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 mechanisms responsible for reocclusion after percutaneous transluminal angioplasty are still poorly understood. The effects of angioplasty on arterial morphology, deoxyribonucleic acid (DNA) synthesis (3H-thymidine incorporation) and lipid metabolism (14C-oleate incorporation) were studied in renal arteries of 24 male mongrel dogs. Balloon-dilated (identified by Evans blue dye accumulation) and adjacent normal arterial segments were collected 90 min and 2, 5 and 14 days after the procedure. The immediate vascular response was endothelial cell denudation and platelet accumulation. Two weeks after angioplasty, healing of the luminal surface by "endothelial-like" cells, mild smooth muscle cell proliferation and an angiogenic response with capillary growth into the media were observed. DNA synthesis was increased in balloon-dilated segments at day 5 compared with adjacent nonballoon-dilated artery. This increase in DNA synthesis persisted in the 2 week postangioplasty segments. Additionally, angioplasty produced both quantitative and qualitative changes in arterial lipid synthesis. The most dramatic change was an increase in sterol esterification that was apparent as early as 90 min after angioplasty; the change persisted through day 5 but diminished toward baseline by day 14. Angioplasty-induced alterations of arterial metabolism parallel aspects of the atherogenic process and may be involved in the pathogenesis of postangioplasty reocclusion, particularly in the presence of additional risk factors, such as hyperlipemia.
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PMID:Proliferative and lipid metabolism response to balloon angioplasty in canine renal arteries. 213 45

Sodium nitrite administered in the drinking water to Long-Evans rats during pregnancy and lactation severely affected erythropoietic development, growth, and mortality in their offspring. Pregnant rats were maintained throughout gestation on 0.5, 1, 2, or 3 g NaNO2/liter. There were no significant differences between treated and control litters at birth. Thereafter, pups of treated dams on 2 and 3 g NaNO2/liter gained less weight, progressively became severely anemic, and began to die by the third week postpartum. By the second week postpartum, hemoglobin levels, RBC counts, and mean corpuscular volumes of these pups were all drastically reduced compared to controls. Blood smears showed marked anisocytosis and hypochromasia. Gross chylous serum lipemia and fatty liver degeneration were noted. Histopathology demonstrated cytoplasmic vacuolization of centrilobular hepatocytes and decreased hematopoiesis in bone marrow and spleen. Administration of 1 g NaNO2/liter resulted in hematological effects but did not affect growth or mortality. NaNO2 (0.5 g/liter) was at or near the no observed effect level. Cross-fostering indicated that treatment during the lactational period was more instrumental in producing lesions than treatment during the gestational period. The data presented are consistent with the lactational induction of severe iron deficiency in the neonate.
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PMID:Evaluation of the developmental toxicity of sodium nitrite in Long-Evans rats. 369 23

Body fat distribution can be assessed by computed tomography (CT). The ratio of umbilicus was used to classify obese subjects as having visceral fat obesity (VFO) or subcutaneous fat obesity (SFO). Serum triglyceride and total cholesterol levels and plasma glucose area in an oral glucose tolerance test were higher in patients with VFO than in those with SFO. Significant positive correlations were demonstrated between V/S ratio and plasma glucose area, serum triglyceride level, and total cholesterol level as well as systolic or diastolic blood pressure. VFO was more frequently associated with coronary artery disease. Moreover, VFO was more often accompanied by multiple risk factors than was SFO. Steady-state plasma glucose (SSPG) level was significantly higher in patients with VFO than with SFO, suggesting that insulin resistance may be more remarkable in VFO than in SFO. Furthermore, visceral fat accumulation was also associated with these complications even in nonobese subjects. Visceral fat area (VFA) was significantly correlated with fasting plasma glucose, serum triglyceride, and total cholesterol levels. Animal models such as Goto-Kakizaki (GK) rats with ventromedial hypothalamus (VMH) lesions and Otsuka-Long-Evans-Tokushima-Fatty (OLETF) rats were accompanied by visceral fat accumulation and an early stage of aortic atherosclerosis. Aging, sex hormone, genetic, and dietary factors and physical inactivity may induce visceral fat accumulation. Visceral fat is characterized by its high lipogenic activity as well as its accelerated lipolytic activity. High levels of portal free fatty acids (FFAs) may eventually result in an enhancement of hepatic triglyceride synthesis, causing hyperlipidemia. High portal FFA levels would also induce insulin resistance, thereby causing glucose intolerance, hypertension, and finally atherosclerosis. We propose a term, "visceral fat syndrome," as a highly atherogenic state, which includes visceral fat accumulation, glucose intolerance (insulin resistance), hyperlipidemia, and hypertension.
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PMID:Insulin resistance and body fat distribution. 887 8

Cardiovascular diseases remain to be the 4th rank of top ten causes of mortality in Taiwan in recent years. Atherosclerosis and coronary artery disease, which often culminating in the occurrence of myocardial infarction and congestive heart failure, are responsible for the majority of these death. One of the prominent features of atherosclerotic lesion is local accumulation of lipids, mainly in the forms of cholesteryl ester and free cholesterol, either within cells or extracellularly in matrix. Repeated endothelial injury and enhanced lipid infiltration are critical events in the development of atherosclerosis. Plasma lipoproteins may enter the arterial wall through endothelium, either transcellularly via vesicular transport or paracellularly via intercellular junction. Our previous studies have demonstrated that most of the arterial endothelial cells in mitosis are associated with the leakage of fluorescently labeled albumin and low density lipoproteins. Subsequently, such transendothelial leakage of macromolecules is also shown to be associated with endothelial cell death as assessed by immunocytochemical staining for IgG. These findings suggested that transiently leaky junctions occurring during endothelial cell turnover may provide potentially important pathways for increasing transport or leakage of macromolecules, including atherogenic LDL, across the vascular endothelium. Electron microscopic study using horseradish peroxidase as a tracer revealed markedly widening of intercellular junctions around endothelial cells in mitosis providing direct evidence in support of "cell turnover-leaky junction" theory for the localization of atherogenesis. Hypertension, smoking, diabetes, and hyperlipidemia are well-known major risk factors for atherosclerosis and coronary heart disease. In a series of investigations, we examined the hypothesis that hypertension smoking, diabetes, and hyperlipidemia increase the arterial endothelial cell turnover and hence transendothelial macromolecular transport, which may have some implications in increasing lipid entry and thus, accelerating atherogenesis. Animal experiments were performed in adult male spontaneously hypertensive rats (SHR), Wistar-Kyoto (WKY) normotensive rats, and Sprague-Dawley (SD) rats. SHRs were used as hypertensive group with WKY rats as normotensive control. SD rats were given nicotine at a dose of 5 mg/Kg body wt/ day in their drinking water to mimic smoking effect over a period of 6 weeks. Diabetes was induced in SD rats by single intraperitoneal injection of 60 mg/Kg body wt of streptozotocin. The duration of diabetes was 6 weeks. Also, SD rats were fed a diet containing 5% cholesterol for 6 weeks to induce hyperlipidemia. Age-matched rats of comparable number served as control for each experimental group. In en face preparations of thoracic aorta, mitotic endothelial cells were identified by hematoxylin staining, immunoglobulin G-containing dying or dead endothelial cells were detected by an indirect immunoperoxidase method, and endothelial leakage to Evans blue-albumin (EBA) complexes (5 minutes after intravenous injection) was visualized and quantified by fluorescence microscopy. The results showed that SHR, chronic oral nicotine-treated rats, diabetic, rats, and hyperlipidemic rats, when compared to control rats, had higher values for the frequency of endothelial cell death and the number density of EBA leaky foci in the aorta. These findings suggested that hypertension, cigarette smoking, diabetes mellitus, and hyperlipidemia become risk factors in atherogenesis by increasing the rate of arterial endothelial cell turnover and the associated endothelial cell turnover and the to the consequent enhanced entry of atherogenic lipoproteins into the arterial wall and accelerated atherogenesis.
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PMID:Risk factors, endothelial cell turnover and lipid transport in atherogenesis. 903 45

The liver plays a central role in lipoprotein metabolism. In particular, very-low density lipoprotein (VLDL) is assembled in the hepatocytes and secreted into the blood circulation. The VLDL is then catabolized to low-density lipoprotein by lipoprotein lipase and hepatic triglyceride lipase. Obese subjects, especially those with visceral fat accumulation, are frequently associated with hyperlipidemia, non-insulin-dependent diabetes mellitus (NIDDM), and hypertension. The mechanism of hyperlipidemia in visceral fat obesity has not yet been elucidated. Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an animal model of NIDDM, characterized by obesity with visceral fat accumulation, hyperlipidemia, and late-onset insulin resistance. To elucidate the mechanism of hyperlipidemia observed in OLETF rats, we focused on the production of VLDL by the liver and investigated hepatic messenger RNA (mRNA) levels of microsomal triglyceride transfer protein (MTP), acyl-coenzyme A synthetase (ACS), and apolipoprotein B (apo B), which play important roles in VLDL synthesis and secretion. In 6-week-old OLETF rats, in which insulin resistance had not been manifested, visceral fat weight was already higher and portal free fatty acid (FFA) and VLDL-triglyceride levels were elevated compared with the control rats. Hepatic ACS activity and mRNA levels, and MTP mRNA levels were also increased in OLETF rats, whereas apo B mRNA levels were similar; these results suggest that the enhanced expression of both ACS and MTP genes associated with visceral fat accumulation before developing insulin resistance may be involved in the pathogenesis of hyperlipidemia in obese animal models with NIDDM.
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PMID:Enhanced expression of hepatic acyl-coenzyme A synthetase and microsomal triglyceride transfer protein messenger RNAs in the obese and hypertriglyceridemic rat with visceral fat accumulation. 946 57

The recently developed Otsuka Long-Evans Tokushima Fatty (OLETF) rat is known to develop insulinopenic diabetes after a prolonged period in a condition resembling non-insulin-dependent diabetes mellitus (NIDDM). We examined the effect of pharmacological intervention with a potent intestinal alpha-glucosidase inhibitor, acarbose, on the metabolic and histopathologic changes in this rat model. The first two groups of rats received an acarbose-rich diet (150 mg/100 g normal chow) from 12 weeks of age (ie, before the onset of diabetes) or from 28 weeks of age (ie, after the onset of diabetes), while a third group received the acarbose-rich diet for the initial 16 weeks only (from 12 to 28 weeks of age). A control group received standard rat chow. Acarbose-fed rats gained less weight or lost weight despite increased food intake when switched to the acarbose-rich diet. Acarbose also reduced visceral adipose depots and fasting triglyceride (TG), glucose, and insulin levels. At the end of the study at 72 weeks, the pancreatic wet weight and insulin content were significantly higher in the treated groups versus control rats. The morphological changes observed in control rats, such as atrophy of the pancreas and reduced number and size of islets, were not present in acarbose-treated rats. Rats fed acarbose from 12 to 28 weeks of age gradually gained weight after switching to standard chow, and hyperinsulinemia, hyperglycemia, and hyperlipidemia appeared (in that order). The pancreatic insulin content in these rats was significantly higher and the visceral adipose depot was significantly smaller than in control rats. Our study demonstrates that acarbose prevented and reversed the metabolic derangement and histopathological changes in genetically diabetic rats. Moreover, treatment with acarbose even for a short period produced a marked delay in the development of insulin insensitivity and frank diabetes.
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PMID:Metabolic abnormalities in the genetically obese and diabetic Otsuka Long-Evans Tokushima Fatty rat can be prevented and reversed by alpha-glucosidase inhibitor. 1009 12

1. The influence of angiotensin-converting enzyme (ACE) inhibitor is investigated in enalapril on renal function in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of spontaneously non-insulin-dependent diabetes (NIDDM). 2. Enalapril (5 mg/kg) or vehicle was administered once daily by gastric gavage to 22-week-old male OLETF rats for 32 weeks. Blood pressure, albuminuria, creatinine clearance, plasma glucose, serum insulin and lipids were determined before and during the treatment. Renal haemodynamics was examined at the end of the treatment. 3. Enalapril lowered blood pressure mildly but significantly. In the vehicle-treated rats, urinary albumin excretion increased from 0.75 +/- 0.16 mg/mg creatinine (Cr) to 8.65 +/- 0.78 mg/mg Cr. Enalapril significantly blunted the development of albuminuria from 0.66 +/- 0.12 mg/mg Cr to 5.19 +/- 0.67 mg/mg Cr (P < 0.008) without significant influence on creatinine clearances. Enalapril also significantly blunted the rise in serum cholesterol and triglyceride prior to the development of massive albuminuria. Enalapril did not affect bodyweight, plasma glucose or insulin levels. Renal haemodynamics assessed by inulin and p-aminohippuric acid clearances were similar in both groups at the end of the treatment. 4. These results reconfirmed that the ACE inhibitor has protective effects on nephropathy in NIDDM. Massive albuminuria was preceded by increase in serum lipids in OLETF rats, which supports the view that hyperlipidaemia exacerbates glomerular injury in chronic renal disease. Enalapril attenuated the rise in serum lipids, suggesting that the beneficial effects of the compound on renal injury in OLETF rats might also be mediated through the action of affecting serum lipids.
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PMID:Hyperlipidaemia and the progression of nephropathy in OLETF rats: effect of angiotensin-converting enzyme inhibitor, enalapril. 1047 73

Microsomal triglyceride transfer protein (MTP) plays a central role on secretion of lipoprotein from the liver and the intestine. MTP catalyzes the transfer of triglyceride, cholesteryl ester and phosphatidylcholine between membranes and lipoproteins. In human, defect of MTP activity, result from mutations encoding the MTP large subunit, is the primary cause of abetalipoproteinemia. To investigate the association between hyperlipidemia with obese and MTP, We used Otsuka Long-Evans Tokushima Fatty rat, an animal model of obesity with visceral fat accumulation, hyperlipidemia. In animals, very-low density lipoprotein-triglyceride levels were elevated compared with the control rats. Hepatic mRNA levels of acyl-coenzyme A synthetase, and MTP were also elevated. These results suggest that the enhanced expression of both ACS and MTP genes associated with visceral fat accumulation may be involved in the pathogenesis of hyperlipidemia in obese animal models.
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PMID:[The role of microsomal triglyceride transfer protein in metabolism of apo B-containing lipoprotein]. 1063 97

Otsuka Long-Evans Tokushima Fatty (OLETF) rats were established as a new model of non-insulin-dependent diabetes mellitus. An oral adsorbent, AST-120, is effective in removing such uremic toxins as indoxyl sulfate and delays the progression of chronic renal failure (CRF). This study was designed to determine the effects of AST-120 on the progression of CRF in uninephrectomized OLETF (1/2NxOLETF) rats and the localization of indoxyl sulfate in their kidneys. Four weeks after unilateral nephrectomy, 14 OLETF rats were divided into two groups; AST-120-administered and control 1/2NxOLETF rats. Long-Evans Tokushima Otsuka rats, which are genetically similar to the OLETF rats but not diabetic, were also included. After the administration of AST-120 for 36 weeks, we examined the effects of AST-120 on renal functional and pathological changes in the three groups. The control 1/2NxOLETF rats showed marked hyperglycemia, hyperlipidemia, renal failure, glomerular sclerosis, and tubulointerstitial injury. The administration of AST-120 to the 1/2NxOLETF rats retarded the progression of renal dysfunction and fibrosis, as well as hyperlipidemia, and reduced serum and urinary levels of indoxyl sulfate. Immunohistochemistry showed that AST-120 markedly reduced the overload of indoxyl sulfate in tubular epithelial cells, especially dilated tubules, of the 1/2NxOLETF rats. In conclusion, AST-120 delayed the progression of renal failure and fibrosis in 1/2NxOLETF rats and decreased the overload of indoxyl sulfate on renal tubular cells.
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PMID:An oral adsorbent ameliorates renal overload of indoxyl sulfate and progression of renal failure in diabetic rats. 1115 53

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


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