# Microbe-Related Modulation of Neointimal Hyperplasia after Arterial Injury

> **NIH NIH R03** · NORTHWESTERN UNIVERSITY · 2020 · $79,000

## Abstract

PROJECT SUMMARY/ABSTRACT
While it is increasingly evident that gut microbiota are drivers of chronic inflammatory conditions including
diabetes mellitus and obesity, the influence of host-gut microbial cross-talk on inflammation in peripheral
arteries and arterial remodeling after injury is not well understood. Specifically, although it is accepted that local
and systemic inflammation drive the development of restenosis after cardiovascular interventions such as
bypass surgery, balloon angioplasty, and stenting, the role of gut microbes as the source or regulators of the
inflammatory process is not well delineated. The PI has previously demonstrated that modulation of gut
microbiota by antibiotics to permit expansion of gram-negative organisms is associated with exacerbated
neointimal hyperplasia development after balloon angioplasty in a rat model of arterial injury. In addition, germ-
free wildtype mice have attenuated inflammation and neointimal hyperplasia development after arterial injury.
Finally, the PI observed that exchanging microbiota between rats from genetically different strains resulted in
modulation of strain-related neointimal hyperplasia phenotypes and local arterial and systemic inflammation
after angioplasty. We also established that the relative abundance of 8 specific gut microbial genera regardless
of cage sharing status or rat strain correlated significantly with neointimal hyperplasia development. Taken
together, these preliminary data support our hypothesis that specific gut microbiota have a disease-modifying
effect on neointimal hyperplasia by regulating the host inflammatory response. To explore this hypothesis, we
propose the following aims for this 2-year proposal: Aim 1) To investigate the direct contribution of specific
microbial communities on neointimal hyperplasia and inflammation. Aim 2) To evaluate the effect of specific
reference bacterial strains on neointimal hyperplasia development and inflammation. Insights on how these
specific microbial communities and community members drive host intestinal, arterial, and systemic
inflammation to affect arterial remodeling will potentially uncover novel microbe-related therapeutic targets that
can be used to prevent and treat restenosis in patients undergoing vascular reconstruction.

## Key facts

- **NIH application ID:** 9985160
- **Project number:** 5R03HL146880-02
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** KAREN J. HO
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $79,000
- **Award type:** 5
- **Project period:** 2019-08-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9985160

## Citation

> US National Institutes of Health, RePORTER application 9985160, Microbe-Related Modulation of Neointimal Hyperplasia after Arterial Injury (5R03HL146880-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9985160. Licensed CC0.

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