Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to investigate the histological characteristics of atheromatous carotid plaque, and to analyze the relationship between the angiographic findings and the clinical features. We retrospectively reviewed 55 cases of carotid endarterectomy for extracranial internal carotid artery stenosis, who were treated at our institute from January 1995 to December 1997. The histological examination included hematoxylin-eosin staining, Masson-trichrome staining, and immunostaining for antismooth muscle antibody and anti-CD68 antibody. The main compositions of the carotid plaque included synthetic type vascular smooth muscle cells and extracellular matrix. The histological findings showed ulceration in 49 (89.1%) cases, calcium deposits in 42 (76.4%) cases, and an inflammatory reaction in 44 (80.0%) cases. Neurological abnormalities were strongly associated with plaque ulceration (P = 0.045) and an inflammatory reaction (P = 0.013), whereas no correlation existed regarding calcium deposits (P = 0.173). The angiographic findings showed ulceration in 46 (83.6%) cases. Plaque ulceration in the angiography findings showed no statistically significant correlation with the histologic findings (P = 0.410) and preoperative neurologic abnormalities (P = 0.059). All of the atherosclerotic risk factors such as hypertension, smoking, diabetes mellitus, hyperlipidemia, and myocardial infarction had no statistically significant correlation with the histological features of the carotid plaque. In conclusion, the main compositions of carotid plaque were synthetic-type vascular smooth muscle cells and extracellular matrix. The histological ulceration and inflammatory reaction of the plaque showed a statistically significant correlation with the preoperative neurologic symptoms, whereas no correlation was seen in the calcium deposits. Angiographic ulceration showed no correlation with the histological findings or preoperative neurologic abnormalities. In addition, the histological findings showed no correlation with the atherosclerotic risk factors.
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PMID:The relationship between the angiographic findings and the clinical features of carotid artery plaque. 1064 81

On a variety of fronts, chronic infection has been found to be significantly associated with the development of atherosclerosis and the clinical complications of unstable angina, myocardial infarction, and stroke. For the most part, these are still just associations. Specific causative relationships on par with that determined between H. pylori and peptic ulcer disease have not yet been established. Potential mechanisms whereby chronic infections may play a role in atherogenesis are myriad. In the case of C. pneumoniae, the effect may result from direct vessel wall colonization, which may damage the vessel directly or indirectly by initiating immunologic responses. In other cases, the effect may simply be that of enhancing the preexisting chronic inflammatory response of the body to standard risk factors, such as hyperlipidemia. Even though the infectious agent may not directly infect the vessel wall, it may perform its critical role from afar. Chronic infection might also influence preexisting plaque by enhancing T cell activation or other inflammatory responses that may participate in the destabilization of the intimal cap. Chronic infection may play a role in the initiation, progression, or destabilization of atherosclerotic plaques. The infectious agents with the most evidence to support a causative role in atherosclerosis include C. pneumoniae and cytomegalovirus. Evidence is mounting for a variety of other potential agents, including H. pylori, various periodontal agents, and even hepatitis A. Future studies are expected to elucidate further the pathophysiologic relationship between chronic infection and atherosclerosis and to evaluate the potential of a variety of treatment approaches, including antibiotics.
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PMID:Chronic infection and coronary artery disease. 1068 31

Since the recent publication of 3 studies on the use of antibacterials in patients with coronary artery disease (CAD), there has been a phenomenal interest in the role of infection in the genesis of CAD. It is now generally accepted that inflammation accompanies atherosclerosis from its initiation to the evolution of end-events. Inflammation may occur in response to traditional risk factors, such as hyperlipidaemia, smoking and diabetes mellitus. There is a recent resurgence of the concept that inflammation may have an infectious basis. This concept is based on the identification of microorganisms in the atherosclerotic plaque and seropositivity. The data on eradication of the offending organism with antibiotics and prevention of atherosclerosis-related events have, however, been inconsistent. This may reflect lack of precise understanding of steps leading to atherosclerosis and the evolution of acute ischaemic events. Further work in this area may help identify subsets of patient populations within which infection may play a causative role in the genesis of CAD. Targeted therapy then may be considered logical.
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PMID:Inflammation, infection and atherosclerosis: do antibacterials have a role in the therapy of coronary artery disease? 1073 May 42

The rapid increase of life expectancy during the last half of the 20th century is changing the expression of cardiovascular disease and of its risk factors. These findings are examined by the separate consideration of atheromatous plaque formation and vascular wall stiffening, known as arteriosclerosis. in humans, these processes may progress together, but in some other species as the rat, only vascular wall stiffening is observed. A saturated fat- and cholesterol-rich diet produces the early appearance of lipidic plaques, which progress to fibrous, sometimes ulcerated, thrombotic lesions. This progression is age dependent; the establishment of lipidic plaques is not. Vascular wall stiffening, characterized by an increase of the collagen-elastin ratio and diffuse deposition of calcium and lipids is also age dependent (arteriosclerosis). Although hyperlipidemia appears to be involved both in plaque formation and wall thickness progression, the detailed mechanisms are not identical. In the oldest age group (above 80 years and in centenarians), high cholesterol values may not be a risk factor as in younger individuals. Among the cellular and molecular mechanisms involved, immune factors and modifications in receptor coupling appear to play a major role. These mechanisms are described in some detail.
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PMID:Aging of the vascular-wall and atherosclerosis. 1081 5

The MBL gene, encoding mannose-binding lectin, determines interindividual variation in susceptibility to certain infectious agents, such as Chlamydia pneumoniae. We examined whether infection-susceptibility alleles of MBL, called "non-A alleles," would be associated with increased carotid plaque area (CPA), an intermediate phenotype of atherosclerosis. In 164 subjects, we measured CPA with 2-dimensional ultrasound. We also determined traditional atherosclerosis risk factors and genotyped all subjects for MBL codons 52, 54, and 57. We used ANOVA to determine sources of variation for CPA and tested the hypothesis that the presence of a single MBL non-A "infection-susceptibility" allele was associated with increased CPA; 45.7% of subjects had at least one non-A allele. ANOVA showed that CPA was significantly associated with MBL genotype, age, smoking, hypertension, and hyperlipidemia (P < 0.05). When MBL was used as the sole independent variable in the regression analysis, the association with CPA was even more significant (P = 0.009). Subjects with at least one MBL non-A allele had significantly higher CPA than subjects homozygous for the MBL A allele and were significantly more likely to have CPA in excess of the sample median. Thus, infection-susceptibility alleles of MBL were associated with increased CPA in this study sample; these alleles may be a determinant of interindividual differences in atherosclerosis risk.
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PMID:Infection-susceptibility alleles of mannose-binding lectin are associated with increased carotid plaque area. 1082

The remarkable extent to which interactions between the plasma lipoproteins, inflammatory factors and the haemostatic system contribute to the response to injury and growth of the plaque in atherosclerosis is being increasingly documented. High plasma concentrations of very-low density (VLDL) and low-density lipoproteins (LDL), together with oxidatively modified LDL and lipoprotein (a), can induce responses in vascular endothelial cells, smooth muscle cells, monocytes/macrophages, platelets, neutrophils and humoral factors that are in a variety of ways both procoagulant and antifibrinolytic. Plasma high-density lipoproteins appear to promote anticoagulant mechanisms. Post-prandial lipaemia is associated with transient changes in factor VII which may be indicative of temporary hypercoagulability. The cellular and humoral effects of LDL and VLDL on the haemostatic system appear to be largely reversible, which may help to explain the prompt improvement in the atherothrombotic state gained by correction of hyperlipidaemia.
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PMID:Lipoproteins and the haemostatic system in atherothrombotic disorders. 1085 85

To clarify carotid arterial changes in female patients with arteriosclerosis obliterans (ASO) and aortic aneurysm (AA), ultrasonographic (US) findings of the extra-cranial carotid arteries were studied in 26 patients with ASO (ASO group), and 31 patients with AA (AA group), compared to 38 controls (control group) with neither ASO nor AA. ASO was diagnosed with an ankle pressure index less than 0.9, while AA was done with computed tomography or angiography. Half of the patients with ASO were in stage II of the Fontaine clinical staging, and angiography, performed in 12, showed femoral arterial obstruction in 10. Most AA patients were abdominal aortic aneurysm. Using a high-resolution, real-time, B-mode US instrument, the diameter and wall thickness of the common carotids were measured bilaterally in the end-diastolic phase, and occlusive changes and plaque were estimated. As a risk factor for arteriosclerosis, hypertension, diabetes, hyperlipidemia, and cigarette smoking were assessed, in addition to the age, body height and weight. Mean ages of each group were 73 to 76.3 year-old. There was no significant difference between them in body height and weight. Diabetes, cigarette smoking, and cerebrovascular disease were frequent in the ASO group, whereas ischemic heart disease was frequent in the AA group. US findings revealed that carotid lesions were mostly plaque, and bilateral carotid lesions were significantly more frequent in the ASO and AA groups. The mean wall thickness of the carotids was greater in the AA and ASO groups, although dilated carotid arteries, namely arteriomegaly, was more frequent in the AA group than in the ASO and control groups. Stepwise regression analyses demonstrated that strong correlations were seen between carotid lesion and two variables [vessel diseases (ASO/AA) and cigarette smoking], between carotid diameter and three variables (age, AA, and wall thickness), and between the wall thickness and three variables (age, vessel diseases and diameter). These findings showed that atherosclerosis was not only frequent in female patients with ASO and AA, but arteriomegaly was characteristic in female patients with AA. Therefore, it suggested that circulatory disturbance in whole organs due to arteriosclerosis should be paid attention even in female patients with ASO and AA as well as male patients. Furthermore, it is considered that systemic fragility of the arterial media and ectasia could be present extensively in patients with AA.
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PMID:[Ultrasonographic findings of carotid arteries in female patients with arteriosclerosis obliterans and aortic aneurysm]. 1087 74

Pharmaceutical therapy of hyperlipidemia is clearly beneficial. In the patient without established heart disease however, conventional risk assessment is imprecise and determining which patients are at highest versus lowest risk is a common clinical conundrum. It is well established that the most powerful determinant to risk is the overall extent/severity of coronary disease. Electron beam tomography (EBT) and quantification of coronary artery calcium has been shown to provide a valid non-invasive surrogate to atherosclerotic plaque burden. Screening patients who are considered to be at traditional intermediate to high risk by first using EBT can refine the broad-based population risk to a more individual basis. Data that is based upon a model developed for application of EBT are presented, which discuss its potential as a cost effective application to guide statin therapy in intermediate and high-risk sub-groups.
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PMID:Cost effectiveness of coronary calcification scanning using electron beam tomography in intermediate and high risk asymptomatic individuals. 1087 14

The increased risk of hyperlipidemia on the development of complications of atherosclerosis is well established. Cholesterol-lowering therapies lead to a decrease in the incidence of vascular thrombotic events that is out of proportion to the reduction in plaque size. This suggests that the occurrence of acute thrombosis overlying a disrupted plaque is influenced by changes in lipid levels. The influence of acute hyperlipidemia on the development of thrombosis overlying an atherosclerotic plaque in vivo has not been extensively studied. We used a murine model of vascular injury induced by a photochemical reaction to elicit thrombus formation overlying an atherosclerotic plaque. Fifteen apolipoprotein E-deficient mice were maintained on normal chow until the age of 30 weeks. Five days before the induction of thrombosis, 6 mice were started on a high fat diet, and 9 mice were continued on normal chow. Mice then underwent photochemical injury to the common carotid artery immediately proximal to the carotid bifurcation, where an atherosclerotic plaque is consistently present. Mice maintained on normal chow developed occlusive thrombi, determined by cessation of blood flow, 44+/-5 minutes (mean+/-SEM) after photochemical injury, whereas mice fed a high fat chow developed occlusive thrombosis at 27+/-3 minutes (P<0.02). Histological analysis confirmed the presence of acute thrombus formation overlying an atherosclerotic plaque. These studies demonstrate a useful model for assessing the determinants of thrombosis in the setting of atherosclerosis and show that acute elevations in plasma cholesterol facilitate thrombus formation at sites of atherosclerosis after vascular injury.
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PMID:Hyperlipidemia promotes thrombosis after injury to atherosclerotic vessels in apolipoprotein E-deficient mice. 1089 25

Apolipoprotein-E (apoE) protects against coronary artery disease via hepatic removal of atherogenic remnant lipoproteins, sequestration of cholesterol from vessel walls and local anti-oxidant, anti-platelet and anti-inflammatory actions. ApoE gene transfer may thus ameliorate a hyperlipidaemic profile and have beneficial effects at lesion sites to prevent or regress atherosclerosis, a concept endorsed by adenoviral-mediated hepatic expression studies. Here, using plasmid vectors expressing allelic human apoE2 or apoE3 isoforms, skeletal muscle was evaluated as an effective secretory platform for apoE gene augmentation. Transfected myoblasts and myotubes were found to efficiently secrete recombinant apoE in vitro as spherical 10-16 nm lipoprotein particles with pre-beta mobility. Intramuscular plasmid injection in apoE(-/-) mice, which develop spontaneous atherosclerotic plaque and xanthoma resulted in expression and secretion of apoE. Human apoE mRNA was detected by RT-PCR in injected muscles and, although concentrations of apoE3, which is rapidly cleared from plasma, were near ELISA detection limits, levels of plasma apoE2 were measurable (17.5 +/- 4.3 ng/ml). To assess whether muscle-based expression of apoE2 could inhibit atherogenesis, long-term follow-up studies were conducted. Although hyperlipidaemia was not reduced in treated animals, end-point pathology showed clear retardation of atherosclerotic and xanthomatous lesions. Up to 9 months following a single apoE2 plasmid administration, atherosclerotic lesion coverage in proximal aorta was significantly reduced by 20-30% (P < 0.01), whereas development of gross dorsal xanthoma (>5 mm diameter) was effectively reduced to zero. We conclude that expression of apoE from ectopic muscle sites has therapeutic potential to limit progression of atherosclerosis.
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PMID:Intramuscular injection of a plasmid vector expressing human apolipoprotein E limits progression of xanthoma and aortic atheroma in apoE-deficient mice. 1103 Jul 60


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