# Activated Protein C and Cardiac Inflammatory Response

> **NIH NIH R01** · UNIVERSITY OF SOUTH FLORIDA · 2020 · $185,342

## Abstract

Abstract
 Activated protein C (APC) was first identified as a natural anticoagulant enzyme. Besides its anti-
coagulant activity, APC exerts cytoprotective effects such as anti-inflammatory and anti-apoptosis. It has
revealed that APC reduces the mortality rate and apoptotic rate during cardiac ischemia and reperfusion.
However, the mechanism involved in cardioprotection stimulated by APC is still unclear. The objective of this
project is to illustrate the mechanism by which APC mediates cardioprotection against ischemic injury. Our
preliminary data demonstrated that the administration of APC reduced myocardial infarction during ischemia and
reperfusion. AMP-activated protein kinase (AMPK), a cardioprotective signaling, was activated in APC treated
mouse heart. Moreover, ischemia and reperfusion-induced stress-activated protein kinase (SAPK/JNK) signaling
was attenuated by APC treatment. We hypothesize that APC protects against myocardial ischemic injury by
triggering crucial signaling pathways to modulate substrates metabolism and reducing inflammatory response
under ischemic stress. Three specific aims will be addressed to test the hypothesis: 1) determine the modulation
of AMP activated protein kinase signaling by APC derivatives during ischemia and reperfusion in the heart; 2)
determine the effect of APC derivatives on inflammatory response during ischemia and reperfusion in the heart;
3) determine the mechanisms by which APC modulates glucose transport that reduces ROS responsible
inflammatory response in the ischemic heart. APC may decrease the pro-inflammatory factors during cardiac
ischemia and reperfusion to reduce heart injury. We also will figure out whether anticoagulant domain of APC is
not important for its cardioprotction against ischemia and reperfusion injury, which will provide evidence that
recombinant APC without anticoagulant activity can be used for therapy of ischemic heart disease without risk
of bleeding.

## Key facts

- **NIH application ID:** 10134637
- **Project number:** 3R01GM124108-04S1
- **Recipient organization:** UNIVERSITY OF SOUTH FLORIDA
- **Principal Investigator:** Ji Li
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $185,342
- **Award type:** 3
- **Project period:** 2018-05-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10134637

## Citation

> US National Institutes of Health, RePORTER application 10134637, Activated Protein C and Cardiac Inflammatory Response (3R01GM124108-04S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10134637. Licensed CC0.

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