# Modeling Multiscale Immuno-Mechanics in Aortic Disease

> **NIH NIH R01** · YALE UNIVERSITY · 2023 · $491,820

## Abstract

PROJECT SUMMARY - MODELING MULTISCALE IMMUNO-MECHANICS IN AORTIC DISEASE
Most vascular diseases result from, or lead to, diminished biomechanical function. Consistent with homeostatic
processes tending to oppose detrimental changes in soft tissues, many vascular diseases can be attributed to
compromised or lost homeostasis. Whereas mechanical homeostasis is well appreciated in large arteries, it has
recently been recognized that inflammation can contribute to tissue homeostasis, though also to disease initiation
and progression. There is, therefore, a need to understand together the mechano-biological and immuno-
biological control of arterial geometry, composition, properties, and function. The overall goal of this project is to
develop and test general data-informed computational models of immuno-mechanics from molecule to matrix.
Given that hypertension is a significant risk factor for diverse vascular diseases, we will illustrate the utility of our
computational model by focusing on mouse models of hypertensive aortic remodeling while examining effects of
sex within the context of immune status and age of onset of the hypertension relative to different stages of aortic
development. Early onset hypertension in children and adolescents is reaching epidemic proportions in the USA,
but is poorly understood. We will thus gather extensive data sets that will inform and validate our novel multiscale
computational models while revealing critical new understanding of aortic development and hypertensive risk.
Given the complementary roles of mechanical and inflammatory homeostasis, a key goal of pharmacotherapy
should be to support tissue homeostasis while limiting or preventing pathological processes. Thus, we will also
collect data to contrast the efficacy of reducing either the mechanical stress (anti-hypertensive) or the oxidative
stress (anti-inflammatory), or both. We hypothesize that the efficacy of a type of drug, or combination thereof,
will depend on the time of onset of hypertension, particularly given that very early onset hypertension can alter
aortic development by establishing new homeostatic states and set-points. To our knowledge this important
understanding has not yet been addressed within a rigorous experimental-theoretical framework. This work will
be founded on prior advances by our group – including consistent biomechanical phenotyping that ensures
reproducibility and fundamental new concepts such as mechanobiological stability that ensure mathematical and
biomechanical rigor – but will significantly extend these concepts to build a unique systems understanding of
immuno-mechanics. This work is significant because of the pressing need to understand better many soft tissue
diseases, particularly hypertension and its alarming increased affliction of children and adolescents (as noted by
the CDC and many others); it is innovative in its approach (modeling immuno-mechanics, delineating innate and
adaptive immunity) and focus (hyperte...

## Key facts

- **NIH application ID:** 10532786
- **Project number:** 5R01HL155105-02
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Jay D. Humphrey
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $491,820
- **Award type:** 5
- **Project period:** 2022-01-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10532786

## Citation

> US National Institutes of Health, RePORTER application 10532786, Modeling Multiscale Immuno-Mechanics in Aortic Disease (5R01HL155105-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10532786. Licensed CC0.

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