# Studying guinea pig development to discover how natural collateral arteries form

> **NIH NIH R21** · STANFORD UNIVERSITY · 2021 · $236,347

## Abstract

PROJECT SUMMARY
 Coronary artery disease (CAD) is the leading cause of death worldwide and poses a significant
burden on healthcare and patient quality of life. It is caused by pathology of the coronary arteries that
occludes blood flow to ventricular heart muscle. Existing revascularization treatments, such as coronary
artery bypass grafts (CABG) or percutaneous coronary interventions, are not an option for all patients
and have significant failure rates. One alternative approach could be induction of collateral arteries,
which are a rare subset of arteries that bridge two conventional arteries and provide an alternative route
for blood flow (i.e., natural bypasses). A small subset of human patients develops collateral arteries,
and elevated collateral blood flow increases survival in humans. Thus, stimulating collateral arteries
could be a useful treatment for CAD, yet their developmental mechanisms and biological
functions are poorly understood.
 Our laboratory will utilize the normal biology of guinea pig hearts to discover mechanisms of
collateral artery development. Guinea pigs are completely resistant to permanent coronary artery
occlusion due to numerous collateral arteries, which are absent in most mammals including mice. In
preliminary data, our laboratory discovered that guinea pig collateral arteries develop during embryonic
development, a feature that will greatly facilitate discovery. We propose to use a comparative biology
approach that uncovers collateral artery developmental mechanisms by comparing guinea pig
and mouse embryonic hearts. (Aim1) We will use whole mount immunohistochemistry and single
cell RNA sequencing to perform cellular resolution comparisons between developing guinea pig and
mouse hearts. Genes and pathways correlating with collateral arteries (i.e. guinea pig hearts) will be
considered candidate drivers of their development. (Aim2) We will next functionally test these
candidates by introducing them into neonatal mouse hearts and assessing whether they induce
collateral artery development.
 Upon completion of these aims, we will have fully established the guinea pig as a model to aid
the study of collateral arteries. This includes compiling a guinea pig heart cell atlas, identifying how the
guinea pig heart compares with mouse, and testing select candidate collateral inducers. Success will
motivate a longer-term project with translational implications for CAD.

## Key facts

- **NIH application ID:** 10195510
- **Project number:** 1R21HL157827-01
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Mary Red-Horse
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $236,347
- **Award type:** 1
- **Project period:** 2021-05-14 → 2023-04-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10195510

## Citation

> US National Institutes of Health, RePORTER application 10195510, Studying guinea pig development to discover how natural collateral arteries form (1R21HL157827-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10195510. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*