Dual Role of Matrix Metalloproteinases (Matrixins) in Intimal Thickening and Atherosclerotic Plaque Rupture

2005 ◽  
Vol 85 (1) ◽  
pp. 1-31 ◽  
Author(s):  
Andrew C. Newby
Keyword(s):  
Myocardial Infarction ◽  
Extracellular Matrix ◽  
Matrix Metalloproteinases ◽  
Vessel Wall ◽  
Plaque Rupture ◽  
Coronary Thrombosis ◽  
Wall Stress ◽  
Intimal Thickening ◽  
Vessel Wall Thickness ◽  
Tissue Ischemia

Intimal thickening, the accumulation of cells and extracellular matrix within the inner vessel wall, is a physiological response to mechanical injury, increased wall stress, or chemical insult (e.g., atherosclerosis). If excessive, it can lead to the obstruction of blood flow and tissue ischemia. Together with expansive or constrictive remodeling, the extent of intimal expansion determines final lumen size and vessel wall thickness. Plaque rupture represents a failure of intimal remodeling, where the fibrous cap overlying an atheromatous core of lipid undergoes catastrophic mechanical breakdown. Plaque rupture promotes coronary thrombosis and myocardial infarction, the most prevalent cause of premature death in advanced societies. The matrix metalloproteinases (MMPs) can act together to degrade the major components of the vascular extracellular matrix. All cells present in the normal and diseased blood vessel wall upregulate and activate MMPs in a multistep fashion driven in part by soluble cytokines and cell-cell interactions. Activation of MMP proforms requires other MMPs or other classes of protease. MMP activation contributes to intimal growth and vessel wall remodeling in response to injury, most notably by promoting migration of vascular smooth muscle cells. A broader spectrum and/or higher level of MMP activation, especially associated with inflammation, could contribute to pathological matrix destruction and plaque rupture. Inhibiting the activity of specific MMPs or preventing their upregulation could ameliorate intimal thickening and prevent myocardial infarction.

Human Carotid Atherosclerotic Plaque Growth Function and Progression Simulation Using Meshless GFD and Statistical Methods Based on Multi-Year In Vivo MRI

2008 ◽  
Author(s):  
Chun Yang ◽  
Joseph D. Petruccelli ◽  
Zhongzhao Teng ◽  
Chun Yuan ◽  
Gador Canton ◽  
...  
Keyword(s):  
Atherosclerotic Plaque ◽  
Wall Thickness ◽  
Vessel Wall ◽  
Plaque Rupture ◽  
Patient Specific ◽  
Tracking Data ◽  
Plaque Progression ◽  
Vessel Wall Thickness ◽  
Plaque Growth

Atherosclerotic plaque rupture and progression have been the focus of intensive investigations in recent years. The mechanisms governing plaque progression and rupture process are not well understood. Using computational models based on patient-specific multi-year in vivo MRI data, our recent results indicated that 18 out of 21 patients studied showed significant negative correlation between plaque progression measured by vessel wall thickness increase (WTI) and plaque wall (structural) stress (PWS) [1]. In this paper, a computational procedure based on meshless generalized finite difference (MGFD) method and serial magnetic resonance imaging (MRI) data was introduced to simulate plaque progression. Participating patients were scanned three times (T1, T2, and T3, at intervals of approximately 18 months) to obtain plaque progression data. Vessel wall thickness (WT) changes were used as the measure for plaque progression. Starting from T2 plaque geometry, plaque progression was simulated by solving the solid model and adjusting wall thickness using plaque growth functions iteratively until time T3 is reached. Numerically simulated plaque progression showed very good agreement with actual plaque geometry at T3 given by MRI data. We believe this is the first time plaque progression simulation results based on multi-year patient-tracking data are reported. Multi-year tracking data and MRI-based progression simulation add time dimension to plaque vulnerability assessment and will improve prediction accuracy.

PATHOGENETIC AND ANGIOGRAPHIC FEATURES IN UNSTABLE ANGINAAND OTHER ACUTE CORONARY SYNDROMES

1987 ◽  
Author(s):  
V Fusler ◽  
L Badimon ◽  
V Turitto ◽  
JJ Badimon ◽  
PC Adams ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Unstable Angina ◽  
Acute Coronary Syndromes ◽  
Vessel Wall ◽  
Plaque Rupture ◽  
Thrombus Formation ◽  
Arterial Injury ◽  
Coronary Syndromes ◽  
Wall Interaction ◽  
Q Wave

Angiography in patients with unstable angina or myocardial infarction with subtotal coronary occlusions reveals eccentric stenoses with irregularborders suggesting ruptured atherosclerotic plaques. In addition, the closer the angiogram is to the time of chest pain the higher is the likelihoodof observing a thrombotic filling defect distal to the stenotic region. Thus, we: 1) have investigated the relationship among platelet-vessel wall interaction, rheology, andthrombogenicsubstrate and 2) propose a hypothesisaccounting for thrombosis in the acute coronary syndromes.1) Platelet Vessel Wall Interactions, Rheology and Substrate - We have studied substrate and rheology in both an 'ex vivo' perfusion chamber and 'in vivo'swine model. Qur results, combinedwith those of others, show the following:-Platelet Vessel Wall Interaction and Thrombus Formation - a) In superficial arterial injury plateletsadherevia platelet membrane glycoprotein (GP) lb to the vessel wall to form a monolayer. Von Willebrand Factor (vWF), a high molecular weight glycoprotein found in plasma, platelets, and endothelial cells, binds GPIb and supports platelet adhesion. Platelet derived growth factors(PDGF) from these adherent platelets may contribute to atherogenesis. b) In deep arterial injury, plateletsare stimulated by three pathways -arachidonate, ADP and the "third pathway" -leading to exposure of platelet receptors (GPIIb/IIIa), and subsequent aggregation. Fibrinogenand vWF participate in aggregation bybinding to GPIIb/IIIa. Simultaneously, thrombin stimulates aggregation andthe formation of fibrin that stabilizes platelet aggregates, c) Both a platelet monolayer and aggregation with thrombosis, produce vasoconstriction due to release of platelet products (serotonin, thromboxane A2,and PDGF).- Rheology - a) Stenotic lesions produce a high local shear rate, whichenhances platelet-vessel wall interaction and, in the presence of acute rupture, platelet deposition and subsequent thrombus formation, b) Platelet deposition and thrombosis are particularly favored if the site of rupture includes the stenosis with its high shear rate,while the stasis in the post-stenotic region favors proprogationof thrombus.- Substrate - a) Plaque rupture produces a rough surface and exposes collagen and fat to flowing blood. Thisstimulates mural thrombosis, b) Such thrombus is either fixed or labile depending on the degree of plaque rupture or damage.2) Acute and Subacute Coronary Syndromes - The above observations in the swine model, coupled with recent clinical and pathological observations support the following:-Unstable Angina - Mild or restricted plaque rupture with or without activated mural thrombus, by increasingthe stenosis, explains the increase in exertional angina; subsequent labile thrombosis with platelet-related vasoconstriction explains the resting angina.-Q Wave Myocardial Infarction - The thrombus is occlusive and fixed or persistent because the damage to the vessel wall or to the plaque is more severe or extensive than in unstable angina.-Non-Q Wave Myocardial Infarction -In this syndrome, intermediate between unstable angina and Q wave myocardial infarction, the occlusive thrombus is more transient than in Q wave infarction because of less substrate exposure or damage.

Proteomic profiling of acute coronary thrombosis reveals a local decrease in pigment epithelium-derived factor in acute myocardial infarction

2012 ◽  
Vol 123 (2) ◽  
pp. 111-119 ◽  
Author(s):  
Klaus Distelmaier ◽  
Christopher Adlbrecht ◽  
Johannes Jakowitsch ◽  
Oswald Wagner ◽  
Christopher Gerner ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Plaque Rupture ◽  
Coronary Thrombosis ◽  
Pigment Epithelium ◽  
Coronary Plaque ◽  
Diabetic Patients ◽  
Label Free ◽  
Proteomic Profiling ◽  
Pigment Epithelium Derived Factor

Thrombotic occlusion of an epicardial coronary artery on the grounds of atherosclerotic plaque is considered the ultimate step in AMI (acute myocardial infarction). However, the precise pathophysiological mechanisms underlying acute coronary occlusion are not fully understood. We have analysed proteomic profiles of systemic plasma and plasma derived from the site of coronary plaque rupture of non-diabetic patients with STEMI (ST-segment elevation myocardial infarction). Label-free quantification of MS/MS (tandem MS) data revealed differential regulation of complement cascade components and a decrease in anti-thrombotic PEDF (pigment epithelium-derived factor) between CS (culprit site)-derived plasma and systemic plasma. PEDF, which is known to have a protective role in atherothrombosis, was relatively decreased at the CS, with a level of expression inverse to local MMP-9 (matrix metalloproteinase-9) activity. CS plasma displayed enhanced proteolytic activity towards PEDF. Proteomics of coronary thrombus aspirates indicate that PEDF processing is associated with coronary plaque rupture.

scholarly journals Coronary Thrombosis without Dissection following Blunt Trauma

2016 ◽  
Vol 2016 ◽  
pp. 1-4 ◽  
Author(s):  
Archana Sinha ◽  
Michael Sibel ◽  
Peter Thomas ◽  
Francis Burt ◽  
James Cipolla ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Blunt Trauma ◽  
Coronary Occlusion ◽  
Plaque Rupture ◽  
Coronary Thrombosis ◽  
Artery Dissection ◽  
Coronary Artery Dissection ◽  
First Case ◽  
St Elevation ◽  
Ivus Imaging

Blunt trauma to the chest resulting in coronary thrombosis and ST elevation myocardial infarction (STEMI) is a rare but well-described occurrence in adults. Angiography in such cases has generally disclosed complete epicardial coronary occlusion with thrombus, indistinguishable from the findings commonly found in spontaneous plaque rupture due to atherosclerotic disease. In all previously reported cases in which coronary interrogation with intravascular ultrasound (IVUS) was performed in association with acute revascularization, coronary artery dissection was implicated as the etiology of coronary thrombosis. We present the first case report of blunt trauma-associated coronary thrombosis without underlying atherosclerosis or coronary dissection, as documented by IVUS imaging.

scholarly journals Coronary embolism due to possible thrombosis of prosthetic aortic valve - the role of optical coherence tomography: case report

2021 ◽  
Vol 5 (7) ◽  
Author(s):  
Raminta Kavaliauskaite ◽  
Tatsuhiko Otsuka ◽  
Yasushi Ueki ◽  
Lorenz Räber
Keyword(s):  
Myocardial Infarction ◽  
Optical Coherence Tomography ◽  
Aortic Valve ◽  
Vessel Wall ◽  
Plaque Rupture ◽  
Left Ventricular ◽  
Valve Prosthesis ◽  
Optical Coherence ◽  
Prosthetic Aortic Valve ◽  
Coronary Embolism

Abstract Background Coronary embolism is an important non-atherosclerotic cause of acute myocardial infarction (AMI) that requires an individualized diagnostic and therapeutic approach. Although certain angiographic criteria exist that render an embolic origin likely, uncertainty remains. Optical coherence tomography (OCT) is a high-resolution intracoronary imaging technology that enables visualization of thrombus and the underlying coronary vessel wall, which may be helpful to distinguish between an atherosclerotic and non-atherosclerotic origin of AMI. Case summary  A 50-year-old male was admitted with ongoing chest pain. Eleven years ago, he underwent implantation of a mechanical aortic valve prosthesis due to degenerated bicuspid valve with normal coronaries on preoperative angiography. The electrocardiogram showed anterior ST-segment elevation. Emergent angiography revealed total occlusion of the proximal left anterior descending artery (LAD). Thrombus was aspirated along with administration of intravenous glycoprotein IIbIIIa inhibitor. Except the apical part of the LAD showing distal embolization, coronary flow was completely re-established with no evidence of significant atherosclerosis. Stents were not implanted on the basis of the OCT finding, which demonstrated at the site of occlusion a normal vessel wall without atherosclerosis that could explain an erosion or plaque rupture event. Transoesophageal echocardiography confirmed a floating structure in the left ventricular outflow tract, suggesting that an embolus originating from the prosthetic aortic valve obstructed the LAD. The international normalized ratio 2 days prior to presentation measured 1.9. Discussion  This case illustrates the utility of OCT to rule out the atherosclerotic aetiology of myocardial infarction and to avoid unnecessary stenting.

Development of a Quantitative Mechanical Test of Atherosclerotic Plaque Stability

2010 ◽  
Author(s):  
Ying Wang ◽  
Jinfeng Ning ◽  
Michael A. Sutton ◽  
Susan M. Lessner
Keyword(s):  
Myocardial Infarction ◽  
Atherosclerotic Plaque ◽  
Plaque Rupture ◽  
Mechanical Test ◽  
Coronary Thrombosis ◽  
Plaque Stability ◽  
Fibrous Cap ◽  
Clinical Observations ◽  
Poor Understanding ◽  
Atherosclerotic Plaque Rupture

Atherosclerotic plaque rupture is the main cause of myocardial infarction, coronary thrombosis and stroke. Current clinical observations suggest that an advanced plaque features a thin, collagen-rich fibrous cap infiltrated by macrophages, overlying a large lipid core rich in lipid-laden macrophages. However, due to relatively poor understanding of mechanisms associated with plaque rupture, there is no quantitative standard for plaque stability estimation.

scholarly journals Takotsubo Cardiomyopathy

2015 ◽  
Vol 10 (1) ◽  
pp. 25 ◽  
Author(s):  
Esha Sachdev ◽  
C Noel Bairey Merz ◽  
Puja K Mehta ◽  
◽  
◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Takotsubo Cardiomyopathy ◽  
Acute Stress ◽  
Plaque Rupture ◽  
Coronary Thrombosis ◽  
Coronary Microvascular Dysfunction ◽  
Coronary Syndrome ◽  
Menopausal Women ◽  
Post Menopausal

Takotsubo cardiomyopathy (TTC) is an acute, stress-induced cardiomyopathy with an increased prevalence in post-menopausal women. The syndrome is most frequently precipitated by an acute emotional or physical stressor and mimics acute myocardial infarction with symptoms, electrocardiogram (ECG) changes and cardiac troponin elevation that are indistinguishable from those caused by plaque rupture or coronary thrombosis. Diagnosis of TTC is made when coronary angiography reveals no obstructive coronary artery disease and the left ventricle demonstrates apical ballooning and basal hypercontractility. Other ventricular patterns have also been described. An abnormal myocardial response to the catecholamine surge from an emotional or a physical stressor is implicated in the pathophysiology, but the reasons for the high prevalence of TTC presentations in post-menopausal women are unknown. Several mechanisms including multi-vessel coronary vasospasm, endothelial and coronary microvascular dysfunction and direct catecholamine toxicity have been proposed. No specific guidelines for treatment of TTC have been established, but treatment is based on the American Heart Association/ American College of Cardiology guidelines for acute coronary syndrome/acute myocardial infarction and heart failure guidelines. In this review article, we discuss the characteristic clinical presentation of TTC and the commonly proposed mechanisms.

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