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)

Biological interactions between the bone and the blood vessels are gradually being clarified. To investigate the relationship between bone mineral density and atherosclerosis in hemodialysis patients, we examined the bone mineral density and the intima-media thickness of the carotid artery in 83 dialysis patients with non-diabetic nephropathy (44 men and 39 women) aged from 23 to 83 years. The duration of hemodialysis ranged from 2 to 344 months. The bone mineral density of the radius was measured by dual-energy X-ray adsorptiometry, and the ratio of this value to the standard value for the same age and gender was calculated ( Z-score). As an index of atherosclerosis, the intima-media thickness of the carotid artery was measured by high resolution B-mode ultrasonography. Then the relationship between the Z-score and various factors was examined using Spearman's rank correlation analysis and multiple regression analysis. The Z-score showed a negative correlation with the duration of hemodialysis, the carotid intima-media thickness, and the levels of alkaline phosphatase, intact parathyroid hormone, and low-density lipoprotein cholesterol by Spearman's rank correlation analysis. In addition, the Z-score showed a positive correlation with the lipoprotein (a) level and a negative correlation with the duration of hemodialysis, intima-media thickness, intact parathyroid hormone, and low-density lipoprotein cholesterol by multiple regression analysis. These findings suggest that the decrease of bone mineral density in hemodialysis patients is correlated with secondary hyperparathyroidism and hyperlipidemia, which are factors known to promote atherosclerosis, and thus bone density changes might be related to the progression of atherosclerosis, or vice versa.
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PMID:Bone mineral density may be related to atherosclerosis in hemodialysis patients. 1459 55

Diabetic patients have a two- to four-fold increase in macrovascular disease compared with non-diabetic subjects, with coronary heart disease (CHD) and stroke being the most common causes of death in type 2 diabetes. Diabetic nephropathy has become the most common single cause of end-stage renal disease in industrialized countries. Risk factors, including hyperglycaemia, high blood lipids and high blood pressure (BP), often co-exist in diabetic subjects. One recent metaanalysis, including more than 90,000 patients with a 12.4-year follow-up, has demonstrated a continuous increase in the relative risks of morbidity and mortality with increasing blood glucose concentration. Both the Multiple Risk Factor Intervention Trial (MRFIT) and the United Kingdom Prospective Diabetes Study (UKPDS) have confirmed in diabetes the close relationship between total cholesterol levels and elevated risk of cardiovascular events. For every 1 mmol/l increase in low-density lipoprotein cholesterol in type 2 diabetes, the relative risk of CHD increases by 1.57. Furthermore, about 40% of newly diagnosed diabetic patients are also hypertensive. Elevated BP is related to the presence of left ventricular hypertrophy (LVH) and, indeed, LVH is observed in more than 70% of diabetic patients with hypertension. Several studies in diabetes have proven treatment benefits when different risk factors are addressed. The need for tighter control of cardiovascular risk factors in diabetic patients is clear. This may include better control of raised BP, hyperlipidaemia and hyperglycaemia as well as closer monitoring for the appearance of LVH and microalbuminuria. There is a clear need to translate the results of clinical trials into everyday clinical practice.
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PMID:The need for tighter control of cardiovascular risk factors in diabetic patients. 1276 60

Oxidative stress has emerged as an important pathogenic factor in the development of long-term complications, such as atherosclerosis and nephropathy, in patients with diabetes. Whereas multiple enzymes and processes can contribute to oxidative stress, recent studies indicate that a multicomponent phagocyte-type NADPH oxidase is a major source of reactive oxygen species (ROS) production in many nonphagocytic cells, including fibroblasts, vascular smooth muscle cells, endothelial cells, renal mesangial cells, and tubular cells. Under physiologic conditions, nonphagocytic NADPH oxidases have very low-level constitutive activity. However, enzyme activity can be upregulated both acutely and chronically in response to stimuli such as growth factors, cytokines, high glucose, and hyperlipidemia. ROS production by the oxidase may serve a signaling role or may lead to oxidative damage. This article reviews current knowledge of the nonphagocyte-NADPH oxidases at both structural and biochemical levels and discusses the possible role of these enzymes in the pathophysiology of diabetic nephropathy.
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PMID:ROS generation by nonphagocytic NADPH oxidase: potential relevance in diabetic nephropathy. 1287 35

Diabetic nephropathy has become the single largest cause of end-stage renal disease (ESRD) worldwide. Until recently, it was thought that once a patient developed overt proteinuria, diabetic nephropathy was irreversible and inevitably progressed to ESRD. However, the reversal of lesions caused by diabetic nephropathy (e.g., glomerular basement membrane thickening and mesangial matrix increase) has been demonstrated in a series of patients who underwent a pancreas transplantation 10 years prior to the reversal. Remission of nephrotic range proteinuria has also been reported in some patients with type 1 diabetes from the Collaborative Study Group during a median follow-up of 3 years of angiotensin-converting enzyme (ACE) inhibitor administration; no deterioration of renal function was observed in these patients. Remission and regression in nephropathy of type 1 diabetes patients have also been reported when blood pressure was controlled aggressively. Recent clinical trials have demonstrated that angiotensin II receptor blocker (ARB) preserved renal function and slowed the progression of nephropathy to ESRD in patients with type 2 diabetes. Since many patients with type 2 diabetes manifest with a metabolic syndrome, multifactorial intensive treatment is necessary; such treatment includes behavior modifications, dietary intervention, exercise, and smoking cessation. In this population, pharmacological therapy targeting hyperglycemia, hypertension (including ARB/ACE inhibitor), and hyperlipidemia in cases of type 2 diabetes is also necessary.
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PMID:Remission and regression of diabetic nephropathy. 1292 17

Diabetic nephropathy is the leading cause of end-stage renal disease in Western countries, but only a portion of diabetic patients develop diabetic nephropathy. Dyslipidemia represents an important aspect of the metabolic imbalance in diabetic patients. In this study, we addressed the impact of combined hyperlipidemia and hyperglycemia on renal pathology. Kidneys from wild-type (WT) or LDL receptor-deficient BALB/cBy mice (BALB.LDLR-/-) were examined at 22 weeks of age. Diabetes was induced by administration of streptozotocin and mice were randomly assigned to either standard chow or Western diet. Chow fed BALB.LDLR-/- mice did not demonstrate renal abnormalities, whereas BALB. LDLR-/- mice fed a Western diet showed occasional glomerular and tubulointerstitial foam cells. Diabetic WT mice had modestly increased glomerular cellularity and extracellular matrix. Hyperlipidemic and diabetic BALB.LDLR-/- mice exhibited an increase in glomerular cellularity and extracellular matrix, accumulation of glomerular and tubulointerstitial foam cells and mesangial lipid deposits. The tubular epithelium demonstrated pronounced lipid induced tubular degeneration with increased tubular epithelial cell turnover. Hyperlipidemia and hyperglycemia seem to act synergistically in inducing renal injury in the BALB.LDLR-/- mouse. This model of diabetic nephropathy is unique in its development of tubular lesions and may represent a good model for hyperlipidemia-exacerbated diabetic nephropathy.
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PMID:Hyperglycemia and hyperlipidemia act synergistically to induce renal disease in LDL receptor-deficient BALB mice. 1467 36

Dyslipidemia is a major factor responsible for coronary heart disease and its reduction decreases coronary risk in patients with diabetes mellitus. However, the association of dyslipidemia with microvascular complications and the effect of intervention with lipid-lowering therapy in diabetes have been less investigated. We present the systematic review of association and intervention studies pertaining to dyslipidemia and microvascular disease in diabetes and also review possible mechanisms. Dyslipidemia may cause or exacerbate diabetic retinopathy and nephropathy by alterations in the coagulation-fibrinolytic system, changes in membrane permeability, damage to endothelial cells and increased atherosclerosis. Hyperlipidemia is associated with faster decline in glomerular filtration rate and progression of albuminuria and nephropathy. Recent evidence also suggests a role of lipoprotein(a) in progression of retinopathy and nephropathy in patients with diabetes mellitus. Lipid-lowering therapy, using single agents or a combination of drugs may significantly benefit diabetic retinopathy and diabetic nephropathy. In particular, hydroxymethyl glutaryl coenzyme A reductase inhibitors may be effective in preventing or retarding the progression of microvascular complications because of their powerful lipid-lowering effects and other additional mechanisms. However, most of the data are based on short-term studies, and need to be ascertained in long-term studies. Until more specific guidelines are available, aggressive management of diabetic dyslipidemia, according to currently accepted guidelines, should be continued for the prevention of macrovascular disease which would also benefit microvascular complications.
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PMID:The role of lipids in the development of diabetic microvascular complications: implications for therapy. 1472 67

Diabetic nephropathy is related to glomerular extracellular matrix (ECM) accumulation that leads to glomerulosclerosis. Fluvastatin as a lipid-lowering medicine significantly prevents diabetic nephropathy, probably not only through its lipid-lowering action, but also mainly through its direct suppression of glomerular ECM accumulation. To test this hypothesis, in the present study, a five-sixths nephrectomized (5/6Nx) rat model to induce a renal ECM accumulation without coexistence of hyperlipidemia was used to investigate the effect of fluvastatin on renal function, glomerular ECM accumulation and expression of connective tissue growth factor (CTGF). 5/6Nx induced a significant nephropathy in rats at 13 weeks, indicated by renal dysfunction including increases in blood urine nitrogen, creatinine and urinary protein excretion, and renal histopathological changes. Administration of fluvastatin significantly prevented the renal dysfunction and histological abnormalities in the 5/6Nx rats. Furthermore, both significant suppression of matrix metalloproteinases (MMPs) activity such as MMP-2 and significant activation of tissue inhibitors of MMP (TIMPs) such as TIMP-2 observed in the 5/6Nx rats were almost completely prevented by fluvastatin, resulting in a significant prevention of glomerular ECM accumulation. For upstream mediator of ECM accumulation, 5/6Nx significantly up-regulated CTGF mRNA expression, but fluvastatin treatment prevented CTGF up-regulation. These results suggest that fluvastatin, as one of well-known lipid-lowering agents, plays an important role in the prevention of nephropathy, likely through suppression of CTGF-mediated ECM accumulation. Therefore, fluvastatin may be a potential candidate for developing a pharmaceutical approach to the prevention of diabetic nephropathy due to its both lipid-lowering and direct anti-renal ECM accumulation actions.
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PMID:Fluvastatin prevents nephropathy likely through suppression of connective tissue growth factor-mediated extracellular matrix accumulation. 1473 71

Diabetes now accounts for >40% of patients with ESRD. Despite significant progress in understanding diabetic nephropathy, the cellular mechanisms that lead to diabetes-induced renal damage are incompletely defined. For defining changes in protein expression that accompany diabetic nephropathy, the renal proteome of 120-d-old OVE26 transgenic mice with hypoinsulinemia, hyperglycemia, hyperlipidemia, and proteinuria were compared with those of background FVB nondiabetic mice (n = 5). Proteins derived from whole-kidney lysate were separated by two-dimensional PAGE and identified by matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrometry. Forty-one proteins from 300 visualized protein spots were differentially expressed in diabetic kidneys. Among these altered proteins, expression of monocyte/neutrophil elastase inhibitor was increased, whereas elastase IIIB was decreased, leading to the hypothesis that elastin expression would be increased in diabetic kidneys. Renal immunohistochemistry for elastin of 325-d-old FVB and OVE26 mice demonstrated marked accumulation of elastin in the macula densa, collecting ducts, and pelvicalyceal epithelia of diabetic kidneys. Elastin immunohistochemistry of human renal biopsies from patients with type 1 diabetes (n = 3) showed increased elastin expression in renal tubular cells and the interstitium but not glomeruli. These results suggest that coordinated changes in elastase inhibitor and elastase expression result in increased tubulointerstitial deposition of elastin in diabetic nephropathy. The identification of these coordinated changes in protein expression in diabetic nephropathy indicates the potential value of proteomic analysis in defining pathophysiology.
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PMID:Alterations in the renal elastin-elastase system in type 1 diabetic nephropathy identified by proteomic analysis. 1497 67

Large-scale clinical trials have shown that the oral adsorbent AST-120 improves renal function and delays the initiation of dialysis in chronic renal failure (CRF) secondary to chronic glomerulonephritis. If renal failure progresses via common mechanisms, then the same effects can be expected in diabetic nephropathy. However, no study on diabetic nephropathy has been reported. Thus, we enrolled patients with statistically significant progression of CRF secondary to diabetic nephropathy, and analyzed the changes in renal function after AST-120 therapy, and the clinical factors associated with response to therapy. We enrolled 276 patients with diabetic nephropathy, whose serum creatinine (Scr) had increased from 3.4 to 4.5 mg/dL during the 4.5 +/- 3.7 months prior to the study. These patients took AST-120 at a dose of 5.0 +/- 1.4 g/day for 6 months. The clinical data were analyzed by dividing the patients into three groups based on the changes in Scr after AST-120 therapy, with responders showing a decrease (N = 82), partial responders showing <1.5-fold increase (N = 144), and non-responders showing >/=1.5-fold increase (N = 50). AST-120 significantly lowered the slope of 1/Scr-time line, suggesting that AST-120 suppressed the progression of renal impairment. No responders required dialysis, whereas 24.3% of the partial responders and 36.0% of the non-responders started dialysis therapy. In responders, the 1/Scr-time slope showed a negative-to-positive shift and serum urea nitrogen decreased significantly, whereas the improvement was moderate in partial responders and minimal in non-responders. Among responders, AST-120 therapy significantly improved renal function despite the presence of hypoproteinemia, hyperlipidemia, anemia or hypertension in many patients. The beneficial effect of AST-120 was significantly more marked in patients with blood pressure controlled within the normal ranges and hematocrit maintained at 30% or above. AST-120 reversed renal dysfunction or delayed the initiation of dialysis therapy in patients with progressive aggravation of CRF secondary to diabetic nephropathy, independent of hypoproteinemia, hyperlipidemia, anemia and hypertension. Active use of AST-120 may be recommended in patients with good control of blood pressure and hematocrit above 30%.
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PMID:Protective effect of an oral adsorbent on renal function in chronic renal failure: determinants of its efficacy in diabetic nephropathy. 1515 77

Hyperlipidemia not only may be relevant to cardiovascular disease in diabetes but may also play a role in the development and progression of diabetic nephropathy. Furthermore, there is increasing evidence that advanced glycation end products (AGE) play an important role in diabetic renal disease. The objectives of this study were first to characterize renal injury in diabetic apolipoprotein E knockout (apo E-KO) mice and second to explore the role of AGE in the development and progression of renal disease in this model. Diabetes was induced by injection of streptozotocin in 6-wk-old apo E-KO mice. Diabetic animals received no treatment or treatment with the inhibitor of AGE formation aminoguanidine (1 g/kg per d) or the cross-link breaker [4,5-dimethyl-3-(2-oxo2-phenylethyl)-thiazolium chloride] ALT-711, which cleaves preformed AGE (20 mg/kg per d) for 20 wk. Nondiabetic apo E-KO mice as well as nondiabetic and diabetic C57BL/6 mice served as controls. Compared with nondiabetic apo E-KO mice, induction of diabetes in apo E-KO mice resulted in accelerated renal injury characterized by albuminuria and glomerular and tubulointerstitial injury. These abnormalities were associated with increased expression of collagen type I and type IV and transforming growth factor-beta1 (TGF-beta1), increased alpha-smooth muscle actin immunostaining and macrophage infiltration, and increased serum and renal AGE. The two treatments, which attenuated renal AGE accumulation in a disparate manner, were associated with less albuminuria, structural injury, macrophage infiltration, TGF-beta1, and collagen expression. The accelerated renal injury that was observed in diabetic apo E-KO mice was attenuated by approaches that inhibit renal AGE accumulation.
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PMID:Accelerated nephropathy in diabetic apolipoprotein e-knockout mouse: role of advanced glycation end products. 1528 98


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