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Oxidized Cardiolipin as a Novel Pro-Inflammatory Factor

a pro-inflammatory factor and oxidized cardiolipin technology, applied in the direction of antibody medical ingredients, peptide/protein ingredients, depsipeptides, etc., can solve the problems of insufficient prediction by biomarkers, ineffective treatment methods, and inability to achieve optimal prediction by biomarkers, so as to increase the anti-oxcl response

Inactive Publication Date: 2011-10-13
MEDIRISTA BIOTECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0050]A cutoff value may be chosen so that concentrations of anti-oxCL higher than said cutoff value is not associated with an increased risk of developing a cardiovascular disease, an auto-immune disease or inflammatory condition.

Problems solved by technology

Auto-immune disease and inflammatory conditions are major health problems in the Western world and increasingly in developing countries.
Treatment modalities against inflammation in these diseases vary, but in general have not been successful, with Rheumatoid arthritis as a possible exception and there is a clear need of new types of treatment.
Further, prediction by use of biomarkers is not optimal, and in many cases there is a great need of new types of treatment.

Method used

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  • Oxidized Cardiolipin as a Novel Pro-Inflammatory Factor

Examples

Experimental program
Comparison scheme
Effect test

example 1

Chemical Treatments of Cardiolipin

[0103]Native cardiolipin and oxidation product were further analyzed by mass spectrometry, FIG. 1. Native cardiolipin from bovine heart yielded two major signals, corresponding to the double charged anion (m / z 724.0), the single charged anion (m / z 1447). The oxidized derivative peaks from both double charged and single charged ions in the oxidized fraction were 8 m / z units apart, suggesting progressively oxidized cardiolipins.

example 2

Endothelial Cells and Adhesion Molecules

[0104]To study whether oxCL can stimulate endothelial cells to express adhesion molecules, HUVECs from passage 3 to 5 were incubated for 24 h with OxCL or native CL. Results suggested oxCL can significantly increase both ICAM-1 and VCAM-1 expression. But native CL did not show the same effect (FIG. 2). Both the increased expression of ICAM-1 and VCAM-1 (CD54 and CD106) induced by oxCL were significantly inhibited by Annexin A5 (FIG. 3).

example 3

IL-6 Production

[0105]10×6 HUVECs were seeded at 6 well plates. oxCL could stimulate endothelial cells produce 564.3±142.02 (pg / ml) IL-6 from the supernant. Annexin A5 significantly decreased Il-6 level to 276.4±28.62 (pg / ml). Comparing with the control group, both native CL and Annexin A5 themselves could not significantly increase endothelial cell Il-6 levels (FIG. 4). This supports the hypothesis that oxCL stimulates the IL-6, which is a known inflammatory marker, e.g. oxCL might be involved in inducing / mediating inflammatory responses.

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Abstract

Low levels of antibodies reactive with oxidised Cardiolipin (oxCL) in mammals are related to an increased risk of developing cardiovascular diseases, auto-immune diseases or inflammatory conditions. High levels can have a protective function and in general there is a negative association between manifestations of these conditions and antibodies against oxCL. Thus, based on their relations methods of monitoring, determining and diagnosing as well as methods of immunisation and therapy of these diseases and conditions are provided.

Description

FIELD OF THE INVENTION[0001]The present invention relates to methods of monitoring, determining, or influencing the level of antibodies against oxidized cardiolipin (anti-oxCL) in a bodily fluid from a mammal. It is shown that low level of anti-oxCL is correlated with a higher risk of developing cardiovascular disease, auto-immune diseases or inflammatory conditions. Thus, the invention relates also to a kit and the use of anti-oxCL as a diagnostic marker for determining the risk of developing a cardiovascular disease, an auto-immune disease or an inflammatory condition. Further, the invention relates to the use of agents for activation immunotherapy and for the manufacture of a medicament for treating, preventing, and / or reducing the risk of developing a cardiovascular disease, an auto-immune disease or an inflammatory condition.BACKGROUND OF THE INVENTION[0002]Auto-immune disease and inflammatory conditions are major health problems in the Western world and increasingly in develop...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K39/395A61P9/00A61P3/10A61P25/28A61P19/02C07K16/00A61P9/12A61P25/00A61P11/06C07F9/10C07K14/00G01N33/566A61K38/17A61P9/10
CPCA61K38/1709C07K16/18G01N33/564G01N33/92G01N2800/24G01N2800/32G01N2800/50G01N2800/104G01N33/5308C07K2317/76C07K16/44G01N2800/324G01N2800/2871A61P11/06A61P19/02A61P25/00A61P25/28A61P29/00A61P9/00A61P9/10A61P9/12A61P3/10
Inventor FROSTEGARD, JOHAN
Owner MEDIRISTA BIOTECH
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