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Journal of Internal Medicine Dec 2014Atherosclerosis is a silent chronic vascular pathology that is the cause of the majority of cardiovascular ischaemic events. The evolution of vascular disease involves a... (Review)
Review
Atherosclerosis is a silent chronic vascular pathology that is the cause of the majority of cardiovascular ischaemic events. The evolution of vascular disease involves a combination of endothelial dysfunction, extensive lipid deposition in the intima, exacerbated innate and adaptive immune responses, proliferation of vascular smooth muscle cells and remodelling of the extracellular matrix, resulting in the formation of an atherosclerotic plaque. High-risk plaques have a large acellular lipid-rich necrotic core with an overlying thin fibrous cap infiltrated by inflammatory cells and diffuse calcification. The formation of new fragile and leaky vessels that invade the expanding intima contributes to enlarge the necrotic core increasing the vulnerability of the plaque. In addition, biomechanical, haemodynamic and physical factors contribute to plaque destabilization. Upon erosion or rupture, these high-risk lipid-rich vulnerable plaques expose vascular structures or necrotic core components to the circulation, which causes the activation of tissue factor and the subsequent formation of a fibrin monolayer (coagulation cascade) and, concomitantly, the recruitment of circulating platelets and inflammatory cells. The interaction between exposed atherosclerotic plaque components, platelet receptors and coagulation factors eventually leads to platelet activation, aggregation and the subsequent formation of a superimposed thrombus (i.e. atherothrombosis) which may compromise the arterial lumen leading to the presentation of acute ischaemic syndromes. In this review, we will describe the progression of the atherosclerotic lesion along with the main morphological characteristics that predispose to plaque rupture, and discuss the multifaceted mechanisms that drive platelet activation and subsequent thrombus formation. Finally, we will consider the current scientific challenges and future research directions.
Topics: Atherosclerosis; Blood Coagulation; Endothelium, Vascular; Fibrinolysis; Humans; Necrosis; Plaque, Atherosclerotic; Rupture, Spontaneous; Thrombosis
PubMed: 25156650
DOI: 10.1111/joim.12296 -
European Journal of Pharmacology Dec 2017An ideal animal model of atherosclerosis resembles human anatomy and pathophysiology and has the potential to be used in medical and pharmaceutical research to obtain... (Review)
Review
An ideal animal model of atherosclerosis resembles human anatomy and pathophysiology and has the potential to be used in medical and pharmaceutical research to obtain results that can be extrapolated to human medicine. Moreover, it must be easy to acquire, can be maintained at a reasonable cost, is easy to handle and shares the topography of the lesions with humans. In general, animal models of atherosclerosis are based on accelerated plaque formation due to a cholesterol-rich/Western-type diet, manipulation of genes involved in the cholesterol metabolism, and the introduction of additional risk factors for atherosclerosis. Mouse and rabbit models have been mostly used, followed by pigs and non-human primates. Each of these models has its advantages and limitations. The mouse has become the predominant species to study experimental atherosclerosis because of its rapid reproduction, ease of genetic manipulation and its ability to monitor atherogenesis in a reasonable time frame. Both Apolipoprotein E deficient (ApoE) and LDL-receptor (LDLr) knockout mice have been frequently used, but also ApoE/LDLr double-knockout, ApoE3-Leiden and PCSK9-AAV mice are valuable tools in atherosclerosis research. However, a great challenge was the development of a model in which intra-plaque microvessels, haemorrhages, spontaneous atherosclerotic plaque ruptures, myocardial infarction and sudden death occur consistently. These features are present in ApoEFbn1 mice, which can be used as a validated model in pre-clinical studies to evaluate novel plaque-stabilizing drugs.
Topics: Animals; Atherosclerosis; Disease Models, Animal; Plaque, Atherosclerotic
PubMed: 28483459
DOI: 10.1016/j.ejphar.2017.05.010 -
Circulation Apr 2020Physical activity and exercise training are effective strategies for reducing the risk of cardiovascular events, but multiple studies have reported an increased... (Review)
Review
Physical activity and exercise training are effective strategies for reducing the risk of cardiovascular events, but multiple studies have reported an increased prevalence of coronary atherosclerosis, usually measured as coronary artery calcification, among athletes who are middle-aged and older. Our review of the medical literature demonstrates that the prevalence of coronary artery calcification and atherosclerotic plaques, which are strong predictors for future cardiovascular morbidity and mortality, was higher in athletes compared with controls, and was higher in the most active athletes compared with less active athletes. However, analysis of plaque morphology revealed fewer mixed plaques and more often only calcified plaques among athletes, suggesting a more benign composition of atherosclerotic plaques. This review describes the effects of physical activity and exercise training on coronary atherosclerosis in athletes who are middle-aged and older and aims to contribute to the understanding of the potential adverse effects of the highest doses of exercise training on the coronary arteries. For this purpose, we will review the association between exercise and coronary atherosclerosis measured using computed tomography, discuss the potential underlying mechanisms for exercise-induced coronary atherosclerosis, determine the clinical relevance of coronary atherosclerosis in middle-aged athletes and describe strategies for the clinical management of athletes with coronary atherosclerosis to guide physicians in clinical decision making and treatment of athletes with elevated coronary artery calcification scores.
Topics: Athletes; Computed Tomography Angiography; Coronary Angiography; Coronary Artery Disease; Exercise; Female; Humans; Male; Plaque, Atherosclerotic; Prevalence; Risk Factors; Vascular Calcification
PubMed: 32310695
DOI: 10.1161/CIRCULATIONAHA.119.044467 -
Journal of the American College of... Sep 2019It has been believed that most acute coronary events result from the rupture of mildly stenotic plaques, based on studies in which angiographic information was available... (Review)
Review
It has been believed that most acute coronary events result from the rupture of mildly stenotic plaques, based on studies in which angiographic information was available from many months to years before the event. However, serial studies in which angiographic data were available from the past as also within 1 to 3 months of myocardial infarction have clarified that nonobstructive lesions progressively enlarged relatively rapidly before the acute event occurred. Noninvasive computed tomography angiography imaging data have confirmed that lesions that did not progress voluminously over time rarely led to events, regardless of the extent of luminal stenosis or baseline high-risk plaque morphology. Therefore, plaque progression could be proposed as a necessary step between early, uncomplicated atherosclerosis and plaque rupture. On the other hand, it has been convincingly demonstrated that intensive lipid-lowering therapy (to a low-density lipoprotein cholesterol level of <70 mg/dl) halts plaque progression. Given the current ability to noninvasively detect the presence of early atherosclerosis, the importance of plaque progression in the pathogenesis of myocardial infarction, and the efficacy of maximum lipid-lowering therapy, it has been suggested that plaque progression is a modifiable step in the evolution of atherosclerotic plaque. A personalized approach based on the detection of early atherosclerosis can trigger the necessary treatment to prevent plaque progression and hence plaque instability. Therefore, this approach can redefine the traditional paradigm of primary and secondary prevention based on population-derived risk estimates and can potentially improve long-term outcomes.
Topics: Acute Coronary Syndrome; Acute Disease; Atherosclerosis; Disease Progression; Humans; Plaque, Atherosclerotic
PubMed: 31537271
DOI: 10.1016/j.jacc.2019.08.012 -
International Journal of Molecular... Apr 2020Atherosclerosis is a lipoprotein-driven inflammatory disorder leading to a plaque formation at specific sites of the arterial tree. After decades of slow progression,... (Review)
Review
Atherosclerosis is a lipoprotein-driven inflammatory disorder leading to a plaque formation at specific sites of the arterial tree. After decades of slow progression, atherosclerotic plaque rupture and formation of thrombi are the major factors responsible for the development of acute coronary syndromes (ACSs). In this regard, the detection of high-risk (vulnerable) plaques is an ultimate goal in the management of atherosclerosis and cardiovascular diseases (CVDs). Vulnerable plaques have specific morphological features that make their detection possible, hence allowing for identification of high-risk patients and the tailoring of therapy. Plaque ruptures predominantly occur amongst lesions characterized as thin-cap fibroatheromas (TCFA). Plaques without a rupture, such as plaque erosions, are also thrombi-forming lesions on the most frequent pathological intimal thickening or fibroatheromas. Many attempts to comprehensively identify vulnerable plaque constituents with different invasive and non-invasive imaging technologies have been made. In this review, advantages and limitations of invasive and non-invasive imaging modalities currently available for the identification of plaque components and morphologic features associated with plaque vulnerability, as well as their clinical diagnostic and prognostic value, were discussed.
Topics: Animals; Atherosclerosis; Biomarkers; Diagnostic Imaging; Disease Susceptibility; Humans; Molecular Imaging; Multimodal Imaging; Plaque, Atherosclerotic; Reproducibility of Results; Sensitivity and Specificity
PubMed: 32340284
DOI: 10.3390/ijms21082992 -
Journal of Atherosclerosis and... Jul 2023Intracranial branch atheromatous disease (BAD) is a pathological condition characterized by the occlusion of a relatively large perforating branch (700-800 µm) near the... (Review)
Review
Intracranial branch atheromatous disease (BAD) is a pathological condition characterized by the occlusion of a relatively large perforating branch (700-800 µm) near the orifice of a parent artery due to atherosclerotic plaque-based thrombus (microatheroma). BAD is refractory to treatment and follows a course of progressive exacerbation, especially motor paralysis. Uniform treatment for common atherothrombotic cerebral infarction or lacunar infarction does not prevent the progressive exacerbation of BAD, and consequently affects functional prognosis. To date, various combinations of treatments have been investigated and proposed to attenuate the worsening symptoms of BAD. However, no therapy with established efficacy is yet available for BAD. Since it is the most difficult condition to treat in the area of cerebral infarction, the establishment of optimal treatment methods for BAD is keenly awaited. This review presents an overview of the acute treatments available for BAD and discusses the prospects for optimal treatment.
Topics: Plaque, Atherosclerotic; Humans; Intracranial Thrombosis; Cerebral Infarction; Stroke, Lacunar; Dual Anti-Platelet Therapy
PubMed: 37183021
DOI: 10.5551/jat.RV22003 -
Cell Mar 2015One-fourth of all deaths in industrialized countries result from coronary heart disease. A century of research has revealed the essential causative agent:... (Review)
Review
One-fourth of all deaths in industrialized countries result from coronary heart disease. A century of research has revealed the essential causative agent: cholesterol-carrying low-density lipoprotein (LDL). LDL is controlled by specific receptors (LDLRs) in liver that remove it from blood. Mutations that eliminate LDLRs raise LDL and cause heart attacks in childhood, whereas mutations that raise LDLRs reduce LDL and diminish heart attacks. If we are to eliminate coronary disease, lowering LDL should be the primary goal. Effective means to achieve this goal are currently available. The key questions are: who to treat, when to treat, and how long to treat.
Topics: Animals; Cardiovascular Diseases; Cholesterol; Coronary Vessels; Dietary Fats; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Plaque, Atherosclerotic; Receptors, LDL
PubMed: 25815993
DOI: 10.1016/j.cell.2015.01.036 -
Redox Biology Aug 2017Atherosclerosis is a multifocal alteration of the vascular wall of medium and large arteries characterized by a local accumulation of cholesterol and non-resolving... (Review)
Review
Atherosclerosis is a multifocal alteration of the vascular wall of medium and large arteries characterized by a local accumulation of cholesterol and non-resolving inflammation. Atherothrombotic complications are the leading cause of disability and mortality in western countries. Neovascularization in atherosclerotic lesions plays a major role in plaque growth and instability. The angiogenic process is mediated by classical angiogenic factors and by additional factors specific to atherosclerotic angiogenesis. In addition to its role in plaque progression, neovascularization may take part in plaque destabilization and thromboembolic events. Anti-angiogenic agents are effective to reduce atherosclerosis progression in various animal models. However, clinical trials with anti-angiogenic drugs, mainly anti-VEGF/VEGFR, used in anti-cancer therapy show cardiovascular adverse effects, and require additional investigations.
Topics: Angiogenesis Inhibitors; Animals; Clinical Trials as Topic; Disease Progression; Humans; Neovascularization, Pathologic; Oxidative Stress; Plaque, Atherosclerotic
PubMed: 28212521
DOI: 10.1016/j.redox.2017.01.007 -
Swiss Dental Journal 2017Rupture of an atherosclerotic plaque is the usual initiating event in an acute coronary syndrome (ACS). Persistent thrombotic occlusion at the site of plaque rupture...
Rupture of an atherosclerotic plaque is the usual initiating event in an acute coronary syndrome (ACS). Persistent thrombotic occlusion at the site of plaque rupture results in acute myocardial infarction. The early management of the patient is essential and crucially affects the prognosis of an ACS. Management includes the relief of ischemic pain and the initiation of an antithrombotic therapy, including an antiplatelet and anticoagulant therapy with aspirin and heparin to prevent further thrombosis of or embolism from an ulcerated plaque.
Topics: Acute Coronary Syndrome; Anticoagulants; Coronary Thrombosis; Drug Therapy, Combination; Early Medical Intervention; Humans; Myocardial Infarction; Plaque, Atherosclerotic; Platelet Aggregation Inhibitors; Prognosis; Rupture, Spontaneous
PubMed: 28266687
DOI: No ID Found -
Journal of Internal Medicine Nov 2015Atherosclerosis is a maladaptive, nonresolving chronic inflammatory disease that occurs at sites of blood flow disturbance. The disease usually remains silent until a... (Review)
Review
Atherosclerosis is a maladaptive, nonresolving chronic inflammatory disease that occurs at sites of blood flow disturbance. The disease usually remains silent until a breakdown of integrity at the arterial surface triggers the formation of a thrombus. By occluding the lumen, the thrombus or emboli detaching from it elicits ischaemic symptoms that may be life-threatening. Two types of surface damage can cause atherothrombosis: plaque rupture and endothelial erosion. Plaque rupture is thought to be caused by loss of mechanical stability, often due to reduced tensile strength of the collagen cap surrounding the plaque. Therefore, plaques with reduced collagen content are thought to be more vulnerable than those with a thick collagen cap. Endothelial erosion, on the other hand, may occur after injurious insults to the endothelium instigated by metabolic disturbance or immune insults. This review discusses the molecular mechanisms involved in plaque vulnerability and the development of atherothrombosis.
Topics: Animals; Cysteine Proteases; Endothelium, Vascular; Humans; Inflammation; Matrix Metalloproteinases; Plaque, Atherosclerotic; Rupture, Spontaneous; Thromboembolism
PubMed: 26260307
DOI: 10.1111/joim.12406