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- Frostegard, J, et al.
(författare)
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Circulating oxidized low-density lipoprotein is increased in hypertension
- 2003
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Ingår i: Clinical Science. - 1470-8736. ; 105:5, s. 615-620
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Tidskriftsartikel (refereegranskat)abstract
- Oxidized low-density lipoprotein (OxLDL) and autoantibodies to OxLDL (aOxLDL) are implicated in the development of atherosclerosis. The objective of this study was to determine the importance of these factors in hypertension, a major risk factor for atherosclerosis. Samples were obtained from I I I men with established hypertension (diastolic pressure > 95 mmHg) from the Swedish component of an ongoing hypertension study (European Lacidipine study on Atherosclerosis, ELSA) and from 75 normotensive control men, who were from a Swedish population-screening programme (diastolic pressure < 80 mmHg). The presence of carotid atherosclerosis and the intima-media thicknesses were determined by ultrasonography. A monoclonal antibody to OxLDL, EO6, was used to determine oxidation epitopes in LDL. aOxLDL of IgG and IgM subclass were tested by ELISA against OxLDL. Hypertensive men had increased OxLDL levels compared with normotensives (P = 0.002), whereas autoantibodies tested were largely similar between groups. There was no association between the antibodies tested, or OxLDL and carotid atherosclerosis. Age was not associated with OxLDL or aOxLDL measurements. Taken together, our findings indicate that OxLDL is elevated in hypertensive men, which may predispose to atherosclerosis in hypertension. In contrast, aOxLDL levels were unchanged and the role of aOxLDL may depend on disease stage and/or type.
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- Jensen-Urstad, K, et al.
(författare)
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Cardiac valvular abnormalities are frequent in systemic lupus erythematosus patients with manifest arterial disease
- 2002
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Ingår i: Lupus. - : SAGE Publications. - 0961-2033 .- 1477-0962. ; 11:11, s. 744-752
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to study cardiac valve morphology and function and ventricular function in systemic lupus erythematosus(SLE) patients with and without co-existingcardiovascular disease (CVD) and in populationcontrols.Twenty-six women (52§ 8.2 years) with SLE (SLE cases) and a history of CVD (angina pectoris, myocardial infarction, cerebral infarction or intermittent claudication) were compared with 26 age-matched women with SLE but without manifest CVD (SLE controls) and 26 age-matched control women (population controls). Echocardiography was performed to assess valvular abnormalities and manifestations of ischaemic heart disease. Thirteen of the 26 SLE cases but only one of the SLE controls and one of the population controls had cardiac valvularabnormalities.Three of the SLE cases had already undergonevalve replacement and another had significant aortic insufficiency; the other nine had thickening of mainly mitral leaflets without hemodynamic significance. Among SLE cases, patients with valvular abnormalities had higher homocysteine (P < 0.001) and triglyceride (P=0.02) concentrations than patients without valvular disease. In contrast atherosclerosis as determined by IMT, oxidized LDL as measured by the monoclonal antibody E06, autoantibodiesagainst epitopesof OxLDL (aOxLDL) or phospholipids (aPL), disease duration or activity, or acute phase reactants did not differ between SLE cases with or without valvular abnormalities.Valvular abnormalitieswere not more common in SLE cases with stroke as compared to those with myocardial infarction, angina or claudication. In conclusion, valvular abnormalities are strongly associated with CVD in SLE. Raised levels of homocysteine and triglycerides characterize patients with cardiac valve abnormalities.
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- STEMME, S, et al.
(författare)
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T lymphocytes from human atherosclerotic plaques recognize oxidized low density lipoprotein
- 1995
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 92:9, s. 3893-3897
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Tidskriftsartikel (refereegranskat)abstract
- Atherosclerosis, an underlying cause of myocardial infarction, stroke, and other cardiovascular diseases, consists of focal plaques characterized by cholesterol deposition, fibrosis, and inflammation. The presence of activated T lymphocytes and macrophages and high expression of HLA class II molecules are indicative of a local immunologic activation in the atherosclerotic plaque, but the antigen(s) involved has not yet been identified. We established T-cell clones from human atherosclerotic plaques using polyclonal mitogens as stimuli and exposed the clones to potential antigens in the presence of autologous monocytes as antigen-presenting cells. Four of the 27 CD4+ clones responded to oxidized low density lipoprotein (oxLDL) by proliferation and cytokine secretion; this response was dependent on autologous antigen-presenting cells and restricted by HLA-DR. All clones that responded to oxLDL secreted interferon gamma upon activation, but only one produced interleukin 4, suggesting that the response to oxLDL results in immune activation and inflammation but may not be a strong stimulus to antibody production. No significant response to oxLDL could be detected in CD4+ T-cell clones derived from the peripheral blood of the same individuals. Together, the present data suggest that the inflammatory infiltrate in the atherosclerotic plaque is involved in a T-cell-dependent, autoimmune response to oxLDL.
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- Tsimikas, S, et al.
(författare)
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High-dose atorvastatin reduces total plasma levels of oxidized phospholipids and immune complexes present on apolipoprotein B-100 in patients with acute coronary syndromes in the MIRACL trial
- 2004
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 110:11, s. 1406-1412
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Tidskriftsartikel (refereegranskat)abstract
- Background-Oxidized phospholipids (OxPL) are present within atherosclerotic plaques and bound by lipoprotein (a) [Lp(a)] in plasma. This study evaluated the impact of atorvastatin on oxidized LDL (OxLDL) in patients with acute coronary syndromes (ACS). Methods and Results-OxLDL-E06 (OxPL content on apolipoprotein B-100 [apoB] detected by antibody E06), apoB-100 immune complexes (apoB-IC), OxLDL autoantibodies, and Lp(a) levels were measured in 2341 patients at baseline and after 16 weeks of treatment with atorvastatin 80 mg/d or placebo. The OxLDL-E06 and apoB-IC data are reported per apoB-100 particle (OxPL/apoB, IC/apoB) and as total levels on all apoB-100 particles (total apoB-OxPL and total apoB-IC [eg, OxPL/apoB or IC/apoBXapoB-100 levels]). Compared with baseline values, atorvastatin reduced apoB-100 (-33%), total apoB-OxPL (-29.7%), total apoB-IC IgG (-29.5%), and IgM (-25.7%) (P<0.0001 for all), whereas no change or an increase was observed with placebo. When normalized per apoB-100, compared with placebo, atorvastatin increased OxPL/apoB (9.5% versus -3.9%, P<0.0001) and Lp(a) (8.8% versus -0.7%, (P<0.0001). A strong correlation was noted between OxPL/apoB and Lp(a) (R=0.85, P<0.0001), consistent with previous data that Lp(a) binds OxPL. Conclusions-After atorvastatin treatment, total OxPL on all apoB-100 particles was decreased. However, there was enrichment of OxPL on a smaller pool of apoB-100 particles, in parallel with similar increases in Lp(a), suggesting binding by Lp(a). These data support the hypothesis that atorvastatin promotes mobilization and clearance of proinflammatory OxPL, which may contribute to a reduction in ischemic events after ACS.
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