# Harnessing Neu5Gc sialidases to treat Neu5Gc-associated atherosclerosis

> **NIH NIH F30** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $38,242

## Abstract

Project Summary/Abstract
One of the fundamental challenges facing cardiovascular research is the treatment of atherosclerosis, the single
greatest cause of cardiovascular disease worldwide. Red meat consumption has long been linked to increased
atherosclerosis incidence in humans, although not in other non-human mammals. A potential human-specific
mechanism proposes that atherosclerosis is partly driven by an antibody-mediated reaction to the nonhuman
sialic acid Neu5Gc, a molecule that is heavily enriched in red meat. Neu5Gc is structurally similar to the human
sialic acid Neu5Ac, but humans cannot produce Neu5Gc due to an evolutionary loss of the CMAH enzyme gene.
However, ingested Neu5Gc can be incorporated into the glycoconjugates of human cells, including endothelial
cells. Cell culture and mouse models have shown that the presence of circulating anti-Neu5Gc antibodies leads
to activation of endothelial inflammation pathways and increased atherosclerosis plaque size and necrotic core
volume. Removal of Neu5Gc from endothelial glycoconjugates could therefore reduce activity of the
inflammatory pathways that lead to atherosclerosis.
This research seeks to use novel bacterial sialidases (enzymes that can cleave Neu5Gc) in a mouse model to
reduce Neu5Gc uptake and incorporation into endothelial glycoconjugates, thereby mitigating atherosclerosis
development. If successful, Neu5Gc sialidases would represent a new class of atherosclerosis treatment agents
to pursue. Specifically, the aims of this proposal are to: (1) to enrich bacterial species producing Neu5Gc
sialidases in gut microbiota, thereby reducing intestinal Neu5Gc uptake and preventing incorporation into
endothelial glycoconjugates; and (2) to inject the sialidase Sia26 to therapeutically release Neu5Gc from
endothelial glycoconjugates after it has been incorporated. A humanized (Cmah-/-) mouse model of
atherosclerosis will be used to provide the physiological context critical for studying Neu5Gc-associated
atherosclerosis risk. Together, these aims will address the effect of Neu5Gc sialidases on atherosclerosis
through Neu5Gc cleavage in the gut and in circulation. The proposed studies will clarify the role of Neu5Gc as a
human-specific trigger of atherosclerosis and investigate the potential of Neu5Gc sialidases as a novel treatment
strategy.

## Key facts

- **NIH application ID:** 9991243
- **Project number:** 1F30HL152666-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Joanna Coker
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $38,242
- **Award type:** 1
- **Project period:** 2020-09-30 → 2022-09-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9991243

## Citation

> US National Institutes of Health, RePORTER application 9991243, Harnessing Neu5Gc sialidases to treat Neu5Gc-associated atherosclerosis (1F30HL152666-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9991243. Licensed CC0.

---

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