# Role of RhoA in small AAA growth

> **NIH VA I01** · VA NORTHERN CALIFORNIA HEALTH CARE SYS · 2022 · —

## Abstract

Project Summary/Abstract
An abdominal aortic aneurysm (AAA) is a vascular condition where a major blood vessel in the body can
degenerate, balloon in size leading to ultimate rupture and sudden death. Currently, an AAA is identified through
imaging studies performed as part of a screening study or incidentally when evaluating for other abdominal
pathology. Given that the most important clinical parameter in predicting rupture is the maximal aortic diameter,
a normal aorta of 2.0 cm or less requires no further evaluation, whereas a large aorta >5.5 cm in men and >5.0
cm in women requires surgery. Based upon a large VA population based prospective analysis, 20% of veterans
with small aortas (3.0-5.4 cm) will grow rapidly and may pose a threat to the life of the veteran. Unfortunately,
we do not know which small AAAs will grow rapidly, others slowly, and still others not at all. Failure to identify
rapidly growing small AAAs will lead to a certain but preventable death. Thus, there is a critical need to develop
predictive markers for rapidly growing small AAAs so that surgery can be performed timely.
The medical management of small AAA is one of the top research priorities in the care of the Veterans with
vascular disease. We hope to establish our central hypothesis that RhoA mediated monocyte adhesion to the
aortic endothelium leads to endothelial barrier injury, subsequent monocyte transmigration, increased aortic wall
destruction, and ultimate small AAA growth. This hypothesis will be tested by the following specific aims: 1) To
determine whether the activation of RhoA in monocytes from Veteran subjects with a growing small AAA
will lead to increased monocyte adhesion, and endothelial barrier injury, 2) To determine whether
monocyte RhoA plays a causal role in AAA formation in the animal model, 3) To determine whether high
RhoA protein activity isolated in the monocytes from Veteran subjects with small AAA will predict the
growth of the small AAA (>0.1 cm/year). Current studies have shown the possibility of RhoA as a biomarker
for disease in both AAA formation and growth. RhoA and monocyte activity were identified to be highly expressed
in both the serum and aortic tissue from subjects with AAA compared to age-matched controls, The role of RhoA
in comparing human subjects with growing AAA or stable AAA has yet to be elucidated. To date, there is a lack
of translatability of the data obtained from tissue in human subjects (late in the disease process) or findings from
animal models to the human patient with small AAAs. The innovation of this project is the connection between
the use of RhoA and monocyte activity into an overarching mechanism of biomarkers, leading to future novel
therapies to control small AAA growth. This is a translational study using human Veteran subjects with the readily
available 1,169 veterans identified with small AAAs (3.0-5.4 cm) collected over a 10-year period to make the
completion of the proposed study feasible. Ultim...

## Key facts

- **NIH application ID:** 10295147
- **Project number:** 5I01CX001683-04
- **Recipient organization:** VA NORTHERN CALIFORNIA HEALTH CARE SYS
- **Principal Investigator:** Zhenheng Guo
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2018-10-01 → 2023-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10295147

## Citation

> US National Institutes of Health, RePORTER application 10295147, Role of RhoA in small AAA growth (5I01CX001683-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10295147. Licensed CC0.

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