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)

The open loop gain of the rapidly acting arterial pressure control system was estimated in 15 Watanabe heritable hyperlipidaemic (WHHL) rabbits aged 3-31 months. Twenty five normal Japanese white rabbits, aged 6-30 months, were used as controls. After being anaesthetised by an intravenous injection of pentobarbital sodium, the rabbits were bled by 2 ml X kg-1 body weight within 1-2 s through a catheter inserted into the aortic arch. The arterial pressure change after this rapid haemorrhage was recorded for more than 2 min by a catheter placed in the aortic arch. The open loop gain was calculated as (delta API/delta APS)-1, where delta API was the immediate fall and delta APS the steady state fall. The pulse pressure, delta API, and delta APS increased and the open loop gain decreased with age in the WHHL rabbits, but the mean arterial pressure did not change significantly with age. After aortic denervation the open loop gain also decreased with age in the WHHL rabbits. These results indicate that the progress of atherosclerosis with aging in the Watanabe heritable hyperlipidaemic rabbit decreases the vascular compliance and impairs the arterial pressure restoring function of the rapidly acting arterial pressure control system.
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PMID:Effect of atherosclerosis on the responsiveness of the rapidly acting arterial pressure control system in WHHL rabbits. 370 54

Lipoprotein(a) (Lp(a)) is considered a vascular pathogen of outstanding importance. High plasma levels of this lipoprotein are associated with premature arterial disease; however, the mechanisms involved have not been clarified. The atherosclerotic process is increasingly regarded as a chronic inflammatory reaction in the arterial wall where oxidation-mediated endothelial injury involving modified forms of low-density lipoprotein (LDL) seems to be a key event. Autoimmune pathways are involved in the progression of atherosclerosis and humoral response to oxidatively modified LDL can be considered among these pathways. A number of factors can be encountered in the pathogenesis of the accelerated arterial disease seen in patients with antiphospholipid (Hughes) syndrome (APS) and systemic lupus erythematosus (SLE). Among these, high levels of Lp(a) have been described in both and increasing evidence indicates that patients with antiphospholipid antibodies (aPL) are under oxidative stress. Recent studies suggest that the so-called 'oxidation theory of atherosclerosis' may also be applied to Lp(a). This fact makes this lipoprotein potentially suitable as a target of the immune system and antibodies reacting against oxidatively-modified Lp(a) by malondialdehyde have been recently described in APS and SLE. It is therefore likely that an immune response to the oxidized moiety of Lp(a) might be influential in the pathogenicity of this lipoprotein and, subsequently, of atherosclerosis.
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PMID:Lipoprotein(a) oxidation and autoantibodies: a new path in atherothrombosis. 1080 89

Overwhelming evidence spanning three decades has consistently shown that coronary artery disease is a major cause of morbidity and mortality in Systemic Lupus Erythematosus. Traditionally this was explained by abnormalities of the lipid profile induced by prolonged steroid treatment. Subsequently, antiphospholipid antibodies were presented as an additional cardiovascular risk factor. Recently, antibodies towards high-density lipoprotein and antiapolipoprotein A-I have been identified. These, together with anti-beta2 glycoprotein-1, interfere with the major antioxidant defence of patients with SLE and with primary antiphospholiqid syndrome exposing them to the atherogenic potential of enhanced oxidative stress. The present review discusses how the latter auto-antibodies, together with abnormalities of their target lipid auto-antigens, could enhance the risk of atherosclerosis in SLE and APS.
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PMID:Atherosclerosis, oxidative stress and auto-antibodies in systemic lupus erythematosus and primary antiphospholipid syndrome. 1263 99

The Committee reviewed cardiac involvement in the antiphospholipid antibody syndrome. The Committee's recommendations are: Valve abnormalities: anticoagulation is recommended for symptomatic patients with valvulopathy. Prophylactic antiplatelet therapy may be appropriate for asymptomatic patients (recommended by 13/17 experts in an independent review). Committee members disagreed whether corticosteroid therapy is helpful, but agree that distinguishing among presumptive valvulitis (valve thickening on echocardiogram), valve deformity and vegetations is important, as treatment implications may differ. Occlusive arterial disease (angina, myocardial infarction): the Committee recommends aggressive treatment of all risk factors for atherosclerosis (hypertension, hypercholesterolaemia, smoking) and liberal use of folic acid, B vitamins and cholesterol-lowering drugs (preferably statins). Hydroxychloroquine for cardiac protection in APS patients may be considered. The Committee also recommends warfarin anticoagulation for those who have suffered thrombosis in the absence of atherosclerosis, but recognizes that developing data may support the use of antiplatelet agents instead. Intracardiac thrombi: the Committee recommends intensive warfarin anticoagulation, and consultation with cardiac surgeons when appropriate. Ventricular dysfunction: the Committee has no recommendations on this aspect of cardiac disease. Pulmonary hypertension: the Committee recommends intensive anticoagulation with warfarin and clinical trials of bosentan, epoprostenol and other new agents.
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PMID:Cardiac disease in the antiphospholipid syndrome: recommendations for treatment. Committee consensus report. 1289 91

Large increases in mortality related to premature atherosclerosis with coronary artery disease and stroke have been reported during the last few years in patients with systemic lupus erythematosus (SLE). Studies found relative risks of 5 to 7 for myocardial infarction in SLE patients. The traditional risk factors fail to fully account for accelerated atherosclerosis in SLE and APS, in addition prolonged glucocorticoid therapy and long duration of SLE seem to be of importance. The disease SLE per se is an independent risk factor. The current pathogenic hypothesis for atherosclerosis involves an inflammatory response, autoantibodies, immune complexes (containing antibodies to phospholipids, to oxidized LDLs, and to endothelial cells), CD40/CD40 ligand interactions, and bacterial or viral infections responsible for an immune response. The determination of classic and new risk factors, together with specific autoantibody titers and the use of Doppler carotid ultrasound, are useful methods to detect early atherosclerosis. Therapeutic strategies, including early risk factor intervention and effective control of inflammation, are essential to reduce morbidity and mortality and should be incorporated into the management of connective tissue disease with the goal of protecting patients against atherosclerosis.
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PMID:[Accelerated atherosclerosis in rheumatic systemic diseases as an example of systemic lupus erythematosus--what is the consequence?]. 1590 83

Antiphospholipid syndrome is characterized by arterial or venous thrombosis, and the presence of antiphospholipid antibodies (aPL). APL are considered to be a cause of an acquired hypercoagulable state leading to stroke and transient ischemic attack (TIA). We examined the causes in 50 young patients with ischemic stroke. The most prevalent cause was atherosclerosis and the incidence of APS was 12.5%. APL comprise a heterogeneous group of autoantibodies, such as beta2-glycoprotein I dependent anticardiolipin antibody (beta2-GPIaCL), lupus anticoagulant (LA), and other antiphospholid-protein antibodies. We examined the incidence and the pathogenic role of antiphospholipid protein antibodies. The subjects comprised 250 patients (155 male, 95 females) with ischemic stroke, aged 26 to 92 years (mean 72 years). We measured beta2-GPI aCL, IgG aCL, LA, phosphatidyserine dependent antiprothrtombin antibody (PS-PT), antiphosphatidyl-serine antibody (PS), antiphosphatidyl-inositol antibody (PI) in each patient. The incidence of beta2-GPI aCL, IgG aCL, LA, phosphatidyserine, PS-PT, PS, and PI was 2.8%, 12%, 9.2%, 7.2%, 9.6%, and 8.8%, respectively. The incidence of young stroke patients under 50 years was 5.2%. Among 13 young stroke patients, 5 had SLE. Among 23 patients with LA., 18 (78%) patients had PS-PT. Anti-PS-PT antibody is closely related to LA. Antinuclear antibody was detected in 79% of the patients with aPS and/or aPI. We compared the carotid ultrasonographic findings in positive aPI or aPS patients with those in negative ones. Increased IMT, plaque score and carotid stenosis were more common in aPI and aPS-positive patients than in negative ones Three of 5 patients who showed positive beta2-GPI, aCL and LA, simulataneously, had sysyemic lupus erythematosus as an immulological background. Two of 3 patients with PI and/or PS and beta2-GPI and/or LA were patients with SLE. Antiphospholipid antibody was considered to be a risk factor of stroke, especially in SLE and/or young female patients. The incidence of lupus anticoagulant is more common than beta2-GPI aCL in ischemic stroke. In SLE patients with stroke, multi-antiphospholipid-protein antibodies was inclined to be present. LA is closely related to ant-PS-PT and aPI and aPS are associated with anti-nuclear antibody and precipitation of atherosclerosis.
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PMID:[Antiphospholipid syndrome and stroke]. 1644 44

Atherosclerosis is a chronic inflammatory disorder characterized by immune cell activation, inflammation driven plaque formation and subsequent destabilization. In other disorders of an inflammatory nature, the chronic inflammatory state per se has been linked to acceleration of the atherosclerotic process which is underlined by an increased incidence of cardiovascular disease (CVD) in disorders such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and antiphopholipid (Hughes) syndrome (APS). In addition to systemic inflammation, additional mechanisms have been put forward that are more specific for the pathophysiology of the individual chronic inflammatory disorders.
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PMID:Atherogenesis in rheumatology. 1663 62

Experimental evidence reveals that aPL are not only markers of APS, but also may play a causative role in the development of vascular thrombosis and pregnancy morbidity. The pathogenic mechanisms of aPL seem to be heterogeneous, including endothelial cell activation, the direct inhibition of the activated protein C pathway, abnormalities in platelet function, and in complement activation. aPLs induce proadhesive, proinflammatory, and procoagulant molecules that provide a persuasive explanation for induction of thrombosis in APS. Cardiac manifestations in APS include valve abnormalities (valve thickening and vegetations), occlusive arterial disease (atherosclerosis and myocardial infarction), intracardiac emboli, ventricular dysfunction, and pulmonary hypertension. aPL may be associated with accelerated atherosclerosis in APS patients. Valve disease is the most important and most common cardiac manifestation of APS. The precise mechanism by which valves become deformed is not yet fully known.
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PMID:Cardiac manifestations in the antiphospholipid syndrome. 1688 80

APS is rare in the pediatric age, but it represents an interesting phenomenon because most of the known "second hit" risk factors such as atherosclerosis, smoking, hypertension, contraceptive hormonal treatment, and pregnancy are not present in childhood. This could also be the reason for the prevalence of some clinical manifestations rather than others in PAPS. On the other hand, the increased frequency of infectious processes in the childhood age is likely responsible for the relatively high prevalence of non-pathogenic and transient aPL. Such points raise the problem of a different diagnosis or monitoring approach in pediatric APS. Of particular interest is the special entity of neonatal APS, which represents an in vivo model of acquired autoimmune disease, in which transplacentally acquired aPL cause thrombosis in the newborn. International registries for pediatric and neonatal APS are currently in place; epidemiologic, clinical, and laboratory re-search will help to shed light on all the still obscure aspects of this fascinating but rare disorder in the very young. Finally, treatment is less aggressive overall in pediatric APS, given the reluctance to anticoagulate children over the long term. Studies on the outcome of pediatric APS and the relative risks of prolonged anticoagulation in children are necessary to determine the type and duration of anticoagulation therapy.
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PMID:Pediatric antiphospholipid syndrome. 1688 84

Autoantibodies targeting beta2-glycoprotein l (beta2-GPI), a component of the atherosclerotic plaque, are commonly found in patients with acute ischemic syndromes. Serum samples from APS (antiphospholipid syndrome) patients and from cardiovascular patients exhibiting acute atherosclerotic syndromes were analyzed for IgG and IgA antibodies in both anti-beta2-GPI and anticardiolipin (aCL) ELISA assays. All of the APS samples used here were positive in both assays. Serum samples from 382 atherosclerosis patients were also analyzed for IgG and IgA antibodies in the same assays. In sharp contrast to the APS samples, we found that only 1% of the samples from atherosclerosis patients were positive for IgA aCL, and 1.6% positive for IgG aCL, whereas 35.6% were positive for IgA anti-beta2-GPI and only 1.6% for IgG anti-beta2-GPI. The antigenic specificity of 29 serum samples from atherosclerosis patients was evaluated. Six different recombinant domain-deleted mutants (DM) of human beta2-GPI and full-length human beta2-GPI (wild-type) were used in competitive inhibition assays to inhibit the autoantibodies from binding in the anti-beta2-GPI ELISA assays. Domain-deleted mutants D--345 and D--45 inhibited the binding in the IgA anti-beta2-GPI assay, suggesting that these autoantibodies recognize domain 4 of the beta2-GPI molecule. These results clearly show that IgA anti-beta2-GPI autoantibodies from atherosclerotic patients are distinct from IgA autoantibodies found in APS samples.
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PMID:Patients with atherosclerotic syndrome, negative in anti-cardiolipin assays, make IgA autoantibodies that preferentially target domain 4 of beta2-GPI. 1708 32


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