# Multi-Scale Integration of Extracellular Matrix Mechanics in Vascular Remodeling

> **NIH NIH R01** · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · 2020 · $414,300

## Abstract

PROJECT ABSTRACT
Increased stiffness in large elastic arteries is a significant contributor to the progression of cardiovascular
disease. Diabetic patients show accelerated large arterial stiffening at a relatively young age compared to
nondiabetic subjects. Biomechanical and biochemical changes have been associated with vascular remodeling
in diabetic patients. As a long-lived extracellular matrix (ECM) protein, elastin provides the elasticity necessary
for cyclic deformation of the arterial wall. The cumulative effects of biochemical exposure encountered during
aging and disease can greatly compromises its mechanical function. However little is known about the
important pathophysiological effects of the coupled biochemical and mechanical changes on the cardiovascular
system. This lack of understanding is most likely to be correlated with the understudied ECM mechanics and
the lack of experimental techniques to reveal the structural, mechanical, and biochemical interactions among
ECM constituents in arterial remodeling. Elastin and collagen are the major ECM constituents in large elastic
arteries. The structural and mechanobiological interactions between elastin and collagen, the primary load-
bearing components in the arterial wall, are important for properly functioning arteries. However in all previous
structural models of arteries, interactions among ECM constituents are usually ignored.
The overall goal of this proposed work is to develop a multi-scale model of ECM mechanics that biochemical
modifications and ECM interactions, and use this model to study the biochemical, structural, and mechanical
remodeling of arterial ECM in large elastic arteries from humans and mice with diabetes with two specific aims:
Specific aim 1: Create a multi-scale structural-chemo-mechanical model of ECM mechanics that integrate the
intrinsic mechanical, structural, and biochemical interactions among ECM constituents; and Specific Aim 2:
Use the model to study the multi-scale mechanical, structural, and biochemical remodeling of ECM in diabetes.
Consideration of the interactions between elastin and collagen is an innovative idea and may lead to a major
advancement in structure-based constitutive modeling. Biochemical modifications of ECM represent an
important emerging area in the field of constitutive modeling of soft biological tissues in aging and many
diseases. The proposed work using a structural deterministic approach to incorporate fibrous network
structure, advanced imaging technique, and rigorous mechanical testing made it possible to develop a multi-
scale model of ECM mechanics and interactions. Combining with a study in diabetes, this research approach
has a great potential to unravel the underlying key mechanisms of ECM remodeling. Due to the important
reciprocal interactions between cells and ECM, looking at the ECM may open up new perspectives in
therapeutic interventions. Results form this study will provide new understandings on the underlying
...

## Key facts

- **NIH application ID:** 9994104
- **Project number:** 5R01HL098028-08
- **Recipient organization:** BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
- **Principal Investigator:** Yanhang Katherine Zhang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $414,300
- **Award type:** 5
- **Project period:** 2010-12-15 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9994104

## Citation

> US National Institutes of Health, RePORTER application 9994104, Multi-Scale Integration of Extracellular Matrix Mechanics in Vascular Remodeling (5R01HL098028-08). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9994104. Licensed CC0.

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