# CARDIAC MITOHORMESIS PROTECTS AGAINST DIABETIC CARDIOMYOPATHY THROUGH MITOPHAGY: EVALI ADMINISTRATIVE SUPPLEMENT

> **NIH NIH R00** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2020 · $180,124

## Abstract

PROJECT SUMMARY
This application is being submitted in response to NOT-HL-19-724. The use of e-cigarettes has been rapidly
increasing among young adults in the US but the health effects of prolonged e-cigarette use are unknown. The
toxicity of e-cigarette was recently highlighted by the large number of recent cases of acute lung injury associated
with e-cigarette use or vaping (EVALI), resulting in a total of 2,807 hospitalized EVALI cases or deaths. Whether
these cases are linked to the vaping of illicit compounds-containing e-liquids or the widely used nicotine-
containing e-liquids remain to be determined. Importantly, characterization of EVALI patients who had to be
rehospitalized or died after initial discharge revealed the presence of one or more comorbities including cardiac
disease, respiratory diseases and diabetes which suggests certain cohort of e-cigarette users are at increased
risk of EVALI. In this Supplement to the Parent R00 HL130416, we propose to leverage patient-derived human
induced pluripotent stem cell (iPSC) platform towards determing the pathogenesis of EVALI as a consequence
of e-cigarette or its constituents and how the presence of susceptibility factors may worsen the outcome. We
hypothesize diseased iPSC-derived cells will exhibit increased cytotoxicity compared to healthy cells when
exposed to e-cigarette and its constituents. Aim 1 will be based on the differentiation of iPSCs representing
different risk factors (healthy, diabetes alone, diabetes with cardiomyopathy) into endothelial cells and alveolar
epithelial cells. Upon exposure of these cells to e-cigarette or vitamin E acetate and its toxic derivative ketene,
phenotypic characterization of cellular health will be performed to determine which of these constituents induces
the most toxicity. In Aim 2, we will investigate the mechanism of e-cigarette-induced endothelial dysfunction and
focus on the p62/NRF2/KEAP1 anti-oxidative stress pathway since we observed that only healthy cells had
sustained levels of p62 upon exposure. We will also perform proteomic profiling of exosomes isolated from
healthy and diseased iPSC-ECs upon exposure in order to identify novel biomarkers that can potentially predict
the development of EVALI. In summary, this Administrative Supplement proposal will create novel opportunities
to establish a human-based iPSC repository representing different risk factors that can be used to evaluate
health outcomes from vaping. The combination of biochemical methodologies coupled with proteomics will also
allow a deeper mechanistic understanding behind the increased susceptibility of certain patients against EVALI
and provide biomarkers that may be predictive of EVALI development.

## Key facts

- **NIH application ID:** 10115974
- **Project number:** 3R00HL130416-05S1
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Sang Ging Ong
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $180,124
- **Award type:** 3
- **Project period:** 2016-08-15 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10115974

## Citation

> US National Institutes of Health, RePORTER application 10115974, CARDIAC MITOHORMESIS PROTECTS AGAINST DIABETIC CARDIOMYOPATHY THROUGH MITOPHAGY: EVALI ADMINISTRATIVE SUPPLEMENT (3R00HL130416-05S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10115974. Licensed CC0.

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