# The Role of TP-R on Alcohol-Induced Multi-Organ Damage: Liver and Heart

> **NIH NIH P50** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2024 · $241,763

## Abstract

It is well-established that liver is the primary target of ethanol action and alcohol-associated liver
disease (AALD) is a major health concern in general population. It should also be noted that the
incidence of heart disease due to chronic alcohol consumption continues to rise owing to the
increased chronic alcohol drinking habits among humans. It is becoming increasingly evident that a
strong positive correlation exists between alcohol-associated liver injury (AALD) and alcoholic
cardiomyopathy (ACM). It has recently become clear that the combination of obesity with heavy
drinking exacerbates ethanol-induced organ injury. Thus, there is an urgent need to define
mechanisms by which obesity and alcohol either individually or in combination, promote liver and
cardiac injury. Central to our hypothesis is that thromboxane-prostanoid receptor (TP-R) is a
common link between AALD and ACM. TP-R is a G-protein coupled receptor, expressed in all
tissues, and is activated by thromboxane A2 as well as isoprostanes, eicosanoids mediating
inflammatory response and oxidative stress. TP-R is known to play a role in the pathophysiology of
several chronic inflammatory diseases, such as cardiovascular disease and certain autoimmune
diseases. Little is known, however about a role for TP-R in modulating obesity and alcohol-related
disorders. We present exciting preliminary data in this proposal that ethanol-induced hepatic
inflammation is greatly attenuated in TP-R-KO mice. Interestingly, our preliminary data also show
that TP-R expression is significantly higher in human peripheral blood mononuclear cells (PBMCs)
collected from patients with obesity or CVD compared to control subjects and therefore, its
involvement in both AALD and ACM might be important, and present opportunities for treatment.
Based on previous reports and our preliminary data, we hypothesize that in the presence of obesity,
chronic alcohol consumption promotes liver and cardiac injury and this effect is mediated at least in
part, via activation of TP-R through its effects on inflammation and oxidative stress. We will use
nutritional, genetic, and molecular approaches to determine the role of TP-R in altering AALD and
ACM. In Aim 1, we will define the role of hepatocyte-TP-R in modulating ethanol- and/or obesity-
induced liver injury and cardiomyopathy in mice. In Aim 2, we will assess the role of cardiomyocyte-
TP-R in modulating ethanol- and/or obesity-induced liver injury and cardiomyopathy in mice. Overall,
the proposed research will uncover the role of TP-R in modulating AALD and ACM in the presence
or absence of obesity, to identify potential mechanisms, and to set the stage for the development of
effective therapeutic agents for human patients affected by the metabolic complications of obesity
and/or excess ethanol consumption.

## Key facts

- **NIH application ID:** 10797029
- **Project number:** 5P50AA030407-02
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** Saraswathi Viswanathan
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $241,763
- **Award type:** 5
- **Project period:** 2023-02-28 → 2028-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10797029

## Citation

> US National Institutes of Health, RePORTER application 10797029, The Role of TP-R on Alcohol-Induced Multi-Organ Damage: Liver and Heart (5P50AA030407-02). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10797029. Licensed CC0.

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