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)

Poloxamer 407 (P-407) induces hyperlipidemia in the rat. It was the purpose of this investigation to determine if chronic P-407 administration would produce atherogenic arterial lesions in the C57BL/6 mouse, a strain reported to be susceptible to hyperlipidemia-induced atherosclerotic plaque formation. One injection (i.p.) of P-407 (0.5g/kg) produced hypercholesterolemia in the mouse that peaked at 24 h and returned to control levels by 96 h following treatment. Four groups of mice were maintained: (1) saline injected (C); (2) P-407-injected (0.5g/kg every 3rd day) (P); (3) P-407 injected plus cholic acid in the diet (PC); and (4) mice fed a high cholesterol (CHOL) diet containing cholic acid (HF). Mice from each group were sacrificed following 90, 145, 200, or 300 days of treatment. Plasma lipid concentrations, hepatic CHOL concentrations (145 and 300 day), and aortic atherogenic lesion areas were measured. Plasma CHOL and triglyceride remained at control levels throughout the 300 days in the C group. CHOL of the HF animals plateaued at approximately 225 mg/dl. P-407 produced CHOL concentrations of 600 mg/dl in P mice and 1000-1500 mg/dl in PC animals. There was no lesion formation in C mice. However, by 90 days lesions were present in the three other groups. Size of the lesions progressed through day 300 with the largest lesions (184.33 + 27.99 mu2 x 10(-3)) being present in the PC mice. HF and P animals had lesions of 70.50 + 11.35 and 43.33 + 7.88 mu2 x 10(-3), respectively. This study provides an animal model where atherogenesis has been produced with hyperlipidemia induced using a chemical agent.
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PMID:Poloxamer 407-induced atherogenesis in the C57BL/6 mouse. 954 38

Proliferation of arterial smooth muscle cells has held center stage as the culprit in restenosis for almost two decades. Many strategies for combating restenosis target smooth muscle replication. However, none have proven beneficial in clinical trials. Indeed, inhibition of smooth muscle proliferation in human patients might produce the undesired effect of destabilizing vulnerable atherosclerotic plaques because these cells furnish the collagen responsible for the biomechanical strength of the plaque. Actually, in some cases the benefit of angioplasty may depend on stimulating smooth muscle replication and collagen elaboration, converting an "unstable" to a more stable plaque. Moreover, recent clinical and experimental evidence suggests that restenosis depends less on neointimal hyperplasia than on constrictive remodeling (i.e., advential scarring, producing a smaller lumen), a process independent of smooth muscle replication. The recognition that plaques vulnerable to disruption often do not produce flow-limiting stenoses highlights a need for reassessment of the strategies to treat or prevent the acute coronary syndromes. We should strive to treat aggressively risk factors such as hyperlipidemia whose control appears to stabilize plaques. Trials are even underway comparing such risk factor management with coronary artery intervention. If we could identify potentially unstable atheroma before they are evident, clinically, we might even contemplate angioplasty of nonsignificant stenoses to induce smooth muscle cell proliferation and reinforce the plaque's fibrous cap. This proposal may seem preposterous, yet we perform "primary" angioplasty every day in patients with an acute myocardial infarction whose "culprit" lesions underlying the thrombus are often not critical. Our knowledge of the biology of restenosis has lagged behind our practice of coronary intervention. Advances in understanding the biology of the complications of interventional therapy, hand in hand with technical advances, should help us to devise more rational and enduring approaches to benefiting our patients.
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PMID:The smooth muscle cell: sinner or saint in restenosis and the acute coronary syndromes? 966 82

Investigation of the pathogenesis of arteriosclerosis and/or atherosclerosis has been progressed using molecular biology. New concepts have been developed and, receptors and substances have been found clinically and experimentally, which have led us to create new methods of evaluating or diagnosing the grade of atherosclerosis lesion. Dealing with the new concepts or knowledge in this symposium, this introductory paper describes an overview of pathogenesis of atherosclerosis, from which the new methods of evaluating or diagnosing lesion has been exploited. The injury to the endothelium leads to endothelial cell dysfunction, which initiates the acceleration of LDL oxidation and increases adherence of monocytes, macrophages and T lymphocytes, migrating subendothelially and causing large foam cells to develop because of lipid accumulation. Macrophages and platelets release many growth factors, which accelerate the growth of vascular smooth muscle cells, forming fibrous plaque. In these pathogenic processes of atherosclerosis, angiotensin II participates in releasing growth factor for cell proliferation and hepatocyte growth factor (HGF) participates in revascularization of the sclerotic lesion, suggesting a candidate marker for atherosclerosis. Hyperlipidemia and hypercoagulation are the major factors in advanced atherosclerosis. Using new methods to evaluate or diagnose lesions, further therapy and prevention for atherosclerosis will progress in future.
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PMID:[Introductory review of diagnostic approach to arteriosclerosis]. 972 32

Hyperlipidemia is recognized as one of the major risk factors for the development of coronary artery disease and progression of atherosclerotic lesions. Dietary therapy together with hypolipidemic drugs are central to the management of hyperlipidemia, which aims to prevent atherosclerotic plaque progression, induce regression, and so decrease the risk of acute coronary events in patients with pre-existing coronary or peripheral vascular disease. In patients at high risk of coronary artery disease but without evidence of atherosclerosis, treatment is designed to prevent the premature development of coronary artery disease, whereas in those with hypertriglyceridemia, treatment aims to prevent the development of hepatomegaly, splenomegaly, and pancreatitis. The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins, are the most potent lipid-lowering agents currently available, and their use in the treatment of hyperlipidemia provides the focus for this review. Particular emphasis is given to cerivastatin, a new HMG-CoA reductase inhibitor that combines potent cholesterol-lowering properties with significant triglyceride-reducing effects. Recently completed primary and secondary intervention trials have shown that the significant reductions in low-density lipoprotein (LDL) cholesterol achieved with statins result in significant reductions in morbidity and mortality associated with coronary artery disease as well as reductions in the incidence of stroke and total mortality. Such benefits occur early in the course of statin therapy and have led to suggestions that these drugs may possess antiatherogenic effects over and above their capacity to lower atherogenic lipids and lipoproteins. Experimental studies have also shown statin-induced improvements in endothelial function, decreased platelet thrombus formation, improvements in fibrinolytic activity, and reductions in the frequency of transient myocardial ischemia.
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PMID:Current and future treatment of hyperlipidemia: the role of statins. 973 40

Statins, i.e. HMG-CoA (3-hydroxymethyl-glutaryl co-enzyme A) reductase inhibitors, are widely used in the treatment of hyperlipidaemia. Several large trials published during recent years have clearly shown treatment with statins to reduce coronary heart disease morbidity and mortality rates, the beneficial effects being manifest sooner than expected. Despite the smallness of changes in lumen diameter during statin treatment, as measured with coronary angiography, the decrease in clinical events has been impressive. The question has therefore arisen of whether statins have other beneficial effects in addition to their lipid-lowering property. Several studies have been made of the effects of statin treatment on such variables as endothelial function, cellular immunity, lipoprotein oxidation, rheological factors, and the stabilisation of atherosclerotic plaque. Although the various statins differ in structure, there is a lack of comparative studies. However, available data suggest the beneficial effects of statins on other variables to be probably dependent on their primary lipid-lowering property.
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PMID:[Statins have other beneficial properties besides their cholesterol lowering effect]. 974 80

The acute platelet response and chronic smooth muscle cell (SMC) proliferation following aortic injury in apolipoprotein E-deficient mice was investigated. The purpose of this study was to evaluate whether thrombus formation would occur following plaque injury, to determine the type of thrombus that developed, and to evaluate SMC proliferation. Aortic injury was performed by squeezing the aorta between forceps. The response to injury reflects the findings primarily associated with plaque disruption. An attempt was made to exclude the use of injured vascular segments that showed marked injury to the media to minimize the effects that medial SMCs may have in thrombus formation. Acute and chronic experiments following injury were terminated at 30 min and at 2 weeks, respectively. Injury in normal and heterozygous mice and nonplaque injury in apolipoprotein E-deficient mice were accompanied by endothelial denudation. In apolipoprotein E-deficient mice, plaque injury, which released plaque contents, foam cells and fragments of foam cells, was followed by thrombus formation that contained degranulating platelets mixed with fibrin. Large platelet-fibrin aggregates were in close contact with disrupted plaques and were mixed with foam cell debris. In addition, small thrombi were in nonplaque areas following plaque disruptions. These thrombi were not associated with injury to the media and most likely represent a heightened thrombogenicity associated with plaque disruption. At 2 weeks following injury, a thickened neointima was present in both wild type and mutant mice. Lipid filled cells were seen only in the media but not in the intima of apo E -/- vessels at 2 weeks. The results suggest that plaque injury in homozygous apolipoprotein E-deficient mice promotes platelet-fibrin thrombus formation and that these thrombi are primarily associated with disrupted plaque contents. The results also suggest that the platelet response and SMC proliferation induced by aortic injury are not altered by hyperlipidemia caused by apolipoprotein E deficiency.
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PMID:Aortic atherosclerotic plaque injury in apolipoprotein E deficient mice. 986 72

The relationship between plasma lipid abnormalities and the risk for cardiovascular disease is now clearly established. In addition to quantitative abnormalities such as increased plasma LDL-cholesterol and decreased HDL-cholesterol levels, lipid qualitative abnormalities are likely to play an important role in the pathogenesis of atherosclerosis. Indeed, dense triglyceride-rich LDL particles are atherogenic. Moreover, oxidized LDL are associated with increased cardiovascular risk and may play a central role in the pathogenesis of the atherosclerotic plaque. Fasting triglyceride level has rarely been shown to be an independent risk factor for cardiovascular disease, in the general population, but plasma triglyceride levels, following an oral fat load, seem to be a better marker. Recent intervention studies have shown an early effect of HMGCoA-reductase inhibitors in reducing cardiovascular morbidity and mortality, suggesting possible additive actions of statins on the atherosclerotic plaque, on the endothelial function and on thrombosis. The Care study shows that a clinical benefit with pravastatin treatment, in secondary prevention, can be obtained in patients with LDL-cholesterol above 125 mg/dl. If all the primary and secondary intervention studies have shown reduction of cardiovascular morbidity and mortality with hypolipidemic drugs, we also have to keep in mind the positive results from the dietary intervention studies, showing beneficial actions of diets rich in vitamins, fibers and omega 3 fatty acids. In clinical practice, compliance of the patient to his treatment is often difficult to achieve and many studies have shown that control of hyperlipidemia is frequently inaccurate and needs to be reinforced. A comprehensive education of the hyperlipidemic patient is urgently needed in order to improve his knowledge about hypolipidemic diet and to obtain his motivation which is essential for a long term compliance.
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PMID:[Cardiovascular risk and dyslipidemias]. 986 55

Apolipoprotein E3-Leiden (APOE3-Leiden) transgenic mice develop hyperlipidemia and are highly susceptible to diet-induced atherosclerosis. We have studied the progression and regression of atherosclerosis using immunohistochemistry. Female transgenic mice were fed a moderate fat diet to study atherosclerosis over a longer time period. Fatty streaks arose in the intima and consisted of lipid filled macrophages which differed in origin. All macrophages expressed the macrophage scavenger receptor while two thirds expressed sialoadhesin and were positive for an antibody recognizing marginal zone macrophages (MOMA-1). All macrophages were negative for the scavenger receptor MARCO and 50% were positive for CD4. Small fatty streaks contained CD-3 positive T-lymphocytes which were for more than 70% CD4-positive. ICAM-1 was positive both in atherosclerotic and control mice. In early plaques, fibrosis was observed on the luminal and medial site of the foam cells while smooth muscle cells were only observed in the fibrous cap. To study regression, we used a high fat, high cholesterol diet to rapidly induce atherosclerosis (14 weeks). The animals were then fed normal chow. Subsequently, atherosclerosis was assayed over time (4, 8, 16 weeks). Cholesterol levels dropped in 4 weeks to control levels. The animals did not show a significantly decrease in plaque size over time. but the percentage macrophages was significantly smaller in the animals after 4 weeks. In conclusion, the APOE3-Leiden mouse is a useful model to study the progression and regression of atherosclerosis.
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PMID:Progression and regression of atherosclerosis in APOE3-Leiden transgenic mice: an immunohistochemical study. 1020 77

Recent data suggests that autoimmune factors play an important role in the pathogenesis of atherosclerosis. In this context several autoantigens have been shown to elicit an immune response that results in accelerated atherosclerotic plaque formation. In the present study, we investigated whether elevated titers of anti-oxidized low density lipoprotein (oxLDL), anticardiolipin and antibodies to beta2-glycoprotein I (beta2GPI) can predict subsequent restenosis in patients undergoing percutaneous transluminal coronary angioplasty (PTCA). A total of 74 consecutive patients (52 males, 22 females) with coronary artery disease were enrolled in the study. All patients underwent successful PTCA prior to which blood was drawn for the antibody analysis. The PTCA was followed by a clinical evaluation. Patients with recurrent chest pains underwent a repeated angiography and 34 of the 74 patients (46%) experienced restenosis. Patients positive for the presence of anti-oxLDL antibodies were more likely to develop restenosis within 6 months when compared with patients with no subsequent restenosis (relative-risk of 1.87; P< 0.05). Presence of anti-oxLDL antibodies was associated with hyperlipidemia (r = 0.25; P < 0.05) but not with other risk factors for atherosclerosis. Positivity for anticardiolipin or anti-beta2GPI antibodies which associate with a prothrombotic state, was not effective in predicting lumen narrowing. Thus, the presence of elevated levels of anti-oxLDL antibodies is associated with a higher risk for coronary restenosis following PTCA.
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PMID:Anti-oxidized low density lipoprotein antibody determination as a predictor of restenosis following percutaneous transluminal coronary angioplasty. 1042 30

Since the Chlamydia pneumoniae (C. pneumoniae)-specific antibody was shown to be associated with acute myocardial infarction and chronic coronary heart disease, the role of C. pneumoniae in the etiology of cardiovascular disease has been studied by a number of groups. We investigated the association between the C. pneumoniae-specific antibody, measured by microimmunofluorescence, risk factors for cardiovascular disease, and atherosclerosis in a randomly selected urban population. Overall, immunoglobulin-G (IgG) seroprevalence to C. pneumoniae in this sample of 1,034 subjects was 58%, whereas IgA seroprevalence was 32%. There was a decline in seropositivity with age for IgG but not IgA. Men were more likely than women to be IgG (66% vs 51%, chi-square p = 0.001) and IgA seropositive (36% vs 28%, chi-square p = 0.005). Current smokers had higher IgA seropositivity than nonsmokers (43% vs 30%). Those patients with a family history of cerebrovascular disease were more likely to have IgG antibody than those without (75% vs 57%, chi-square p= 0.007). Neither IgG nor IgA seropositivity was associated with the standard risk factors of hypertension, hyperlipidemia, or family history of ischemic heart disease, nor was seropositivity associated with carotid intima medial thickening (IMT) or atherosclerotic plaque as measured by carotid B-mode ultrasound. There was no difference between those participants who were IgG or IgA seropositive and seronegative in measurements of mean IMT, prevalence of abnormal IMT, and percentage with atherosclerotic plaque. In conclusion, although C. pneumoniae was associated with several risk factors for cardiovascular disease in a large cross-sectional population, we found no independent association between seroprevalence to C. pneumoniae and carotid atherosclerosis as measured by carotid IMT.
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PMID:Lack of association between seropositivity to Chlamydia pneumoniae and carotid atherosclerosis. 1051 82


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