Abstract: The present invention provides markers and methods for determining whether a subject, particularly a human subject, has or is at risk of developing, a disease such as cardiovascular disease, diabetes mellitus, insulin resistance, metabolic syndrome, NAFLD (Nonalcoholic Fatty Liver Disease) or NASH (Nonalcoholic Steatohepatitis) (e.g., within the ensuing year, two years, and/or three years). The present application also relates to the use of such markers and methods for monitoring the status of such diseases in a subject or the effects of therapeutic agents on subjects with such diseases.

Abstract: A purified polypeptide includes an ApoA1 mimetic or fragment thereof that are resistant to oxidation.

Abstract: The present invention provides methods for treating cancer in a subject, as well as related compositions and kits that employ a therapeutic agent, or a nucleic acid sequence encoding a therapeutic agent, selected from apolipoprotein A-1 (ApoA1) or biologically active fragment, an ApoA1 mimetic, an agent that increases expression of ApoA1, or a binding agent specific for oxidized ApoA1. In certain embodiments, the ApoA1 or ApoA1 mimetic is at least partially oxidation resistant.

Abstract: Diagnostic tests for characterizing an individual's risk of developing or having a cardiovascular disease. In one embodiment the present diagnostic test comprises determining the level of myeloperoxidase (MPO) activity in a bodily sample obtained from the individual or test subject. In another embodiment, the diagnostic test comprises determining the level of MPO mass in a bodily sample obtained from the test subject. In another embodiment, the diagnostic test comprises determining the level of one or more select MPO-generated oxidation products in a bodily sample obtained from the test subject. The select MPO-generated oxidation products are dityrosine, nitrotyrosine, methionine sulphoxide or an MPO-generated lipid peroxidation products.

Abstract: The present invention provides methods and markers for characterizing a subject's, particularly a human subject risk of having cardiovascular disease. The present invention also provides methods of characterizing a subject's risk of developing cardiovascular disease. In another embodiment, the present invention provides methods for characterizing a subject's risk of experiencing a complication of cardiovascular disease or major adverse cardiac event within 1, 3, or 10 years. In another embodiment, the present invention provides a method for determining whether a subject presenting with chest pain is at risk near term of experiencing a heart attack or other major adverse cardiac event. The present methods are especially useful for identifying those subjects who are in need of highly aggressive CVD therapies as well as those subjects who require no therapies targeted at inhibiting or preventing CVD or complications of CVD.

Abstract: Provided herein are diagnostic and prognostic methods, diagnostic and prognositic markers, and methods for evaluating anti-inflammatory agents or drugs in subjects with asthma and/or an analogous disease associated with high oxidative and nitrative stress at the disease site. In certain embodiments, the methods comprise a step of assaying for decreased levels of superoxide dismutase activity in the blood, serum, or plasma of the subject. In certain embodiments, the methods comprise a step of assaying for elevated levels of one or more oxidatively-modified SOD isoforms or species in the blood, serum or plasma of the subject. Also provided are diagnostic kits for use in the present invention. In certain embodiments, such kits comprise at least one binding reagent that specifically binds to at least one oxidatively-modified SOD species.

Abstract: Diagnostic tests for characterizing an individual's risk of developing or having a cardiovascular disease. In one embodiment the present diagnostic test comprises determining the level of myeloperoxidase (MPO) activity in a bodily sample obtained from the individual or test subject. In another embodiment, the diagnostic test comprises determining the level of MPO mass in a bodily sample obtained from the test subject. In another embodiment, the diagnostic test comprises determining the level of one or more select MPO-generated oxidation products in a bodily sample obtained from the test subject. The select MPO-generated oxidation products are dityrosine, nitrotyrosine, methionine sulphoxide or an MPO-generated lipid peroxidation products.

Abstract: Methods for characterizing a test subject's, particularly a human test subject's, risk of having cardiovascular disease or developing cardiovascular disease are provided. Also provided are methods for characterizing a test subject's risk of experiencing a complication of cardiovascular disease near term. The methods comprise determining levels of one or more carbamylated biomarkers in a bodily fluid of the test subject and/or comparing these levels with a reference value. In certain embodiments, the carbamylated biomarkers are carbamylated albumin, carbamylated fibrinogen, carbamylated immunoglobulin and carbamylated apolipoprotein A. In other embodiments, particularly where the test subject does not have clinical evidence of renal disease, the carbamylated biomarker is free and/or total peptide-bound homocitrulline.

Abstract: Methods of characterizing a test subject's risk of having or developing cardiovascular disease are provided. The methods include using an analytic device to determine levels of choline-related trimethylamine-containing compounds such as trimethylamine N-oxide, choline, or betaine in a biological sample obtained from the subject and comparing the levels of the choline-related trimethylamine-containing compound in the subject's biological sample to a control value. The test subject's risk of having cardiovascular disease is then characterized as higher if the levels of the choline-related trimethylamine-containing compound are higher than the control value. Also provided are methods of identifying a subject at risk of experiencing a complication of atherosclerotic cardiovascular disease, and methods of evaluating the efficacy of a cardiovascular therapeutic agent in a subject with cardiovascular disease using levels of choline-related trimethylamine-containing compounds.

Abstract: Provided herein methods for determining whether a subject, particularly a human subject, is at risk of developing, having, or experiencing a complication of cardiovascular disease, and methods of treating subjects who are identified by the current methods of being at risk for cardiovascular disease. In one embodiment, the method comprises determining levels of one or more oxidized apolipoprotien A-I related biomolecules in a bodily sample from the subject. Also, provided are kits and reagents for use in the present methods. Also provided are methods for monitoring the status of cardiovascular disease in a subject or the effects of therapeutic agents on subjects with cardiovascular disease. Such method comprising determining levels of one or more oxidized apolipoprotein A-I related molecules in bodily samples taken from the subject over time or before and after therapy.

Abstract: A diagnostic method of monitoring anti-inflammatory and/or antioxidant actions of therapeutic agents comprises determining the level of at least one systemic marker indicative of inflammation or oxidation in a bodily sample taken from a subject at base line or following administration of the therapeutic agent. The marker includes at least one of MPO activity, MPO mass, select MPO-generated oxidation products, and combinations thereof. The level of the systemic marker is compared with a predetermined value to monitor the anti-inflammatory and/or antioxidant actions of the therapeutic agent.

Abstract: The present invention provides methods and agents for treating subjects who have or are at risk of developing or having cardiovascular disease. Such agents inhibit binding of myeloperoxidase (MPO) to a molecule comprising the MPO binding site of apolipoprotein A-1 (apoA-1) and include a peptide fragment of apoA-1 comprising at least 4 contiguous amino acids in SEQ ID. NO: 2, a modified form of the apo-1 fragment comprising one or more D amino acids, a retro-inverso form of the apoA-1 peptide fragment, an organo-mimetic of the apoA-1 peptide fragment, a peptide-mimetic of the apoA1 peptide fragment, or a nucleic acid encoding the apo A-1 peptide fragment. The present invention also provides methods of identifying or screening test agents for treating subjects having or at risk of having or developing CVD.

Abstract: A diagnostic method of monitoring anti-inflammatory and/or antioxidant actions of therapeutic agents comprises determining the level of at least one systemic marker indicative of inflammation or oxidation in a bodily sample taken from a subject at base line or following administration of the therapeutic agent. The marker includes at least one of MPO activity, MPO mass, select MPO-generated oxidation products, and combinations thereof. The level of the systemic marker is compared with a predetermined value to monitor the anti-inflammatory and/or antioxidant actions of the therapeutic agent.

Abstract: The invention features methods and compositions for diagnosis, including prognosis, of conditions associated with decreased arginine bioavailability (which can result from dysregulated arginine metabolism, e.g., due to increased arginase activity) by assessing in a sample from a subject the ratio of arginine to one or more, usually two or more, modulators of arginine bioavailability. In one embodiment, the ratio of arginine to (ornithine+citrulline) is assessed to aid in diagnosis.

Abstract: Provided herein methods for determining whether a subject, particularly a human subject, is at risk of developing, having, or experiencing a complication of cardiovascular disease, and methods of treating subjects who are identified by the current methods of being at risk for cardiovascular disease. In one embodiment, the method comprises determining levels of one or more oxidized apolipoprotein A-I related biomolecules in a bodily sample from the subject. Also, provided are kits and reagents for use in the present methods. Also provided are methods for monitoring the status of cardiovascular disease in a subject or the effects of therapeutic agents on subjects with cardiovascular disease. Such method comprising determining levels of one or more oxidized apolipoprotein A-I related molecules in bodily samples taken from the subject over time or before and after therapy.

Abstract: The invention features methods and compositions for diagnosis, including prognosis, of conditions associated with decreased arginine bioavailability (which can result from dysregulated arginine metabolism, e.g., due to increased arginase activity) by assessing in a sample from a subject the ratio of arginine to one or more, usually two or more, modulators of arginine bioavailability. In one embodiment, the ratio of arginine to (ornithine+citrulline) is assessed to aid in diagnosis.

Abstract: Provided herein are methods for assessing the risk a subject or patient without significant evidence of cardiovascular disease has of experiencing a major adverse cardiac event or requiring revascularization near term. Also provided are methods of determining whether a subject who has experienced a major adverse cardiac event is at risk of experiencing a recurrent major adverse cardiac event near term. The present methods comprise determining the levels of paraoxonase 1 enzymatic activity in the blood, serum, plasma, or any combination of said bodily fluids in the subject.

Abstract: A purified polypeptide includes an ApoA1 mimetic or fragment thereof that are resistant to oxidation.

Abstract: Methods for characterizing the near term risk of experiencing a major adverse cardiac event in a patient presenting with chest pain are provided. In one embodiment the method comprises determining the level of myeloperoxidase (MPO) activity in a bodily sample obtained from the patient. In another embodiment, the method comprises determining the level of MPO mass in a bodily sample obtained from the patient. In another embodiment, the method comprises determining the level of one or more select MPO-generated oxidation products in a bodily sample obtained from the patient. The select MPO-generated oxidation products are dityrosine, nitrotyrosine, chlorotyrosine, methionine sulphoxide or an MPO-generated lipid peroxidation product.

Abstract: A method of detecting ovarian cancer in a female test subject comprising determining the amount of plasmenyl-PA or a biomarker having a mass charge ratio of approximately 655.3 in a sample of a bodily fluid taken from the female test subject and comparing the amount of plasmenyl-PA (or the biomarker) in the sample of the bodily fluid taken from the female test subject to a range of amounts of plasmenyl-PA (or the biomarker) found in samples of bodily fluids taken from a group of normal female subjects of the same species as the female test subject and lacking ovarian cancer, whereby a lower amount of the plasmenyl-PA (or the biomarker) in the sample of the bodily fluid taken from the female test subject indicates the presence of ovarian cancer.