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)

To assess the cardiological status of patients with long-term lupus nephritis we evaluated 30 patients (mean age 43 +/- 11 years) with lupus nephritis lasting from at least 10 years (mean 15 +/- 5 years). At the time of cardiological evaluation the mean plasma creatinine was 132.6 +/- 11.1 mumol/l and in 28 patients lupus had been quiescent for at least 3 years. Fourteen patients (46.6%) showed one or more cardiac abnormalities: 10 had valvular lesions (1 verrucous endocarditis, 9 thickening and stiffness of one or more valves)--4 patients had regional myocardial akinesis as a consequence of a previous cardiac infarct (one had valvular abnormalities too). One patient had pulmonary hypertension probably secondary to pulmonary vasculitis. No patient had pericarditis. These cardiac abnormalities proved to be statistically correlated with the number of ARA criteria (p = 0.045), the number of lupus flares (p = 0.004), the serum levels of cholesterol (p = 0.04) and of triglycerides (p = 0.025) as well as the duration of hypercholesterolemia (p = 0.005) and of hypertriglyceridemia (p = 0.007). In conclusion, in patients with long-term lupus nephritis cardiac lesions are frequent. The main lesions are non-verrucous valvulopathy (probably a consequence of healing verrucous endocarditis) and cardiac infarct (caused by an accelerated atherosclerosis). On the contrary cardiac lesions caused by active lupus as pericarditis, myocarditis and verrucous endocarditis are rare.
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PMID:Cardiologic abnormalities in patients with long-term lupus nephritis. 769 32

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.
Atherosclerosis 1994 May
PMID:The role of lipids in nephrosclerosis and glomerulosclerosis. 794 52

The normal vascular wall contains resident leukocytes, notably tissue macrophages (histiocytes) and mast cells, that confer a rapid, eicosanoid-dependent vasoconstrictor response to agonists typical of leukocytes, such as the complement-derived anaphylatoxin C5a or the formylated peptide f-Met-Leu-Phe (isolated organ methodology). The eicosanoid-dependent vasomotor response is even more intense in pathologies that involve leukocyte infiltration of the blood vessel wall, such as atherosclerosis and serum sickness in the rabbit. The leukocyte compartment of the blood vessel is the likely source of vasoactive mediators (eicosanoids, radicals, cytokines) of physiopathological importance, with possible application in cardiac ischemia, lupus nephritis, vasculitides, and graft rejection. This line of investigation may be compared to the discovery and characterization of endothelium-dependent vasomotor responses. However, the problem is experimentally more demanding: histological correlations, experiments based on leukocyte depletion, reconstitution, and enrichment are useful approaches to document this form of circulatory control.
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PMID:Evidence for vascular tone regulation by resident or infiltrating leukocytes. 893 61

Increasing amounts of evidence support the involvement of inflammation and immunity in atherogenesis, but mediators of communication between the major cell types in atherosclerotic plaques are poorly defined. Cells in human atherosclerotic lesions express the immune mediator CD40 and its ligand CD40L (also known as CD154 or gp39). The interaction of CD40 with CD40L figures prominently in both humoral and cell-mediated immune responses. CD40L-positive T cells accumulate in atheroma, and, by virtue of their early appearance, persistence and localization at sites of lesion growth and complication, activated T cells may coordinate important aspects of atherogenesis. Interruption of CD40L-CD40 signalling by administration of an anti-CD40L antibody limits experimental autoimmune diseases such as collagen-induced arthritis, lupus nephritis, acute or chronic graft-versus-host disease, multiple sclerosis and thyroiditis. Ligation of CD40 on atheroma-associated cells in vitro activates functions related to atherogenesis, including induction of proinflammatory cytokines, matrix metalloproteinases, adhesion molecules and tissue factor. However, the role of CD40 signalling in atherogenesis in vivo remains unknown. Here we determine whether interruption of CD40 signalling influences atherogenesis in vivo in hyperlipidaemic mice. Treatment with antibody against mouse CD40L limited atherosclerosis in mice lacking the receptor for low-density lipoprotein that had been fed a high-cholesterol diet for 12 weeks. This antibody reduces the size of aortic atherosclerotic lesions by 59% and their lipid content by 79%. Furthermore, atheroma of mice treated with anti-CD40L antibody contained significantly fewer macrophages (64%) and T lymphocytes (70%), and exhibited decreased expression of vascular cell adhesion molecule-1. These data support the involvement of inflammatory pathways in atherosclerosis and indicate a role for CD40 signalling during atherogenesis in hyperlipidaemic mice.
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PMID:Reduction of atherosclerosis in mice by inhibition of CD40 signalling. 967 6

In children, systemic lupus erythematosus (SLE) is often more severe than in adults. Renal disease is very common in SLE, with clinical symptoms of renal involvement occurring in 30%-70% of patients. In the absence of appropriate treatment the child may die from the disease or progress rapidly to renal failure. However, aggressive treatment regimens, in particular corticosteroids, carry the risk of growth retardation, accelerated atherosclerosis, and severe infectious complications. Lupus nephritis is classified into six groups depending on the severity of the histological lesions. The most-appropriate treatment for optimal efficacy with minimal side-effects depends on the disease severity. Mild lesions (class I or II) require only careful follow-up to identify any disease progression. Patients with class III nephropathy (focal and segmental glomerulonephritis) may have mild clinical symptoms, in which case no specific therapy is indicated, or more-severe symptoms of the nephrotic syndrome, hypertension, and sometimes moderate renal insufficiency. These patients require the same aggressive therapy as those with class IV disease (diffuse proliferative glomerulonephritis). Our current protocol starts with three methylprednisolone pulses followed by 1.5 mg/kg per day oral prednisone and six monthly pulses of cyclophosphamide. After a second renal biopsy the patient may be maintained on azathioprine while the prednisone dosage is slowly tapered. In children with milder disease we use lower doses of oral prednisone (1-1.5 mg/kg per day). Patients with membranous glomerulonephritis (class V) require no specific therapy if they have pure membranous nephropathy, but require aggressive therapy if they have the nephrotic syndrome. In those patients who progress to end-stage renal disease, clinical and serological remission is common and renal transplantation can be performed, as recurrence in the transplant is very rare.
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PMID:Treatment of lupus nephritis in children. 1068 69

Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease marked by immune-complex mediated lesions in small blood vessels of various organs, especially the kidneys, although other factors may also be implicated in the pathogenesis of the disease. This article focuses on the role of lipids in the progression of glomerular, vascular and tubulo-interstitial lesions in two patients with lupus nephritis associated with pronounced hyper- and dyslipidemia. The pathogenesis of progressive glomerulosclerosis in both patients appears to be multifactorial. In addition to immune complex mediated lupus glomerulonephritis, progressively active in the first patient, severe nephrotic-range persistent proteinuria, arterial hypertension associated with hyperfiltration and hyperperfusion injuries and, to a minor extent, hyper- and dyslipidemia were observed. Immunological and non-immunological factors were shown to contribute to the development of tubulo-interstitial lesions. In both patients, in addition to local immune deposits, prominent tubulo-interstitial lipid deposits were probably causally related to both hyperlipidemia and the increased permeability of the glomerular filtration barrier. Tubular lesions were highlighted by intracytoplasmic lipid droplets as well as small cleft-like spaces found to be impacted in the tubular lumina. They were seen to penetrate tubular epithelial cells and eventually lodge in the interstitium, surrounded by mononuclear cell infiltrates and foam cells. In both patients, hypertensive angiopathy and extraglomerular vascular immune deposits were demonstrated. In addition, in the second patient, arteriolar and small arterial hyaline was found at the age of 28 years to be full of lipids and calcium precipitates, suggesting a peripheral atherosclerosis-like process which never occurs as a natural age-related condition. In conclusion, all parts of the nephron may be involved in the pathogenetic process causally related or influenced by hyper- or dyslipidemia. Associated either with endothelial cell injury and consequent insudation of lipids in the vascular walls, glomerular filtration barrier injury with hyperfiltration, or tubulo-interstitial lipid deposition, the mechanism of tissue damage by lipids in all parts of the nephron shares similarities with the pathogenesis of systemic atherosclerosis.
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PMID:Role of lipids in the progression of renal disease in systemic lupus erythematosus patients. 1102 Sep 63

Systemic lupus erythematosus (SLE) is an inflammatory chronic disease characterized by the presence of activated helper T-cells that induce a B-cell response, resulting in the secretion of pathogenic autoantibodies and the formation of immune complexes. SLE in children is a disease of low prevalence with a wide range of clinical manifestations, which means that the number of randomized controlled studies are few and usually involve a small number of patients. In recent years, new therapeutic agents have appeared and the role of older treatments has been clarified. Many of these treatments are designed to reduce inflammation. The spectrum is broad and ranges from traditional nonsteroidal anti-inflammatory drugs (NSAIDs) to cytotoxic agents that have anti-inflammatory effects. The current treatment of children or adults depends on the clinical expression of the disease. Minor manifestations usually respond to the administration of NSAIDs, low doses of corticosteroids, hydroxychloroquine, or methotrexate. Thalidomide could be used for refractory skin lesions. Major manifestations can endanger the patient's life and require early, aggressive treatment. Kidney disease and other manifestations have been related to the formation or deposit of tissular immune complexes. Therefore, for years the main aim of treatment has been to suppress the immune response. The immunosuppressant treatments used in children with SLE include high doses of corticosteroids, azathioprine, methotrexate, cyclosporine, and cyclophosphamide. Several combinations of medications have been used to obtain a rapid remission or to reduce the risk of toxicity of prolonged administration of cytotoxic agents. Intravenous gamma-globulin has been successfully used in the treatment of lupus nephritis, vasculitis, and acute thrombocytopenia. In spite of numerous published studies, the use of these drugs is still controversial. The immunosuppression achieved with these treatments is nonspecific, not always effective, and associated with significant toxicities; the most significant being growth retardation, accelerated atherosclerosis and severe infectious complications. The purpose of new biological therapies is to achieve specific immunosuppression, which makes it possible to design more effective and less toxic therapeutic strategies. Mycophenolate mofetil is a promising alternative in patients who do not respond to high doses of cyclophosphamide or azathioprine. Some recently developed monoclonal antibodies such as anti-CD40L or anti-IL-10, or other molecules such as LJP394 may prove useful in the near future. Finally, stem cell transplantation may be proposed in patients with severe juvenile-onset SLE who do not respond to any treatment.
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PMID:Treatment options for juvenile-onset systemic lupus erythematosus. 1196 May 13

Atherosclerosis-mediated coronary artery disease is a significant cause of mortality in lupus patients. Both an activated immune system and hyperlipidemia are implicated in the pathogenesis of the atherosclerotic lesions of lupus. In this study, the increases in anticardiolipin antibodies, total cholesterol, and LDL cholesterol with age were significantly lowered by fish oil and food restriction, either alone or in combination. Food restriction also significantly decreased the elevation in anti-dsDNA antibody production seen with age in ad libitum groups. Interestingly, effects of food restriction and fish oil on both lipid profile and autoantibody production were seen from a young age. Accumulation of leukocytes in the blood vessels and deposition of IgG in the glomerular mesangium also were suppressed by food restriction. Thus, beneficial effects of fish oil and food restriction on lupus nephritis and survival could be, at least in part, due to their selective effect on atherogenic risk factors.
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PMID:Food restriction and fish oil suppress atherogenic risk factors in lupus-prone (NZB x NZW) F1 mice. 1264 57

Although many cardiovascular complications have been described in systemic lupus erythematosus (SLE), aortic involvement is rare. We report here a 51-year-old woman who suffered from SLE and died of a rupture of abdominal aortic aneurysm. She was diagnosed as having SLE in 1981, and administered prednisolone. She was admitted to our hospital for the treatment of nephrotic syndrome and hypocomplementaemia in December, 1996. Kidney biopsy revealed lupus nephritis(type IV of WHO classification). Methylprednisolone and cyclophosphamide pulse therapies were started, which resulted in an incomplete remission of nephrotic syndrome. After discharge, her clinical course was uneventful, and the dose of prednisolone was tapered. On April 22, 2001, she developed sudden abdominal pain and was admitted to a nearby hospital. Abdominal CT showed calcification of the aorta and an abdominal aortic aneurysm of 6.3 x 8 cm. She died of a rupture of abdominal aneurysm on the first hospital day. We think that prolonged prednisolone therapy might play a major role in accelerating atherosclerosis, which could result in aortic aneurysmal enlargement in this patient. Considerable attention should be paid to patients with SLE who are given prednisolone to detect and prevent vascular complications such as aneurysm.
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PMID:[A case of systemic lupus erythematosus patient who died of rupture of abdominal aortic aneurysm]. 1463 66

Systemic lupus erythematosus (SLE) is a multifactorial polysystemic autoimmune disorder. Although life expectance in SLE has been improved by adequate immune suppressive therapy, the importance of chronic renal failure has not been reduced. Among late complications of the disease accelerated atherosclerosis attempts increasing attention. Dyslipoproteinemia and increased concentration of lipoproteins are important risk factors of atherosclerotic cardiovascular complication in SLE. Serum lipid parameters of 50 patients with lupus were examined in the present work. Thirty patients had histologically proven lupus nephritis (LN+), while the other group did not have renal involvement (LN-). Serum triglyceride, total cholesterol, LDL-C and apolipoprotein B (apoB) concentrations were significantly higher in the lupus nephritis (LN+) group. On the other hand, HDL-C and apoAI levels were also elevated in patients with LN. As a consequence of that, LDL-C/HDL-C and the apoB/apoAI ratios did not differ between patients with or without kidney involvement. This concluded the authors to measure the concentration of lipoprotein (a) in SLE patients, as Lp(a) is known to be an independent risk factor of atherosclerosis. Results indicated a significantly increased Lp(a) concentration in patients with lupus nephritis as compared to the LN- group. All but 2 patients without kidney involvement had lower than 100 mg/L Lp(a) concentration, while 27% of patients with lupus nephritis has an Lp(a) level between 100-300 mg/L. Further more, Lp(a) concentration was higher than 300 mg/L in 13% of the LN+ group. In a good correlation of these observations patients with nephritis suffered more frequently from deep venous thrombosis and ischaemic heart disease. The frequencies of hypertension and non-insulin dependent diabetes mellitus were slightly elevated in patients with nephritis. Present results suggest the importance of elevated lipoprotein (a) concentration in patients with lupus nephritis, further increasing the risk of athero-thrombotic cardiovascular complications.
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PMID:[Lipid profile in patients with systemic lupus erythematosus, with special focus on lipoprotein(a) in lupus nephritis]. 1502 32


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