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)

We report the clinicopathologic analysis of 23 tumors from 22 patients with lipidized fibrous histiocytoma (FH), which has been an underrecognized variant of cutaneous FH. The 16 men and 6 women patients (male/female ratio, 2.7:1) ranged in age from 21 to 82 years (median, 50 years). The location of the tumor was concentrated strikingly in the lower limb, especially around the ankle, hence the alternative informal designation of "ankle-type" FH. The tumors showed relatively large size compared with those of conventional FH, ranging up to 8 cm in greatest dimension (median, 2.5 cm), and tended to be polypoid and yellowish in color. Hyperlipidemia was only a rare and perhaps incidental association in two cases. Histologically, lipidized FH was characterized by accumulation of numerous foam cells, smaller numbers of siderophages, and stromal hyalinization typically appearing "wiry," keloidlike, or osteoidlike, although focal features of ordinary FH almost always coexisted and were identified as a focal storiform or curlicue pattern of spindle tumor cells, epidermal hyperplasia, and peripheral "entrapped" dermal collagen. Although follow-up data are limited, the prognosis appears to be good with no recurrence, even after incomplete excision. These clinicopathologic features highlight lipidized FH as a distinctive variant, which can be distinguished from ordinary or other variants of FH, as well as from other foam cell-rich cutaneous lesions, especially xanthoma.
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PMID:Lipidized fibrous histiocytoma: clinicopathologic analysis of 22 cases. 1077 Apr 32

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 experimental model of Golden Syrian hamster subjected to concomitant hyperlipemia (diet-induced) and diabetes (by streptozotocin injection) for 24 weeks is characterised by the prevalence of micro- and macroangiopathies. We have used the hyperlipemic-diabetic (HD) hamsters to investigate: a) whether there is an alteration in the reactivity of the resistance arteries (mean internal diameter: 210-250 microm), b) if present, which are the structural and biochemical changes that accompany the functional modifications, and c) to examine the pathomorphological changes induced by the association of hyperlipemia and diabetes on vital organs such as myocardium and kidney glomeruli. To these aims, biochemical assays of plasma components, light- and electronmicroscopy, myographic, morphometric and spectrofluorimetric techniques were used. The mesenteric resistance arteries of HD hamsters exhibited (as compared to similar arteries in normals) a decreased contractile response to noradrenaline (1.86+/-0.35 vs. 2.43+/-0.21), and an impeded endothelium dependent relaxation to acetylcholine (approximately 61.40% vs. approximately 79.80%). The association of hyperlipemia with diabetes induced changes in morphology of the resistance arteries consisting in approximately 10% increase of the intima plus media cross-sectional area, approximately 20% decrease of the vascular lumen area, and approximately 2.85 fold augmentation of the wall to lumen ratio. The resistance arteries exhibited structural modifications of the endothelium (up to 8 copies of Weibel-Palade bodies/endothelial cell), and smooth muscle cells (secretory phenotype), and in the vessels media small calcification cores appeared embedded in a hyperplasic extracellular matrix. The vascular mesenteric bed of the HD hamsters contained approximately 2.30 and approximately 1.30 fold increased concentrations of AGE-collagen and pentosidine, respectively, above the normal values. The HD hamsters displayed also modifications that may be dependent on or may lead to an increase in blood pressure, such as: a) approximately 2 fold increase in the activity of serum angiotensin converting enzyme; b) approximately 4.8 fold enhancement of erythrocytes fragility (as a measure of the oxidative stress); c) left ventricular hypertrophy associated with a progressive disarray of cardiomyocyte contractile fibers, interruptions of the Z bands, and accumulation of collagen-rich extracellular matrix indicative of interstitial fibrosis; d) the kidney glomerular capillaries appeared partially or totally collapsed, with a thickened basement membrane which appeared polymorphic, and in some locations made up of successive layers connected by fine bridges and intercalated nodules; in addition, an increase (approximately 1.50 fold) of the mesangial volume was indicative of glomerulosclerosis.
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PMID:The effects of simultaneous hyperlipemia-hyperglycemia on the resistance arteries, myocardium and kidney glomeruli. 1087 2

We investigated the age-related changes in blood coagulation, fibrinolysis, and platelet aggregation in male WBN/Kob rats, animals that exhibit spontaneously diabetes mellitus at more than 6 months of age. The rats aged 6 months or more showed significant hyperglycemia, hypoinsulinemia, and hyperlipidemia. As changes in coagulation parameters, the data indicated significant increases in factors II, V, VII, VIII, IX, X, and XII activities; a significant decrease in antithrombin III activity in rats more than 6 months of age; significant increases in fibrinogen level and factor XI activity; and significant decreases in prothrombin time and activated partial thromboplastin time in those more than 9 months of age. As changes in fibrinolytic parameters, the animals showed significant decreases in plasminogen and tissue-type plasminogen activator, and significant increases in alpha2-plasmin inhibitor and plasminogen activator inhibitor at more than 6 months of age. In addition, there were significant correlations between the plasma levels of coagulation/fibrinolytic markers and the 4-hour fasting glucose or lipids. Furthermore, they displayed significant increases in ADP- or collagen-induced platelet aggregation and in cholesterol/phospholipid molar ratio in platelets at more than 9 months of age. The increase in cholesterol/phospholipid ratio may be responsible for hyperaggregation of platelets in diabetic animals. These findings suggest that WBN/Kob rats are suitable for research on blood coagulation abnormalities in diabetes. However, further studies are needed to clarify the details of the mechanisms involved.
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PMID:Age-related changes in coagulation, fibrinolysis, and platelet aggregation in male WBN/Kob rats. 1089 50

We studied the mural distribution of collagen types I and III and tropoelastin in enhanced experimental atherogenesis induced in rabbits by hyperlipidemia superimposed by hypertension. Animals were fed a high-cholesterol diet for 5 weeks and also subjected to midthoracic aortic coarctation for 4 weeks. Serum cholesterol levels were increased and blood pressure was elevated proximal to the coarctation. Foam cell lesions developed in the aorta proximal to the coarctation. In situ hybridization and immunohistochemistry showed that gene expression of collagen types I and III and tropoelastin was upregulated, with a differential distribution across the arterial wall. New collagen type I was mainly distributed in the intima, the outer media, and the adventitia. New collagen type III was spread more uniformly across the wall, including the adventitia, whereas tropoelastin was mainly localized in intimal foam cell lesions. Morphometric data showed an increase in wall thickness. These results suggest that collagen types I and III play a role in remodeling of the aortic wall in response to hypertension. The remarkable involvement of the adventitia in this response indicates that the adventitia is an important component of the arterial wall. Tropoelastin is closely associated with foam cell lesion formation, suggesting a role for this component in atherogenesis as well.
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PMID:Hypercholesterolemia superimposed by experimental hypertension induces differential distribution of collagen and elastin. 1111 54

Using Otsuka Long Evans Tokushima Fatty (OLETF) rats, a model of human non-insulin-dependent diabetes mellitus (NIDDM) that exhibits hypertension, obesity, hyperglycemia and hyperlipidemia, the role of local angiotensin II in cardiovascular complications at early stages of NIDDM was characterized. OLETF rats were given an angiotensin converting enzyme (ACE) inhibitor, cilazapril (10 mg/kg/day) or vehicle from the age of 5 weeks to 20 weeks. Arteriolar, intermediate and venular capillary proportions were determined by the double-staining method and levels of collagen and non-collagenous proteins were determined by the selective dye-binding method in heart tissues. In OLETF rats at 20 weeks of age, capillary network remodeling (i.e., an increase in arteriolar portions and a decrease in venular portions) and an increase in collagen content were detected. Cilazapril not only exerted favorable effects on markers of diabetes, but also prevented capillary network remodeling and ameliorated the increase in collagen content. These results suggest that 1) capillary network remodeling and increase in extracellular matrix protein levels precede the onset of overt NIDDM in OLETF rats, and 2) angiotensin II may be involved in the pathogenesis of cardiac complications in the early stages of NIDDM.
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PMID:Coronary capillary remodeling in non-insulin-dependent diabetic rats: amelioration by inhibition of angiotensin converting enzyme and its potential clinical implications. 1121 33

The acyl-CoA:cholesterol acyltransferase (ACAT) enzyme is thought to be responsible for foam cell formation and the subsequent progression of atherosclerosis. The apolipoprotein E and low density lipoprotein receptor double knockout (apoE/LDLr-DKO) mouse is an animal model that develops severe hyperlipidaemia and atherosclerosis. Here we have examined the effect of oral administration of an ACAT inhibitor, F-1394, on atherosclerosis in apoE/LDLr-DKO mice fed a regular chow diet. In en face analysis, a dose of 10, 30, or 100 mg kg(-1) day(-1) F-1394 for 10 weeks reduced the extent of lesions visible in the aorta by 24, 28 and 38%, respectively, as detected by staining with oil red O, without affecting serum cholesterol level in these mice. At the highest dose 100 mg kg(-1) day(-1) of F-1394, the reduction was statistically significant. For quantitative analysis of the cellular and non-cellular components comprising the lesions at the aortic sinus, the effects of an oral dose of 100 mg kg(-1) day(-1) F-1394 for 15 weeks were studied. There was a significant reduction (31.9%) in the oil-red O-stained area in cross-sections of the aortic sinus. In addition, the neointimal area, as well as levels of ACAT-1 protein tended to be decreased (15.2 and 25.8%, respectively, not significant). However, the areas containing macrophages, smooth muscle cells, and collagen were not affected by F-1394. In vitro, F-1394 attenuated foam cell formation in mouse peritoneal macrophages. These results indicate that ACAT may be primarily responsible for lipid accumulation in atherosclerotic lesions, and that its inhibition diminishes the lipid deposition via a direct effect on macrophages in the arterial wall.
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PMID:Direct effect of an acyl-CoA:cholesterol acyltransferase inhibitor, F-1394, on atherosclerosis in apolipoprotein E and low density lipoprotein receptor double knockout mice. 1148 9

Obesity, which has reached epidemic proportions in the United States and other western countries, may be complicated by hypertension, an increased incidence of renal cancer or proteinuria. Patients with obesity-associated proteinuria show focal glomerulosclerosis and glomerulomegaly on biopsy, usually have minimal clinical edema and relatively normal levels of serum albumin, cholesterol and blood pressure, and can progress to end-stage renal disease. Severe obesity may also be an additive risk factor in patients with preexisting nephropathy or reduced renal mass. The pathophysiology of obesity-associated proteinuria is unclear but may include hyperfiltration, increased renal venous pressure, glomerular hypertrophy, hyperlipidemia and increased synthesis of vasoactive and fibrogenic substances, including angiotensin II, insulin, leptin and transforming growth factor-beta1. These substances may individually or interactively affect glomerular hyperfiltration, mesangial cell hypertrophy and matrix production, and the production of collagen, fibronectin, transforming growth factor-beta and other fibrogenic mediators of change. Although angiotensin-converting enzyme inhibition has proven to have an impact, perhaps temporarily, on obesity-associated proteinuria in humans, weight reduction early in the course of the disease would appear the most important therapeutic approach.
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PMID:Obesity and renal disease. 1198 Dec 64

Adiponectin, also referred to as AdipoQ or ACRP30, is a plasma protein produced and secreted exclusively from adipose tissue. The protein contains a collagen-like domain and a C1q-like globular domain. A protease-generated globular segment enhances fatty acid oxidation in muscles, thereby modulating lipid and glucose metabolism. Plasma adiponectin levels are inversely correlated with the severity of insulin resistance. A recent genome-wide scan study mapped a susceptibility locus for type 2 diabetes and the metabolic syndrome to chromosome 3q27, where the adiponectin gene is located. Here, we screened Japanese patients with type 2 diabetes and age- and BMI-matched nondiabetic control subjects for mutations in adiponectin gene. We identified four missense mutations (R112C, I164T, R221S, and H241P) in the globular domain. Among these mutations, the frequency of I164T mutation was significantly higher in type 2 diabetic patients than in age- and BMI- matched control subjects (P < 0.01). Furthermore, plasma adiponectin concentrations of subjects carrying I164T mutation were lower than those of subjects without the mutation. All the subjects carrying I164T mutation showed some feature of metabolic syndrome, including hypertension, hyperlipidemia, diabetes, and atherosclerosis. Our findings suggest that I164T mutation is associated with low plasma adiponectin concentration and type 2 diabetes.
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PMID:Association of adiponectin mutation with type 2 diabetes: a candidate gene for the insulin resistance syndrome. 1208 69

Platelet activation, impairment of fibrinolysis, activation of the coagulation pathway, and dyslipidemia are important factors in the pathogenesis and progression of ischemic heart disease, and patients generally need to use an antiplatelet agent. Lipid-lowering cerivastatin, a novel 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, was administered to 20 patients with primary mixed hyperlipidemia for the assessment of the effect of cerivastatin on lipid levels, plasma fibrinogen concentration, factor VII, VIII, and X levels, plasminogen and antiplasmin concentrations, platelet count, and aggregation (adenosine diphosphate [ADP], collagen, and epinephrine induced). Assessments were made immediately after 2 months of a standard lipid-lowering diet, 4 weeks of placebo administration, and 4 weeks of cerivastatin treatment. Cerivastatin achieved significant reductions in triglyceride, total cholesterol, and low-density lipoprotein cholesterol levels. The significant improvement of the lipid profile was associated with platelet aggregation reduction in vitro stimulated by ADP, collagen, and epinephrine (P < .05, P = .05, P < .005, respectively). Significantly lower levels of factor VII and fibrinogen were observed (P = .001, P < .0001) immediately after cerivastatin treatment. No significant differences were detected in factor VIII level, plasminogen and antiplasmin concentrations, and platelet count after cerivastatin treatment. It was concluded that cerivastatin in mixed hyperlipidemia can exert beneficial changes on specific hemostatic variables and platelet aggregation in addition to its positive effects on plasma lipid values.
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PMID:Treatment with cerivastatin in primary mixed hyperlipidemia induces changes in platelet aggregation and coagulation system components. 1241 40


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