in late adolescence/early adulthood. The exact mechanism, by which activated microglia cells then triggers further neurodegeneration, must now be investigated in broader detail. Thus, these animal models can be used to understand the pathophysiology of schizophrenia better especially concerning the interaction of immune activation, inflammation, and neurodegeneration. This could also lead to the development of anti-inflammational treatment options and of preventive interventions.

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