# MIF and Cardiovascular Inflammation

> **NIH NIH R01** · UNIVERSITY OF SOUTH FLORIDA · 2022 · $373,750

## Abstract

Project Summary
Clinical studies have reported a higher incidence of surgical stress-induced acute injury in the elderly. The
mortality after cardiac surgery, atherosclerosis, sepsis, or coronary angioplasty in patients older than 60 years
of age appears to be related to a decline in intrinsic resistance to surgical stress-related acute injury. The
mechanisms responsible for the atherosclerosis-related vascular intolerance in aging are incompletely
understood and the signaling pathways involved in regulating cellular responses to acute injury related
inflammation arising from surgical stress remain largely unknown. The blocked vessels by atherothrombosis
cause ATP depletion and subsequent AMP accumulation, which activates AMP-activated protein kinase
(AMPK), a central component of the cellular stress response that regulates oxidative metabolism towards ATP
restoration under stress conditions. AMPK regulates pathways that control the oxidative stress-related
vascular inflammation. We have reported that an aging-related reduction in the macrophage migration
inhibitory factor (MIF)-AMPK signaling cascade is an important contributing factor leading to increased
sensitivity to reactive oxygen species (ROS) by surgical ligation of the left anterior descending coronary artery.
Accordingly, we hypothesize that aging is associated with a decline in the ability of vascular cells to render the
MIF-AMPK signaling cascade active in response to inflammation caused by atherosclerosis, thus resulting in
exacerbated vascular injury. We will test this hypothesis in the following specific aims: Aim 1, define the role of
the MIF receptor in age-related impaired AMPK signaling in response to vascular inflammation by oxidative
stress; and Aim 2, evaluate the capability of small-molecule MIF agonist to improve stress-induced MIF-AMPK
activation in the cardiovascular system. In this manner, we seek to advance our understanding of the
mechanisms behind aging-related alterations in cardiac AMPK signaling pathways in response to inflammation
by surgical ligation of the coronary artery. Furthermore, we propose both exercise and a novel pharmacological
strategy aimed at ameliorating oxidative stress-induced vascular inflammation that occurs in the older
population.

## Key facts

- **NIH application ID:** 10450128
- **Project number:** 5R01HL158515-02
- **Recipient organization:** UNIVERSITY OF SOUTH FLORIDA
- **Principal Investigator:** Ji Li
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $373,750
- **Award type:** 5
- **Project period:** 2021-07-15 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10450128

## Citation

> US National Institutes of Health, RePORTER application 10450128, MIF and Cardiovascular Inflammation (5R01HL158515-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10450128. Licensed CC0.

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