# Novel Neural Mechanisms underlying Lung-Heart Pathological Crosstalk

> **NIH NIH R01** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2021 · $539,046

## Abstract

Pulmonary and cardiovascular diseases are leading causes of morbidity and mortality worldwide. Several
pulmonary diseases are associated with cardiovascular complications, and vice versa. Therefore, an
understanding of cardio-pulmonary interaction and the effects of disease and therapeutic interventions on
cardio-pulmonary status is central to the management of patients with cardiopulmonary diseases. Over the past
several decades, the interest in the cardiopulmonary critical care field has been largely focused on the
mechanical interaction between the two organs. However, little attention has been given to a potential
cardiopulmonary neural interaction via their shared autonomic ganglia. Considering the fact that the lungs and
heart anatomically share common spinal afferents (i.e. T1-T4 dorsal root ganglia (DRG)) and efferent (i.e.
stellate and T2-T4 sympathetic chains) nervous systems, here we hypothesize that damage to one organ
(either heart or lung) will trigger a neuro-inflammatory cascade that includes macrophage activation in
autonomic ganglia common to both organs. This results in alterations in both afferent and efferent sensitivities in
both organs. To test this hypothesis, we will determine 1) if cardiac injury such as myocardial infarction (MI)
chronically causes macrophage activation in T1-T4 DRGs and stellate ganglia, thus increasing both
sympathetic afferent and efferent sensitivity to and from the heart and lungs; 2) if bleomycin-induced lung
injury also causes macrophage activation in both T1-T4 DRGs and stellate ganglia, resulting in increased
cardiac afferent and efferent sensitivity and cardiac arrhythmias. We will use highly integrative techniques
including molecular (western blot, immunofluorescence and RNA-seq analysis), cellular (patch clamp) and
whole animal experiments (measuring cardiopulmonary afferent reflexes, chronic conscious ECG telemetry
recording and pressure-volume loop analysis of cardiac function) to test these hypotheses. The most exciting
concept created by this proposal is that the heart and lung can reciprocally interact to sensitize their afferent and
efferent autonomic pathways through macrophage activation at the level of their shared autonomic ganglia. To
the best of our knowledge, this is a completely new mechanism, which has not been recognized before.
The long-term impact of this study is the identification of macrophage infiltration into the peripheral nervous
system as a new therapeutic target to treat cardiac and pulmonary diseases.

## Key facts

- **NIH application ID:** 10136083
- **Project number:** 5R01HL152160-02
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** HANJUN WANG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $539,046
- **Award type:** 5
- **Project period:** 2020-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10136083

## Citation

> US National Institutes of Health, RePORTER application 10136083, Novel Neural Mechanisms underlying Lung-Heart Pathological Crosstalk (5R01HL152160-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10136083. Licensed CC0.

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