The Role of Inflammation in Plaque Rupture

2002 ◽  
pp. 86-101
Keyword(s):  
Plaque Rupture

Current Concepts in Cardiovascular Pathology: The Role of LDL Cholesterol in Plaque Rupture and Stabilization

1998 ◽  
Vol 104 (2) ◽  
pp. 14S-18S ◽  
Author(s):  
Peter Libby ◽  
Uwe Schoenbeck ◽  
Francois Mach ◽  
Andrew P Selwyn ◽  
Peter Ganz
Keyword(s):  
Ldl Cholesterol ◽  
Plaque Rupture ◽  
Cardiovascular Pathology

scholarly journals Research Progress on the Relationship between Atherosclerosis and Inflammation

Biomolecules ◽  
2018 ◽  
Vol 8 (3) ◽  
pp. 80 ◽  
Author(s):  
Yuhua Zhu ◽  
Xuemei Xian ◽  
Zhenzhen Wang ◽  
Yingchao Bi ◽  
Quangang Chen ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Plaque Rupture ◽  
Chronic Inflammatory Disease ◽  
Research Progress ◽  
Bioactive Lipids ◽  
Inflammatory Signaling ◽  
Vascular Stenosis ◽  
Unstable Atherosclerotic Plaque ◽  
Atherosclerotic Plaque Rupture

Atherosclerosis is a chronic inflammatory disease; unstable atherosclerotic plaque rupture, vascular stenosis, or occlusion caused by platelet aggregation and thrombosis lead to acute cardiovascular disease. Atherosclerosis-related inflammation is mediated by proinflammatory cytokines, inflammatory signaling pathways, bioactive lipids, and adhesion molecules. This review discusses the effects of inflammation and the systemic inflammatory signaling pathway on atherosclerosis, the role of related signaling pathways in inflammation, the formation of atherosclerosis plaques, and the prospects of treating atherosclerosis by inhibiting inflammation.

Role of Microparticles in Hemostasis and Thrombosis

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. SCI-10-SCI-10
Author(s):  
Nigel Mackman
Keyword(s):  
Venous Thrombosis ◽  
Vessel Wall ◽  
Mononuclear Cells ◽  
Plaque Rupture ◽  
Pulmonary Arteries ◽  
Membrane Vesicles ◽  
Murine Models ◽  
Plasma Membrane Vesicles ◽  
Membrane Asymmetry

Abstract SCI-10 Microparticles (MPs) (also known as or microvesicles) are submicron plasma membrane vesicles released from activated or apoptotic cells. Current estimates indicate that MPs are ∼200 nm in diameter. They are formed as membrane blebs and have phosphatidylserine exposed on the surface due to a loss of membrane asymmetry. MPs containing tissue factor (TF) are highly procoagulant. We recently developed an assay to measure TF activity of MPs isolated from plasma. We found that healthy individuals contain low levels of TF+ MPs, but levels are increased in many pathological conditions associated with thrombosis, such as sepsis, cardiovascular disease, sickle cell disease, diabetes mellitus, and cancer. We have analyzed the role of TF+ MPs in various murine models of thrombosis and in different patient populations. Work in collaboration with Bruce and Barbara Furie demonstrated that leukocyte-derived TF+ MPs contributed to microvascular thrombosis in a model of laser injured cremaster arterioles using healthy mice. Further studies have been performed using different murine models of disease. Arterial thrombosis is mostly caused by rupture of atherosclerotic plaques and leads to myocardial infarction and stroke. In hypercholesterolemic LDLR−/− mice we observed increased levels of hematopoietic cell-derived TF+ MPs that were associated with a prothrombotic state. These TF+ MPs may enhance thrombosis after plaque rupture. Indeed, we observed more fibrin deposition in the laser injury model of thrombosis in hypercholesterolemic mice than controls. Importantly, we found that simvastatin reduced TF expression in mononuclear cells and levels of TF+ MPs in the plasma in these hypercholesterolemic mice. Venous thrombosis occurs without significant damage to the vessel wall and is associated with embolization of clot fragments that can block pulmonary arteries. Venous clots appear to form due to changes in the vessel wall, stasis, and/or increased coagulability of the blood. We have analyzed levels of TF+ MPs in murine cancer models and cancer patient samples. We and other have found that tumors release TF+ MPs into the circulation. In one study, we found that pancreatic patients with the highest levels of MP TF activity develop thrombosis. These results suggest that TF+ MPs may enhance venous thrombosis in cancer patients by binding to activated endothelium. Further studies are needed to determine if levels of TF+ MPs in the circulation can be used to identify patients at risk for thrombosis. Disclosures: Mackman: Merck: Consultancy; Daiichi: Consultancy; Daiichi: Research Funding.

scholarly journals Insights Into the Role of Infection in Atherogenesis and in Plaque Rupture

Circulation ◽  
2009 ◽  
Vol 119 (24) ◽  
pp. 3133-3141 ◽  
Author(s):  
Stephen E. Epstein ◽  
Jianhui Zhu ◽  
Amir H. Najafi ◽  
Mary S. Burnett
Keyword(s):  
Plaque Rupture

scholarly journals Role of Matrix Metalloproteinase-8 in Atherosclerosis

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Sébastien Lenglet ◽  
François Mach ◽  
Fabrizio Montecucco
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Matrix Metalloproteinase ◽  
Plaque Rupture ◽  
Experimental Atherosclerosis ◽  
Atherosclerotic Plaques ◽  
Regulatory Pathways ◽  
Neutrophil Collagenase

Plaque rupture is the main cause of acute myocardial infarction and stroke. Atherosclerotic plaques have been described to be vulnerable and more prone to rupture when they are characterized by thin, highly inflamed, and collagen-poor fibrous caps and contain elevated levels of proteases, including metalloproteinases (MMPs). Initiation of collagen breakdown in plaques requires interstitial collagenases, a MMP subfamily consisting of MMP-1, MMP-8, and MMP-13. Previous reports demonstrated that MMP-1 and MMP-13 might be overexpressed in both human and experimental atherosclerosis. Since neutrophils have been only recently reported in atherosclerotic plaques, the role of MMP-8 (formerly known as “neutrophil collagenase”) was only marginally evaluated. In this paper, we will update and comment on evidence of the most relevant regulatory pathways and activities mediated by MMP-8 in atherogenesis.

Comparison of two murine models of thrombosis induced by atherosclerotic plaque injury

2011 ◽  
Vol 105 (S 06) ◽  
pp. S3-S12 ◽  
Author(s):  
Béatrice Hechler ◽  
Christian Gachet
Keyword(s):  
Atherosclerotic Plaque ◽  
Plaque Rupture ◽  
Vascular Lesions ◽  
Murine Models ◽  
Atherosclerotic Lesions ◽  
Human Pathology ◽  
Rupture Model ◽  
Atherosclerotic Plaque Rupture ◽  
Collagen Receptor

SummaryArterial thrombosis occurs at sites of erosion or rupture of atherosclerotic vascular lesions. To better study the pathophysiology of this complex phenomenon, there is a need for animal models of localised thrombosis at sites of atherosclerotic lesions with closer resemblance to the human pathology as compared to commonly used thrombosis models in healthy vessels. In the present study, we describe and compare a new model of thrombosis induced by atherosclerotic plaque rupture in the carotid artery from ApoE-/- mice using a suture needle to a milder model of ultrasound-induced plaque injury. Needle injury induces atherosclerotic plaque rupture with exposure of plaque material and formation of a thrombus that is larger, nearly occlusive and more stable as compared to that formed by application of ultrasounds. These two models have common features such as the concomitant involvement of platelet activation, thrombin generation and fibrin formation, which translates into sensitivity toward both antiplatelet drugs and anticoagulants. On the other hand, they display differences with respect to the role of the platelet collagen receptor GPVI, the plaque rupture model being less sensitive to its inhibition as compared to the ultrasound-induced injury, which may be related to the amount of thrombin generated. These models represent an improvement as compared to models in healthy vessels and may help identify specific plaque triggers of thrombosis. They should therefore be useful to evaluate new antithrombotic targets.

scholarly journals Potential Mechanisms and Effects of Efferocytosis in Atherosclerosis

2021 ◽  
Vol 11 ◽  
Author(s):  
Lili Wang ◽  
Hongxia Li ◽  
Yuhan Tang ◽  
Ping Yao
Keyword(s):  
Therapeutic Strategy ◽  
Molecular Mechanisms ◽  
Plaque Rupture ◽  
Cerebrovascular Diseases ◽  
Necrotic Core ◽  
Dynamic Regulation ◽  
Physiological Conditions ◽  
Great Progress ◽  
Abnormal Accumulation

Atherosclerosis (AS) is the main pathological basis for the development of cardio-cerebrovascular diseases. Abnormal accumulation of apoptotic and necrotic cells resulted in plaque enlargement, necrotic core formation and plaque rupture in AS. Under physiological conditions, apoptotic cells (ACs) could be effectively phagocytized and cleared by phagocyte-mediated efferocytosis. In contrast, the clearance efficiency of ACs in AS plaque was much lower because of the impaired efferocytosis in AS. Recent findings have made great progress on the molecular mechanisms of efferocytosis process and dynamic regulation, and its dysfunction on organismal health. Yet, there are still few effective treatments for this process. This article reviews the mechanism of efferocytosis and the role of efferocytosis in AS, highlighting a novel therapeutic strategy for AS, which mainly prevents the progression of plaque by targeting efferocytosis.

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