# Lysophosphatidic Acid Mediates Cardiac Inflammation After Acute Infarction

> **NIH NIH R01** · UNIVERSITY OF KENTUCKY · 2020 · $382,500

## Abstract

PROJECT SUMMARY/ABSTRACT
Ischemic heart disease is the leading cause of morbidity and mortality in the U.S. population and is often caused
by acute myocardial infarction (AMI). AMI initiates an inflammatory response leading to increased circulating
inflammatory bone marrow cells (BMCs), particularly monocytes (monocytosis). This response is crucial for
removing dead tissue and initiating the healing process. However, exacerbated inflammatory response following
AMI can be detrimental and is associated with infarct expansion, poor cardiac remodeling and adverse clinical
outcomes. While most studies focus on monocyte production following AMI, the mechanism(s) of monocyte
egress from the bone marrow and early cardiac infiltration after AMI are poorly understood. Our preliminary data
demonstrate the role of the signaling bioactive lipid, lysophosphatidic acid (LPA), in the post-AMI mobilization of
BMCs. LPA, produced by the enzyme autotaxin (ATX), plays a key role in activating inflammatory monocytes,
regulating their peripheral blood count and homing them to sites of inflammation. Preliminary studies also
indicated that LPA levels are elevated early in PB and cardiac tissues after AMI in humans and mice. The long-
term goal is to contribute to development of new clinically useful therapies for AMI injury. The overall objective
of this application is to define LPA mediated signaling pathways linking AMI to the inflammatory BM response.
The rationale for the proposed research is its potential to offer new approaches to reduce inflammation and
improve cardiac recovery after AMI. The central hypothesis is that LPA plays a key role in initiating and
maintaining the post-AMI inflammatory response, thus impairing cardiac recovery. This hypothesis will be tested
by pursuing three specific aims: 1) Identify the molecular mechanism(s) that result in elevated plasma LPA after
AMI, 2) Determine the signaling systems by which ATX/LPA axis promotes monocytosis after AMI, and 3) define
the association between LPA levels, heritable genetic variability in LPA receptor 1 that predicts receptor
expression and monocytosis after AMI in humans. Results of these studies are expected to provide new
mechanistic understanding of AMI-induced ATX/LPA signaling, their contribution to AMI-associated systemic
monocytosis and cardiac inflammation and the role of heritable genetic mutations in monocytosis and
inflammation in humans. To attain this goal, the proposed project will combine human studies with animal models
with genetic manipulation of key components of the ATX/LPA signaling. This group has extensive experience in
studying heart/BM signaling after AMI as well as ATX/LPA signaling pathways. The overall impact of these
studies derives from an innovative focus on the ATX/LPA signaling nexus as a critical mechanism in AMI-induc ed
inflammation and the potential to control post-AMI infarct expansion and subsequent heart failure by dampening
this pathological response.

## Key facts

- **NIH application ID:** 9977877
- **Project number:** 5R01HL138488-04
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** Ahmed Abdel Latif
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $382,500
- **Award type:** 5
- **Project period:** 2017-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9977877

## Citation

> US National Institutes of Health, RePORTER application 9977877, Lysophosphatidic Acid Mediates Cardiac Inflammation After Acute Infarction (5R01HL138488-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9977877. Licensed CC0.

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