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The effect of systemic hypertension on prognosis of myocardial infarction: Understanding, prediction and therapy evaluation

Award Number: R00HL138288
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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The effect of systemic hypertension on prognosis of myocardial infarction: Understanding, prediction and therapy evaluation - Project Summary Thinning of the heart wall and remodeling of the heart left ventricle (LV) are key consequences of myocardial infarction (MI). These consequences can be considerably influenced by pressure overload in the LV as both a risk factor for MI and a cause of pathological myocardial hypertrophy. The effect of antecedent systemic hypertension (ASH) on the LV remodeling due to MI, and more importantly on the success of regenerative medicine therapies following MI remains poorly understood. Our long-term objective for this proposal is to improve our understanding on how the LV adapts to MI under ASH, and to develop an experimentally-validated computational model that can predict this adaptation. Traditional measures such as LV dilation and infarct size used to characterize the LV remodeling provide limited information on cardiac performance. New computational tools are needed to reveal detailed description and prognosis of multiscale remodeling of infarcted LV. Following the hypothesis that the LV wall stress regulates the onset and extent of LV remodeling, we will develop an image-based computational model bridging the gap between local microstructural and mechanical adaptations of LV myocardium and organ-level functional changes. We will then extend this model to simulate and predict possible improvements in the contractility of infarcted myocardium under ASH following stem-cell interventions. This model provides a platform to investigate the role of wall stress restoration in the improvement of myocardial contractility in infarcted hearts with and without ASH. Towards our goal, we propose to determine the regional hypertrophy and remodeling mechanisms from image- based microstructural and mechanical data obtained from normotensive and hypertensive rat models of MI (Aim 1). We will then build a microstructurally-faithful, rat-specific finite element model that accounts for local growth and remodeling and validate it using in vivo data from the rat models of MI (Aim 2). Finally, we will use our computational model to investigate the correlation between the restoration of the wall stress and the success of stem-cell interventions in our rat models of MI (Aim 3). Three specific aims of this proposal are then summarized as: 1. Quantify the time-course heterogeneous hypertrophy and remodeling events at fiber-, tissue-, and organ-levels following MI under ASH. 2. Develop a time-evolving rat-specific computational model of heart and validate the model using in vivo data. 3. Investigate the correlation between wall stress restoration and the efficacy of stem-cell therapy following MI.


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: 2024 ( Subtotal = -$63,721 )
2024	2022	TEXAS A&M ENGINEERING EXPERIMENT STATION	3124 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Cardiovascular Diseases Research	000	5	8/1/2024	NON-COMPETING CONTINUATION	-$63,721
														Subtotal = -$63,721

Issue Date FY: 2022 ( Subtotal = $235,967 )
2022	2022	TEXAS A&M ENGINEERING EXPERIMENT STATION	7607 EASTMARK DR	COLLEGE STATION	TX	77840	BRAZOS	USA	Cardiovascular Diseases Research	000	5	3/18/2022	NON-COMPETING CONTINUATION	$235,967
														Subtotal = $235,967

Issue Date FY: 2021 ( Subtotal = $305,825 )
2021	2021	TEXAS A&M ENGINEERING EXPERIMENT STATION	7607 EASTMARK DR	COLLEGE STATION	TX	77840	BRAZOS	USA	Cardiovascular Diseases Research	001	4	5/25/2021	NON-COMPETING CONTINUATION	$242,104
2021	2020	TEXAS A&M ENGINEERING EXPERIMENT STATION	7607 EASTMARK DR	COLLEGE STATION	TX	77840	BRAZOS	USA	Cardiovascular Diseases Research	000	3	12/10/2020	EXTENSION WITH OR WITHOUT FUNDS	$63,721
														Subtotal = $305,825

Issue Date FY: 2020 ( Subtotal = $249,000 )
2020	2020	TEXAS A&M ENGINEERING EXPERIMENT STATION	7607 EASTMARK DR	COLLEGE STATION	TX	77840	BRAZOS	USA	Cardiovascular Diseases Research	000	3	4/10/2020	EXTENSION WITH OR WITHOUT FUNDS	$249,000
														Subtotal = $249,000

Grand Total All Awards = $727,071

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The effect of systemic hypertension on prognosis of myocardial infarction: Understanding, prediction and therapy evaluation

Award Number: R00HL138288

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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