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Methods and kits for reducing the susceptibility of lipoprotein particles to atherogenic aggregation induced by arterial-wall enzymes

A technology for atherosclerosis and lipoprotein particles, applied in peptide/protein components, biological testing, pharmaceutical formulations, etc.

Inactive Publication Date: 2019-05-21
凯文乔恩威廉姆斯
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Furthermore, current approaches aimed at suppressing immune function do not address the underlying causes of apoB-lipoprotein aggregation and retention and the formation of cholesterol crystals, abnormal cholesterol-rich membranes, denatured apoB, and other deleterious lipoprotein-derived material

Method used

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  • Methods and kits for reducing the susceptibility of lipoprotein particles to atherogenic aggregation induced by arterial-wall enzymes
  • Methods and kits for reducing the susceptibility of lipoprotein particles to atherogenic aggregation induced by arterial-wall enzymes
  • Methods and kits for reducing the susceptibility of lipoprotein particles to atherogenic aggregation induced by arterial-wall enzymes

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0139] LDL particles from LEV-treated hypercholesterolemic mice were far less sensitive to SMase-mediated aggregation than LDL particles from PBS-treated hypercholesterolemic mice

[0140] This example was designed to show in an in vitro (test tube) test that LDL from LEV-treated mice was much more resistant to SMase-mediated aggregation than LDL from control (saline-treated) mice. Testing of the sensitivity of LDL to aggregation was performed according to the existing literature (9, 10, 16). This example is important because SMase-mediated accumulation of LDL is expected to be an important contributor to atherosclerotic plaques associated with cardiovascular disease.

[0141] Production of LEVs

[0142] The procedure used in this example to prepare LEVs from POPC is as follows: In a sterile bio-cabinet, the procedure is performed under a decontaminated atmosphere (e.g. HEPA-filtered air), with all surfaces and equipment cleaned and sterilized . Synthetic, pure, dry, gran...

Embodiment 2

[0151] Effect of LEV treatment on LDL composition

[0152] The 16 LDL samples from Example 1 were also subjected to compositional analysis. Lipids were extracted by the Folch procedure under nitrogen in the presence of lipid antioxidants and then subjected to an automated high-throughput tandem mass spectrometry procedure (described in detail previously) (15).

[0153] The results are shown in Figure 4 . exist Figure 4 In , an asterisk indicates a statistically significant difference between the results obtained with LEV-injected mice and PBS-injected mice. Treatment of mice with a single injection of LEV resulted in a decrease in the molar ratio of sphingomyelin to phosphatidylcholine (SM:PC) in the LDL of the mice.

[0154] In LDL samples from LEV-injected mice compared to LDL from PBS-injected mice (controls), there was a statistically significant increase in the overall PC:protein ratio, and in the UC:PC ratio, UC: There was a statistically significant reduction in ...

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Abstract

Methods of decreasing, in a human or other animal, the susceptibility of atherogenic particles to aggregation induced by sphingomyelinase, the methods comprising administering vesicles to the animal.Also similar methods directed at the formation of cholesterol crystals, abnormal cholesterol enrichment of cell membranes, and denaturation of Apo B.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit of US Provisional Application Serial No. 62 / 382,368, filed September 1, 2016. The entire disclosure of the aforementioned provisional application is hereby incorporated by reference in its entirety. technical field [0003] The field of the invention is the reduction of the susceptibility of low density lipoprotein particles (LDL) and similar particles to aggregation by arterial wall enzymes such as sphingomyelinase in humans. Background technique [0004] The ability to reduce the extent of atherosclerotic damage in humans is a major goal of modern medicine. [0005] Despite the success of plasma LDL-lowering therapy in the treatment of atherosclerotic cardiovascular disease (ASCVD), patients treated with optimal statin therapy (1, 2) and even newer PCSK9 inhibitors (3, 4) exhibited a considerable residual risk for ASCVD events. There is a need for new approaches beyond current ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/24A61K8/55A61K9/127G01N33/50G01N33/92
CPCG01N33/92A61K9/0019A61P9/00A61K38/1709G01N33/50A61K9/0029A61K9/127
Inventor 凯文·乔恩·威廉姆斯
Owner 凯文乔恩威廉姆斯
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