# 8OH-G miR-483 contributes to the aging-accelerated atherosclerosis

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2022 · $237,000

## Abstract

Project Summary/Abstract
Atherosclerosis is a sequela of aging, in part, because aging exacerbates the atherogenic factors (e.g., oxidative
stress), which induces endothelial cells (ECs) senescence. MicroRNAs (miRs) are ubiquitously involved in
epigenetic regulation of gene expression by targeting the 3’-untranslated region (3’UTR) of the protein-encoded
transcripts. Recently, we have reported that the miR-483 endows anti-endoMT, anti-fibrotic, and anti-
inflammatory effects on the endothelium, contributing to a homeostatic endothelium. Emerging evidence
indicates that oxidative stress can cause hydroxylation of guanine (G) in miRs to generate 8-oxo-7,8-dihydro
guanosine (8OH-G) which induces the guanine-to-uracil (G-U) transversion of miRs. Because 8OH-G pairs with
adenine (A), the oxidative stress-modified miRs no longer target their authentic mRNA effectually. This
epitranscriptomic change results in distinctive functions in the cell, therefore sways the disease process. In the
newly conducted pilot studies, we found elevated levels of 8OH-G miR-483 in senescent ECs in culture and
vascular intima in aging mice. Moreover, EC function is affected by the molar ratio of miR-483/8OH-G miR-483,
revealed by RNA-seq. These newly acquired results lead to the overarching hypothesis that the aging-induced
miR-483 to 8OH-G miR-483 transversion causes EC senescence and dysfunction. Mechanistically, this miR
epitranscriptomic change alters mRNA targetomes in ECs, which instigates aging-induced EC dysfunction and
thereby aggravating atherosclerosis. To test this hypothesis, the following two specific aims are proposed: Aim
1. To delineate the molecular mechanism by which aging-induced 8OH-G miR-483 impairs EC function.
Specifically, we will decipher the 8OH-G miR-483 epitranscriptomes by investigating the aging-associated G-to-
U transversion of miR-483 and the specificity of 8OH-G-miR-483 targeting mRNAs. We will also study the
sequelae of 8OH-G miR-483 with respect to EC senescence. Aim 2. To investigate the atheroprone effect of
8OH-G miR-483 in aging mice. We will introduce atherosclerosis in young and aged iEC-miR-483-Tg and their
wildtype littermate mice. Atherosclerosis and vascular functions will be compared among young and old mice as
functions of G-to-8OH-G miR-483 ratio and deduced 8OH-G miR-483 regulatory network. With the use of in vitro
and in vivo experimental models, this exploratory research proposal will decipher the role of miR-483 to 8OH-G
miR-483 transversion in EC biology and aging-deteriorated atherosclerosis.

## Key facts

- **NIH application ID:** 10452425
- **Project number:** 1R21AG075450-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Ming He
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $237,000
- **Award type:** 1
- **Project period:** 2022-06-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10452425

## Citation

> US National Institutes of Health, RePORTER application 10452425, 8OH-G miR-483 contributes to the aging-accelerated atherosclerosis (1R21AG075450-01A1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10452425. Licensed CC0.

---

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