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Integrated proteomic and metabolomics analysis of thrombotic myocardial infarction

Award Number: SC1GM139730
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/01/2021
PERIOD OF PERFORMANCE END DATE: 01/31/2025

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Integrated proteomic and metabolomics analysis of thrombotic myocardial infarction - Project Summary / Abstract: Acute myocardial infarction (MI) is defined as myocardial ischemia, the inadequate supply of blood to heart muscle, followed by myocardial cell death. Multiple causes of acute MI are widely recognized and can be categorized as thrombotic, non-thrombotic, and acute MI secondary to coronary procedures. The mechanistic cause of a thrombotic MI is the rupture or erosion of an atherosclerotic plaque that results in the formation of a thrombus, or blood clot, which occludes the flow of blood. In contrast, non-thrombotic MI occurs secondary to mechanisms which create an oxygen supply and demand imbalance, but are not associated with atherosclerotic plaque rupture or disruption. Given that myocardial cell death is the pathological characteristic that is common to all acute MI, non-invasive diagnostics for acute MI are based on the detection of myocardial cell death. Currently non-invasive diagnostics for differentiating thrombotic MI from non-thrombotic MI do not exist which results in sub-optimal treatment and diminished patient safety. Further, it is not known how the impacts on metabolism and biological processes differ between thrombotic and non-thrombotic MI. In this project, we will address both of these problems. We will develop a diagnostic method for the non-invasive differentiation of thrombotic MI versus non-thrombotic MI that will enable earlier, safer, and more precise targeting of therapeutics to patients suffering from acute MI. We will determine biological processes that differ between thrombotic and non-thrombotic MI, which will suggest targets for therapeutic intervention that are specific to the underlying cause of an acute MI. In Aim 1 we will utilize high resolution mass spectrometry to determine the absolute concentration of over 500 proteins in previously collected plasma samples from human subjects who were experiencing an acute MI for which the cause (thrombotic versus non-thrombotic) was determined. This will enable us to determine which proteins report on the cause of the acute MI as opposed to the presence of myocardial cell death. A critical advantage of our study design is that we have repeated measures from the same human subjects: at the time of presentation, 6 hours post-presentation, and at a stable event-free follow-up timepoint 3 months after the acute MI. In Aim 2 we will integrate this data with our existing data on the abundances of metabolites and lipids generated from the same human subject samples. This integrated data will facilitate an in-depth analysis of the differences between thrombotic and non-thrombotic MI in the activities of metabolic pathways, receptor-ligand binding events, and other biochemical reactions. Further we will conduct data- dependent systems biology analyses that will highlight proteins, metabolites, and lipids that are co-abundant in plasma and will evaluate how the topology of these related entities differs between thrombotic and non- thrombotic MI. In Aim 3 we will develop a statistical classifier for the determination of the underlying cause of an acute MI. We will conduct a blinded evaluation of the performance of this classifier in a second cohort.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = -$209,229 )
2025	2024	NEW MEXICO STATE UNIVERSITY	1050 STEWART ST.	LAS CRUCES	NM	88003	DONA ANA	USA	Biomedical Research and Research Training	000	4	6/10/2025	NON-COMPETING CONTINUATION	-$209,229
														Subtotal = -$209,229

Issue Date FY: 2024 ( Subtotal = $222,000 )
2024	2024	NEW MEXICO STATE UNIVERSITY	1050 STEWART ST.	LAS CRUCES	NM	88003	DONA ANA	USA	Biomedical Research and Research Training	000	4	1/30/2024	NON-COMPETING CONTINUATION	$199,800
2024	2024	NEW MEXICO STATE UNIVERSITY	1050 STEWART ST.	LAS CRUCES	NM	88003	DONA ANA	USA	Biomedical Research and Research Training	001	4	8/2/2024	NON-COMPETING CONTINUATION	$22,200
														Subtotal = $222,000

Issue Date FY: 2023 ( Subtotal = $222,000 )
2023	2023	NEW MEXICO STATE UNIVERSITY	1050 STEWART ST STE E1200	LAS CRUCES	NM	88003	DONA ANA	USA	Biomedical Research and Research Training	000	3	2/3/2023	NON-COMPETING CONTINUATION	$199,800
2023	2023	NEW MEXICO STATE UNIVERSITY	1050 STEWART ST STE E1200	LAS CRUCES	NM	88003	DONA ANA	USA	Biomedical Research and Research Training	001	3	2/24/2023	NON-COMPETING CONTINUATION	$22,200
														Subtotal = $222,000

Issue Date FY: 2022 ( Subtotal = $222,000 )
2022	2022	NEW MEXICO STATE UNIVERSITY	1050 STEWART ST STE E1200	LAS CRUCES	NM	88003	DONA ANA	USA	Biomedical Research and Research Training	001	2	6/14/2022	NON-COMPETING CONTINUATION	$22,200
2022	2022	NEW MEXICO STATE UNIVERSITY	1050 STEWART ST STE E1200	LAS CRUCES	NM	88003	DONA ANA	USA	Biomedical Research and Research Training	000	2	1/20/2022	NON-COMPETING CONTINUATION	$199,800
														Subtotal = $222,000

Issue Date FY: 2021 ( Subtotal = $222,000 )
2021	2021	NEW MEXICO STATE UNIVERSITY	1050 STEWART ST STE E1200	LAS CRUCES	NM	88003	DONA ANA	USA	Biomedical Research and Research Training	000	1	2/1/2021	NEW	$222,000
														Subtotal = $222,000

Grand Total All Awards = $678,771

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Integrated proteomic and metabolomics analysis of thrombotic myocardial infarction

Award Number: SC1GM139730

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 02/01/2021

PERIOD OF PERFORMANCE END DATE: 01/31/2025

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