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)

Hyperlipidemia, especially hypercholesterolemia, may contribute to glomerulosclerosis as it does to atherosclerosis. Low density lipoprotein (LDL) stimulates the production of extracellular matrix by mesangial cells in culture as well as the proliferation of mesangial cells. This study was carried out to examine the effects of LDL on the type IV collagen (CIV) production by cultured rat mesangial cells (CRMC). Subconfluent CRMC monolayers which were grown in RPMI with 20% lipid-free fetal calf serum for 48 h were challenged with LDL (0, 50, 100, 150 and 200 micrograms/ml) for another 48 h. LDL was prepared from normal human plasma. Mesangial cell proliferation was examined by [3H]-thymidine uptake. Production of CIV was evaluated as the expression of CIV on the cell surface by flow-cytometric analysis. The collagen synthesis was measured by the [3H]-proline uptake. Total RNA was extracted from CRMC at 6 and 24 h of incubation with 150 micrograms/ml LDL, and Northern blotting and hybridization was performed with cDNAs for alpha 1-CIV, for 72-kD collagenase and for tissue inhibitor of metalloproteinase (TIMP)-2. The amount of total mRNA was corrected with beta-actin mRNA. Mesangial cell proliferation increased in all concentrations studied and had a peak value of 221% with 150 micrograms/ml of LDL. Expression of CIV increased by 30-60% in 100-200 micrograms/ml of LDL. Collagen synthesis also increased by 50-70% in 150-200 micrograms/ml of LDL. The mRNA ratio (procollagen alpha 1(IV)/beta-actin) increased to 133% at 24 h. The mRNA ratio (TIMP-2/beta-actin) increased to 137% at 24 h. mRNA ratios at 6 h showed no change.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of low density lipoprotein on type IV collagen production by cultured rat mesangial cells. 793 24

Hyperlipidemia and lipoprotein abnormalities are often encountered in patients with nephrotic syndrome or chronic renal disease and also in those undergoing haemodialysis and with renal transplant. Even though the significance of lipid deposition in renal tissue and the role of lipoproteins in the pathogenesis of renal disease in man is unclear, experimental and clinical data indicate a possible damaging effect of a disturbed lipid metabolism on the kidney. In humans, glomerular lipid deposition is observed in genetic diseases such as Fabry's disease, lecithin:cholesterol acyltransferase activity (LCAT) deficiency and arteriohepatic dysplasia, and in diseases with acquired disturbance of lipid metabolism such as nephrotic syndrome and cholestatic liver disease. Studies on animals with lupus nephritis, aminonucleoside nephrosis, reduced renal mass, diabetes mellitus or systemic hypertension have shown that cholesterol can increase the incidence of glomerulosclerosis. As most of these studies have been performed in the rat, which has a different lipoprotein profile to that of man, these results should be carefully interpreted with regard to their relevance for humans. In vitro cell culture studies on human glomerular cells have given some preliminary insights into the cellular mechanisms of lipid induced glomerular damage. Apo E-containing lipoproteins, which are pathologically elevated in many renal diseases, are avidly taken up by human mesangial cells. These cells seem to play a central role in the initiation of glomerulosclerosis by inducing proliferation and production of excess extracellular matrix. Lipoproteins are able to stimulate DNA synthesis in these cells, and increase the synthesis of mitogens and extracellular matrix protein. The pathogenic role of oxidized lipoproteins has not yet been defined. Human mesangial cells do not seem to take up these modified lipoproteins. However, macrophages infiltrate glomeruli and may constitute the stimulus for the generation of minimally modified lipoproteins and their cellular uptake. The data from animal experiments suggest that treatment that corrects hyperlipidemia may have an ameliorative effect on renal function. Thus, there are strong indications that lipoproteins may play a critical role in mediating the development of glomerulosclerosis.
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PMID:The role of lipids in nephrosclerosis and glomerulosclerosis. 794 52

Low-density lipoprotein apheresis (LDL-A) was performed for nine episodes of steroid-resistant nephrotic syndrome in eight patients. The clinical and immunohistological findings were analysed retrospectively. Six of the patients had focal glomerular sclerosis (FGS), one had minimal-change nephrotic syndrome (MCNS), and one had membranous nephropathy (MN) with FGS. The LDL-A treatment, carried out 2-13 times (mean 7.33 +/- 4.05) for one nephrotic episode, at average intervals of 3-16 days (mean: 8.5 +/- 5.1 days) and combined with steroid pulse therapy and the administration of an antihyperlipidaemic agent in some cases, led to rapid amelioration of hyperlipidaemia. In six nephrotic episodes (5 patients) more than 50% reduction of proteinuria occurred (less than 3.5 g/day) (response-group). A significant elevation of serum albumin (more than 3.0 g/dl) was obtained in five of these episodes. The other three patients were resistant (resistant-group). The number of and intervals between LDL-A treatments in the response group (5 +/- 2.8 times and 5.8 +/- 4.1 days) were significantly less than those in the resistant-group (12.0 +/- 0.8 times and 13.2 +/- 1.8 days) (P < 0.05). After LDL-A, significant reductions were observed in the serum total cholesterol (T-CHO), phospholipid (PL), triglyceride (TG), free-CHO (F-CHO), and beta-lipoprotein (beta-lipo) (P < 0.05). HDL-cholesterol (HDL-C) increased somewhat after LDL-A. Further, Ccr was elevated in all nephrotic episodes, except in one patient who manifested renal failure after 6 months.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Does LDL-apheresis in steroid-resistant nephrotic syndrome affect prognosis? 805 31

We treated hyperlipidemia in patients with nephrotic syndrome (NS) using pravastatin for more than one year. There were 7 cases consisting of 3 with minimal change nephrotic syndrome (MCNS), 1 with focal glomerulosclerosis (FGS), 1 with proliferative glomerulonephritis (PGN), 2 with membranous glomerulonephritis (MGN) and 1 of unknown origin. Three cases consisted of frequent relapsers, and 4 were steroid-resistant. Six randomly selected age- and sex-matched nephrotic patients were used as controls. The daily excretion of proteinuria was not decreased after pravastatin treatment, but, the serum albumin rose from 3.1 +/- 1.1 to 3.4 +/- 1.0 mg/dl. The serum total cholesterol level was significantly reduced from 401 +/- 174 mg/dl to 331 +/- 103 mg/dl in spite of an absence of marked change in the control group. However, there were no significant changes in the triglyceride and lipoprotein levels. The atherogenic index was 7.1 +/- 3.7 before and 2.8 +/- 1.7 after pravastatin treatment, respectively. Improvement of renal function defined by delta decrement of renal function per year (0.08 +/- 0.06 vs. 0.12 +/- 0.26) was observed after the discontinuation of pravastatin administration in 3 out of 4 intractable cases. We conclude that pravastatin has a potent effect in reducing the serum level of total cholesterol, but not triglyceride in NS. Furthermore, pravastatin can induce renal dysfunction especially in patients with intractable nephrotic syndrome.
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PMID:Pravastatin administration to hyperlipidemia in patients with nephrotic syndrome. 813 36

Hyperlipidaemia is strongly suggested to contribute to the pathogenesis of glomerular sclerosis. This study intends to clarify the effects of either a lipid lowering agent, lovastatin (LO) or protein restriction (PR) on adriamycin (ADR)-induced progressive glomerular sclerosis in rats. During the study period both serum cholesterol and triglyceride were significantly reduced in ADR-injected rats with either lovastatin administration (ADR-LO) or protein restriction (ADR-PR) compared to those without such treatment (ADR-NP). At week 22, urinary protein excretion, serum creatinine, blood urea nitrogen, glomerular sclerosis and tubulointestinal alterations, which were marked in ADR-NP, were ameliorated in both ADR-LO and ADR-PR rats. ADR-LO resulted in a body weight similar to that in ADR-NP while ADR-PR induced a marked weight loss. An antihyperlipidaemic agent, such as lovastatin, seems to be a useful tool for the prevention of renal deterioration.
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PMID:Effects of anti-hyperlipidaemic agent or dietary protein restriction on progressive renal deterioration in adriamycin-induced nephropathy in rats. 822 31

This study was undertaken to determine the role of angiotensin II (AII) in the development of glomerulosclerosis, using an AII receptor antagonist in an animal model of hyperlipidemia. Hyperlipidemic Imai rats were employed because they spontaneously develop glomerulosclerosis; this is especially true in males. Group 1 (n = 5) received no specific therapy. Group 2 (n = 5) was treated with enalapril at a dosage of 50 mg/l in drinking water starting at 6 weeks of age. Group 3 (n = 5) and group 4 (n = 6) were treated with the AII receptor antagonist DuP 753 at a respective dosage of 15 mg/l (low-dose DuP) and 150 mg/l (high-dose DuP) in drinking water. Body weight, blood pressure, urinary protein, serum albumin, cholesterol, BUN and serum creatinine were measured and compared among the groups from 12 to 24 weeks of age. Enalapril and high-dose DuP were almost equally effective in controlling systemic hypertension. Each treatment significantly reduced proteinuria (172 +/- 112 and 152 +/- 72 mg/kg/day at 24 weeks) as compared with that in the controls (421 +/- 147 mg/kg/day; p < 0.05 and p < 0.01, respectively). Hypercholesterolemia also decreased (82 +/- 4 and 89 +/- 6 mg/dl) as compared with that of the controls (141 +/- 48 mg/dl; both p < 0.05). Glomerulosclerosis index (SI) was significantly higher in the untreated control rats (55 +/- 26) than in the enalapril-treated rats (2 +/- 3; p < 0.005) and the high-dose-DuP-treated rats (6 +/- 6, p < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of an angiotensin II receptor antagonist on the progression of renal failure in hyperlipidemic Imai rats. 828 94

Although hyperlipidemia is a well-recognized complication of the nephrotic syndrome, the precise interaction of human glomerular cells and human lipoproteins, abnormal in lipid and protein composition, has not been clearly defined. This study examines receptor mediated binding, internalization and degradation as well as intracellular cholesterol metabolism of apoB-100 containing LDL and apoB,E containing IDL, isolated from patients with the nephrotic syndrome (N = 6), in human glomerular epithelial cells and skin fibroblasts. In the patients, serum LDL cholesterol level was increased threefold and IDL elevenfold as compared to healthy subjects. IDL of nephrotic patients contained 72% more cholesterol than IDL of healthy controls. No difference in lipid/protein composition was found in the LDL density range. Therefore, nephrotic and control LDL showed identical affinities for receptor mediated binding, internalization and degradation. Furthermore, inhibition of intracellular sterol synthesis and cholesteryl ester formation after incubation with LDL was comparable. In contrast, cholesterol-rich IDL of nephrotic patients was taken up by glomerular epithelial cells with higher affinity than LDL and control IDL, as well as intracellular sterol synthesis was suppressed more effectively than by control IDL. The cholesterol esterification rate of IDL from patients was enhanced 3.5-fold as compared to control IDL. In comparison to fibroblasts, glomerular epithelial cells showed about 15% of the maximal capacity for LDL uptake, but 31% for IDL from nephrotic patients. The data indicate that hypercholesterolemia of nephrotic origin cannot be explained by reduced ligand binding for LDL. ApoE containing IDL, which accumulate in nephrotic patients, were avidly taken up by glomerular epithelial cells via receptor dependent pathway. These lipoproteins could therefore play the predominant role in glomerular lipid accumulation and development of glomerulosclerosis.
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PMID:Receptor-mediated uptake of IDL and LDL from nephrotic patients by glomerular epithelial cells. 830 35

Arterial hypertension is a dominant pathogenetic factor for glomerulosclerosis. Nevertheless metabolic factors such as hyper- or dyslipoproteinemia may significantly modify and accelerate the process of glomerular scarring. Hyperlipidemia and lipoprotein abnormalities are often encountered in patients with nephrotic syndrome and chronic renal disease. Although the significance of lipid deposition in renal tissue and the role of lipoproteins in the pathogenesis of renal disease in man has not yet been clearly defined, experimental and clinical data indicate a damaging effect of disturbed lipid metabolism on the kidney. In humans glomerular lipid deposition is observed in several genetic diseases, including lecithin-cholesterol acyltransferase activity deficiency. Studies on animals with reduced renal mass, diabetes mellitus or arterial hypertension have shown that hypercholesterolemia increases the incidence of glomerulosclerosis. Especially the interaction of arterial hypertension and dyslipoproteinemia leads to a rapid and pronounced development of glomerulosclerosis. As most of these studies have been performed in the rat, which has a different lipoprotein profile than man, these results should be carefully interpreted with regard to their relevance for humans. In vitro cell culture studies on human glomerular cells have provided insight into the possible cellular mechanisms of lipid-induced glomerular damage. Apoprotein E containing lipoproteins that are pathologically elevated in many renal diseases are avidly taken up by human glomerular cells. Mesangial cells seem to play a central role in the initiation of glomerulosclerosis by proliferation and production of excess extracellular matrix. Lipoproteins are able to stimulate DNA synthesis in these cells and increase the synthesis of mitogens and matrix proteins. The pathogenetic role of modified, oxidized lipoproteins has not yet been elucidated.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Arterial hypertension and hyperlipidemia as determinants of glomerulosclerosis. 830 44

The hyperlipidemia associated with the nephrotic syndrome is well characterized. There is, however, a paucity of data in humans on the risk factors for atherosclerotic heart disease and the role of hyperlipidemia on the risk of progression of renal disease in this population. In our study, we retrospectively evaluated a large uniform population of patients (mean creatinine, 1.78 mg/dL; mean 24-hour proteinuria, 7.1 g) with idiopathic nephrotic syndrome for the presence of risk factors for coronary artery disease. One hundred patients with either focal segmental glomerulosclerosis (n = 56) or membranous nephropathy (n = 44) were assessed for the following cardiovascular risk factors: male sex or postmenopausal female, hyperlipidemia, hypertension, smoking history, and left ventricular hypertrophy. Sixty-six percent of the patients were either male or postmenopausal females; 35% were smokers. Hypertension and left ventricular hypertrophy were present in 53% and 13% of patients, respectively. Eighty-seven percent, 53%, and 25% of patients had a total cholesterol of more than 200 mg/dL, more than 300 mg/dL, and more than 400 mg/dL, respectively. Low-density lipoprotein cholesterol was greater than 130 mg/dL and greater than 160 mg/dL in 77.2% and 64.9% of patients, respectively. Virtually all patients (99%) had at least one risk factor for cardiovascular disease; over two thirds (68%) had two risk factors and over one quarter (26%) had three risk factors. In comparing the group that progressed to renal failure with the groups that did not, the initial mean serum cholesterol was lower in the group that progressed (292 mg/dL v 388 mg/dL, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The nephrotic syndrome, lipids, and risk factors for cardiovascular disease. 832 76

Considerable experimental evidence indicates that hyperlipidemia can induce glomerular injury. The importance of lipids in the progression of established glomerular disease has not been established and is of clinical relevance because of the frequent association of lipid abnormalities with human renal disease. In the present study, 26-week-old hyperlipidemic obese Zucker rats (OZRs) with established nephropathy were treated for a period of 18 weeks with daily injections of the cholesterol synthesis inhibitor lovastatin (4 mg/kg). Compared with control OZRs treated with vehicle, lovastatin-treated OZRs had significantly (P < 0.05) lower serum cholesterol and triglyceride levels throughout the treatment period. Blood pressure and urine albumin excretion in lovastatin-treated OZRs were reduced over the first 12 weeks of therapy, but increased toward the levels in the control OZRs at the end of the protocol. After 18 weeks of therapy, the incidence of glomerulosclerosis in lovastatin-treated OZRs (23.2% +/- 5.8%) was approximately half of that in vehicle-treated OZRs (44.6% +/- 7.7%) (P < 0.05). The reduction in glomerular injury in lovastatin-treated OZRs was not associated with changes in either glomerular area or glomerular macrophage content. In separate experiments, mesangial cells were cultured from glomeruli isolated from 26-week-old proteinuric OZRs. Lovastatin (5 to 40 mumol/L) caused a significant dose-dependent inhibition of serum-stimulated mesangial cell DNA synthesis. The inhibitory effects of lovastatin were completely prevented in the presence of exogenous mevalonate (100 mumol/L). Thus, lovastatin retarded the progression of established glomerular disease in OZRs.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lovastatin retards the progression of established glomerular disease in obese Zucker rats. 832 99


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