# (CIRCADIAN) Circadian Disruption as Mediator of Cardiometabolic Risk in Air Pollution

> **NIH NIH R35** · CASE WESTERN RESERVE UNIVERSITY · 2022 · $960,396

## Abstract

ABSTRACT
Particulate matter air pollution <2.5µm (PM2.5) is the leading environmental risk factor globally, contributing more
to global mortality than AIDS, malaria, tuberculosis and wars/famines combined. The health risks associated
with PM2.5 are predominantly from cardiovascular (CV) causes, with data supporting a major public health impact
due to disorders such as type 2 diabetes. Building on the substantial successes of our research program, that in
large part have provided the foundational basis for our understanding of mechanisms of PM2.5-induced
cardiometabolic disorders, we propose an innovative framework of translational investigations. Our new data
provide compelling links between PM2.5 exposure and circadian rhythm (CR) disruption through epigenetic
reprogramming, resulting in metabolic dysfunction and insulin resistance. In accordance with the NIEHS
Translational Research Framework, we propose an ambitious plan encompassing 3 goals over 8 years that will
encompass harmonized studies involving concentrated ambient PM2.5 exposures (animal) and human
intervention trials across the ambient exposure spectrum, predicated and supported by results from genome
wide association and mendelian randomization approaches, that will identify pathways of air pollution mediated
CV risk. Leveraging on-going translational clinical trials of air pollution reduction using personalized strategies in
vulnerable populations in Beijing, and through one new study involving mitigation of air pollution (ITS-MY-AIR),
we will evaluate the impact of exposure reduction on CR disruption/sleep and metabolic endpoints. Collectively,
results from this project will help shed important new light on air pollution, its impact on CR and cardiometabolic
disorders and provide influential data on protective effects of personal intervention strategies, that together could
change public health policy.

## Key facts

- **NIH application ID:** 10452498
- **Project number:** 5R35ES031702-02
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** Sanjay Rajagopalan
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $960,396
- **Award type:** 5
- **Project period:** 2021-07-17 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10452498

## Citation

> US National Institutes of Health, RePORTER application 10452498, (CIRCADIAN) Circadian Disruption as Mediator of Cardiometabolic Risk in Air Pollution (5R35ES031702-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10452498. Licensed CC0.

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