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Biomarker for coronary artery disease

A mammalian, atherosclerotic technology, used in disease diagnosis, biomaterial analysis, animal/human peptides, etc., and can solve problems such as unreliability

Inactive Publication Date: 2016-03-09
BOARD OF RGT UNIV OF NEBRASKA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Noninvasive imaging including computed tomography (CT) and magnetic resonance (MR) coronary angiography (CTA and MRA) is unreliable in detecting these CAD lesions

Method used

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  • Biomarker for coronary artery disease
  • Biomarker for coronary artery disease
  • Biomarker for coronary artery disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0193] Ox-LDL and proteins modified with aldehydes induce proinflammatory, immune, and atherosclerotic effects through malondialdehyde / acetaldehyde (MAA) adducts shared by both

[0194] It has long been known that Ox-LDL and subsequent uptake by macrophages located on the vessel wall of the aorta increases the risk of atherosclerotic lesions and plaque formation. Malondialdehyde / acetaldehyde modified proteins (MAA) exist and appear to be associated with the development and progression of human atherosclerosis. The aim of the study was to determine whether there is an association between MAA-modified proteins and Ox-LDL, which could explain their potential role in the development of atherosclerosis.

[0195] method

[0196] The mouse aortic endothelial cell line CRL-2167 was used to determine whether MAA-modified proteins or Ox-LDL might induce cytokine expression and / or secretion. Briefly, these cells were exposed to various concentrations of LDL, Ox-LDL, human serum album...

Embodiment 2

[0200] Novel biomarkers for assessment of vulnerable plaque in patients with atherosclerotic disease and dose-formed myocardial infarction

[0201] Oxidized proteins are involved in the development and progression of atherosclerosis. Malondialdehyde (MDA)-acetaldehyde (AA) adduct (MAA) is produced and is the dominant epitope formed after incubation of proteins with the oxidative product MDA. The aim of the study was to evaluate anti-MAA adduct antibodies as markers of cardiac arterial disease.

[0202] Antibodies (biomarkers) to MAA protein adducts were analyzed in serum samples from normal controls, patients with acute myocardial infarction (MI), early coronary artery disease (CAD) and advanced state coronary artery disease.

[0203] For the determination of MAA protein adducts in serum samples, ELISA plates were coated with human albumin or human albumin MAA. Sera from individuals were diluted and added to appropriate wells. Antibody binding was detected using a peroxidas...

Embodiment 3

[0214] Increased MAA-protein adducts and anti-MAA antibodies in patients with atherosclerotic disease and acute myocardial infarction: new biomarkers for the assessment of vulnerable plaque

[0215] Oxidized proteins are involved in the development and progression of atherosclerosis. Malondialdehyde / acetaldehyde (MAA) modified LDL is highly oxidized and dominant epitopes are formed after protein modification with MAA. MAA-modified proteins also bind to scavenger receptors on endothelial cells and macrophages and promote the release of pro-inflammatory cytokines. MAA-modified proteins have been detected in the JCR rat model of atherosclerosis.

[0216] Target :

[0217] The objectives of this study were to evaluate tissues from patients with atherosclerosis to verify the presence of MAA-adducted proteins and to determine the levels of circulating anti-MAA antibodies in these patients.

[0218] method :

[0219] Serum samples from normal controls (N=82), stable angina (N...

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PUM

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Abstract

In various embodiments methods are provided for identifying a mammal having an elevated risk for an adverse cardiac event (e.g. an MI) and / or determining the prognosis for the mammal. In certain embodiments the methods comprise determining, or causing to be determined, the presence and / or level of antibodies that bind a malondialdehyde-acetaldheyde adduct (MAA adduct) in a biological sample from the mammal, where an elevated level of anti-MAA adduct antibodies, as compared to the level found in a normal healthy mammal is an indicator that that said mammal has one or more atherosclerotic lesions and / or is at elevated risk for a myocardial infarction.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to and benefits of USSN 61 / 451729 filed March 11, 2011, which is hereby incorporated by reference in its entirety for all purposes. [0003] Statement of Government Support [0004] [Not applicable] Background of the invention [0005] Sequelae of atherosclerosis, such as peripheral arterial occlusive disease, coronary artery disease, and apoplexy, remains one of the leading causes of death in the United States, Europe, and much of Asia. Specifically, coronary artery disease (CAD) is the leading cause of mortality in the United States and the cause of death for 1 in 2.7 Americans. [0006] The development of atherosclerosis is considered a chronic progressive inflammation of the arterial vessel wall, which is characterized by a complex interplay of growth factors, cytokines and cellular interactions. Generally, LDL and other proteins become oxidized, bind and activate endothelial cells...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N33/564
CPCG01N33/564G01N2800/324G01N2440/10A61P9/10G01N33/6854C07K16/06C07K16/18C07K16/42C07K14/47G01N33/686A61K49/00G01N33/5308
Inventor 杰弗里·M·蒂勒丹尼尔·R·安德森迈克尔·J·杜里埃
Owner BOARD OF RGT UNIV OF NEBRASKA