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 conducted an immunohistological investigation on the pathogenesis of interstitial foam cell formation in patients with idiopathic membranous nephropathy (MN). The patients were divided into two groups: Group I consisted of 23 MN patients with interstitial foam cells; Group II consisted of the other 159 patients without foam cells. Age at renal biopsy, duration of proteinuria, blood pressure and other clinical parameters were not significantly different between the two groups. The proportion of nephrotic patients in Group I was 52.2% (12/23), and was not significantly different from that in Group II (48.4%, 77/159). Renal biopsy specimens were examined by immunoperoxidase studies using monoclonal antibodies. The interstitial foam cells were positive for EBM11 (CD68) and 25F9, which are markers of macrophage (M phi) and mature M phi, respectively, but did not express markers of T cells. In interstitial infiltrating cells, both M phi and T cells were observed, but mature M phi were seldom seen. Furthermore, LFA-1 and ICAM-1, but not ICAM-3 (the third ligand for LFA-1) were observed in the interstitial foam cells. LFA-1 and ICAM-3 were observed mainly in interstitial infiltrating cells, but ICAM-1 was observed to a much lesser extent in these cells. These results suggest that interstitial foam cells in MN may be independent of severe hyperlipidemia and proteinuria, and that there may be different mechanisms underlying the accumulation of interstitial foam cells and infiltrating m phi s. Further investigations are required to clarify the pathogenesis of interstitial foam cells in renal tissue.
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PMID:[Clinicopathological study of interstitial foam cells in idiopathic membranous nephropathy. Consideration of the appearance of interstitial foam cells in renal tissue]. 871 10

We developed an animal model for non-insulin-dependent diabetes mellitus, a genetically obese rat strain, Wistar fatty. These rats show obesity-related features such as hyperinsulinemia and hyperlipemia, and only males develop diabetic features including hyperglycemia, glucoseuria and polyuria as they age. Histopathological study demonstrated a deposition of PAS-positive granules in the epithelial cells and a diffuse thickening of the mesangial area and moderate changes of the renal tubules. We found that ICAM-1 is expressed on the glomeruli of male Wistar fatty rats and the expression is associated with the development of nephropathy; it is weak at 5 weeks, becomes markedly strong at 15 weeks and progresses further at 29 weeks of age. We tried in vivo administration of monoclonal antibody, anti-ICAM-1 alone or together with anti-LFA-1 into male Wistar fatty rats during the period from 5 weeks to 17 weeks of age. The treatment, however, could not prevent the development of nephropathy. ICAM-1 expressed on the glomeruli of Wistar fatty rats seems not to play a key role in development of the nephropathy by mediating leukocyte infiltration. It will be a useful marker of the development of the disease.
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PMID:Expression of ICAM-1 on glomeruli is associated with progression of diabetic nephropathy in a genetically obese diabetic rat, Wistar fatty. 880 76

Low and oscillatory shear stresses are major features of the hemodynamic environment of sites opposite arterial flow dividers that are predisposed to atherosclerosis. Atherosclerosis is a focal inflammatory disease characterized initially by the recruitment of mononuclear cells into the arterial wall. The specific characteristics of the hemodynamic environment that facilitate the generation of arterial inflammatory responses in the presence of, for example, hyperlipidemia are unknown. We show here that prolonged oscillatory shear stress induces expression of endothelial cell leukocyte adhesion molecules, which are centrally important in mediating leukocyte localization into the arterial wall. Vascular cell adhesion molecule-1 was upregulated an average 9-fold relative to endothelial monolayers in static culture. Intercellular adhesion molecule-1 and E-selectin exhibited 11-fold and 7.5-fold increases, respectively. Upregulation of these adhesion molecules was associated with enhanced monocyte adherence. Cytokine stimulation of surface vascular cell adhesion molecule-1 was maximally induced after 6 and 8 hours of cytokine incubation. Oscillatory shear stress for these time periods elicited respective vascular cell adhesion molecule-1 levels of 16% and 30% relative to those observed for cytokine stimulation. Surface intercellular adhesion molecule-1 induction by cytokine stimulation for 24 hours was found to be approximately five times the level detected after 24 hours of oscillatory shear stress. Experiments performed in the presence of the antioxidant N-acetylcysteine demonstrated that the expression of vascular cell adhesion molecule-1 could be almost totally abolished, whereas that of intercellular adhesion molecule-1 was typically reduced by approximately 70%. These results imply that oscillatory shear stress per se is sufficient to stimulate mononuclear leukocyte adhesion and, presumptively, migration into the arterial wall. These results further indicate that atherosclerotic lesion initiation is likely related, at least in part, to unique signals generated by oscillatory shear stress and that the mechanism of upregulation is, to some extent, redox sensitive.
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PMID:Oscillatory shear stress stimulates adhesion molecule expression in cultured human endothelium. 952 57

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

Induction of acute pancreatitis follows a uniform mechanism independent of the different etiologic factors such as gallstones, alcohol, ischemia, hyperlipidemia, hypercalcemia, hereditary and others. Each cause seems to affect primarily the acinar cell, resulting in premature intracellular activation of trypsinogen and other digestive enzymes. Activated enzymes and oxygen free radicals injure the acinar cell and cause a release of cytokines and vasoactive mediators, attract inflammatory cells and activate the vascular endothelium as well as the expression of adhesion molecules. The disturbance of the pancreatic microcirculation induces a progression from edematous to necrotizing pancreatitis independent of the early intracellular events, including protease activation. Specific therapy must be directed towards microperfusion failure as a secondary pathogenetic step, since the initial enzyme activation and cytokine release is irreversible by the time of clinical presentation. In experimental designs comparable to the clinical situation the following therapeutic principles have proven beneficial: increase of blood fluidity by dextran, inhibition of leukocyte-endothelium interaction by ICAM-1 antibodies, and blockade of local vasoconstriction by endothelin-receptor antagonists.
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PMID:[New pathophysiologic knowledge about acute pancreatitis]. 1078 41

One of the critical events in the early stage of atherosclerosis is the focal accumulation of lipid-laden foam cells derived from macrophages. In various cholesterol-fed animal models of atherosclerosis, it was found that localized attachment of circulating monocytes to arterial endothelial cells appears to precede the formation of foam cells. It has been suggested that monocyte recruitment into early lesions is depend upon the endothelial adhesiveness for monocytes and lymphocytes. In vivo and in vitro experiments have identified molecules, such as ICAM-1, VCAM-1 and P-selecin, those can support the adhesion of monocytes and lymphocytes. Moreover oxidized LDL, lysophosphatidylcholine and oxidized fatty acids induce the expression of not only these adhesion molecules but also scavenger receptors, such as CD-36, SR-A and LOX-1. Recently we isolated and characterized the novel receptors for oxidized LDL, named LOX-1 and SR-PSOX. The expression of LOX-1 is found on endothelial cells, smooth muscle cells and macrophages. Whereas SR-PSOX expresses on macrophages. We address in this paper on the significance of hyperlipidemia, especially oxidized LDL and its receptors in terms of atherosclerosis.
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PMID:[Hyperlipidemia and atherosclerosis]. 1202 85

A variety of systemic risk factors, including smoking, hypertension, hyperlipidemia and diabetes have been found to promote atherosclerosis. Although these elements affect blood vessels equally, clinically significant lesions develop at predictable locations, i.e., major branch points and bifurcations. This suggests that the development of clinically significant atherosclerotic plaques involves a complex interplay between vascular anatomy, vascular biology and hemodynamic forces. Cyclic strain, circumferential pulsatile pressure exerted upon a vessel wall, has been found to cause changes in endothelial cells that tend to disfavor atherosclerosis formation. Cultured endothelial cells have been shown to migrate, proliferate and alter cytoskeletal alignment in response to cyclic strain. Levels of macromolecules such as prostacyclin, endothelin, nitric oxide and tissue plasminogen activator have been found to be altered by cyclic strain. Additionally, cyclic strain has been shown to stimulate expression of cellular adhesion molecules such as ICAM-1 and intracellular second messenger systems such as the adenylate cyclase-cAMP, diacylglycerol-IP3, and protein kinase C pathways. This article reviews the most current pertinent literature and summarizes the presently known effects of cyclic strain on endothelial cells.
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PMID:Molecular and biological effects of hemodynamics on vascular cells. 1535 57

Morphological changes in the hepatic sinusoid with old age are increasingly recognized. These include thickening and defenestration of the liver sinusoidal endothelial cell, sporadic deposition of collagen and basal lamina in the extracellular space of Disse, and increased numbers of fat engorged, nonactivated stellate cells. In addition, there is endothelial up-regulation of von Willebrand factor and ICAM-1 with reduced expression of caveolin-1. These changes have been termed age-related pseudocapillarization. The effects of old age on Kupffer cells are inconsistent, but impaired responsiveness is likely. There are functional implications of these aging changes in the hepatic sinusoid. There is reduced sinusoidal perfusion, which will impair the hepatic clearance of highly extracted substrates. Blood clearance of a variety of waste macromolecules takes place in liver sinusoidal endothelial cells (LSECs). Previous studies indicated either that aging had no effect, or reduced the endocytic capacity of LSECs. However, a recent study in mice showed reduced endocytosis in pericentral regions of the liver lobules. Reduced endocytosis may increase systemic exposure to potential harmful waste macromolecules such as advanced glycation end products Loss of fenestrations leads to impaired transfer of lipoproteins from blood to hepatocytes. This provides a mechanism for impaired chylomicron remnant clearance and postprandial hyperlipidemia associated with old age. Given the extensive range of substrates metabolized by the liver, age-related changes in the hepatic sinusoid and microcirculation have important systemic implications for aging and age-related diseases.
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PMID:Old age and the hepatic sinusoid. 1848 14

Increased reactive oxygen species (ROS) and hyperlipidemia can promote arterial thrombus. We evaluated the potential of a partially hydrolyzed guar gum (PHGG) as dietary fiber on lipid profiles and FeCl3-induced arterial thrombosis in the high fat-diet fed hamsters. Our in vitro results found that PHGG is efficient to scavenge O2-*, H2O2, and HOCl. High fat-diet increased plasma triglyceride, total cholesterol, LDL, VLDL, methylguanidine and dityrosine level and accelerated FeCl3-induced arterial thrombosis formation (from 463 +/- 51 to 303 +/- 45 sec). Low dose PHGG supplement significantly decreased the total cholesterol, LDL, methylguanidine and dityrosine level and delayed the time for arterial thrombosis formation (528 +/- 75 sec). High dose PHGG supplement decreased the level in triglyceride, total cholesterol, LDL and VLDL and further delayed the time for arterial thrombus (671 +/- 36 sec). The increased Bax protein and decreased Bcl-2 and HSP-70 protein expression was found in the carotid and femoral arteries of high fat-diet hamsters. Low and high dose of PHGG supplement decreased Bax expression and increased Bcl-2 and HSP-70 protein expression. We found that FeCl3 significantly enhanced intercellular adhesion molecule-1 and 4-hydroxynonenal expression in the endothelial site of damaged artery after 150-sec FeCl3 stimulation. PHGG supplement decreased the endothelial ICAM-1 and 4-hydroxynonenal expression after 150-sec FeCl3 stimulation. Based on these results, we conclude that PHGG supplement can increase antioxidant protein expression and thus decrease oxidative stress induced arterial injury.
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PMID:Partially hydrolyzed guar gum supplement reduces high-fat diet increased blood lipids and oxidative stress and ameliorates FeCl3-induced acute arterial injury in hamsters. 1927 78

Aim of this study was to evaluate microvascular reactivity (MVR) by laser Doppler flowmetry in Type 2 diabetes mellitus (T2DM) with hyperlipidemia during three years of simvastatin treatment. Additionally, markers of endothelium and fibrinolysis were evaluated. Twenty patients with T2DM and hyperlipidemia were treated with 20 mg of simvastatin daily for 3 months, treatment was then interrupted for 3 months (wash-out) and again started and maintained continually up to total of 36 months of follow-up. Maximal perfusion (max), velocity of perfusion increase (max/t) and percent increase of perfusion compared to baseline (%) was measured during post-occlusive reactive hyperemia (PORH) and thermal hyperemia (TH). VCAM-1, ICAM-1, E-selectin and P-selectin were used as markers of endothelium, tissue plasminogen activator (tPA) and its inhibitor (PAI-1) as markers of fibrinolysis. Baseline MVR in diabetic patients was comparable to controls. MVR decreased at months 3, 12, and 36 compared to baseline (PORHmax 26+/-12, 35+/-17, 26+/-11 vs. 56+/-30 PU, p<0.05, THmax 67+/-19, 81+/-37, 58+/-24 vs. 134+/-70 PU, p<0.01, PORHmax/t 2.0+/-1.4, 2.8+/-1.7, 1.9+/-1.3 vs. 7.7+/-7.4 PU/s, p<0.05, THmax/t 1.1+/-0.6, 1.0+/-0.4, 0.7+/-0.4 vs. 1.5+/-0.7 PU/s, p<0.05.
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PMID:Microvascular Reactivity and Endothelial Function in Type 2 Diabetic Patients with Hyperlipidemia Treated with Simvastatin: 3-year Follow-up. 2005 81


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