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)

Autoimmune vascular inflammation and oxidative stress (lipid peroxidation) are common in systemic autoimmune diseases and contribute to the oxidative modification of low-density lipoprotein (oxLDL) and oxLDL/beta2GPI complex formation. Circulating oxLDL/beta2GPI complexes have been detected in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). The presence of antibodies to oxLDL/beta2GPI complexes indicates that these complexes are immunogenic, and the coexistence of complexes and antibodies has pointed to an active proatherogenic role in the development of autoimmune vascular complications. Immunohistochemical staining of atherosclerotic lesions suggest that these complexes are formed in the arterial wall and released into circulation. The in vitro macrophage uptake of oxLDL/beta2GPI complexes was significantly increased in the presence of antiphospholipid antibodies, either beta2GPI-dependent anticardiolipin or anti-beta2GPI antibodies, suggesting that macrophage Fcgamma receptors are involved in lipid intracellular influx and foam cell formation. These findings provide an explanation for the accelerated development of atherosclerosis seen in SLE and APS. The presence of circulating oxLDL/beta2GPI complexes and IgG antibodies to these complexes indicate significant vascular injury and oxidative stress as well as an active role in autoimmune-mediated atherothrombosis.
Lupus 2008 Oct
PMID:Autoimmune-mediated atherothrombosis. 1882 52

Several systemic autoimmune conditions, including rheumatoid arthritis, systemic lupus erythematosus and antiphospholipid syndrome, are characterised by enhanced atherosclerosis and, consequently, higher cardiovascular morbidity and mortality rates. The association of these diseases with atherosclerosis suggests a common pathogenic mechanism. Genomic and proteomic studies performed on atherosclerotic plaques have further confirmed the presence of a gene and protein profile similar to that observed in autoimmune diseases with cardiovascular risks. Human sera and body fluids have been analysed and have resulted in the identification of auto-antibodies that can be used as diagnostic markers in specific autoimmune diseases, and proteomic fingerprints of blood cells, tissues and body fluids have resulted in the identification of individual proteins or patterns of protein expression that are deregulated. The information provided by these proteomic studies is of diagnostic and therapeutic potential. In this review, we discuss new approaches available for assessing thrombotic risk in autoimmune diseases, focusing in the genomic and proteomic methods now available to deep into the origin of the mechanisms associated with vascular involvement in systemic autoimmune diseases. The increasing data available suggests that when treating patients with these autoimmune disorders, paying attention to the increased risk of cardiovascular disease is essential.
Lupus 2008 Oct
PMID:Genomics and proteomics: a new approach for assessing thrombotic risk in autoimmune diseases. 1882 55

Systemic lupus erythematosus (SLE) often coexists with other diseases. Diabetes mellitus (DM) is an example and patients with overlap SLE-DM can present with clinical features common to both disorders. In this review, we describe the patients with overlap SLE-DM, focussing on the clinical features common to both diseases that these patients can present, and on the challenges of managing such complications. A detailed review of the patients' notes (n = 485) was performed. At every outpatient appointment the patients' urine was tested for glucose, protein and blood. Patients with persistent glycosuria were investigated with fasting blood glucose and a glucose tolerance test to help make the diagnosis of DM. Particular note was made of those patients whose symptoms could be due to SLE, DM or both. Nine patients with DM were identified. Three had type 1 DM, four had type 2 DM and two were considered to have steroid-induced DM. Among these patients, three had renal involvement (two with WHO class IV lupus nephritis); two had peripheral neuropathy (one had a mixed sensory and motor neuropathy, one had a sensory peripheral neuropathy); two patients had retinopathy and cataracts and one had angina. The combination of SLE and DM is uncommon but the predisposition to renal, peripheral neuropathy and retinal disease means that great care must be taken when deciding which clinical feature is due to which disease, because active SLE requires additional immunosuppression whereas DM requires optimization of the metabolic control. Interestingly, although in theory patients with SLE and DM are in double-jeopardy of developing atherosclerosis, to date, only one of our overlap patients has developed angina.
Lupus 2008 Nov
PMID:Diabetes mellitus complicating systemic lupus erythematosus - analysis of the UCL lupus cohort and review of the literature. 1885 20

Little is known about qualitative abnormalities of high-density lipoproteins (HDL) in systemic lupus erythematosus (SLE). We studied distribution and composition of HDL subclasses in 30 premenopausal women with uncomplicated SLE, and 18 controls matched for age and sex. Plasma and HDL lipids were determined by colorimetric enzymatic assays, HDL size distribution by native gradient polyacrylamide gel electrophoresis (PAGE) and apolipoproteins in HDL by sodium dodecyl sulphate denaturing PAGE. Compared with controls, SLE patients had significantly lower proportions of HDL(2b) (-14.7%) and higher proportions of HDL(3b) (+8.8%) and HDL(3c) (+23.3%). Cholesteryl ester (-18%) and apolipoprotein AI (-9%) were lower, whereas triglycerides (+32%) and apolipoprotein E (+27%) were higher in SLE HDL (P < 0.05; for all). In the whole population, stepwise regression analysis showed that only insulin concentrations (R(2) = 0.327) and plasma total apo AI (R(2) = 0.114) accounted independently to the variance in HDL size. This study shows that HDL distribution and composition are abnormal in non-complicated SLE patients. These HDL abnormalities have been reported to be associated to impaired atheroprotective properties of HDL and prevalence of coronary heart disease. Therefore, they may contribute to the premature atherosclerosis observed in young women with SLE.
Lupus 2008 Nov
PMID:High-density lipoproteins are abnormal in young women with uncomplicated systemic lupus erythematosus. 1885 21

As endothelial dysfunction is one of the earliest signs of atherosclerosis, which is accelerated in systemic lupus erythematosus (SLE), we assessed whether vascular responses of the cutaneous microcirculation are disturbed in SLE patients and influenced by Raynaud's phenomenon (RP). Laser Doppler fluxmetry (LDF) was used in combination with iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP), an endothelium-dependent and endothelium-independent vasodilator respectively. 42 SLE patients with inactive disease, 12 of whom had RP and 19 age- and sex-matched controls were included. Furthermore, traditional and non-traditional risk factors for cardiovascular disease (CVD) were assessed, and markers of inflammation and endothelial activation were measured. Vascular responses of SLE patients without RP did not differ from controls. However, SLE patients with RP exhibited decreased vasodilatation compared with controls. SLE patients with RP also had longer arrival times of ACh and SNP than controls. Markers of inflammation and von Willebrand factor were increased in SLE patients. Smoking, the presence of SLE and RP were negatively associated with vascular responses in univariate analysis. In multivariate analyses, the only independent variable of vascular responses to ACh and SNP was the presence of RP. Despite signs of endothelial activation, SLE patients with inactive disease do not have altered vascular responses in the microcirculation compared with controls. In SLE patients with RP, cutaneous vascular responses to both ACh and SNP are impaired. Therefore, LDF of the microcirculation seems not to be the appropriate method to distinguish those SLE patients with an increased risk to develop CVD.
Lupus 2008 Nov
PMID:Vascular responsiveness in the microcirculation of patients with systemic lupus erythematosus is not impaired. 1885 25

Individuals suffering from systemic lupus erythematosus (SLE) are predisposed to accelerate cardiovascular disease. Our laboratory has recently developed an animal model of SLE-accelerated atherosclerosis. We have shown that, following 8 weeks feeding high fat Western diet, radiation chimeras consisting of SLE-derived haematopoietic cells transferred to low-density lipoprotein (LDL)r(-/-) mice (LDLr.Sle) have increased atherosclerosis compared with C57Bl/6 bone marrow recipients (LDLr.B6). However, this feeding regimen resulted in significant mortality in SLE-susceptible mice compared with controls with surviving animals having extremely elevated serum cholesterol (>500 mg/dL) and increased serum markers of kidney pathology. To test the hypothesis that SLE-associated autoimmune dysregulation can exacerbate atherosclerosis under more mild serum cholesterol conditions (approximately 200 mg/dL), we examined SLE and lesion development in radiation chimeras fed either a normal chow or high fat Western diet for 8 weeks. High fat fed LDLr.Sle mice exhibited increased mortality and were significantly more hypertensive. LDLr.Sle mice had greater titres of antibodies against dsDNA, oxLDL and phospholipid compared with controls. Lupus-susceptibility increased the atherosclerotic lesions and the percentage of CD4(+) T cells in the lesions of proximal aortas, independent of diet. These data show that increased dyslipidemia resulting from high-fat feeding can exacerbate autoimmunity and associated vascular complications. Conversely, they also show that autoimmune dysregulation can accelerate atherosclerosis in LDLr-deficient animals independent of feeding high fat diet. Collectively this study provides additional evidence that the accelerated atherosclerosis observed in SLE is autoimmune associated.
Lupus 2008 Dec
PMID:Accelerated atherosclerosis is independent of feeding high fat diet in systemic lupus erythematosus-susceptible LDLr(-/-) mice. 1902 74

To evaluate the relationships between arterial stiffness, disease activity and end-organ damage in systemic lupus erythematosus (SLE), non-invasive vascular assessments were made on 32 female SLE patients and 32 female normal controls. The patients had significantly increased brachial-ankle pulse wave velocity (PWV) (13.06 +/- 1.79 vs. 11.50 +/- 1.00 m/s; P < 0.001), heart-ankle PWV (8.98 +/- 1.16 vs. 7.88 +/- 0.73 m/s; P < 0.001), carotid augmentation index (AI) (21.6 +/- 17.2% vs. 5.4 +/- 14.0%; P = 0.001) and carotid intima-medial thickness (IMT) (0.753 +/- 0.132 vs. 0.644 +/- 0.092 mm; P = 0.002) when compared with controls. The disease activity and organ damage were evaluated by SLE disease activity index (SLEDAI) and systemic lupus international collaborating clinics (SLICC) damage index. Patients with active disease (SLEDAI > or = 3) had significantly higher carotid AI (34.4 +/- 9.7% vs. 17.8 +/- 17.3%, P < 0.05) than stable ones (SLEDAI < 3) and those with organ damage (SLICC > or = 1) had significantly higher heart-ankle PWV (9.69 +/- 1.13 vs. 8.61 +/- 1.02 m/s, P < 0.05) than those with SLICC = 0. After making adjustments for age, body mass index (BMI) and blood pressure, carotid AI was found to show correlation with SLEDAI and haPWV with SLICC. A carotid AI value of 33.3% identified SLEDAI > or = 3 with a sensitivity of 83% and a specificity of 80%, whereas a heart-ankle PWV value of 9.0 m/s identified SLICC > or = 1 with a sensitivity of 91% and a specificity of 67%. In conclusion, SLE was an independent risk factor of sub-clinical atherosclerosis and arterial stiffness may identify the presence of active disease.
Lupus 2008 Dec
PMID:Increased arterial stiffness correlated with disease activity in systemic lupus erythematosus. 1902 77

Detection of early carotid vascular disease in patients with systemic lupus erythematosus (SLE) is considered mandatory for evaluation of subclinical atherosclerosis (ATS), and various ultrasonographic (US) parameters have been proposed. In the present investigation, 33 SLE and 33 healthy age-matched females have been studied by colour-coded sonography of the common carotid artery, assessing intima-media thickness (IMT), vascular strain (VS), vascular distensibility (VD), vascular stiffness (VSf) and pressure-strain elastic modulus (PSEM) as possible markers of early ATS. Patients with SLE, despite equivalent exposure to "traditional" cardiovascular risk factors, presented a higher mean IMT of the common carotid artery than healthy subjects (0.7 +/- 0.2 mm vs 0.5 +/- 0.1 mm - P < 0.0001). Of the stiffness parameters, patients with lupus showed a mean VSf of 0.72 +/- 0.38 vs 0.54 +/- 0.14 in controls (P < 0.0001) and a mean PSEM of 6.0 +/- 2.8 Pa vs 3.0 +/- 1.4 Pa in controls (P < 0.0001). Mean VS and VD were significantly lower in patients with SLE than in healthy subjects (P < 0.0001). Among individuals with IMT < 0.6 mm, patients with SLE presented more compromised stiffness parameters. IMT was shown to be a useful parameter in the evaluation of vascular damage, even in a "sub-clinical" phase, while stiffness parameters provide additional details regarding endothelial and vessel functional state. Combined evaluation may allow ATS to be detected in the early stages in patients with SLE.
Lupus 2009 Mar
PMID:Stiffness parameters, intima-media thickness and early atherosclerosis in systemic lupus erythematosus patients. 1921 64

Carotid-radial pulse wave velocity (PWV), aortic augmentation index (AIx) and endothelium-dependent flow-mediated dilatation (FMD) have been repeatedly showed to be related to premature atherosclerosis and cardiovascular diseases in different settings of population. The increased arterial stiffness and endothelium dysfunction may add to premature aging of the arteries in systemic lupus erythematosus (SLE) patients. Still data about arterial stiffness and endothelium function in inflammatory rheumatic diseases are not well described. The aim of this study was to determine the PWV, its derivate marker AIx and FMD and factors possibly influencing them in young SLE women without significant organ damage. Thirty women between 23 and 55 years with an established SLE diagnosis and 66 healthy women were consequently included in the study and both groups were comparable according to age, body mass index (BMI), serum lipid profile and creatinine. PWV was determined by measuring carotid-radial pulse wave transit time with the help of applanation tonometry and AIx, its derivate marker, was calculated as a difference between two waveform peaks expressed as a percentage of the pulse pressure. The FMD was performed by obtaining the repeated scans of the brachial artery at rest and during reactive hyperemia. In SLE women, PWV and AIx were significantly higher and FMD was not different from controls. In linear multiple stepwise regression analysis if patients and controls were both considered, PWV was weakly related to mean blood pressure (MBP), AIx was mostly predicted by age and MBP and FMD was predicted by the diameter of blood vessel, BMI, high density lipoproteins. If the sole SLE setting was analyzed, PWV was not related to any of the pending parameters, AIx turned out to be related to organ damage measured by Systemic Lupus International collaborative Clinics (SLICC) index and age, and FMD obtained strong and significant relation with vessel diameter, and BMI, and disease duration. Regardless of the small number of study group patients, we can state that controlling for MBP and taking measures towards organ damage prevention can partially slow down the process of early atherosclerosis in SLE patients.
Lupus 2009 May
PMID:Arterial wall dysfunction in systemic lupus erythematosus. 1939 54

We tested the hypothesis that concentrations of adipocytokines are altered in SLE and associated with coronary atherosclerosis, insulin resistance and inflammation. Concentrations of resistin, leptin, adiponectin and visfatin were measured in 109 patients with SLE and 78 control subjects. Coronary calcification was measured using electron beam-computed tomography, and insulin resistance was defined by the homeostasis model assessment index. Concentrations of adiponectin (28.7 +/- 17.9 vs 22.0 +/- 15.3 microg/mL, P = 0.003), leptin (41.1 +/- 49.9 vs 19.8 +/- 24.6 ng/mL, P < 0.001) and visfatin (7.5 +/- 10.5 vs 4.5 +/- 2.8 ng/mL, P < 0.001) were higher in patients with SLE than in controls. These differences remained significant after adjustment for age, race, sex and body mass index (BMI; all P values < 0.02). Concentrations of resistin (10.7 +/- 7.6 vs 9.1 +/- 5.1 ng/mL, P = 0.41) did not differ in patients and controls. In patients with SLE, leptin was positively associated with BMI (rho = 0.80, P < 0.001), insulin resistance (rho = 0.46, P < 0.001) and C-reactive protein (CRP) (rho = 0.30, P = 0.002), whereas adiponectin was negatively associated with the same factors (rho = -0.40, P < 0.001; rho = -0.38, P < 0.001; rho = -0.22, P = 0.02, respectively). None of the adipocytokines were associated with coronary atherosclerosis in SLE. In conclusion, patients with SLE have increased concentrations of adiponectin, leptin and visfatin. Lower concentrations of adiponectin and higher concentrations of leptin are associated with insulin resistance, BMI and CRP in patients with SLE.
Lupus 2009 Aug
PMID:Adipocytokines in systemic lupus erythematosus: relationship to inflammation, insulin resistance and coronary atherosclerosis. 1957 4


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