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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This paper attempts to further delineate the similar pathobiologic mechanisms involved in the atherosclerosis and glomerulosclerosis processes. In particular, recent experimental data in models of both processes have focused on the roles of hypercholesterolemia and the monocyte/macrophage in propagating these lesions. In a nonimmune toxic glomerulopathy, chronic aminonucleoside nephrosis, our laboratory has demonstrated an important role for the glomerular macrophage, which is increased in number in temporal association with the onset of albuminuria, in propagating initial glomerular injury to glomerulosclerosis. In addition, a superimposition of dietary hypercholesterolemia further augments this heightened glomerular macrophage number and activates systemic macrophages. These data suggest a synergistic role between the hypercholesterolemia of nephrosis and the surge in glomerular macrophage number following initial glomerular injury in establishing a cascade of intercellular events that culminates in glomerulosclerosis. The intriguing histologic and immunohistochemical similarities between the evolving fatty streak in the atherosclerotic vessel wall and the progressive glomerular lesion leading to glomerulosclerosis suggest analogous pathobiologic mechanisms.
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PMID:Analogous pathobiologic mechanisms in glomerulosclerosis and atherosclerosis. 204 67

The mechanisms responsible for hyperfiltration in diabetes mellitus (DM) as well as for the initiation and progression of diabetic nephropathy are not fully elucidated. Enhanced prostaglandin E2 (PGE2) production has been invoked in the former and thromboxane (TXB2) and hyperlipidemia in the latter. Fish oil (FO)-enriched diets can favorably alter eicosanoid synthesis and serum lipid profiles. We therefore examined the effects of a FO-enriched diet on glomerular filtration (GFR), proteinuria, glomerular eicosanoid production, and serum lipids in rats with streptozotocin-induced DM (STZ-DM). Groups of 5-8 rats with STZ-DM were maintained on low insulin and then pair-fed with isocaloric diets enriched with either FO (20% w/w) or beef tallow (BT; 20% w/w). GFR was determined in the same animals at onset of diet and after 8 and 20 weeks on the respective diets by [14C]inulin clearance using implanted osmotic minipumps each time. Significant hyperfiltration was present initially and GFR did not change on either diet for 20 weeks, in spite of a significant and greater than 50% decrease in all prostaglandins (PGE2, TXB2, PGF2 alpha, 6-keto, PGF1 alpha) produced by glomeruli isolated from DM/FO as compared to DM/BT or control rats. FO diet completely corrected the hypertriglyceridemia of diabetes and significantly reduced the mild and early proteinuria of DM. The decrease in proteinuria and the correction of hyperlipidemia of DM by a FO-enriched diet may be beneficial in the long term not only for the development of diabetic glomerulopathy, but also for the accelerated atherosclerosis of DM.
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PMID:Effects of fish oil on glomerular function in rats with diabetes mellitus. 240 55

A 41-year-old male with a 25-year history of diabetes mellitus requiring 25 to 30 units of neutral protamine hagedorn (NPH) insulin daily was found dead at home. Recent history revealed that he was well until the last four days of life when he had the onset of nausea, vomiting, and anorexia coinciding with procurement of a new bottle of insulin from his pharmacist. Pertinent autopsy findings included coronary and aortic atherosclerosis, a peptic ulcer, and diabetic glomerulopathy. Chemical analysis of the vitreous humor, including glucose (813 mg/dL) and acetone (40 mg/dL), revealed that he died of diabetic ketoacidosis. Further investigation revealed that the pharmacist had accidentally substituted regular insulin, with a duration of action of up to 6 h as opposed to 24 to 28 h, for NPH. Cultures of blood and of the regular insulin yielded no growth. Analysis of this case emphasizes the importance of obtaining a careful medical and medication history and the usefulness of vitreous electrolytes when investigating a sudden death in a diabetic.
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PMID:Pharmaceutical error resulting in fatal diabetic ketoacidosis. 308 89

Abnormal renal diseases including nephrotic syndrome and chronic renal failure are associated with hyperlipidemia, significance of abnormal lipid metabolism has been thought to be limited in some inherited renal diseases. However, recent studies have postulated that glomerulosclerosis is induced by hyperlipidemia and is in common with atherosclerosis. This involvement is found in the progressive renal disorders, e.g., focal glomerular sclerosis, diabetic nephropathy and glycogen storage disease. Interaction between macrophages and mesangial cells may play an important role in such conditions. This evidence is supported by experimental models with hyperlipidemia. On the other hand, discovery and new hereditary metabolic disorders, such as type III hyperlipoproteinemia and lipoprotein glomerulopathy, shows that apolipoprotein (apo) E abnormalities are responsible for the glomerular lesions. Especially, lipoprotein glomerulopathy has specific features different from those of lipid-induced renal diseases. In this disease, apo E Sendai which results from new substitution (Arginine 145-->Proline) may induce intraglomerular lipoprotein thrombi characteristic of lipoprotein glomerulopathy.
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PMID:Abnormal lipid metabolism and renal disorders. 916 48

In the present paper, longitudinal studies in non-insulin-dependent diabetes mellitus (NIDDM) dealing with risk factors, especially microalbuminuria, blood pressure, and glycemic control, and the course of the kidney function are addressed. The definition of microalbuminuria, limits for abnormal albuminuria, and possible causes of microalbuminuria in NIDDM are discussed. Microalbuminuria is a major independent risk marker for early mortality, and new studies indicate that even "high normoalbuminuria" carries a risk. Furthermore, risk markers agreed on among various studies include apart from abnormal albuminuria, age and preexisting cardiovascular disease, whereas there is some inconsistency concerning glycemic control, lipoproteins, and even hypertension. People with microalbuminuria, NIDDM patients as well as nondiabetics, share an increased prevalence of atherosclerosis and its risk factors as well as an increased TER(alb). Albuminuria in NIDDM may thus have two different causes: general vascular disease and diabetic glomerulopathy. The clinical course of renal function is with large interindividual variation in both patients with or without overt proteinuria. Systolic blood pressure, glycemic control, and level of albuminuria appear to determine the deterioration in kidney function and progression of albuminuria, and to influence the overall prognosis, thus being obvious items for intervention. Long-term intervention studies demonstrating improved survival are, however, still awaited.
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PMID:Microalbuminuria, blood pressure, metabolic control, and renal involvement: longitudinal studies in white non-insulin-dependent diabetic patients. 932 21

Lipid abnormalities are associated with various disorders ranging from generalized atherosclerosis to renal diseases, including lipoprotein glomerulopathy that is characterized by glomerular lipoprotein thrombi and causes type III hyperlipoproteinemia, proteinuria, and renal failure. This study examines lipoprotein glomerulopathy, which recurred in a transplanted kidney. Molecular biologic analysis of the patient's apolipoprotein (apo) E gene demonstrated E2/E5 type variants. Immunohistochemical analysis of the diseased kidney demonstrated various lipid peroxidation-specific protein adducts, suggesting a potential role of oxidative stress in this disorder. Recurrence in the transplanted kidney suggested a pathogenic role of extraglomerular humoral component(s) resulting from abnormal lipoprotein metabolism, presumably linked to apo E and other genetic or acquired factor(s). Furthermore, the finding that the patient showed pathologic abnormalities in the transplanted kidney with no clinical signs or symptoms of renal disease indicated that lipoprotein glomerular damage progresses early before any clinical manifestations.
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PMID:Apolipoprotein E2/E5 variants in lipoprotein glomerulopathy recurred in transplanted kidney. 1040 16

Epidemiologic studies indicate that hyperglycaemia is responsible for microangiopathy, but that its role in macroangiopathy is more controversial. The relative risk of coronary heart disease (CHD) is 2- to 3-fold greater for diabetic men and 3- to 5-fold greater for diabetic women. It is greater for lower limb arteriopathy (4- to 6-fold) and amputations (10- to 20-fold). Although relative risk is rather constant for different populations, absolute CHD risk depends on other risk factors and the rate of risk in the non-diabetic population. Yet hyperglycaemia is also a causal factor for CHD risk, as demonstrated in cohort studies of Type 1 diabetic patients without diabetic glomerulopathy or any associated CHD risk factors, and especially in diabetic Pima Indians who are genetically protected against hypercholesterolaemia and hypertension. Finally, according to WESDR and UKPDS data, the 10-year risk of cardiovascular mortality increases by 10% for every 1% increase in HbA1c value. Hyperglycaemia can be linked to atherogenesis through several pathways: gluco-oxidation of the extracellular matrix inducing accelerated atherosclerosis, endothelial dysfunction, with a decreased production or inactivation of NO, a thrombogenic tendency, with increase in PAI1, Willebrandt factor and platelet aggregation, and last (but not least) dyslipidaemia subsequent to lipoprotein glycooxidation and increased production of VLDL. Hyperglycaemia was associated with hyperlipoproteinaemia and high plasma triglyceride levels, low plasma HDL levels and high plasma levels of small and dense LDL in three high risk populations: diabetic women, Asian migrants, and the Finnish population of Kupsio. Moreover, impaired glucose tolerance appears to be a CHD risk marker indicative of insulin resistance apparently responsible for atherosclerosis related to an association of CHD risk factors rather than to hyperinsulinaemia. The precedence of insulin resistance over onset of Type 2 diabetes is consistent with the existence, at diagnosis, of clinical complications of atherosclerosis in 20% of cases, as confirmed in the UKPDS study. Finally, though blood glucose control by sulphonylureas and insulin does not appear to be deleterious, these drugs have not shown their efficacy in reducing macrovascular adverse events in Type 2 diabetes, either because the cumulative incidence of events is inadequate (DCCT) or the efficacy of long-term hypoglycaemic effects is not apparent (UKPDS). Moreover, these studies have shown that exogenous as well as endogenous hyperinsulinaemia can lead to increase in weight, with potentially atherogenic android fat distribution. In conclusion, though the correlation between hyperglycaemia and microangiopathy is linear and well-established worldwide (with every 1% increase or decrease in HbA1c resulting in a 30% increase or decrease in microangiopathic events), the same is not true for macroangiopathy, whose prevalence is variable among populations. Thus, CHD mortality due to diabetes is 5-fold lower in France than in Finland, though the Monica study indicates a disparity within the French community.
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PMID:[Epidemiology of cardio-vascular complications of diabetes]. 1042 88

A proposed analogy between atherosclerosis and glomerulosclerosis suggests that factors that contribute to the development of atherosclerosis, ie, oxidatively modified (lipo)proteins, may also participate in glomerular injury. Although the nature of the in vivo oxidants has not been clearly identified, increasing evidence suggested the myeloperoxidase (MPO)-H(2)O(2)-halide system to be responsible for the damage observed in leukocyte-dependent glomerulonephritis. MPO, a heme protein secreted by activated phagocytes, may generate modified/oxidized proteins in vivo via intermediate formation of hypochlorous acid (HOCl)/hypochlorite. HOCl, a reactive oxygen species and powerful oxidant, can convert (lipo)proteins into atherogenic forms in vitro and in vivo. Here we demonstrate the presence of HOCl-modified proteins in glomeruli of patients with membranous glomerulonephritis using monoclonal antibodies that do not cross-react with other oxidative modifications. Immunostaining for HOCl-modified epitopes in human minimal change glomerulopathy revealed glomeruli that were unreactive, although the number of MPO-positive cells/glomerulus was slightly increased in comparison to controls. In contrast to minimal change glomerulopathy, a pronounced infiltration of mononuclear cells/glomerulus in membranoproliferative glomerulonephritis is in line with pronounced staining for HOCl-modified epitopes. Immunostaining was detected in intracapillary cells and immune complex deposits within the glomerular basement membrane. In human membranous glomerulonephritis (Stages I to III), staining for HOCl-modified proteins was localized at the basement membrane and podocytes. Staining of serial sections revealed colocalization of HOCl-modified epitopes and MPO in glomerular peripheral basement membranes. Subsequently, tubulointerstitial staining for HOCl-modified epitopes was observed in foam cells at the border of the cytoplasm and in damaged tubular epithelia in focal advanced chronic lesions. Our results indicate that oxidative modification of the basement membrane structure by phagocyte-derived HOCl may be of importance for glomerular defects. The observed colocalization of HOCl-modified proteins and MPO in podocytes and adjacent basement membranes strengthens the assumption that the MPO-H(2)O(2)-halide system contributes to glomerular dysfunction in patients with membranous glomerulonephritis.
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PMID:Immunohistochemical detection of hypochlorite-modified proteins in glomeruli of human membranous glomerulonephritis. 1179 21

Lipoprotein glomerulopathy (LPG) is a hereditary disorder characterized by intraglomerular lipoprotein thrombi and increased serum apolipoprotein (apo) E. Patients with LPG usually manifest with nephrotic syndrome, and some progress to renal failure; however, no effective therapeutic regimen has been established for this disease. We experienced a patient with LPG for whom bezafibrate treatment was very effective. This 30-year-old Japanese woman had nephrotic syndrome and type III hyperlipoproteinemia. Renal biopsy showed markedly dilated capillary lumina containing massive lipoprotein thrombi. Plasma apo E concentration was elevated to twice that of normal controls. She was proved to be a heterozygote of apo E2 Kyoto (Arg25Cys). After 2 years treatment with bezafibrate (400 mg/day), her plasma albumin gradually increased from 2.1 to 4.0 mg/dl, and intraglomerular lipoprotein thrombi disappeared almost completely. Bezafibrate decreased plasma apo E and dramatically increased high density lipoprotein (HDL)-cholesterol. The decrease in apo E was observed mainly in the pre-beta-fraction, not in the alpha fraction. Lipidological analyses of our patient suggest that the origin her lipoprotein thrombi may be mainly from pre-beta-lipoproteins and that HDL might be involved in resolving lipoprotein thrombi. Our case suggests that administration of fibrates such as bezafibrate may be a novel therapeutic strategy for resolving intraglomerular thrombi and improving nephrotic syndrome in patients with LPG.
Atherosclerosis 2003 Aug
PMID:Disappearance of intraglomerular lipoprotein thrombi and marked improvement of nephrotic syndrome by bezafibrate treatment in a patient with lipoprotein glomerulopathy. 1292 81

Apolipoprotein E (ApoE) is a major constituent of plasma lipoproteins with many biological actions of great significance. Beyond the known influence of ApoE polymorphisms on serum lipid profile, the pathogenesis of atherosclerosis, and the development of neurodegenerative disorders, ApoE also has a major role in the pathogenesis and progression of a variety of renal diseases, as well as in the atherosclerotic complications associated with them. Briefly, the polymorphisms of ApoE are major determinants of plasma lipid levels in uremic patients. They may affect the risk for cardiovascular disease in this population, predispose to the development of diabetic nephropathy, influence the severity of certain glomerulopathies, and regulate mesangial and glomerular functions locally in the kidney microenvironment. Finally, certain mutations of the ApoE gene are associated with a recently described nephropathy, termed lipoprotein glomerulopathy.
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PMID:Apolipoprotein E and renal disease. 1475 87


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