Functional assay of high-density lipoprotein

• US 6,869,568 B2
• Filed: 06/05/2003
• Issued: 03/22/2005
• Est. Priority Date: 03/31/2000
• Status: Expired due to Fees

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Fogelman, Alan M., Navab, Mohamad, Hama, Susan
• Primary Examiner(s): WALLENHORST, MAUREEN
• Application Number:
  US10/455,243
• Publication Number:
  US 20040057871A1
• Time in Patent Office: 656 Days
• Field of Search: 422/55, 422/56, 422/58, 436/63, 436/71, 436/164, 436/169, 436/170
• US Class Current: 422/421
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: C12Q 1/42 involving phosphatase
• CPC Class Codes: G01N 2500/10 involving cells
• CPC Class Codes: G01N 2800/044 Hyperlipemia or hypolipemia, e.g. dyslipidaemia, obesity
• CPC Class Codes: G01N 33/573 for enzymes or isoenzymes
• CPC Class Codes: G01N 33/92 involving lipids, e.g. cholesterol , lipoproteins, or their receptors steroid hormones G01N33/743
• CPC Class Codes: Y10T 436/24 Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry

Abstract

This invention provides novel assays that are prognostic and/or diagnostic for atherosclerosis or risk of atherosclerosis. It was discovered that high density lipoprotein (HDL) or components thereof can prevent the oxidation of lipids (e.g. lipids present in LDLs) and can also repair (reduce) already oxidized lipids and thereby reduce the inflammatory response associated with and characteristic of atherosclerotic plaque formation. Moreover it was a discovery of this invention that individuals vary in the ability of their HDL to afford such protection. Thus an assay of HDL protective and/or repair activity provides a highly effective assay for risk of atherosclerosis and its associated pathologies and such assays are provided herein.

Claims

1. A test device for evaluating the risk of atherosclerosis, said test device comprising:

an inert porous substrate having a receiving area;

a transport medium, the transport medium juxtaposed to said porous substrate;

a test membrane being juxtaposed to said transport medium and comprising a reagent for detecting an oxidized lipid, a non-oxidized lipid and an oxidizing agent.

2. The test device of claim 1, wherein said test membrane further comprises an oxidized lipid.

3. The test device of claim 1, wherein said oxidizing agent is selected from the group consisting of hydrogen peroxide, 13(S)-HPODE, 15(S)-HPETE, HPODE, HPETE, HODE, and HETE.

5. The test device of claims 4 or 2, wherein said oxidized lipid is an oxidized form of a lipid selected from the group consisting of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (Ox-PAPC), 1-palmitoyl-2-oxovaleroyl-sn-glycero-3-phosphorylcholine (POVPC), 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphorylcholine (PGPC), 1-palmitoyl-2-epoxyisoprostane-sn-glycero-3-phosphorylcholine (PEIPC), 1-stearoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (SAPC), 1-stearoyl-2-oxovaleroyl-sn-glycero-3-phosphorylcholine (SOVPC), 1-stearoyl-2-glutaroyl-sn-glycero-3-phosphorylcholine (SGPC), 1-stearoyl-2-epoxyisoprostane-sn-glycero-3-phosphorylethanolamine (Ox-SAPE), 1-stearoyl-2-oxovaleroyl-sn-glycero-3-phosphorylethanolamine (SOVPE), 1-stearoyl-2-glutaroyl-sn-glycero-3-phosphorylethanolamine (SGPE), and 1-stearoyl-2-epoxyisoprostane-sn-glycero-3-phophorylethanolamine(SEI PE).

6. The test device of claims 4 or 2, wherein said oxidized lipid is a component of a low density lipoprotein.

4. A test device for evaluating the risk of atherosclerosis, said test device comprising:

an inert porous substrate having a receiving area;

a transport medium, the transport medium juxtaposed to said porous substrate;

a test membrane being juxtaposed to said transport medium and comprising a reagent for detecting an oxidized lipid, and oxidized lipid.