Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lipoprotein(a) [Lp(a)] represents an LDL-like particle to which the Lp(a)-specific apolipoprotein(a) is linked via a disulfide bridge. It has gained considerable interest as a genetically determined risk factor for atherosclerotic vascular disease. Several studies have described a correlation between elevated Lp(a) plasma levels and coronary heart disease, stroke, and peripheral atherosclerosis. In healthy individuals, Lp(a) plasma concentrations are almost exclusively controlled by the apo(a) gene locus on chromosome 6q2.6-q2.7. More than 30 alleles at this highly polymorphic gene locus determine a size polymorphism of apo(a). There exists an inverse correlation between the size (molecular weight) of apo(a) isoforms and Lp(a) plasma concentrations. The standardization of Lp(a) quantification is still an unresolved task due to the large particle size of Lp(a), the presence of two different apoproteins [apoB and apo(a)], and the large size polymorphism of apo(a) and its homology with plasminogen. A working group sponsored by the IFCC is currently establishing a stable reference standard for Lp(a) as well as a reference method for quantitative analysis. Aside from genetic reasons, abnormal Lp(a) plasma concentrations are observed as secondary to various diseases. Lp(a) plasma levels are elevated over controls in patients with nephrotic syndrome and patients with end-stage renal disease. Following renal transplantation, Lp(a) concentrations decrease to values observed in controls matched for apo(a) type. Controversial data on Lp(a) in diabetes mellitus result mainly from insufficient sample sizes of numerous studies. Large studies and those including apo(a) phenotype analysis came to the conclusion that Lp(a) levels are not or only moderately elevated in insulin-dependent patients. In noninsulin-dependent diabetics, Lp(a) is not elevated. Conflicting data also exist from studies in patients with familial hypercholesterolemia. Several case-control studies reported elevated Lp(a) levels in those patients, suggesting a role of the LDL-receptor pathway for degradation of Lp(a). However, recent turnover studies rejected that concept. Moreover, family studies also revealed data arguing against an influence of the LDL receptor for Lp(a) concentrations. Several rare diseases or disorders, such as LCAT- and LPL-deficiency as well as liver diseases, are associated with low plasma levels or lack of Lp(a).
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PMID:Lipoprotein(a) in health and disease. 898 7

To better characterize the heavy proteinuria occasionally described in cholesterol atheroembolic renal disease (CAE), we reviewed the clinical features and histological findings of 24 patients found at renal biopsy to have CAE. Twelve (50%) had a typical clinical presentation soon after an invasive vascular procedure. Eight (33%) underwent biopsies to evaluate proteinuria and four (17%) with insidiously developing renal failure to exclude rapidly progressive glomerulonephritis. All had usual and similar risk factors for CAE; 71% were male, 96% had peripheral vascular disease, 79% had recently undergone an invasive vascular procedure, 74% were hypercholesterolemic, and all were hypertensive. Proteinuria was higher and serum creatinine lower in the proteinuria group. In the nine (38%) nephrotic patients, serum creatinine measurements were lower (2.7 +/- 1.2 v 5.6 +/- 2.4 mg/dL), duration of renal disease to biopsy longer, and time from biopsy to dialysis greater (23.5 +/- 14.8 v 0.03 +/- 0.098 mo, P < 0.05 for all). Focal segmental glomerulosclerosis (FSGS) was observed in 15 (63%) of the biopsy specimens. Although FSGS itself did not occur more commonly in nephrotic patients, these patients did have a higher fraction of segmentally sclerosed glomeruli (0.158 +/- 0.097 v 0.026 +/- 0.050, P < 0.01). A variant of FSGS, the cellular lesion with epithelial cell prominence and capillary loop collapse, was observed in 7 of 9 (78%) patients with nephrotic-range proteinuria, but in only 3 of 12 (25%) patients with lesser degrees of protein excretion (P < 0.05). The cellular lesion was accompanied by higher mean proteinuria, 7.6 +/- 4.3 versus 2.1 +/- 2.4 g/24 hr (P < 0.01). In a larger group of patients with a similar age range as the CAE group who were identified by search of a computerized biopsy database, membranous nephropathy was the only other form of idiopathic glomerulonephritis that occurred with CAE. One of 82 (1.2%) patients with membranous nephropathy also had CAE, compared with 20 of 102 (19.6%) with FSGS (P < 0.0002, chi2). Thus, the finding of FSGS with CAE was not coincidence. Mean follow-up was 20 +/- 26 months (range, 0 to 103 months). Six patients (25%) were followed-up at least 3 years after renal biopsy. These findings indicate that extended survival in CAE is not rare and that heavy proteinuria occurs as part of a chronic disorder with distinctive histological features. Cholesterol atheroembolism with FSGS should be considered in the differential diagnosis of nephrotic syndrome in elderly patients with advanced atherosclerosis.
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PMID:Focal segmental glomerulosclerosis associated with nephrotic syndrome in cholesterol atheroembolism: clinicopathological correlations. 904 Dec 8

A comprehensive study on platelet aggregation, hemostasis, fibrinolysis and serum lipids in relation to peripheral serotonergic system has been performed on 41 nephrotic patients. Enhanced platelet aggregatory responses in both whole blood and in platelet rich plasma (PRP) were found upon stimulation with different agonists when compared to healthy volunteers. Increased levels of fibrinogen, fibrin monomers, and protein C activity were observed in nephrotic patients. Euglobulin clot lysis time was significantly prolonged in nephrotic patients. Activity of tissue plasminogen activator (tPA) inhibitor was higher in nephrotic syndrome, whereas tPA activity was significantly lower in these patients when compared to controls. Urokinase concentration, lipoprotein (a), cholesterol, LDL and VLDL levels were significantly higher in nephrotic patients over controls. Whole blood serotonin was significantly lower, whereas plasma serotonin was significantly higher in nephrotic patients relative to controls. Serotonin uptake and its release from platelets were markedly diminished in patients with nephrotic syndrome. Disequilibrium in the coagulolytic system, platelet hyperactivity, hyperfibrinogenemia, disturbances in peripheral serotonergic system together with lipid abnormalities may contribute to the progression and development of atherosclerosis and an enhanced risk of thromboembolic complications in nephrotic syndrome.
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PMID:Comprehensive study on platelet function, hemostasis, fibrinolysis, peripheral serotonergic system and serum lipids in nephrotic syndrome. 911 50

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

Plasma lipoproteins (LP) may be identified on the basis of density properties or apolipoprotein (apo) composition. ApoB-containing LP occur in VLDL, IDL and LDL. There are several types of apoB-containing LP characterized by specific composition of minor apolipoproteins (apoC, apoE etc.) and lipid constituents (triglycerides and cholesterol), metabolic properties and relative atherogenicity. The alterations of lipoprotein metabolism in renal disease resulting in elevated levels of apoB-containing LP may be reflected in hyperlipidemia. Whereas nephrotic syndrome and heavy proteinuria are associated with increased formation of cholesterol-rich apoB-containing LP in LDL and VLDL, the characteristic feature in renal failure is the accumulation of intact or partially metabolised triglyceride-rich LP in IDL and VLDL. The potentially atherogenic apoB-containing LP have been linked to the pathogenic processes that result in progressive glomerular and interstitial lesions and ultimate loss of renal function. The mechanisms of injury are not fully understood. Receptor- and non-receptor mediated uptake of LP by mesangial cells may induce or accelerate proliferative and sclerotic processes in the glomerular mesangium that are analogous to atherosclerosis in the arterial wall. Changes in glomerular permeability can result in increased filtration of LP that may be internalized by tubular cells and elicit corresponding lesions in the interstitial tissues. The negative impact of proteinuria on the prognosis of renal disease could be mediated in part through an increased filtration of lipoproteins. Induction of hyperlipidemia accelerates glomerular and interstitial damage in experimental renal failure. This can be attenuated by treatment with hypolipemic agents. In patients, increased concentrations of apoB-containing LP are associated with more rapid progression of renal insufficiency in both primary renal disease and diabetic nephropathy. It is, however, presently not known to what extent treatment of the renal dyslipidemia can modify the progression of chronic renal failure. Experimental and clinical evidence suggest that apoB-containing LP may play a pathogenetic role in the progression of renal disease.
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PMID:Progression of renal failure: role of apolipoprotein B-containing lipoproteins. 940 33

To elucidate the mechanism of foam cell formation in the mesangial region of a kidney observed in a familial type III hyperlipoproteinemic patient presenting with diabetes mellitus and nephrotic syndrome, we have examined, in the present study, the effect of human beta-VLDL (apo E2/E2) on foam cell formation in human mesangial cells, since an increase in beta-VLDL is a characteristic feature of this patient. Human beta-VLDL (apo E2/E2) induced foam cell formation in human mesangial cells. The binding of [125I]LDL to human mesangial cells was inhibited completely by both LDL and beta-VLDL. On the other hand, the binding of [125I]beta-VLDL was completely inhibited by beta-VLDL, but partially by LDL. The LDL receptor, but not the VLDL receptor was down-regulated by accumulation of cholesteryl esters. These results suggest that human beta-VLDL (apo E2/E2)-induced foam cell formation in mesangial cells is mediated through both the LDL receptor pathway and the beta-VLDL specific pathway, in which the VLDL receptor is one of the candidates.
Atherosclerosis 1997 Dec
PMID:Human beta-migrating very low density lipoprotein induces foam cell formation in human mesangial cells. 943 Mar 72

Hyperfibrinogenemia is a common feature of the nephrotic syndrome, and contributes to increased tendency for thrombosis and atherosclerosis. Its genesis is not certain, but the increase in liver fibrinogen mRNA in nephrotic rats indicates increased synthesis. Data in humans are scarce. We presently compared synthesis rates of fibrinogen and albumin in nephrotic adults (N = 7; plasma albumin 22.3 +/- 0.7 g/liter, proteinuria 12 g/day) and healthy control subjects (N = 8) using a primed/continuous infusion of the stable isotope L-[1-13C]valine for six hours. Absolute synthesis rate (ASR) of fibrinogen was 31 +/- 3 mg/kg/day in nephrotic subjects and 21 +/- 1 mg/kg/day in control subjects (P < 0.05), and positively correlated with plasma fibrinogen (P = 0.0317). The plasma fibrinogen pool was disproportionately increased in the nephrotic patients (271 +/- 30 mg/kg) compared to the controls (126 +/- 8 mg/kg), suggesting decreased fractional catabolic rate as well. The ASR of albumin was increased from 71 +/- 4 mg/kg/day in the controls to 160 +/- 19 mg/kg/day in the patients (P < 0.0001), and strongly correlated with the ASR of fibrinogen (P = 0.0046). Plasma alpha 2-macroglobulin was also elevated and correlated with the albumin synthesis rate, whereas plasma serum amyloid A and C-reactive protein were not elevated. These data suggest that in nephrotic patients the increased albumin synthesis is associated with an increase in synthesis of a specific and coordinated group of proteins, among which is fibrinogen.
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PMID:Proportionate increase of fibrinogen and albumin synthesis in nephrotic patients: measurements with stable isotopes. 945 16

A young woman was diagnosed with systemic lupus erythematosus at the age of 7 years and incurred an acute myocardial infarction at the age of 17 years. Her risk factors for coronary artery disease include hypertension, hypercholesterolemia, a relatively long disease duration, a fairly active disease as evidenced by the history of nephrotic syndrome and other organ system involvement, and a long history of prednisone use. It is difficult to determine the etiology of this patient's acute myocardial infarction without coronary artery histopathology, but aspects of her presentation (a history of virulent systemic lupus erythematosus, and the angiographic findings of ectasia and aneurysm) suggest that coronary arteritis was the etiology of her accelerated coronary artery disease and subsequent myocardial infarction. Acute myocardial infarction is an uncommon occurrence in premenopausal women less than 30 years old.35 These patients are typically found to have an associated systemic disease such as diabetes mellitus or familial hypercholesterolemia. Systemic lupus erythematosus is a less common systemic disease associated with premature coronary artery disease. Mechanisms of acute coronary syndromes in these patients include accelerated atherosclerosis, active coronary vasculitis, and/or vasospasm with superimposed thrombosis.
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PMID:Acute myocardial infarction in a young woman with systemic lupus erythematosus. 954 9

Patients with renal diseases like nephrotic syndrome, chronic renal failure (uremia) and renal transplantation frequently present disturbances of lipid metabolisms, however their pathogenesis is partially understood. Moreover, cardiovascular diseases are responsible for many deaths in these patients. Although the effect of the dyslipidemias in the development of atherosclerosis in renal diseases is not clear, they probably play a role. Since actually the survival of these patients is substantial, it is important to manage them appropriately with regard to their dyslipidemias. This review will examine the pathogenesis and treatment of dyslipidemias in patients with nephrotic syndrome, chronic renal failure and renal transplantation.
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PMID:[Dyslipidemias in renal diseases: pathogenesis and treatment]. 967 3

The human plasma lipoprotein Lp(a) has gained considerable clinical interest as a genetically determined risk factor for atherosclerotic vascular diseases. Numerous (including prospective) studies have described a correlation between elevated Lp(a) plasma levels and coronary heart disease, stroke and peripheral atherosclerosis. Lp(a) consists of a large LDL-like particle to which the specific glycoprotein apo(a) is covalently linked. The apo(a) gene is located on chromosome 6 and belongs to a gene family including the highly homologous plasminogen. Lp(a) plasma concentrations are controlled to a large extent by the extremely polymorphic apo(a) gene. More than 30 alleles at this locus determine a size polymorphism. The size of the apo(a) isoform is inversely correlated with Lp(a) plasma concentrations, which are non-normally distributed in most populations. To a minor extent, apo(a) gene-independent effects also influence Lp(a) concentrations. These include diet, hormonal status and diseases like renal disease and familial hypercholesterolemia. The standardisation of Lp(a) quantification is still an unresolved problem due to the enormous particle heterogeneity of Lp(a) and homologies of other members of the gene family. Stability problems of Lp(a) as well as statistical pitfalls in studies with small group sizes have created conflicting results. The apo(a)/Lp(a) secretion from hepatocytes is regulated at various levels including postranslationally by apo(a) isoform-dependent prolonged retention in the endoplasmic reticulum. This mechanism can partly explain the inverse correlation between apo(a) size and plasma concentrations. According to numerous investigations, Lp(a) is assembled extracellularly from separately secreted apo(a) and LDL. The sites and mechanisms of Lp(a) removal from plasma are only poorly understood. The human kidney seems to represent a major catabolic organ for Lp(a) uptake. The underlying mechanism is rather unclear; several candidate receptors from the LDL-receptor gene family do not or poorly bind Lp(a) in vitro. Lp(a) plasma levels are elevated over controls in patients with renal diseases like nephrotic syndrome and end-stage renal disease. Following renal transplantation, Lp(a) concentrations decrease to values observed in controls matched for apo(a) type. Controversial data on Lp(a) in diabetes mellitus mainly result from insufficient sample sizes in numerous studies. Large studies and those including apo(a) phenotype analysis have come to the conclusion that Lp(a) levels are not or only moderately elevated in insulin-dependent patients. In non-insulin-dependent diabetics Lp(a) is not elevated. Several rare disorders, such as LCAT and LPL deficiency, as well as liver diseases and abetalipoproteinemia are associated with low plasma levels or lack of Lp(a).
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PMID:Genetics and metabolism of lipoprotein(a) and their clinical implications (Part 1). 1006 65


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