# Biomimetic Vascular Matrix for Vascular Smooth Muscle Cell Mechanobiology and Pathology

> **NIH NIH R56** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2022 · $639,543

## Abstract

SUMMARY
Arterial stiffness is a key risk factor for cardiovascular disease (CVD) events. Change in arterial stiffness
is a significant pathology in vascular injury, atherosclerosis, and coronary disease by which stiffening of
the vessel wall promotes anomalous migration and proliferation of vascular smooth muscle cells
(VSMCs) causing neointima formation of the vessel wall. Yet, the molecular mechanisms by which
pathological ECM stiffness regulates VSMC proliferation and migration associated with pathological ne-
ointima formation are unclear. This research proposal will address this gap by exploring how changes
in arterial stiffness elicit VSMC behaviors that contribute to CVD. More specifically, this work draws upon
newly collected preliminary data that show a novel role for the protein survivin as a key regulator of
stiffness-mediated VSMC proliferation and migration and an effector of arterial stiffening and remodel-
ing. Using mouse and human VSMCs, this study will first explore how vascular ECM stiffness impacts
VSMC migration, proliferation, and chromatin organization at the single-cell level (early stage of disease
progression; Aim 1); and, secondly, determine how pathological ECM stiffness drives neointima for-
mation altering the local mechanical environment of VSMCs in vitro (advanced stage of disease pro-
gression; Aim 2). Lastly, this research proposal will test survivin’s role in regulating both ECM production
and arterial stiffness (in vivo animal model; Aim 2). These aims will be achieved using a 3D cell culture
using a novel in vitro porcine decellularized aorta ECM based (daECM) fibrous scaffold system and
engineered mouse injury models. Briefly, VSMCs isolated from mouse and human aortas will be cultured
on daECM-based nanofibrous scaffolds of different stiffnesses that mimic normal and pathological con-
ditions in the body. The VSMC responses to pathological ECM stiffness will be analyzed using advanced
microscopy to observe changes in cellular/nuclear structure, biomechanical properties, and the RNA
and protein expressions at the single-cell level in vitro. Finally, engineered mice will be used to study
stiffness and VSMC function in intact arteries, performing a histological examination and biochemical
analyses of dissected tissue after stiffness is manipulated by arterial injury, drug treatment, or genetic
mutations. This project will, for the first time, study the molecular and biophysical mechanisms by which
survivin 1) mediates stiffness-sensitive VSMC functions, and 2) contributes to neointima formation and
stiffening, revealing a completely new aspect of survivin biology in VSMCs and in the pathology of arte-
rial stiffness. Overall, this proposal is unique in its ability to identify potential new therapeutic targets for
the treatment of CVDs.

## Key facts

- **NIH application ID:** 10683796
- **Project number:** 1R56HL163168-01
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** Yongho Bae
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $639,543
- **Award type:** 1
- **Project period:** 2022-09-09 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10683796

## Citation

> US National Institutes of Health, RePORTER application 10683796, Biomimetic Vascular Matrix for Vascular Smooth Muscle Cell Mechanobiology and Pathology (1R56HL163168-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10683796. Licensed CC0.

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