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

> **NIH NIH R00** · TEXAS ENGINEERING EXPERIMENT STATION · 2020 · $249,000

## Abstract

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.

## Key facts

- **NIH application ID:** 10091577
- **Project number:** 4R00HL138288-03
- **Recipient organization:** TEXAS ENGINEERING EXPERIMENT STATION
- **Principal Investigator:** Reza Avazmohammadi
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $249,000
- **Award type:** 4N
- **Project period:** 2020-04-15 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10091577

## Citation

> US National Institutes of Health, RePORTER application 10091577, The effect of systemic hypertension on prognosis of myocardial infarction: Understanding, prediction and therapy evaluation (4R00HL138288-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10091577. Licensed CC0.

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