# Beta-catenin in vascular homeostasis and remodeling

> **NIH NIH R01** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2020 · $562,458

## Abstract

Canonical Wnt/beta-catenin (β-ctn) signaling plays a crucial role in embryonic
development and homeostasis of many adult tissues. Conditional inactivation of β-ctn,
the sole downstream mediator of pathway activity, demonstrates its necessity in multiple
diverse processes in vivo. Inactivation of β-ctn in endothelial cells (ECs), for example,
yields embryonic vascular defects limited to the central nervous system, while systemic
vascular development appears normal. Interestingly, our recent studies show that
inactivation of β-ctn in vascular smooth muscle cells (SMCs) in mice causes death by
embryonic day (E) 12.5, with systemic arteries that are dilated and incompetent due to
impaired SMC proliferation, survival, and investment of the developing vascular wall.
Thus during development, SMCs of the systemic circulation require β-ctn expression,
while corresponding ECs do not. Our mechanistic analysis indicates that the former
effect depends in part on critical signals from the β-ctn C-terminal domain that suppress
acetylation and activity of the tumor suppressor p53.
β-ctn functions in the adult vasculature and its potential roles in vascular homeostasis or
remodeling are not well understood. Our preliminary studies indicate that SMC β-ctn
can be inactivated in the adult mouse without immediate vascular consequences, but
that neointimal formation after vascular injury is significantly reduced by its absence.
How β-ctn inhibition affects adult vascular integrity, response to injury, and
atherosclerosis has not been reported. These gaps in our understanding are significant,
because aberrant β-ctn signaling has been implicated in the pathogenesis of multiple
cancers, and thus inhibition of β-ctn serves as a potentially important target in several
emerging anti-neoplastic strategies. This proposal encompasses three aims: first, to
determine how β-ctn suppresses SMC p53 activity, second, to assess β-ctn structural and
N- vs C-terminal signaling functions in vascular homeostasis, injury response, and
atherosclerosis, and third, to test Wnt/β-ctn inhibition as a potential therapeutic strategy
for control of accelerated vascular remodeling and/or atherosclerosis.
Analysis of β-ctn in vascular function is relevant to understanding how new therapies
based on Wnt/β-ctn inhibition may affect vascular homeostasis, and should allow us to
evaluate the safety of such approaches and their potential utility in treatment of vascular
disease.

## Key facts

- **NIH application ID:** 9884555
- **Project number:** 5R01HL133861-04
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** Nicholas E Sibinga
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $562,458
- **Award type:** 5
- **Project period:** 2017-06-15 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9884555

## Citation

> US National Institutes of Health, RePORTER application 9884555, Beta-catenin in vascular homeostasis and remodeling (5R01HL133861-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9884555. Licensed CC0.

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