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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inflammation plays a major role in all phases of atherosclerosis. Stable plaques are characterized by a chronic inflammatory infiltrate, whereas vulnerable and ruptured plaques are characterized by an "active" inflammation involved in the thinning of the fibrous cap, predisposing the plaque to rupture. Although a single vulnerable atherosclerotic plaque rupture may cause the event, there are many other types of plaques, several of which are vulnerable. The existence of multiple types of vulnerable plaques suggests that atherosclerosis is a diffuse inflammatory process. A current challenge is to identify morphologic and molecular markers able to discriminate stable plaques from vulnerable ones, allowing the stratification of patients at high risk for acute cardiovascular and cerebrovascular events before clinical syndromes develop. With that aim in mind, this article summarizes the natural history of atherosclerotic plaques, focusing on molecular mechanisms affecting plaque progression and serum markers correlated with plaque inflammation.
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PMID:Role of inflammation in atherosclerosis. 1797 52

Plaque rupture is the most common type of plaque complication and leads to acute ischaemic events such as myocardial infarction and stroke. Calcification has been suggested as a possible indicator of plaque instability. Although the role of matrix vesicles in the initial stages of arterial calcification has been recognized, no studies have yet been carried out to examine a possible role of matrix vesicles in plaque destabilization. Tissue specimens selected for the present study represented carotid specimens obtained from patients undergoing carotid endarterectomy. Serial frozen cross-sections of the tissue specimens were cut and mounted on glass slides. The thickness of the fibrous cap (FCT) in each advanced atherosclerotic lesion, containing a well developed lipid/necrotic core, was measured at its narrowest sites in sets of serial sections. According to established criteria, atherosclerotic plaque specimens were histologically subdivided into two groups: vulnerable plaques with thin fibrous caps (FCT <100 microm) and presumably stable plaques, in which fibrous caps were thicker than 100 microm. Twenty-four carotid plaques (12 vulnerable and 12 presumably stable plaques) were collected for the present analysis of matrix vesicles in fibrous caps. In order to provide a sufficient number of representative areas from each plaque, laser capture microdissection (LCM) was carried out. The quantification of matrix vesicles in ultrathin sections of vulnerable and stable plaques revealed that the numbers of matrix vesicles were significantly higher in fibrous caps of vulnerable plaques than those in stable plaques (8.908+0.544 versus 6.208+0.467 matrix vesicles per 1.92 microm2 standard area; P= 0.0002). Electron microscopy combined with X-ray elemental microanalysis showed that some matrix vesicles in atherosclerotic plaques were undergoing calcification and were characterized by a high content of calcium and phosphorus. The percentage of calcified matrix vesicles/microcalcifications was significantly higher in fibrous caps in vulnerable plaques compared with that in stable plaques (6.705+/-0.436 versus 5.322+/-0494; P= 0.0474). The findings reinforce a view that the texture of the extracellular matrix in the thinning fibrous cap of atherosclerotic plaque is altered and this might contribute to plaque destabilization.
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PMID:Matrix vesicles in the fibrous cap of atherosclerotic plaque: possible contribution to plaque rupture. 1819 56

To improve the performance of endovascular grafts used for the treatment of abdominal aortic aneurysms, we develop a methodology to analyze the phenomena of type I endoleaks in a non-invasive-stented abdominal aorta. As one aspect of this study, an evaluation of the parietal stresses generated by the blood flow is provided. As blood is known to be a shear-thinning, non-Newtonian fluid, we have chosen to use the Phan-Thien and Tanner model, which can be derived from the rheology of polymer solutions. As a second aspect, we develop an axisymmetric finite-element model of the complete system. An explicit finite-element in-house code, is used to simulate the behavior of the system, which is subjected to hydrostatic pressure and to the stresses generated by the blood flow. As the response of the solid is strongly affected by the response of the fluid, and vice versa, the modeling of a coupled fluid-structure interaction is achieved in this work. This study provides an evaluation of the stresses generated by the blood flow on the aorta's wall. The finite-element model allows to identify biomechanical factors that can influence the propensity of an aneurysm treated with an endograft, to exhibit endoleaks. First observations are made concerning the influence of oversizing of the endograft and the influence of friction coefficients between the aorta, endograft and plaque.
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PMID:Analysis of type I endoleaks in a stented abdominal aortic aneurysm. 1850 63

Atherosclerosis still represents killer number one in industrialized nations, and is starting to have increased impact in developing countries. Atherosclerotic plaques are the net result of a complex interplay between vascular cholesterol deposition, inflammatory activity and extracellular matrix formation. The result is luminal narrowing of arteries, which may ultimately lead to compromised blood flow to essential body organs, most notoriously to the heart. Most of the cardiovascular events that are caused by atherosclerosis, such as acute myocardial infarction or stroke, are the result of a transition of so-called stable atherosclerotic plaques to vulnerable plaques, that are prone to rupture. The direct consequence of atherosclerotic plaque rupture is exposure of thrombogenic plaque constituents to the blood, leading to instant local thrombus formation. The formation of this localized thrombus may ultimately result in sudden obstruction of blood flow and consequent infarction of distal tissue. Clinical risk profiling methods, such as the Framingham and Procam risk scores, are reasonable predictors of myocardial infarction over a 10-year time-span. However, the challenge remains to identify those patients with a very high risk of suffering from myocardial infarction in the coming months. Imaging may provide the necessary diagnostic information to identify such individuals. The transition of stable atherosclerotic plaques to vulnerable plaques is typically heralded by inflammation, thinning of the overlying fibrous cap, and the presence of a large necrotic core. Apoptosis is linked to all of these features of plaque vulnerability, and may, therefore, provide uniquely useful targets for the identification of plaque vulnerability. In recent years, a number of molecular imaging technologies have been developed to image apoptosis, which will be discussed in this review. Further development of apoptosis imaging technologies may aid us in the years to come in the quest to identify patients with critical cardiovascular risks, to treat myocardial infarction in its imminent, instead of its evident phase.
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PMID:PET and SPECT imaging of apoptosis in vulnerable atherosclerotic plaques with radiolabeled Annexin A5. 1918 25

Atherothrombotic vascular diseases, such as myocardial infarction and stroke, are the leading causes of death in the industrialized world. The immediate cause of these diseases is acute occlusive thrombosis in medium-sized arteries feeding critical organs. Thrombosis is triggered by the rupture or erosion of a minority of atherosclerotic plaques that have advanced to a particular stage of "vulnerability." Vulnerable plaques are characterized by certain key features, such as inflammation, thinning of a protective collagenous cap, and a lipid-rich necrotic core consisting of macrophage debris. A number of cellular events contribute to vulnerable plaque formation, including secretion of pro-inflammatory, procoagulant, and proteolytic molecules by macrophages as well as the death of macrophages, intimal smooth muscles cells, and possibly endothelial cells. The necrotic core in particular is a key factor in plaque vulnerability, because macrophage debris promotes inflammation, plaque instability, and thrombosis. Plaque necrosis arises from a combination of lesional macrophage apoptosis and defective clearance of these dead cells, a process called efferocytosis. This review focuses on how macrophage apoptosis, in the setting of defective efferocytosis, contributes to necrotic core formation and how a process known to be prominent in advanced lesions--activation of ER stress signal-transduction pathways--contributes to macrophage apoptosis in these plaques.
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PMID:Macrophage apoptosis in atherosclerosis: consequences on plaque progression and the role of endoplasmic reticulum stress. 1924 35

ER stress occurs in macrophage-rich areas of advanced atherosclerotic lesions and contributes to macrophage apoptosis and subsequent plaque necrosis. Therefore, signaling pathways that alter ER stress-induced apoptosis may affect advanced atherosclerosis. Here we placed Apoe-/- mice deficient in macrophage p38alpha MAPK on a Western diet and found that they had a marked increase in macrophage apoptosis and plaque necrosis. The macrophage p38alpha-deficient lesions also exhibited a significant reduction in collagen content and a marked thinning of the fibrous cap, which suggests that plaque progression was advanced in these mice. Consistent with our in vivo data, we found that ER stress-induced apoptosis in cultured primary mouse macrophages was markedly accelerated under conditions of p38 inhibition. Pharmacological inhibition or genetic ablation of p38 suppressed activation of Akt in cultured macrophages and in atherosclerotic lesions. In addition, inhibition of Akt enhanced ER stress-induced macrophage apoptosis, and expression of a constitutively active myristoylated Akt blocked the enhancement of ER stress-induced apoptosis that occurred with p38 inhibition in cultured cells. Our results demonstrate that p38alpha MAPK may play a critical role in suppressing ER stress-induced macrophage apoptosis in vitro and advanced lesional macrophage apoptosis in vivo.
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PMID:Macrophage deficiency of p38alpha MAPK promotes apoptosis and plaque necrosis in advanced atherosclerotic lesions in mice. 1928 91

Early lesions of lichen sclerosus et atrophicus (LSA) may present as a mild lichenoid tissue reaction, occasionally together with basilar epidermotropism, mimicking early cutaneous T-cell lymphoma, mycosis fungoides (MF) variant. We report a case of extragenital LSA in which both histological patterns were present in the same clinically homogenous and stable lesion. A 27-year-old man presented with a history of white atrophic plaques on the trunk. A biopsy of an abdominal lesion revealed epidermal thinning, a superficial perivascular lymphoid cell infiltrate with focal epidermotropism, mild nuclear atypia and perinuclear halos. Immunophenotyping showed decreased CD5 and CD7, with a slight predominance of CD8-positive T-lymphocytes. All these changes were suggestive of MF. However, a repeat biopsy 3 months later from the same stable plaque revealed features diagnostic of LSA. LSA mimicking early MF histologically has been reported in genital skin. Conversely, MF may clinically and histopathologically resemble LSA. With gene rearrangement studies, clonal proliferation may not be detected in early MF but has been reported to occur in LSA. Awareness of the histopathologic spectrum of LSA within a stable plaque is important to avoid a potential diagnostic pitfall, and should prompt a repeat biopsy.
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PMID:Extragenital lichen sclerosus et atrophicus mimicking cutaneous T-cell lymphoma: report of a case. 1990 17

Today's concept of vulnerable plaque has evolved primarily from the early pioneering work uncovering the pivotal role of plaque rupture and coronary thrombosis as the major cause of acute myocardial infarction and sudden cardiac death. Since the first historical description of plaque rupture in 1844, several key studies by leading researchers and clinicians have lead to the current accepted views on lesion instability. Important to the complex paradigm of plaque destabilization and thrombosis are many discoveries beginning with the earliest descriptions of advanced plaques, reminiscent of abscesses encapsulated by fibrous tissue capable of rupture. It was not until the late 1980s that studies of remodeling provided keen insight into the growth of advanced plaques, beyond the simple accumulation of lipid. The emphasis in the next decade, however, was on a focused shift toward the mechanisms of lesion vulnerability based on the contribution of tissue proteolysis by matrix metalloproteinases as an essential factor responsible for thinning and rupture of the fibrous cap. In an attempt to unify the understanding of what constitutes a vulnerable plaque, morphological studies, mostly from autopsy, suggest the importance of necrotic core size, inflammation, and fibrous cap thickness. Definitive proof of the vulnerable plaque, however, remains elusive because animal or human data supporting a cause-and-effect relationship are lacking. Although emerging imagining technologies involving optical coherence tomography, high-resolution MRI, molecular biomarkers, and other techniques have far surpassed the limits of the early days of angiography, advancing the field will require establishing relevant translational animal models that produce vulnerable plaques at risk for rupture and further testing of these modalities in large prospective clinical trials.
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PMID:Concept of vulnerable/unstable plaque. 2055 50

This review encourages the reader to consider cerebral vascular disease beyond the traditional clinical end points of major motor and speech strokes and to consider the possible impact of embolic cerebral vascular disease on vascular cognitive decline. This article examines the issue of "silent" strokes in the relationship between the structural stability of atherosclerotic carotid plaque and the development of nonmotor symptomatology, including cognitive decline. It addresses the question of the role of carotid emboli in silent stroke and their cognitive sequelae. In a study of endarterectomy patients, we relate plaque elasticity and its development of mechanical strain features and thinning of stabilizing fibrous cap at the point of these mechanical strain features. The possibility that microemboli from such mechanically unstable carotid plaques could contribute to silent strokes led to a study of cognitive function in such patients. A linear relationship between the process of mechanically unstable areas of carotid plaques and cognitive decline suggests a contributory role for such a process in silent strokes.
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PMID:A review of carotid atherosclerosis and vascular cognitive decline: a new understanding of the keys to symptomology. 2064 37

Most finite element models of atherosclerotic arteries do not account for the heterogeneity of the plaque constituents at the microscale. Failure of plaque lesions has been shown to be a local event, linked to stress concentrations caused by cap thinning, inflammation, macroscopic heterogeneity, and recently, the presence of microcalcifications. There is growing evidence that microcalcifications exist in the fibrous cap of plaque lesions. However, their role is not yet fully understood. The goal of the present work is to investigate the effects of localized regions of microcalcifications on the stress field of atherosclerotic plaque caps in a section of carotid artery. This is achieved by performing finite element simulations of three-dimensional fluid-structure interaction models. The material response in the region of microcalcification is modeled using a combination of finite elements, homogenization theory, and a stress concentration function that approximates the average local stresses in the fibrous tissue and microcalcification phases. The results indicate that the circumferential stress in the fibrous tissue phase increases as the volume fraction of microcalcifications is increased, and that the stress exceeds a critical threshold when the fibrous cap thickness is decreased. Furthermore, the presence of the microcalcifications significantly influences the distribution of stress by shifting the maximum circumferential stress away from the cap shoulders, where failure is most common when the effective region of microcalcification is located at the center of the cap. This is a possible explanation of why 40% of plaque ruptures occur away from the shoulder region of the cap.
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PMID:Numerical modeling of stress in stenotic arteries with microcalcifications: a micromechanical approximation. 2118 5


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