Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Platelet activation plays a crucial role in the pathogenesis of coronary heart disease (CHD), peripheral arterial disease (PAD) and cerebral ischaemia, the three main clinical manifestations of atherosclerosis. Circulating-activated platelets are thought to trigger ischaemic complications after angiography, angioplasty and vascular surgery. We studied activation of circulating thrombocytes in patients with PAD and evaluated the influence on platelet activation of intraarterial digital subtraction angiography (DSA) and percutaneous transluminal angioplasty (PTA) in the area of the lower extremities. Our study included 16 control subjects with PAD (clinical stage IIb according to Fontaine), 25 healthy control subjects and 34 PAD patients (clinical stage IIb according to Fontaine), 14 of whom we examined during DSA, 10 during PTA and 10 which we studied during both interventions. To characterize platelet ex vivo activation, the expression of activation-dependent platelet antigens (CD62 and CD63) was measured using flow cytometry. Platelet sensitization was analysed by an additional in vitro activation. Our results show that angioplasty in peripheral vessels causes activation and presumably slight migration or a reduction in the life span of circulating thrombocytes immediately after the PTA procedure and up to 4 h afterwards. DSA was also found to be associated with platelet activation, sensitization and presumptive minor migration or shortened life span of circulating platelets. Immediately after the intervention, PTA seems to influence platelet migration or shortened lifetime of platelets to a greater extent than DSA. We postulate that this is mainly induced by dilatation. More activated and sensitized thrombocytes circulated in patients with PAD compared to healthy control subjects. This supports our assumption that preactivated platelets are particularly involved in activation, sensitization and migration processes or affected by a reduced life span.
 ...
PMID:Activation of circulating platelets in patients with peripheral arterial disease during digital subtraction angiography and percutaneous transluminal angioplasty. 1267 27

The occurrence of cerebral or retinal ischemic symptoms ipsilateral to high-grade internal carotid artery (ICA) stenosis indicates a status of instability with a substantial risk for future major stroke. Additionally, the detection of microembolic signals downstream of ICA stenosis is predictive for future cerebral ischemia in asymptomatic and symptomatic patients. There is substantial evidence that in unstable ICA stenosis plaque rupture and thrombus formation are the most frequent pathoanatomic findings. In contrast, in nearly the half of unstable carotid plaques the lumen surface appears to be intact. Within plaque tissue, the unstable plaque is mainly characterized by a substantial amount of inflammatory cell (i. e. macrophages, T-cells) infiltration. These cells are mainly localized in the fibrous cap near the necrotic core. Produced by macrophages, matrix degrading enzymes (e. g. MMP-9) are overexpressed in the unstable ICA stenosis. Thrombogenicity is mainly determined by the local concentration of activated tissue factor, also expressed by inflammatory cells. Furthermore, a significantly higher rate of apoptotic smooth muscle cells can be found within the fibrous cap of instable carotid stenoses. Whether infection with Chlamydia pneumoniae contribute to instability is unlikely, because a positive association to clinical instability has not been shown up to now. The exact and detailed characterization of the unstable ICA plaque and the correlation of different biological mechanisms to clinical instability may offer the possibility to use it as a human model of unstable atherosclerosis in general and to test the efficacy of new developed anti-atherosclerotic pharmaceutical agents.
 ...
PMID:[The unstable carotid stenosis: definition and biological processes]. 1273

As blood clots it goes through predictable stages that reflect the oxygenation state of hemoglobin within the red cells. One of these stages results in the formation of methemoglobin. This substance acts an endogenous contrast agent when imaged using a T1-weighted magnetic resonance sequence (Magnetic Resonance Direct Thrombus Imaging, MRDTI) - appearing as high signal. MRDTI can therefore be used to detect subacute thrombosis. This technique has been applied in a number of clinical settings arising as a result of thrombosis. Deep vein thrombosis and pulmonary embolism are both readily detected using MRDTI, providing a single imaging modality for the detection of venous thromboembolic disease. The technique is also effective in the peripheral arterial tree. Furthermore, thrombosis within vessel wall atherosclerosis is a marker of vulnerable plaque likely to produce symptoms. The MRDTI technique has thus proved useful in identifying complicated plaque in the carotid arteries in the setting of transient and permanent cerebral ischemia. MRDTI therefore holds promise as a technique that is capable of detecting high risk vessel wall disease prior to significant or permanent end organ damage. Because of the non-invasive nature of magnetic resonance imaging (MRI), application of MRDTI in the research setting for the monitoring of therapeutic interventions in a wide number of settings within vascular disease is very appealing.
 ...
PMID:Magnetic resonance direct thrombus imaging. 1287 Dec 74

One third of cases of cerebral ischemia have no clear etiology. A humoral response to the atherosclerotic plaques components beta2-glycoprotein l (beta2-gpl) and heat-shock proteins (Hsp) might be involved in the pathogenesis of stroke. This case-control study includes a complete profile of anti-beta2-gpl antibodies and testing of IgG antibodies to the 60/65 kilodaltons (kDa) Hsp in stroke patients. Ninety-three patients with acute ischemic stroke and 93 controls were evaluated for age, sex, race, hypertension, smoking, previous cardiopathy, diabetes mellitus, hypercholesterolemia and previous history of cerebral ischemia. lgG/lgM/lgA anticardiolipin (aCL) and anti-beta2-gpl antibodies, as well as lgG antibodies to human 60 kDa Hsp and to Mycobacterium bovis 65 kDa Hsp, were detected by immunoassay. Adjusted odds ratios (OR) were calculated by logistic regression. The adjusted OR for IgA anti-beta2-gpl antibodies was 4.6 (90%Cl 1.5 to 14.3; p = 0.025). The non-adjusted OR for IgG antibodies to Hsp 60 was 26.1. The adjusted OR for IgG antibodies to Hsp 65 was 3.2 (90%Cl 1.2 to 8.3; p = 0.044). The adjusted OR for lgG to any Hsp (60 or 65) was 4.8 (90%Cl 1.9 to 12.1; p = 0.006). This study demonstrates that elevated IgA anti-beta2-gpl and lgG anti-Hsp 60/65 antibodies are associated with increased risk of ischemic stroke. The association occurred independently of other risk factors. This humoral response might link autoimmunity, thrombophilia and atherosclerosis in stroke patients.
 ...
PMID:Antibodies to the atherosclerotic plaque components beta2-glycoprotein I and heat-shock proteins as risk factors for acute cerebral ischemia. 1459 78

Atherosclerosis of the internal carotid artery with resulting stenosis, threatens the patients by cerebral ischaemia. Patients with high-grade stenosis, who have a high risk of stroke, gain profit from the surgery. The surgeon's decision is based on the clinical picture and on the degree of stenosis. The degree of the stenosis indicated for surgery was determined by international multicentric randomized studies and such indication represents the evidence-based medicine. Carotid microendarterectomy is performed at neurosurgical departments. The microsurgical technique enables perfect endarterectomy, eliminates patching and reduces risk of embolisation and vessel dissection. Cerebral ischaemia is a complex problem and carotid microendarterectomy is a part of the complex management of stroke.
 ...
PMID:[Carotid microendarterectomy]. 1460 46

The onset of cerebral ischaemia triggers a cascade of proinflammatory molecular and cellular events. Clinical studies suggest that the strength of this acute response is important in early and late clinical outcomes, early clinical worsening, and extent of brain damage. Variables that are predictors of adverse stroke outcome include erythrocyte sedimentation rate, and levels of C-reactive protein (CRP), interleukin-6, tumour necrosis factor-alpha and intercellular adhesion molecule-1. Current data indicate that inflammation serves to fuel atherosclerosis and can act as the link between atherosclerosis and atherothrombosis. Growing evidence indicates that platelets act as prominent players in the inflammatory component of these disease processes. Thus, upon activation, platelets release a series of cytokines and growth factors and express CD40 ligand, which interacts with the CD40 receptor on other major cell types involved in atherosclerosis/atherothrombosis. In healthy volunteers, CD40L expression in platelets is not significantly inhibited by acetylsalicylic acid (ASA) alone, but is inhibited after treatment with the ADP-receptor antagonist clopidogrel or with clopidogrel plus ASA. Of a range of potential inflammatory biomarkers that have been reported in the literature, the best studied is CRP. Such biomarkers may have clinical utility for refined identification of patients at high risk for atherothrombosis in different arterial beds and for monitoring of therapeutic agents in clinical trials.
 ...
PMID:Role of inflammation in stroke and atherothrombosis. 1473 Feb 51

Despite the great technical advancement of mass spectrometry, this technique has contributed in a limited way to the discovery and quantitation of specific/precocious markers linked to free radical-mediated diseases. Unsaturated aldehydes generated by free radical-induced lipid peroxidation of polyunsaturated fatty acids, and in particular 4-hydroxy-trans-2 nonenal (HNE), are involved in the onset and progression of many pathologies such as cardiovascular (atherosclerosis, long-term complications of diabetes) and neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, and cerebral ischemia). Most of the biological effects of HNE are attributed to the capacity of HNE to react with the nucleophilic sites of proteins and peptides (other than nucleic acids), to form covalently modified biomolecules that can disrupt important cellular functions and induce mutations. By considering the emerging role of HNE in several human diseases, an unequivocal analytical approach as mass spectrometry to detect/elucidate the structure of protein-HNE adducts in biological matrices is strictly needed not only to understand the reaction mechanism of HNE, but also to gain a deeper insight into the pathological role of HNE. This with the aim to provide intermediate diagnostic biomarkers for human diseases. This review sheds focus on the "state-of-the-art" of mass spectrometric applications in the field of HNE-protein adducts characterization, starting from the fundamental early studies and discussing the different MS-based approaches that can provide detailed information on the mechanistic aspects of HNE-protein interaction. In the last decade, the increases in the accessible mass ranges of modern instruments and advances in ionization methods have made possible a fundamental improvement in the analysis of protein-HNE adducts by mass spectrometry, and in particular by matrix-assisted laser desorption/ionization (MALDI) and electrospray ionization (ESI) tandem mass spectrometry. The recent developments and uses of combined analytical approaches to detect and characterize the type/site of interaction have been highlighted, and several other aspects, including sample preparation methodologies, structure elucidation, and data analysis have also been considered.
 ...
PMID:Mass spectrometry for detection of 4-hydroxy-trans-2-nonenal (HNE) adducts with peptides and proteins. 1513 38

Toll-like receptor-4 (TLR4), an important mediator of the innate immune response, is expressed in atherosclerotic lesions. The common single nucleotide exchange (Asp299Gly) of the TLR4 gene has been previously reported to impair TLR4 function and to be associated with a decreased risk of carotid atherosclerosis. Therefore, we aimed to detect the potential impact of TLR4 genotypes on the risk of cerebral ischemia. We studied the prevalence of two common polymorphisms of the TLR4 gene (Asp299Gly and Thr399Ile) in 3 independent study populations: (1.) in a cross-sectional study including 769 patients either with type 1 or type 2 diabetes mellitus, of whom 56 (7.2%) had a history of cerebral ischemia (study 1), (2.) a case-control study (study 2) including 128 consecutive patients with cerebral ischemia, mean age 60 +/- 10.9 years and 139 control subjects, and (3.) a case-control study (study 3) including 171 young adults aged < 50 years with cerebral ischemia and 204 control individuals. In all subjects, Asp299Gly and Thr399Ile were detected by restriction length analysis. The prevalence of the TLR4 genotypes was essentially the same between patients with cerebral ischemia and control subjects in all 3 study populations. Furthermore, there was also no association with the subgroup of atherosclerotic stroke in both case-control studies populations. Although TLR4 polymorphisms are associated with a decreased risk of carotid atherosclerotic lesions, our findings indicate that they do not influence the prevalence of cerebral ischemia. This implies that the Asp299Gly TLR4-allele might have a protective role in carotid atherosclerosis, but not in cerebral ischemia.
 ...
PMID:Lack of association between polymorphisms of the toll-like receptor 4 gene and cerebral ischemia. 1525 89

The majority of strokes (85-90%) result from cerebral ischemia. In most cases extra - and intracranial vessel atherosclerotic changes are considered to be responsible for cerebral ischemia. A sudden failure of cerebral circulation is usually combined with instability of atherosclerotic plaques. Pathologic studies demonstrate that atherosclerosis simultaneously involves the whole arterial vessel tree. The mechanism of atherosclerotic plaque formation is similar in different regions of the arterial system, including the brain supplying arteries. The essence of atherosclerosis appears to be an excessive inflammatory-fibroproliferative response to various forms of the arterial wall injury. The development of unstable plaques is closely related to the inflammatory process involving the arterial wall. Immunological factors seem to play an important role in the development of atherosclerotic changes and their destabilization. Imaging techniques for arteries supplying the brain are known. None of them gives a clear answer about plaque instability. Taking into account the role of the inflammatory process in the pathogenesis and instability of atherosclerotic changes, measurement of serologic markers of plaque instability seems to be complementary to imaging methods for diagnosis of unstable atherosclerotic plaques. The inflammatory aspect of atherosclerosis should be reflected in the prophylaxis of the central nervous system vascular disorders.
 ...
PMID:[Atherosclerotic plaque instability and ischemic stroke: the role of inflammatory and immunologic factors. Practical implications]. 1535 34

Cerebrovascular risk represents a progressive and evolving concept owing to the particular distribution of risk factors in patients with ischemic stroke and in light of the newest stroke subtype classifications that account for pathophysiological, instrumental, and clinical criteria. Age represents the strongest nonmodifiable risk factor associated with ischemic stroke, while hypertension constitutes the most important modifiable cerebrovascular risk factor, confirmed by a host of epidemiological data and by more recent intervention trials of primary (HOT, Syst-Eur, LIFE) and secondary (PROGRESS) prevention of stroke in hypertensive patients. To be sure, a curious relationship exists between stroke and diabetes. Although the Framingham Study, The Honolulu Heart Program, and a series of Finnish studies reported a linear relationship between improved glucose metabolism and cerebral ischemia, the clinical and prognostic profile of diabetic patients with ischemic stroke remains to be fully understood. Our group, on the basis of TOAST classification--a diagnostic classification of ischemic stroke developed in 1993 that distinguishes five different clinical subtypes of ischemic stroke: large-artery atherosclerosis (LAAS), cardioembolic infarct (CEI), lacunar infarct (LAC), stroke of other determined origin (ODE), and stroke of undetermined origin (UDE), and now extensively used in clinical and scientific context--analysed the prevalence of cerebrovascular risk factors and the distribution of TOAST subtypes in more 300 patients with acute ischemic stroke in two consecutives studies that reported the significant association between diabetes and the lacunar subtype and a better clinical outcome for diabetic patients, most likely related to the higher prevalence of the lacunar subtype. Well-confirmed are the roles of cigarette smoking, atrial fibrillation, and asymptomatic carotid stenosis as cerebrovascular risk factors. Particularly interesting seems to be the function of inflammation markers (CRP, TNF-alpha, IL-1 beta, ISPs) as potential risk factors. Still elusive remains the association between cholesterol serum levels and stroke, on the basis of the epidemiological data regarding this causative relationship, confirmed only by the results of intervention trials (4S, LIPID, CARE, HPS, ASCOT). Ultimately, cerebrovascular risk appears peculiar owing to the unique relationship between some modifiable risk factors (mainly diabetes and cholesterol) and the possible preferential association with stroke subtypes and specific cerebrovascular risks.
 ...
PMID:Cerebrovascular risk factors and clinical classification of strokes. 1563 Jun 37


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>