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 increased risk of premature cardiovascular disease (CVD) in rheumatoid arthritis (RA) patients may depend on traditional risk factors but may also be attributable to RA-specific risk factors such as disease-related dyslipidemia, or cytokines such as tumor necrosis factor-alpha (TNF-alpha). TNF-alpha is a proinflammatory cytokine that can produce widespread deleterious effects when expressed in large amounts. It is produced in the heart by both cardiac myocytes and resident macrophages under conditions of cardiac stress, and is thought to be responsible for many of the untoward manifestations of cardiac disease. TNF-alpha may play a role in the triggering and perpetuation of atherosclerosis. Treatment with biologic agents directed against TNF-alpha has significant clinical benefits in inflammatory diseases such as RA and may be able to reduce cardiovascular risk. The disappointing results of the recent studies to antagonize TNF-alpha in CVD may have various explanations. However, the effects of TNF-alpha blockers on incident cases of congestive heart failure (CHF) in RA remains controversial. Due to the lack of evidence of a beneficial effect of anti-TNF-alpha agents in treatment of CHF, they should not be used to treat patients with New York Heart Association (NYHA) class III or IV heart failure.
Lupus 2005
PMID:Tumor necrosis factor-alpha, biologic agents and cardiovascular risk. 1621 87

Thiazolidinediones (TZDs) are selective ligands of peroxisome-proliferator-activated receptor gamma increasingly used in the treatment of type 2 diabetes. Both in vitro and in vivo studies provide evidence that TZDs have anti-inflammatory properties. TZDs inhibit macrophage activation and decrease inflammatory cytokine expression and release in macrophage and monocyte. In vivo, treatment with TZDs decreases circulating mononuclear cells nuclear NF-kB content while increasing, in the same cells, expression of IkB, an NK-kB inhibitor. Furthermore, TZD treatment results in decreased plasma levels of inflammation and cardiovascular risk markers such as CRP, MMP9, PAI-1 and sCD40 in both obese and type 2 diabetic patients. Finally, TZDs induce synoviocyte apoptosis and reduce secretion of TNFalpha, IL-6 and IL-8 in synoviocyte from rheumatoid arthritis patients. TZDs might thus be considered for use in clinical trials targeting prevention of atherosclerosis and cardiovascular diseases and in pilot trials exploring the possibility that TZDs might help in the treatment of rheumatic diseases.
Lupus 2005
PMID:Thiazolidinediones and inflammation. 1621 90

Systemic lupus erythematosus (SLE) is associated with premature atherosclerosis. Increasing arterial stiffness is closely associated with atherosclerotic cardiovascular diseases, and pulse wave velocity (PWV) is considered to be an indicator of arterial stiffness. The objective of this study was to identify the relationship between brachial-ankle pulse wave velocity (baPWV) and cardiovascular risk factors in patients with SLE. Age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBS), plasma lipid profile, plasma homocysteine, thiobarbituric acid reactive substances (TBARS), baPWV, ankle-brachial index (ABI), and SLE-related factors were determined in a total of 83 SLE patients (12 males and 71 females). All SLE patients were further classified into two subgroups according to baPWV value (baPWV < 1400 cm/s, n=37 versus baPWV > 1400 cm/s, n=46). The mean baPWV value of studied SLE patients was 1520 +/- 381 cm/s. Age, BMI, SBP, DBP, FBS, TBARS and homocysteine levels were significantly higher in SLE patients with baPWV value > 1400cm/s than in SLE patients with baPWV value < 1400cm/s. In addition, baPWV correlated significantly with age, SBP, DBP, FBS and homocysteine. Moreover, stepwise multiple regression analysis showed that age and SBP were independently associated with baPWV. The results of this study indicate a possible link between vascular stiffness measured by baPWV and cardiovascular risk factors in patients with SLE.
Lupus 2005
PMID:Association of brachial-ankle pulse wave velocity with cardiovascular risk factors in systemic lupus erythematosus. 1633 79

A significant correlation between autoimmune diseases and premature or accelerated coronary atherosclerosis has been found. The objectives of the study were: (a) to evaluate myocardial perfusion defects in patients with autoimmune diseases by contrast echocardiography and nuclear imaging; and (b) to evaluate the prevalence of alterations in subclinical myocardial perfusion defects in autoimmune diseases. Myocardial perfusion in 37 patients was evaluated by contrast echocardiography at rest and with dobutamine and with nuclear imaging. The agreement between the two diagnostic tests at rest was 0.72 (P < 0.0001) and with dobutamine was 0.65 (P < 0.0001). The prevalence of abnormalities in myocardial perfusion in autoimmune diseases by contrast echocardiography and nuclear imaging was 27% and in patients with primary antiphospholipid syndrome was 30%. We concluded that there is a high level of agreement between contrast ecocardiography and nuclear imaging for assessment of myocardial perfusion defects in patients with autoimmune diseases, and their prevalence is similar to that reported in the literature.
Lupus 2006
PMID:Myocardial perfusion defects in patients with autoimmune diseases: a prospective study. Analysis of two diagnostic tests. 1648 44

Oxidative stress and LDL modification (oxLDL) are early pro-atherogenic events. OxLDL binds beta2GPI producing immunogenic oxLDL/beta2GPI complexes. Antibodies to these complexes have been associated with arterial thrombosis in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). Circulating oxLDL/beta2GPI complexes, IgG and IgM antibodies to these complexes were measured by ELISA in 30 SLE patients asymptomatic for cardiovascular disease (mean age 31 years) and 27 age/sex matched healthy controls. Carotid intima-media thickness (IMT) was measured by ultrasound in all patients and controls. Forty-seven percent of SLE presented plaques (median IMT of 0.65 +/- 0.12 mm) while only 7% of the controls had plaques (median IMT of 0.50 +/- 0.04 mm, P < 0.001). Median optical density (OD450nm) for oxLDL/beta2GPI complexes in SLE was 0.244 +/- 0.07, higher than controls (0.174 +/- 0.09, P < 0.001). Median OD for IgG anti-oxLDL/beta2GPI antibodies was also higher in SLE (0.297 +/- 0.26) compared to controls (0.194 +/- 0.07, P < 0.001) while the median OD for IgM antibodies in SLE (0.444 +/- 0.46) was not different than controls (0.326 +/- 0.22, P = 0.267). There was no correlation between IMT and oxLDL/beta2GPI complexes, IgG or IgM antibodies, possibly reflecting the complex interrelationship between these serologic elements and tissue factors in the arterial wall. These results support the hypothesis that oxLDL/beta2GPI complexes and IgG (not IgM) anti-oxLDL/beta2GPI antibodies contribute to the development of autoimmune-mediated atherosclerosis.
Lupus 2006
PMID:Oxidized low-density lipoprotein and beta2-glycoprotein I in patients with systemic lupus erythematosus and increased carotid intima-media thickness: implications in autoimmune-mediated atherosclerosis. 1653 78

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.
Lupus 2006
PMID:Atherogenesis in rheumatology. 1663 62

The efficiency of activating latent transforming growth factor (TGF)-beta1 in systemic lupus erythematosus (SLE) may control the balance between inflammation and fibrosis, modulating the disease phenotype. To test this hypothesis we studied the ability to activate TGF-beta1 in SLE patients and control individuals within the context of inflammatory disease activity, cumulative organ damage and early atherosclerosis. An Activation Index (AI) for TGF-beta1 was determined for 32 patients with SLE and 33 age-matched and sex-matched control individuals by quantifying the increase in active TGF-beta1 under controlled standard conditions. Apoptosis in peripheral blood mononuclear cells was determined by fluorescence-activated cell sorting. Carotid artery intima-media thickness was measured using standard Doppler ultrasound. These measures were compared between patients and control individuals. In an analysis conducted in patients, we assessed the associations of these measures with SLE phenotype, including early atherosclerosis. Both intima-media thickness and TGF-beta1 AI for SLE patients were within the normal range. There was a significant inverse association between TGF-beta1 AI and levels of apoptosis in peripheral blood mononuclear cells after 24 hours in culture for both SLE patients and control individuals. Only in SLE patients was there a significant negative correlation between TGF-beta1 AI and low-density lipoprotein cholesterol (r = -0.404; P = 0.022) and between TGF-beta1 AI and carotid artery intima-media thickness (r = -0.587; P = 0.0004). A low AI was associated with irreversible damage (SLICC [Systemic Lupus International Collaborating Clinics] Damage Index > or = 1) and was inversely correlated with disease duration. Intima-media thickness was significantly linked to total cholesterol (r = 0.371; P = 0.037). To conclude, in SLE low normal TGF-beta1 activation was linked with increased lymphocyte apoptosis, irreversible organ damage, disease duration, calculated low-density lipoprotein levels and increased carotid IMT, and may contribute to the development of early atherosclerosis.
 ...
PMID:Activation of transforming growth factor-beta1 and early atherosclerosis in systemic lupus erythematosus. 1664 81

The CellScan system is a laser scanning cytometer which enables repetitive fluorescence intensity (FI) and polarization (FP) measurements in living cells, as a means of monitoring lymphocyte activation. By monitoring FP changes in peripheral blood lymphocytes (PBL) following exposure to antigenic stimuli, the CellScan may have a role in the diagnosis of autoimmune diseases. Monitoring changes in FI and FP in PBLs from patients with atherosclerosis following exposure to various stimuli, has illustrated the role of the immune system in the atherosclerotic process. The CellScan has also been evaluated as a diagnostic tool for drug-induced allergy, based on FP reduction in PBLs following incubation with the suspected drugs. FI and FP changes in cancer cells have been found to correlate with the cytotoxic effect of different anti-neoplastic drugs, illustrating the potential role of the CellScan system in clinical oncology. In conclusion, the CellScan is a promising new tool with a variety of applications in cell biology, immunology, cancer research and clinical pharmacology.
Lupus 2006
PMID:Application of a static fluorescence-based cytometer: the CellScan in clinical immunology. 1689 79

The Framingham risk score is widely used to identify patients at increased cardiovascular risk, and women with systemic lupus erythematosus (SLE) have a marked increased prevalence of cardiovascular events. Thus, we examined the hypothesis that cardiovascular risk scores would identify women with SLE who had asymptomatic coronary atherosclerosis. Ninety-three women with SLE and 65 control subjects were studied. The Framingham score and a score for younger populations developed from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study were compared in both groups. Coronary atherosclerosis was ascertained by electron beam computed tomography. There were no significant differences in the median (interquartile range) Framingham [5 (2-10) compared to 7 (0-10), P = 0.88] and PDAY [15 (14-18) compared to 16 (13-18), P = 0.99] scores in patients with SLE and controls, respectively. Coronary atherosclerosis was associated with higher Framingham [12 (3-15) compared to 4 (1-8), P = 0.008] and PDAY [17 (15-19 compared to 15 (12-18), P = 0.03)] scores in patients with SLE; however, 99% of patients were classified as low-risk with a 10-year predicted risk of 1% (<1-3%). Our data indicate that cardiovascular risk scores are not adequate for risk stratification in women with SLE. Measurement of coronary calcification may add information to identify asymptomatic women with lupus who might benefit from aggressive preventive measures.
Lupus 2006
PMID:Cardiovascular risk scores and the presence of subclinical coronary artery atherosclerosis in women with systemic lupus erythematosus. 1708 Sep 10

To determine risk factors of accelerated atherosclerosis in patients with systemic lupus erythematosus (SLE), 72 patients with inactive disease and 36 age- and sex-matched controls were included. The intima-media thickness (IMT) of the common carotid artery was determined by ultrasound. Traditional risk factors and disease-related factors were recorded. Cardiovascular risk was estimated using SCORE (systematic coronary risk evaluation). Markers of inflammation, endothelial activation and vascular remodelling (matrix metalloproteinases (MMP-3, MMP-9) and tissue inhibitor of metalloproteinase- 1 (TIMP- 1)) were determined. IMT was increased in patients (0.67 mm+/-0.13 versus 0.61 mm+/-0.11, P < 0.05). Prevalence of hypertension (33% versus 6%, P < 0.001), SCORE (2.2 (1.7-4.2) versus 1.7 (1.3-2.1), P < 0.001), as well as parameters of inflammation (CRP 1.8 (0.6-5.8) mg/L versus 0.6 (0.2-1.0) mg/L, P < 0.001) and endothelial activation (VCAM-1 505 (389-683) ng/mL versus 374 (322-427) ng/mL, P < 0.001) and von Willebrand factor (138 (59-208)% versus 48 (24-92)%, P < 0.001), were increased in patients. Vascular remodelling was altered: MMP-3 and TIMP-1 were increased (18 (10-29) ng/mL versus 8 (5-11) ng/mL, P < 0.001, and 275 (216-352) ng/mL versus 230 (197-268) ng/mL, P < 0.001, respectively), and MMP-9 was decreased in SLE (266 (147-412) ng/mL versus 348 (226-530) ng/mL, P < 0.05). Univariate analyses revealed that in patients IMT was associated with age, systolic blood pressure, SCORE and disease duration. In multivariate analysis, age and SCORE were independent predictors of IMT. In conclusion, SLE patients have an increased IMT, which is associated with traditional risk factors. Non-traditional risk factors, such as endothelial activation, altered vascular remodelling and disease duration, might play an additional role.
Lupus 2006
PMID:Traditional and non-traditional risk factors contribute to the development of accelerated atherosclerosis in patients with systemic lupus erythematosus. 1712 May 95


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