UMLS:C0004153 - FACTA Search

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

E-selectin mediates the rolling of circulating leukocytes on vascular endothelial cells. A polymorphism, in which serine is substituted for arginine at position 128 (S128R) in the EGF domain, has been associated with both early-onset atherosclerosis and SLE. We investigated whether the substitution alters the ligand-binding properties of E-selectin under shear flow by studying the capacity of Chinese hamster ovary cell transfectants expressing wild type (WT) or S128R E-selectin to support interactions of neutrophils, K562 cells or HL60 cells. We initially chose to study non-fucosylated K562 cells. No interactions were observed on WT E-selectin, whereas S128R supported a transient tethering interaction of K562 cells, which was resistant to digestion with either neuraminidase or O-sialoglycoprotein endopeptidase, and, in turn, could result in firm adhesion in the presence of a beta2-integrin. HL60 cells exhibited increased rolling on S128R E-selectin. Although neuraminidase treatment inhibited all HL60 interactions with WT E-selectin, it unmasked transient tethers on S128R. We further observed that S128R recruited significantly more neutrophils than WT E-selectin, without affecting neutrophil rolling velocity. This polymorphism may therefore amplify leukocyte-endothelial cell interactions and may be a factor linking the S128R polymorphism to vascular disease.
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PMID:The S128R polymorphism of E-selectin mediates neuraminidase-resistant tethering of myeloid cells under shear flow. 1178 16

In short-term studies, both in animals and in humans, fish oil seems to exert anti-inflammatory effects. However, these effects may vanish during long-term treatment. There is a possibility that in autoimmune diseases, supplementation of dietary n-3 fatty acids might lead to a decrease in the number of autoreactive T cells via apoptosis, as demonstrated in (NZBXNZW) F1 lupus mice [40]. Thus, the "fade away" effect might be due to regrowth of pathogenic autoreactive cells. In animal models of autoimmune diseases, diets high in n-3 fatty acids from fish oil increase survival and reduce disease severity in spontaneous autoantibody-mediated disease, while n-6 linoleic acid-rich diets appear to increase disease severity. The situation in human disease is probably more complex. Some of the discrepancy between studies can be attributed to methodologic problems. The effect of fish oil is dose, time and disease-dependent. Since the anti-inflammatory effects depend on the balance between n-3 and n-6 fatty acids, the relative proportion of EPA and DHA and possibly co-treatment with dietary vitamin E, the dose/effect ratio may vary between individuals. Furthermore, some animal studies demonstrating efficacy used very high doses that may be incompatible with human consumption. It seems that fish oil is only mildly effective in acute inflammation. In those chronic inflammatory disorders where it was found to be effective, several weeks are necessary to exhibit results. Yet, this mild anti-inflammatory effect, possibly through downregulation of pro-inflammatory cytokine production, leads to striking therapeutic improvement in critically ill patients. Fish oil supplementation seems advantageous especially in acute and chronic disorders where inappropriate activation of the immune system occurs. Fish oil has only a mild effect on active inflammation of diseases such as rheumatoid arthritis, SLE and Crohn's disease, but it could prevent relapse (in some of the studies). In diseases where the inflammation is mild, such as IgA nephropathy, fish oil may slow or even prevent disease progression. The above could explain the observation in some populations of a decreased incidence of inflammatory and autoimmune diseases [3], since the constant consumption of n-3 fatty acids could suppress any autoreactive (or hyper-reactive) T cells. However, if there is already an existing disease, increased consumption might not be beneficial over a long period. Therefore, the use of n-3 fatty acids can be recommended to the general healthy population, not only to prevent atherosclerosis but possibly also to reduce the risk of autoimmunity.
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PMID:n-3 fatty acids and the immune system in autoimmunity. 1180 9

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

We retrospectively analysed the data of 1519 antiphospholipid antibody (APLA) positive patients between 1986 and 1999. Among them 637 were considered to have antiphospholipid syndrome (APS) based on the 1999 preliminary classification criteria, while 704 patients had no clinical signs of the syndrome. Our aim was to compare the autoantibody profile and clinical characteristics of primary and secondary APS, moreover to evaluate the associations between different APLA and specific symptoms attributable to APS. In our results, the APLA profiles for primary and SLE-associated secondary APS were similar. Among the evaluated clinical symptoms, cerebrovascular thrombosis was found to be more frequent in the SLE-associated, than in the primary APS group (P = 0.04). We identified important differences in the clinical profile of patient populations with various types of APLA. Venous thrombosis occurred more frequently in subjects withlupus anticoagulant (LA), than in those with IgG or IgM type ACLA (P < 0.0001), while coronary, carotid and peripheral artery thrombosis occurred more often in subjects with IgG or IgM ACLA (P < 0.0001). These findings may support the role of antibodies to cardiolipin or its cofactor, beta2glycoprotein I (beta2-GPI) in the initiation and progression of atherosclerosis. Cerebrovascular thrombosis was detected in larger proportion of LA or IgG ACLA-positive patients compared with to IgM ACLA-positive subjects, while the occurrence of foetal loss was similar in all three groups.
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PMID:Evaluation of clinical and laboratory features of antiphospholipid syndrome: a retrospective study of 637 patients. 1272 54

Diagnosis depends on the clinical manifestations, blood or cerebrospinal fluid study and MRI findings. Acute and subacute intraparenchymal spinal cord disorders are due to vascular disorders or myelitis. Spinal cord infarction is associated with dissecting aortic aneurysm, surgical clipping of aortic aneurysms, aortic atherosclerosis or hypotension from any cause. Hematomyelia results from trauma, vascular malformations, vasculitis, or a coagulation disorder. Acute infectious myelopathies result from direct invasion of the spinal cord by bacteria, parasite, or virus. The cause of acute or subacute inflammatory disease include multiple sclerosis, Devic disease, acute disseminated encephalomyelitis, SLE, or sarciodosis. Sarcoidosis sometimes requires differential diagnosis with cord tumor. Chronic intraparenchymal spinal cord disorders are due to syringomyelia, familial spastic paraplegia, HTLV-1 associated myelopathy, adrenomyeloneuropathy, and vascular malformations. HTLV-1 associated myelopathy present with progressive spastic paraplegia with bladder disturbance and has antibodies to HTLV-1 in the cerebrospinal fluid and serum. Diagnosis of adrenomyeloneuropathy is made by demonstration of elevated levels of very long chain fatty acids in plasma. Vascular malformations are important lesions because they present a treatable cause of progressive myelopathy.
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PMID:[Medical approach to intraparenchymal spinal cord disorders]. 1278 77

We recently reported [J. Lipid Res. 42 (2001), 697; 43 (2002), 1486; 44 (2003), 716] that [beta2-glycoprotein I (beta2GPI) forms complexes with oxidized LDL (oxLDL) and autoantibodies against these complexes are present in patients with SLE and antiphospholipid syndrome (APS). The relationship of beta2GPI/oxLDL complexes and IgG autoantibodies against beta2GPI complexed with oxLig-1 (an oxLDL-derived ligand) with clinical manifestations of APS was studied in 150 APS and SLE patients. The beta2GPI/oxLDL levels of APS patients were similar to those of SLE patients without APS, but they were significantly higher than healthy individuals. There was no difference in the complex levels among the patients with arterial, venous thrombosis, or pregnancy morbidity. IgG anti-beta2GPI/oxLig-1 levels of APS were significantly higher than those of SLE without APS and healthy individuals. Further, antibody levels of APS patients with arterial thrombosis were significantly higher than those patients with venous thrombosis and pregnancy morbidity. Thus, oxidation of LDL leads the complex formation with beta2GPI in SLE and APS patients. In contrast, anti-beta2GPI/oxLig-1 autoantibodies were generated only in APS and were strongly associated with arterial thrombosis. These results suggest that autoantibodies against beta2GPI/oxLDL complexes are etiologically important in the development of atherosclerosis in APS.
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PMID:IgG autoantibodies against beta2-glycoprotein I complexed with a lipid ligand derived from oxidized low-density lipoprotein are associated with arterial thrombosis in antiphospholipid syndrome. 1476 53

The antiphospholipid syndrome (APS) with its typical clinical manifestations of recurrent thrombosis and fetal loss is biochemically defined by the presence of circulating antiphospholipid antibodies (aPL). The disease pattern has raised special interest as a possible link between autoimmunity and atherosclerosis. aPL, oxidized low density lipoproteins (oxLDL), and antibodies to oxLDL (Anti-oxLDL) are suggested to play an important role in atherogenesis. In the present study we compared the serum levels of oxLDL and Anti-oxLDL in APS patients (20 subjects with primary APS; 14 subjects with secondary APS) and nonAPS subjects (24 phenotypically healthy controls samples and 12 patients with systemic lupus erythematosus [SLE]) and investigated associations of the above mentioned parameters with the intima-media thickness (IMT), a clinical surrogate parameter of atherosclerosis.SLE patients with and without APS showed significantly increased levels of Anti-oxLDL as compared to the controls group (p = 0.038 and p = 0.007, respectively). In contrast, oxLDL levels were not significantly different between the controls group and patients. The Anti-oxLDL levels correlated significantly with anticardiolipin (p = 0.002) and beta(2)-glycoprotein I antibodies (p < 0.048), both from IgG isotype. Only SLE patients without APS revealed a significantly elevated production of reactive oxygen species indicating an increased proatherogenic oxidative stress in the circulation (p < 0.002). In the patient groups, the circulating levels of oxLDL and Anti-oxLDL showed no association with atherosclerosis as estimated by IMT. In conclusion, our experimental data do not support the concept of oxidative stress-induced accelerated atherosclerosis in APS patients.
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PMID:[Oxidatively modified lipoproteins and their antibodies in patients with antiphospholipid syndromeand systemic lupus erythematosus]. 1533 57

The risk of cardiovascular disease (CVD) in SLE patients is very high. It is therefore surprising that IL-10 has been discussed both as pathogenic in SLE and as an atheroprotective cytokine. In contrast, TNF is believed to be atherogenic and we recently reported that raised activity in the TNF-system is implicated in SLE-related CVD. Twenty-six (aged 52 +/- 8 years) female patients with SLE and a history of CVD (myocardial infarction, angina, stroke or claudication) were compared with 26 age-matched SLE patients without CVD (SLE controls) or 26 age-matched population controls. The -1087IL-10 gene polymorphism was determined by PCR with restriction endonuclease mapping. Serum IL-10 and TNF-levels were determined by ELISA. The A allele frequency of -1087IL-10 gene in SLE/CVD was higher than in SLE controls (0.62 versus 0.42, p < 0.05). Ten (38%) of 26 SLE/CVD exhibited IL-10 AA genotype compared with five (19%) of 26 SLE controls. Serum IL-10 and TNF-levels were raised in SLE/CVD compared with SLE controls or population controls (p < 0.001). Furthermore, in SLE/CVD, a significantly reduced IL-10:TNF ratio was observed in patients with IL-10 AA genotype compared with AG or GG genotype (0.56 versus 0.77 versus 1.24, p < 0.05). In SLE controls and population controls, individuals with IL-10 GG genotype tended to have higher IL-10:TNF ratio. In conclusion, the A-1087IL-10 allele which has been reported to cause a lower capacity for IL-10 production could contribute to CVD in SLE. Furthermore, the IL-10 AA genotype is associated with reduced ratio of atheroprotective to atherogenic cytokines in SLE patients with CVD.
Atherosclerosis 2004 Dec
PMID:The A-1087IL-10 allele is associated with cardiovascular disease in SLE. 1553 Sep 17

Inflammatory rheumatic diseases are associated with a substantial increase in accelerated atherosclerosis, with complex interactions between traditional and disease-related risk factors. Therefore, cardiovascular risk reduction should be considered as integral to the control of disease activity in the care plans of patients with RA, SLE and, arguably any chronic inflammatory disease. Shared care structures, already established for the monitoring of DMARDs, could be adapted to communicate and monitor cardiovascular risk reduction objectives. We review the evidence for the efficacy of a range of therapeutic strategies, the majority of which impact on both disease activity and cardiovascular risk. The algorithm proposed here attempts to distil the latest advice from specialist panels at the National Cholesterol Education Program and the British Hypertension Society, as well as incorporating the existing data on SLE and RA patients. The algorithm is structured to minimize clinic time and resources necessary to stratify patients into groups for ROUTINE, SUBSTANTIAL or INTENSIVE risk management; the associated table summarizes optimal therapeutic objectives in each of these groups. The implication of this algorithm is that management of cardiovascular risk should be much more aggressive than is currently the norm in patients with chronic inflammatory diseases, such as RA and SLE. Long-term studies of such interventions are needed to further clarify the benefits of intensive cardiovascular risk management in these patients.
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PMID:Disease modification and cardiovascular risk reduction: two sides of the same coin? 1663 80

Mannose binding lectin (MBL) is a serum protein with structure and functions similar to those of complement factor C1q, and is a key molecule in innate immunity. Interestingly, absence or extremely low concentration of serum MBL (MBL deficiency) seems to be a risk factor for occurrence of autoimmune diseases, in particular systemic lupus erythematosus. In addition, individuals with MBL deficiency are at risk of infection when in immunocompromised conditions. The concentration of serum MBL is greatly influenced by relatively common single nucleotide polymorphisms of the MBL gene. Therefore, typing of the MBL gene, or measurement of serum MBL may be valuable for determining the risk of infections in patients with systemic autoimmune diseases, who frequently undergo immunosuppressive therapies. MBL deficiency may also be a risk factor for atherosclerosis and arterial thrombosis, both being common complications of autoimmune diseases. On the other hand, MBL may be pathological in tissue injuries, and the precise roles of MBL in autoimmune diseases, and the value of MBL gene typing or serum MBL measurement in a clinical setting are yet to be clarified. Recently, presence of anti-MBL autoantibodies in sera of SLE patients has been reported. The significance of this autoantibody remains to be elucidated.
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PMID:Mannose binding lectin: genetics and autoimmune disease. 1608 Oct 27

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